ESSENTIAL PHARMACOTHERAPEUTICS To all those who believe in Humanity First Edition

Transcription

ESSENTIAL PHARMACOTHERAPEUTICS
To all those who believe in Humanity
First Edition
Dr Sunil Chaudhry MD, Ph.D (AM), Dsc (AM)
Head -Medical Affairs, Bayer Pharmaceuticals Pvt Ltd
Adhoc Board Member in Pharmacy, SNDT University &
Visiting Faculty CU Shah College of Pharmacy
Ex-Associate Professor, Pharmacology,
Lokmanya Tilak Municipal Medical college,
Sion, Mumbai- 400022.
Publishers
Mukesh Vora Publications
Mumbai.
Distribution
"Our Knowledge is the amassed thought and experience
of innumerable minds"
- Ralph Waldo Emerson
1-A
1-B
Copyright reserved
© Dr S. Chaudhry (E-mail : [email protected])
First Edition : November 2004
Publisher
Mukesh Vora
Editors
Prof. Savita Shahani (Head Dept. of Pharmacology LTMC, Sion, Mumbai)
Dr. Suresh Maroli (Incharge Nuclear Medicine, LTMC, Sion, Mumbai)
Dr. Debora Natalia - Situmeang (Head Medical Regional Office, Bayer, Singapore)
Phototypeset
Tanushree Enterprises
2/24, Municipal Chawl,
Dr. E. Moses Road,
Opp. Geeta Cinema,
Worli Naka, Mumbai -18.
E-mail : [email protected]
2-A
2-B
PROLOGUE
FOREWORD
Pharmacology has undergone tremendous changes in last decade and hence
every part of this text is thoroughly revised and attempts has been made to
furnish the reader with all the latest information. This book is meant for all those
who aspire to read the core of the concept in pharmacology such as, Pharmacy
Students, Medical Students, Paramedical Students & Nursing Staff or those
appearing for competitive examinations.
Pharmacology requires clear understanding and constant reading . For all the
paramedical, its always important to have the clear understanding about the
basics. The lucid presentation in this book will make the easier assimilation of
the concepts. For the sincere effort , I wish author the success
Dr Shashank Joshi ([email protected])
Hon Assoc Professor Endocrinology
Grant Medical college and Sir JJ group of Hospitals
Byculla, Honrary Endocrine and Metabolic Physician
Lilavati Hospital, Bandra-400 050
Readers can now refer to latest information. In this century there is no dearth of
information as this can be procured either through the informative CD`s or through
the internet
The medical text in form of hard print can provide certain aspects which are
easier to understand and assimilate. Hence, this book would provide readers a
quick understanding, but at the same time it is not a substitute to a standard
medical book
We wish our sincere thank to Dr Shashank Joshi who was instrumental to give
the necessary thrust to change the image of book
Dr Sunil Chaudhry
Thane-400607
August 2004
ACKNOWLEGEMENT
Sincerely thank all those who have supported in preparation of this text by
giving their active suggestions. Sincere thanks to Dr B.D. Samant Professor
and Head Dept. of Pharmacology from KEM Hospital & Dr. S. S. Ainapure from
M.G.M Medical College Mumbai. My sincere thanks to Dr. Pradeep Vavia,
Professor UICT, Professor S. Y. Gabhe and Dr. Sushma Mengi, Reader, SNDT
for their valuable suggestion. Also my sincere thanks to Dr Samir Sadekar,
Dr Suresh Bowalekar, Dr. Rajani Shettigar Principal Saraswathi Education
Society, Dombivili. Dr Ravikant Sharma, (Sr Techinal Assistant, DGHS) Mr
Ajay Khanna (Techinal Officer, DGHS) & Mr. P. N. Raokhande (Assistant
Commissnor FDA, Maharashtra.) for their valuable inputs. I also thank Mr.
Kuldip Ambre for his effective inputs and valuable editing of the text.
Dr Sunil Chaudhry
3-A
3-B
GENERAL PHARMACOLOGY
1
Q1.
What is Pharmacology ?
A1.
The term is derived from Greek works "Pharmakon" which means a drug
and logos which means a study. It is the study of drugs. It also embraces
the knowledge of history, source, physical and chemical properties of
drugs.
Q2.
What is Drug ?
A2.
Any substance which changes a physiological function or modifies the
disease process. Drugs are chemicals that produce therapeutically
useful effects.
Q3.
What is Pharmacopoeia ?
A3.
Pharmakon means drug, poiein means make. It is a condensed text
which contains structure, solubility, description, identification, purity,
dosage and storage directions for drugs.
The pharmacopoieas are :
British Pharmacopoiea (BP)
United States Pharmacopoeia (USP)
European Pharmacopoeia (EP)
Indian Pharmacopoeia (IP)
There is also International Pharmacopoiea published by the World Health
Organisation.
Q4.
What are the criteria for drug and drug product quality ?
A4.
1)
3)
Be free from extraneous substances.
4)
Maintain its potency, therapeutic availability and appearance until
used.
5)
Upon administration, release the active ingredient for full biological
availability.
What is meant by the term Pharmacodynamics ?
A5.
What drug does to the body. e.g. Famotidine reduces acid and pepsin
output from parietal cells which reduces the production of hydrochloric
acid which in turn causes healing of peptic ulcers.
It is also the effect of drug on target organs.
Q6.
What is meant by the term Pharmacokinetics ?
A6.
What body does to the drug e.g. Ciprofloxacin is 80% absorbed, 25% is
protein bound and has wide tissue distribution.
It is the study of absorption, distribution, metabolism and excretion of
drug by the body. (ADME)
Q7.
What is Toxicology ?
A7.
Study of the poisonous effects of drugs. It also emphasises on detection,
prevention and treatment of poisoning.
Q8.
What is Agonist ?
A8.
4-A
Contain the same quantity of active ingredient from one dosage
unit to the next.
Q5.
Contain the quantity of each active ingredient claimed on its label,
within the applicable limits of its specifications.
General Pharmacology
2)
A drug which can produce response in form of a change in physiological
function by binding to a receptor. Eg. Acetylcholine acts on receptors in
the intestines and increases the contractions.
4-B
Q9.
What is Antagonist ?
Q11. What is Synergism of Potentiation ?
A9.
It binds to receptor causing no change in physiological function but
prevents an agonist from binding to receptor. Eg. Dicyclomine blocks
receptors in the intestines to prevent the contractile action of
Acetylcholine.
A11. The action of one drug is enhanced by other. Eg. Atenolol enhances the
antihypertensive action of amlodipine. Hydrochlorthiazide similarly
potentiates the action of Losartan.
Q12. What you understand by the term Potency ?
Q10. What is a Receptor ?
A10. An intracellular or extracellular structure which has chemorecognition
properties for specific drugs. Eg. Famotidine acts on H2 receptors which
are present on the parietal cells in the lumen of the gastrointestinal tract
thereby reducing the production of hydrochloric acid.
A12. It is the biological activity per unit weight of drug. Eg. Enalapril is more
potent than Captopril because 2.5 mg of enalapril has same biological
activity as 25 mg of Captopril. Enalapril is 10 times more potent than
Captopril.
Several theories are proposed to explain the drug receptor interactions:
Q13. What you understand by the term Efficacy ?
1)
Rate theory (Paton, 1961) - it is suggested that agonist action
depend on rate of agonist - receptor association and / or dissociation
and this in turn decides the magnitude of drug affects.
2)
Occupation theory (Ariens, 1964) - it assumes that the magnitude
of drug response depends on the proportion (%) of the receptors
occupied by the drug - the maximal affect being, when all the
receptors are occupied.
A13. It is the maximal therapeutic response produced by drug. It is evident
from the clinical studies that the antihypertensive response produced by
captopril and enalapril is similar. Hence both drugs are basically equally
effective in reducing BP. Most of statins such as Lovastatin, Simvastatin
Atorvastatin,Rosuvastatin have similar efficacy, but on terms of potency,
Rosuvastatin, appears to be most potent.
Q14. What are side effects ?
The fundamental types of receptors are :
1)
2)
Silent Receptors - an agonist may bind to a receptor and not produce
a pharmacological response. The relevant condition comes
following long-term usage of drug. This can explain the phenomenon
tolerance, which can lead to drug dependence.
A14. Unwanted and unavoidable pharmacodynamic effects that occur with
therapeutic doses. Eg. the incidence of gastrointestinal side effects
diarrhoea, skin rash are observed with most of broad spectrum antibiotics.
Adverse drug reach on :
It is unintended response to a medicinal product at any dose. For ADR
reporting Med watch form (available in US), Yellow card system (available
in UK), and CIOMS II form (used in all Europe) are generally used.
Spare Receptors - these are not qualitatively different from nonspare receptors. They are not hidden or unavailable and when they
are occupied they can respond.
5-A
5-B
Adverse durg events :
case from a clinical trial is the need for the investigator to assess
the causality for every event separately.
It is unintended response to a medicinal product to any dose but not
necessarily having a reasonable possibility of a caused relatioship.
b.)
PMS-studies are clinical trials that are done after the drug was
registered in a specific country. They normally have abbreviated
protocols and a short case record form to document efficacy and
side effects. It is important to note that cases from PMS-studies are
handled in the same manner as clinical cases described above.
Therefore, the use of the SAE reporting form and the complementary
page is mandatory and the LDSM must make sure that the respective
documents are filled in by the investigator, the monitor or himself.
Drug Safety Reports
1.) Spontaneous Cases
Spontaneous cases are cases where the reporting physician voluntarily
reports an adverse event to any Bayer employee. For this report he may
use any form of communication (phone, fax, E-mail, paper etc.). According
to the CIOMS rules, any spontaneously reported adverse event is assumed
"to have a causal relationship to the suspected drug, as otherwise the
physician would not have reported it".
2.) Non-Spontaneous Cases
The non-spontaneous cases can be divided into three groups, namely
clinical cases, cases from PMS-studies and cases from IM (Intensive
Monitoring )
a.)
Cases from PMS
Q15. What are Toxic effect ?
A15. These are result of over dosage or prolonged use. Eg. kidney damage
follows the long term use of Streptomycin. Hence, Rifampicin is the
preferred drug in treatment of tuberculosis where during initial phase the
four drugs are used.
Clinical cases
Cases from clinical studies are defined by having study protocol
specific case record form (which includes a reporting form for serious
adverse events). These studies follow specific procedures that are
defined in the protocol and the reporting of adverse events as a
mandatory part of these protocols. Such studies are supervised by
clinical monitors employed by company. There is a specific reporting
form for serious adverse events that must be used for clinical trials
and in addition a complementary page must be filled in by the monitor/
LDSM to summarize all SAE-related information.
Q16. What is Dose ?
A16. It is the appropriate amount of drug to produce a desirable effect. It is
expressed in terms of weight, volume or in standard units. Age is an
important factor for determining dose. In children dose is calculated on
the basis of age, weight or the body surface area.
The dose for a child may be calculated from the adult dose e.g. uptil 8
years of age as follows :
Child dose =
The basic difference between a spontaneously reported case and a
6-A
6-B
Age
-----------Age + 12
x
Adult dose
(Young's formula)
Child dose =
Age
-------20
x
Adult dose
(Dilling's formula)
Age (next birthday)
---------------------------x Adult dose
Child dose =
24
(Cowling's formula)
The geriatic age group (> 60 years) represents another subset of patients
who require special consideration. Certain physiological changes
occurring with age, require corresponding pharmacological alterations.
These changes are :
a)
Reduced body weight, body fat, intestinal motility, mesenteric blood
flow, renal function and hepatic metabolising capacity.
b)
Altered adrenoceptor sensitivity and mental function.
Therefore, the elderly often require lesser doses than adults and are
more prone to suffer from adverse drug reactions.
The following terms must be distinguished :
Depot dose
The single dose required to obtain a depot effect.
Fully effective dose
The dose displaying an optimal effect
Loading dose
This is a single or few quickly repeated doses given
in beginning to attain target concentration rapidly.
Maintenance dose
The dose that is repeated at specified intervals to
maintain the steady state of the drug for the desired
therapeutic effect.
Q17. What is Steady State ?
A17. It is a situation where there is minimal fluctuations in plasma levels of
the drug following multiple administration. At the steady state the rate
of drug entering the systemic circulation equals to the rate of elimination.
Time to attain 95% of steady state = 4.3 x T½.
Q18. What is Half-life ?
A18. It is the time taken for the concentration of drug to fall by half its original
value. Depending on the drug, complete elimination from the body takes
about 5 half lives. It is influenced by the route of administration, diffusion
into tissues, plasma protein, tissue binding, metabolism and renal
excretion.
Single dose
Single administration of a certain quantity of a drug.
Maximum dose
The largest dose that can be given without the
appearance of the toxic signs (intoxication).
Maximum daily dose
The quantity of drug that may be maximally
administered in one day.
Q19. What is meant by Bioavailability ?
Threshold dose
The initial dose to be given until the onset of effect.
A19. It is the rate and extent of absorption of a drug as reflected by time and
concentration curve. The estimation of the bioavailability of a drug in a
Saturation dose
The dose required to obtain the effect or the effective
tissue concentration within a certain period of time.
Maintenance dose
The dose that must be continued to be given after
saturation to maintain the effect or concentration.
Massive dose
High initial dose for the rapid attainment of
saturation.
7-A
given dosage form is direct evidence of the efficiency with which a dosage
form performs its int achieve maximum concentration.
AUC
7-B
: Area under curve which signifies bioavailability.
Q19. What is meant by volume of distribution (Vd in litres) ?
A19. =
than the rate of elimination. Cumulative drugs are Aminoglycosides,
such as streptomycin in tuberculosis.
Amount of drug in body (dose in mg)
Conc. of drug in plasma (mg/L)
Q22. What is Placebo ?
The volume of distribution has the following physiological significance :
1)
Drugs with high volume of distribution leave the body slowly and
penetrate deeply into the tissues.
2)
A high volume of distribution indicates better binding to many
receptor sites.
A22. In latin placebo means "I shall please". This is an inert substance
(sucrose, fructose) which is given in the garb of a medicine and acts by
psychological means Eg. patients feels better because he feels that he
has taken a medicine.
Q23. What you understand by terms LD50 and ED50 ?
Eg. Azithromycin, Linezolid and Ciprofloxacin achieve high tissue
concentration.
A23. LD50
: Median Lethal dose or LD50 is the dose in mg/kg which would
be expected to kill half of the animal population.
The Vd of a drug indicates whether the distribution of a drug is extracellular
or intracellular. For example, in a 70 kg man, total volume of body water
is 40 litres of which 25 litres is intracellular and 15 litres is extracellular.
The Vd of aspirin in such a person is 12 litres, suggesting that aspirin
has extracellular distribution.
ED50
: Median effective dose or ED50 is the dose in mg/kg which
produces a desired reaction in half of the animal or human
population.
Q24. What is Therapeutic Index ?
The Vd of a drug is also a crucial determinant of dialysability in overdose
or poisoning cases. A drug with a low Vd is easily dialysable.
A24. The ratio of median lethal dose to median effective dose. The higher
ratio indicates that the drug is more safe. Eg. famotidine, amoxycillin.
The larger the value of therapeutic index, the greater the safety of the
drug. For therapeutic application of a compound, its therapeutic index
must be more than one.
Q20. What is Tolerance and Tachyphylaxis ?
A20. A condition when on continuous use same dose does not give same
desired response and therefore the dose of the drug has to be increased.
Eg. tolerance develops to sedative actions of antihistaminic.
Tachyphylaxis, on the other hand, is the rapid development of tolerance
seen with drugs like ephedrine and tyramine (present in cheese).
The therapeutic index must be viewed as a general index, as some
patients may display extreme sensitivity to certain drugs, e.g. aspirin is
a very safe drug in therapeutic doses in the majority of persons, however,
severe hypersensitivity reactions to small doses of aspirin may occur in
some patients.
Q21. What is meant by Cumulation ?
A21. A drug will cumulate in the body if the rate of administration is more
8-A
8-B
Q25. What are the Routes of Drug Administration ?
Q26. What are the routes of Elimination ?
A25. Oral (O)
A26. It is the process of removal of administrated drug from the body.
Sublingual (SL)
: Commonest mode of a drug administration. Is
safe and convenient.
: Lipid soluble and non-irritating drugs can be given
as tablets to be placed under the tongue where
it dissolves and gets absorbed into the blood
stream. The chief advantage is that the liver is
bypassed, e.g. Nitroglycerine.
It is mainly through kidneys and small quantities of drugs is also excreted
through exhaled air, sweat, saliva, milk and faeces.
Q27. What is Bioequivalence ?
A27. When the in vivo bioavailability of one drug when compared with
bioavailability of same drug of another brand are found to be identical the
drugs are said to be bioequivalent. If the two products are bioequivalent
ideally they should produce similar therapeutic concentrations within
statistical limits and almost similar clinical cure.
Rectal (R)
: This route can be used when the patient is having
recurrent vomiting and certain irritant and
unpleasant drugs can be put inside the rectum.
Eg.Aminophylline.
Cutaneous
: Lipid soluble drugs can be applied over skin
surfaces, Eg. Fusidic acid, bacitracin.
Inhalation
: Volatile liquids and gases can be given by
inhalation. Eg. General anaesthetics.
A28. If two drugs are administered together and if there is a change in
pharmacodynamic or pharmacokinetic action of one or both the drugs it
is said that there is drug interaction between two drugs.
Nasal
: The mucus membrane of nose can absorb various
drugs. Eg. Oxymetazoline as a nasal
decongestant.
Eg. Milk products or antacids reduce the gastrointestinal absorption of
quinolones, tetracyclines etc.
Intramuscular (IM)
: Drugs are injected in one of large skeletal muscle.
The mild irritants can be injected and because
muscle is more vascular the drugs are absorbed
faster.
Intravenous (IV)
: The drug is injected as bolus or infused slowly
over hours in one of the superficial veins. The
dose of the drug which is required is smallest
and the bio-availability is about 100%.
Q28. What is meant by Drug Interaction ?
Q29. What is the significance of Plasma Protein Binding ?
A29. It is the binding of administered drug to the proteins present in blood.
High degree of protein binding makes the drug long acting because the
bound fraction is not available for metabolism or excretion.
Q30. What are the phases in a Clinical Trial ?
A31. After the animal toxicity is conducted in 1 rodent (rat) and 1 non-rodent
(rabbit) model the clinical studies are done in human beings using 1/8 to
1/10 of effective animal dose.
(Before launch of molecule in the market. They should be conducted as
per the good clinical practice)
9-A
9-B
Phase I study
Phase II study
Phase III study
Phase IV study
Bridging studies
: Pharmacodynamic parameters are studied on
human volunteers (number 50-100).
: Here there is effective dose searching and
detailed pharmacokinetic studies are done
(number 100-300).
: Controlled clinical trials are conducted by the
clinician to compare the test drug with the
standard reference drug or a placebo (number
is large).
(After launch of molecule)
: It is an interactive module. Post marketing
surveillance (PMS) : where the drug is in market
and there is an organised reporting about its
side effects by general practitioners,
consultants and hospitals. This is mandatory
for all products in the market.
: These are done in special situations on various
pharmacokinetic or pharmacodynamic
parameters with the aim to fill the lacune in the
international data and also to fill the local
available data, which is required by the
authorities in that country.
Q34. What is meant by Warning ?
A34. It indicates that the drug should be used cautiously in those particular
conditions.
Q35. What do you understand by the term Teratogenicity ?
A35. Administration of certain drugs to pregnant women, specially during first
trimester of pregnancy can result in deformities of the growing foetus.
Such drugs are said to be teratogenic. Eg. Antiepileptics cause foetal
deformity if given during pregnancy.
Q36. Mention the form of Medicaments
Name
Character
Example
1. MIXUTRE
It is a medicament indeed
for oral aministration which
contains dissolved, suspended
or emulsified particles and is
Salicylate mixture
Pectin Kaolin
mixture
usually more than one dose.
2. DRAUGHT
It is a single effective dose of
a mixture
Albendazole Mist
alba draught
3. ENEMA
Liquids intended for rectal
administration
Evacuant enema for
constipation.
Retention enema
for raised intra
cranial pressure and
ulcerative colitis.
4. GUTTAE
Concentrated solutions of
active medicaments usually
Neb. Ephedrine
Gutt. Sada bicarb
Q33. What is meant by Contraindication ?
A33. It indicates that the drug should not be used in a particular condition or
in cases of pregnancy and lactation where the harmful effects of drugs
are more evident eg. Pioglitazone is contraindicated in any condition of
heart failure
10-A
10-B
12.OINTMENT
not exceeding 2 ml., used as
instillation in E.N.T.
5. IRRIGATION
OR
BATH
Liquid preparation in large
volume containing antiseptics
Cetavlon bath
6. LINIMENT
It is a liquid preparation for
external use contains camphor
which has to be applied with
friction.
Turpentine
liniment
Name
Character
Example
7. LOTION
It is a medicament for
application to skin or mucus
membrane acting as soothing
agent or antiseptic
Caladryl lotion
Finely divided drug
intended for internal use.
Dusting powders are for
external use
Seidlitz powder
Nebasulf powder
Made of gelatin. Contains
powdered for liquid drug
Vitamin capsules
Antibiotic Capsules
8. POWDER
9. CAPSULE
11. SUPPOSITORY
Produced by compressing
granules, intended to be
swallowed. It may be film
or enteric coated
Any drug can be in
tablet form.
e.g. - Ondensetron
tablets
Cone shaped medicaments
Dulcolax
with greasy base to be inserted suppositories,
in rectum
Sulphur ointments,
Whitfield's
ointment
or mucus membrane
e.g. Cefadroxyl
10.TABLET
Mixture of active ingredients
with fats, waxes intended for
external application to skin
13.OCCULENIUM
It is eye ointment
a) Prepared aseptically
b) Has a long nozzle
c) Contains unbleached
paraffin
Sofracort ointment
Tobramycin
ointment
Name
Character
Example
14.PLASTER
1. Plaster of paris - for
immobilising joints
2. Self adhesive
3. Diachylon
Gypsona plaster.
15.OCCUSERT
Ellipticle biodegradable
polymer inserted in cul de sac
of eye
Sustained release
pilocarpine to treat
glaucoma
16.PROGRESSTASERT
Intra uterine device releasing
50µg. progesterone daily
Prevents pregnancy
17.TRANSDERMAL
THERAPEUTIC system
Post auricular patch to give
sustained release of drug.
Scopolamine for
motion sickness,
Clonidine for
hypertension
Cantharidin plaster.
Belladona plaster
Q37. Mention the kinetics at the extremes of life
A37
Pediatric pharmacology:
There are pharmacokinetic differences between a child and an adult.
11-A
11-B
(1)
(2)
Absorption:-
Geriatric pharmacology:
The absorption of cephalosporins is less in neonates than in infants. The
topical steroids can cause severe eczema in infants and children. Vitamin
riboflavin can cause higher serum concentration in children.
The incidence of adverse drug reactions in elderly is about 3 times more
as the metabolising capacity of liver and the excretory functions of kidnies
are reduced.
Distribution:-
(1)
New borns have a higher extracellular fluid volume. Total body water is
more and fat content is less. Therefore the absorption and distribution of
fat soluble drugs is reduced, eg. Fat soluble vitamins, griseofulvin.
(3)
Absorption:The absorption of vitamins, sugars and minerals are diminished in
elderly.
(2)
Distribution:-
Plasma protein binding of drugs is decreased in newborn. This is
particularly marked in the presence of hyperbilirubinaemia. Salicylates,
Sulphonamides which are bound to plasma albumin with affinity can
displace bilirubin from albumin binding sites leading to hyperbilirubinaemia
or Kemicterus in new born.Malnutrition states such as Kwashiorkor and
nephrosis can also lead to hypoalbuminaemia.
(3)
Development of blood brain barrier in newborn is incomplete and therefore
lipid soluble drugs have increased permeability to brain such as general
anaesthetics and sedatives.
Clinical considerations:-
Phenytoin, warfarin, and carbenoxolone are less bound lo plasma
proteins in the aged.
Dose of digoxin and chlorpropamide have to be monitored as the
drug excretion rate falls to about 30%. Streptomycin dose should
be reduced in elderly lo about 2/3rd.
Elimination:
Chloramphenicol given in the usual doses can lead to 'Gray baby syndrome
because the liver enzymes are immature and there is defective excretion
of drug. The renal function in the neonate is about 30 to 40% less than of
adult.
(1)
Tetracycline can delay bone growth if given during this time.
(2)
Small dose of phenothiazines, metoclopramide and even chloroquine
can cause acute dystonic reactions in children. Therefore if the
requirement of antiemetic drug is a must, it can be used with caution.
12-A
(1)
Only few drugs should be prescribed and for a minimum period.
(2)
Acute confusional state results in elderly if the blood sugar levels
are lowered immediately in diabetics as the ageing brain adapts to
higher blood glucose levels.
Q38. Mention the common conversion for Weights and Measures
A38
Clinical considerations:-
Elimination:-
12-B
1.
1 Pound (lb) = 16 ounces
2.
1 Ounce = 437 grains.
3.
1 Fluid ounce = 8 fluid drachms = 30 ml.
4.
1 Fluid drachms = 60 minims.
5.
1 drop = 1/20 ml.
6.
1 teaspoonful = 4 ml.
7.
1 desert spoonful = 8 ml.
8.
1 tablespoonful = 15 ml.
9.
1 teacup = 150-180 ml.
Randall for Roeche laboratories in 1960
■
Antitubercular actions of rifampicin were evaluated by Maggi
■
Nifedipine (Adalat ) and Verapamil (Isoptin ) were reviewed by
Fleckenstein in 1978
■
Prostaglandin research by Vane, Moncada and Smith , who received
Nobel Prize in 1982
■
Alpha glucosidase inhibitor, such as Acarbose (Glucobay) for treating
type 2 diabetes in 1983 by Bayer
■
Allylamine antifungals such as Terbinafine and butanefine in 1990
■
First protease inhibitor approved for treating HIV, Saquinivir in 1995
■
Sildenafil approved by US FDA for treating erectile dysfunction in
1998. The recent approval in the same category is for vardenafil
(August 2003).
Q39. Mention the Landmarks in development of Pharmacology
■
Rosiglitazone, Pioglitazone approved by US FDA in 1999
A39
■
Valsartan, Telmisartan used in therapeutics in 2001, for the
management of hypertension
10. 1 standard glass = 240 ml.
11. 1 kilogram = 2.2 pounds.
12. 1 gram = 15 grains
13. 1 litre = 1.76 pints.
14. 1000 mg. = 1 gram.
15. 1000 grams = 1 kilogram
16. a)
b)
c)
1 microgram = 10-6 gram
1 nanogram = 10-9 gram
1 picogram = 10-12 gram.
■
Father of Indian Pharmacology - Colonel Ramnath Chopra
■
Father of American Pharmacology - John Jacob Abel
■
Aspirin discovered as Analgesic in Germany by Dresser, Bayer
Pharma, 1896
■
Insulin discovered by Banting and Best and used clinically on 14th
November 1926
Q40. What are the drug landmarks in the new century ?
A40
■
Penicillin was discovered by Sir Alexander Fleming in 1929, clinically
used by Chain and Florey in 1941
■
Streptomycin was introduced by Waksmann in 1944
■
Lithium used for manic depressive pyschosis by Cade in 1949
■
Anxiolytics such as diazepam and chlordiazepoxide developed by
13-A
13-B
■
Ebastine as an anti-allergic
■
Leflunomide as anti rheumatic drug
■
Gatifloxacin and Moxifloxacin as the newer quinolones
■
Linezolid as antibacterial for gram positive cocci
■
Esomeprazole and Rabeprazole as the newer proton pump inhibitors
■
Valsartan, Telmisartan as antihypertensives
■
Zafirlukast as anti asthmatic
■
Ropinrole for parkinson`s disease
■
Imatinib mesylate in oncology
Q41. Why the new drugs need to be introduced into the market ?
A41
■
To give physician a better flexibility
■
The drug has better efficacy
■
The drug is new and hence there are not reported cases of resistance
■
The drug gives new dimension to the existing therapy such as
Artemisinin compounds gave hope to chloroquine resistant cases
■
The drug has better safety but efficacy may be same. Ticlopidine is
not preferred since it produces neutropenia, unlike newer drug
clopidogrel for the therapy of stroke
■
To have better kinetics so as to have better elimination or
distribution. Azithromycin has stable kinetics as compared to
erythromycin
■
To have better patient compliance. Instead of taking two tablets
separately and loosing the track of one , a single tablet if there are
no pharmaceutical interactions provides patient better opportunity
■
To reduce the side effects produced by other drug. Such as the
combination of Nifedipine and atenolol for hypertension. Atenolol
reduces tachycardia produced by nifedipine
■
The two drugs if used together , then their individual dose may be
reduced. This is seen in many antihypertensive combinations
Q44. Mention the Top 10 Pharmaceutical Companies in India (2003)
A44
■
■
■
■
Q42. Why pharmaceutical product is withdrawn from the market ?
■
A42
■
No significant efficacy as compared to the existing molecules in
market
■
Safety is the issue- Adverse events are reported even during short
term studies
■
The long term postmarketing surveillence shows toxicity
■
There is development of resistance to molecule and better
alternatives are available
■
■
■
■
■
Better therapeutic groups are introduced such as quinolones and hence
sulpha drugs take back seat , similar is the case with tetracyclines and
chloramphenicol. The drug resistant Typhoid fever is now being treated
by the newer cephalosporins
Q45. What are the Top 10 Pharmaceutical products in India (2003)
A45
■
■
■
■
■
Q43. Why is there a need for a fixed drug combination ?
■
A43
■
■
To have synergy or potentiation of effects when the two drugs from
different therapeutic groups are used together.
14-A
Glaxo Smith Kline (GSK)
Cipla
Ranbaxy
Zydus Cadila
Nicholas Piramal
Sun Pharma
Aventis Pharma
Dr. Reddy's Labs
Wockhardt-Merind
Alkem
■
14-B
Corex
Voveran
Taxim
Becosules
Rabipur
Augmentin
Cifran
Betnesol
(Pfizer)
(Novartis)
(Alkem)
(Pfizer)
(Aventis)
(GSK)
(Ranbaxy)
(GSK)
15-A
15-B
Lack of R.B.C. catalase
Increased hepatic
acetylase
Several types of
abnormal plasma
Deficiency of
phenytoin 5-phenyl
hydroxylase
Deficiency of a mixed
function hepatic
microsomal enzyme
which oxidises
bishydroxycourmarin
Acatalasia
Rapid acetylator status
Suxamethonium
sensitivity
Failure to metabolise
phenytoin
Coumarin sensitivity
Mechanism
Most common form
1:2500
Rare
Rare
Autosomal or Xlinked dominant
Unknown
35% Jews
40% Whites
40% Asian Indians
85% Chinese
95% Eskimos
Upto 1% of some
Japanese populations
Occurrence
Autosomal
recessive
Autosomal
dominant
Autosomal
recessive
Inheritance
Bishydroxycoumarin
Phenytoin
Excess anticoagulation
may lead to
haemorrhage
Phenytoin toxicity in
usual doses
Prolonged muscle
relaxation following
suxamethonium
↑ dose requirement ↓
response, generally ↑
toxicity
Isoniazid, hydralazine,
some sulphonamides,
phenelzine, procainamide
Suxamethonium
Approx. 50% suffer
recurrent sepsis of
mouth and pharynx
Effect
Hydrogen peroxide
Drugs Involved
(Ranbaxy)
(Nicholas)
Pharmacogenetic
Variation
■
Mox
Phensedyl cough syrup
Q46. How the genes play an important role in drug metabolism ?
■
16-A
16-B
Reduced affinity of Vitamin
K epoxide reductase of
warfarin
Methaemoglobin reductase
deficiency
Warfarin resistance
Methaemoglobinaemia :
drug induced
haemolysis
Unknown
Autosomal dominant
Increased activity of δamino levulinic acid
synthetase exacerbated by
drugs due to inherited
enzyme deficiencies in the
pathway of haemsynthesis
Inability of taste
phenylthiourea or
phenylthiocarbamide
Porphyria :
exacerbation induced
by drugs
Autosomal recessive
Unknown
Autosomal dominant
Inheritance
Autosomal recessive
(heterozygotes show
some response)
Autosomal dominant
Autosomal recessive
(heterozygotes show
some response)
X-linked incomplete
codominant
Inheritance
Malignant
hyperthermia with
muscular rigidity
Variation
Mechanism
Unknown
Steroid induced raised
intraocular pressure
Pharmacogenetic
80 distinct forms of G6PD.
Chronic deficit of reduced
SH groups exacerbated by
administration of oxidising
drugs
Mechanism
G6PD
deficiency:favism, druginduced haemolytic
anaemia
Variation
Pharmacogenetic
Acute intermittent type
15:1,000,000 in
Sweden; Porphyria
cutanea tarda 1:100 in
Afrikaaners
1:3 of whites
1:20 000 of population
Occurrence
1:100 are heterozygotes
Rare
5% white population
10,000,000 affected in
the world. Probably
protects against malaria
Occurrence
Barbiturates, chloral,
chloroquine, ethanol,
sulphonamides, phenytoin,
griseofulvin
Drugs containing the N-C=S
group such as thiouracils
Some anaesthetics, especially
halothane. Also
suxamethonium
Drugs Involved
Same drugs as for G6PD
deficiency
Warfarin
Glucocorticoids
Many – including 8aminoquinolines,
antimicrobials and minor
analgesics
Drugs Involved
Multiple Choice Questions
Say Yes or No
1.
Drug is only a chemical substance ?
2.
Pharmacokinetics means drug absorption only ?
3.
Receptors are located cellularly and extracellularly ?
4.
Dose is amount to produce therapeutic effects ?
5.
Volume of distribution depends on protein binding and for quionolones it is
more ?
6.
The concept of loading dose is to attain target concentration of drug quickly?
7.
The drug cumulates if the excretion of drug is more than absorption ?
8.
Faster absorption of drug is with IV route as compared to IM ?
9.
Drugs are generally not safe during the first trimester of pregnancy ?
10. Clinical trials are done to know the efficacy and safety of the drug ?
Answers
1.
No
2.
No
3.
Yes
4.
No
5.
Yes
6.
Yes
7.
No
8.
Yes
9.
Yes
10. Yes
17-A
17-B
1.
3.
CARDIO VASCULAR SYSTEM
2
Angina pectoris and management of
myocardial infarction
4.
a)
drugs acting on myocardium :- Diltiazem (Coriem), Verapamil
b)
drugs acting on vasculature :- Nifedipine derivatives (Nicardia)
Haemorhoelogical agent :Pentoxifylline
(Trental)
Angina pectoris is a clinical syndrome of chest pain produced by increasing
cardiac work and relieved by rest. Attacks of angina rarely last for more than a
few minutes. ECG shows ST segment depression of 1 mm or more.
Aims of anginal therapy :- To reduce ischaemia by increasing O2 supply or by
decreasing myocardial O2 demand.
Calcium antagonists :-
5.
(Alters shape of RBCs, allowing them to
reach ischaemic zones)
Potassium Channel Opener
Nicorandil Sodium (Korandil)
Classification of drus used :-
1.
2.
Nitrates :A.
Therapeutic (short acting)
–
–
(Glyceryl trinitrate) GTN,
Octyl nitrite, amyl nitrite
B.
Prophylactic (long acting)
–
Isosorbide dinitrate, Erythrityl
tetranitrate (cardilate)
β Blockers :A.
Cardioselective :(Acting on the b1 receptors only)
Atenolol (Beta-Nicardia)
Metoprolol (Betaloc)
Acebutalol
B.
Membrane stabilizers : - Propranolol (Ciplar)
(Acting on the b1 and b2 receptors) oxyprenolol
Cardiovascular System
18-A
18-B
19-A
19-B
(Sorbitrate)
(Sorbicap)
Isosorbid
dinitrate
3) Nifedipine
recently
Drug
(Nicardia)
Brand
(Ciplar)
(Propal)
(Inderal)
(Angised)
1. Glyceryl
Trinitrate
2) Propranolol
Brand
Drug
Side effects
Calcium mediated
contraction via
calmodulin is
antagonized
(calcium channel
blocker)
tion and cardiac
output, it reduces
mycoardial
oxygen demand.
Incidence of side
effects is about
17%
1) Constipation
2) Flushing, headache, hypotension
3) Hepatotoxicity
4) Gingival
hyperplasia
3) Hypoglycaemia
4) Nightmares,
insomnia
3) As it reduces rate, 5) Allergic rashes
force of contrac-
the release of
from kidney.
Mechanism of
action
A)Cardiac
1. Angina
2. Antiarrhythmic
3. Prevention of
1) Presence of
severe left
ventricular
dysfunction.
2) Advanced atrioventricular block
3) Wolf Parkinson
White syndrome
4) Drug sensitivty
astham
6) Patients on
Insulin therapy
4) Psoriasis
5) Bronchial
3) Ventricular
fibrillation
A) Cardiac
1. Angina
2. Hypertension
3. Raynaud's
disease
4. Acute myocardial infarction.
B. Extracardiac:1. Oesophageal
spasm
2. Exercise induces bronchial
asthma.
3. Spasm of anal
sphincter
1. To antagonize
the effects of
catechols
during
anaesthesia.
2. Tremors
3. Migrain
Special
effects
Dose
10,40,80 mg.
tablets
available
Daily require-
10-20 mg,
retard tablets
or
30 mg
Oros or
extended
release tablets
All calcium channel
blockers increase
rum digoxin concentration when coadministered together.
documented.
effects in cases of
recurrent myocardial
infarcts.
Genetic polymorphism is now
Special
effects
Platelet aggregation
and free fatty acids
are reduced, these
provide beneficial
Therapeutic
Repeated exposure
dose :
to high doses leads
0.5 to 1mg.
to decrease in the
Prophylactic magnitude of most
0.25-0.5 mg pharmacological
prior to the
responses.
physical effort (tolerance)
for Acute
attack 5-10
mg, 6 hrly
oral or SL10mg
chewable
tablets
of 10 mg
(Sorbicap)
have more
sustained
action than
S.L. route.
Prophylactic:1/4 to 1 to 4
times a day as
required.
Dose
recurrent
ment ranges
myocardial
80 to 320 mg.
infarction
4. Hypertension
B) Extracardiac:-
Contraindication Uses
Anti-Anginal drugs
1) Cardiogenic
shock
2) Complete heart
block
A)Cardiac
1. Angina
2. C.C.F
3. Myocardial
infarction
(after 5th
day of the
therapy
B)Extracardiac
1. Achlasia
cardia or
spasm.
2. Reduction
of biliary
3. Cyanide
poisoning
(sodium
nitrite is
used)
Contraindication Uses
1) Severe throbbing As nitrates cause
headche
methhaemoglobi2) Transient episodes naemia, they are to
episodes of weak- be avoided in
ness and dizziness cases of marked
3) Hypotension
anaemia
4) Rise in intraoccular pressure
may precipitate
glaucoma.
Side effects
1) Reduces the
1) Heart failure
excessive sympa- can develop
thetic outflow
suddenly.
2) Antagonizes
2) A V dissociation
1) Reduced the
myocardial
requirement of
oxygen.
2) Cardiac work
is reduced
3) Redistribution
of coronary blood
flow to ischaemic
subendocordium
Mechanism of
action
Anti-Anginal drugs
20-A
20-B
Cromakali
m
Corflo
/Nikor
an
Prevention of angina
• GI upset
• Dizziness,
tinnitus ,
• Bradycard
ia
• AV blocks
Side effects
Enhancement of
myocardial perfusion
Nicorandil
Reduced myocardial
oxygen demand
Contraindi
cations
• Shock
• Hypotens
ion
• Left
ventricula
r failure
Reduced obstruction to
coronary blood flow
Mechanism of
action
The main action
is to open
plasmalemmal
potassium
channels
.Nicorandil
dilates all
vessels
including the
main branches
of coronaries
thereby
improving the
blood flow
Compensatory
tachycardia
Decreased myocardial work
Brand
Dose
5-10mg,
once a
day
Uses
• Angina
pectoris
• Acute
coronary
insufficie
ncy
Special
effects
Since the drug
has a long
duration of
action it needs
to be given,
once or twice
a day
No
development
of tolerance
unlike nitrates
and hence
dose need not
be increased
quite often
Headache is
not observed
with this drug
Nitrates
↓
Vasodilatation
↓
Veins dilate
↓
Reduced venous return to heart
↓
Arterioles dilate
Reduced left ventricular blood volume
↓
Reduced left ventricular end diastolic pressure
↓
Reduced left ventricular
Reduced diastolic
Reduce heart size
stroke volume
intraventricular wall
↓
pressure
Reduced intramyocardial tension
Drug
Fall in blood pressure
Potassium channel openers
Newer antianginal drugs
Action of nitrates in angina pectoris
Calcium antagonists : - Nifedipine and amlodipine are the calcium channel
blockers which act by :-
5.
tt
Decreasing trans membrane Ca influx
Myocardium
Peripheral b lood
vessels
6.
Coronaries
lf C.C.F develops:a)
low salt diet
b)
diuretics
c)
digitalis in moderate dose
Arrhythmias often transiet can be problematic if there is ventricular
tachycardia : lignocaine 5mg/kg I.V. or procainamide 5mg/mt 1.V.
For ventricular Fibrillation : D. C. countercurrent shock
Reduced activation of
myosin AT Pase
Reduced breakdown
of energy rich
phosphates
Decreasing tone
Decreasing tone
For persistent heart block : Transvenous pacing of heart.
7.
Decreasing P. R.
(Peripheral resistance)
Anticoagulant therapy:Heparin 5000U, 6 hrly. for 48 hours, followed by Warfarin
Dilatation & improved
perfusion of
coronaries
3-10 mg/day for 6 weeks.
8.
Decreasing work load
on heart
Complications such as shoulder hand syndrome requires
■
■
↓ O2 consumption by
myocardiu m
9.
↑ O2 supply to
myocardiu m
Management ofmyocardial Infarct:1.
Admit patient in a special intensive coronary care unit.(Before shifting
patient, give Aspirin, Atenolol, Clopidogrel, Isosorbide dinitrate immediately)
2
Fluids only for 24 hours.
3.
Intranasal O2 (Oxygen)
oral prednisolone
physiotherapy
Secondary prevention ofinfarct is done by:
a)
Long term antiarrhythmics if patient complaints of palpitations b
Blockers or amiodarone are used
b)
Antiaggregatory durgs like: - aspirin, dipyridamole, vitamin E, and
ticlopidine can be tried.
Prognosis :
Upredictable
10-15% die in 1st attack
Greatest mortality is in first 48 hours.
4.
Morphine 10 mg 1. M + Phenargant
To reduce pain and also
to induce peripheral
dilatation
21-A
2. Digitalis (Foxglove)
It is a cardiac glycoside used in cases of a failing heart. It does not increase
mycoardial O2 demand like other inotropics.
21-B
Actions :-
Factors increasing digitalis toxicity :-
1.
It increases force of contraction, stroke volume and decreases cardiac
size (due to inhibition of Na+K+AT Pase enzyme).
1.
Large maintenance dose
2.
Diuretics (which deplete potassium)
2.
It slows heart rate due to its partial vagal action.
3.
Hypothyroidism
3.
It decreases atrioventricular conduction and prolongs the effective refractory
period of atrioventricular node.
4.
Hypoxia
5.
Andrenergic drugs
4.
It can cause diuresis due to direct action on renal tubules.
Contraindications: -
Cardiac glycosides :-
I.
High output failure
2.
Wolf Parkinson White syndrome
3.
Recent myocardial infarction.
Digoxin (Lanoxin)
Digitoxin
1. Source
Digitalis Lanata
Digitalis Purpurea
2. Half life (t½)
1.7 days
6 days
3. Protein binding
25% variable
90%
Therapeutic uses:-
4. Absorption form gut
20-80%
100%
1.
5. Maintenance
0.05-0.2 mg
0.125 to 0.5 mg.
In Congesrive cardiac failure, digitalis decreases end diastolic volume,
improves stroke volume and cardiac output, thereby oedema is relieved. It
also improves renal perfusion by decreasing sympathetic tone of renal
vessels.
2.
Atrial fibrilliation:- In this condition it acts by:
Side effects :Cardiac
:
Atriovenricular block, sino atrial block, premature
depolarization, ventricular bigeminy.
Extracardiac :-
a)
Increasing effective refractory period of atrioventricular node.
b)
Decrease propagation of impulses from atrioventricular node to
ventricles.
Eye
:
Haloes around objects.
GIT
:
Anorexia, nausea, vomiting
CNS
:
Drowsiness, delerium.
a)
Increases effective refractory period of atrioventricular node.
Rare
:
Gynaecomastia, urticaria
b)
Decreases ventricular rate by increasing atrioventricular block.
3.
Atrial Flutter:-
The withdrawal of the drug leads to the sinus rhythm.
22-A
22-B
4.
Paroxysmal atrial tachycardia, due to reflex vagal stimulation, conduction
is thereby reduced.
5.
Sick sinus syndrome:- It is because digitalis decreases automaticity at
sino atrial node.
Systolic (mm of Hg)
Diastolic (mm of Hg)
< 120
< 80
Prehypertension
120-139
80-89
Important facts:
Hypertension, Stage 1
140-159
90-99
1.
Hypertension, Stage 2
< 160
> 100
2.
Bio availability of digoxin tablets varies considerably.
Category
Normal
The predisposing factors are heredity, age, obesity, diabetes, smoking
Digitalis is a cumulative drug.
3.
All glycosides are irritant and can cause pain and necrosis on intramuscular
administration.
Types of hypertension :
4.
Digoxin (Lanoxin) comes as 0.25 mg. tablet. 0.0625 mg is the pediatric
dose.
Primary or essential hypertension : The cause of rise of BP is not known
Other measures adopted in congestive cardiac failure:1.
Furosemide in mild C.C.F. as it reduces preload by decreasing circulating
blood volume.
2.
Vasodilators such as glyceryl trinitrate and hydralazine reduce preload
and afterload.
3.
Cardiac stimulants:- such as dopamine, amrinone, milrinone, glucagon
and methylxanthines such as theophylline have short lasting inotropic
action and therefore can be given during emergency in selected conditions.
Hypertension
Hypertension is defined as the systolic blood pressure >130 mm of Hg and
diastolic blood pressure of 85 mm or more in adults above 18 years of age.
Hypertension is further divided into various grades:
Secondary hypertension : The causes are known.
1.
Renal - Renal artery stenosis, renal tumors, renal transplantation
2.
Endocrine - Cushings Syndrome, Pheochromocytoma, Acromegaly,
Hypothyrodism, Hyperparathyrodism
3.
Miscellaneous - Encephalitis, Poliomyelitis
Complications of hypertension
1.
Heart failure - LVF is followed by CCF
2.
Angina pectoris is also associated with transient increase in BP
3.
Renal damage
4.
Haemorrhages
Drugs used in the management of hypertension
Diuretics (Esidrex) (Hydrazide)
Hydrochlorthiazide or chlorthalidione 12.5 - 25 mg / day are diuretic of choice
in uncomplicated mild hypertension. They act by :
23-A
23-B
1.
Producing water loss which reduces plasma and extracellular fluid volume
by 15% and thereby reducing cardiac output.
2.
They reduce sodium load within the body and decrease in intracellular
sodium concentration in vascular smooth muscle may decrease the vessel
contraction. The onset of action is slow and takes usually 2-4 weeks
Classification of β-blockers
1.
Non-selective β-blockers
■
High ceiling diuretics such as frusemide 40 mg / day with potassium
supplementation produces fall in blood pressure. It is indicated in the cases of:
■
Chronic renal failure with hypertension
■
Marked fluid retention due to use of potent vasodilators
e.g. propranolol (Ciplar), oxprenolol (Trasicor)
2.
Selective β-blockers
■
Advantages of diuretics
1.
Smooth action
2.
Sustained action
3.
Low incidence of postural hypotension
4.
Lesser incidence of severe side-effects
5.
Low cost of therapy
They act both on β-1 (present at cardiac and vascular sites) receptors
and β-2 (present in other tissues such as respiratory tract tissues)
receptors
3.
Atenolol (Tenolol) and Metoprolol (Betaloc). These drugs block
basically β1-receptors and hence do not cause bronchoconstriction
as the possible adverse effect like non-selective β-blockers.
b-blockers with α-blocking activities
■
Labetelol (Normadate), Carvedilol (Caslot) and Bisoprolol (Concor)
1. Mechanism of action of β -blockers in reducing
hypertension
β-blocker with α-blocking
activity (e.g. Carvedilol)
Disadvantages
1.
Onset of action slow and unpredictable
2.
Electrolyte imbalance
3.
In many cases monotherapy fails and hence need to be combined
β-receptor block
HR
b-adrenergic blockers
FOC
Vasodilation
Stroke volume
The first clinically used b-blocker was propranolol which was discovered in
1973 by Black & Pirchard. Atenolol and Metoprolol came into therapeutics in
late 70s and ruled for nearly 15 years till the newer b-blockers such as carvedilol
and bisoprolol came into market in mid-90s.
α-receptor block
24-A
Peripheral resistance
CO
BP
24-B
Contraindications
2. Mechanism of action in ischemic heart
disease
β-receptor
block
α-receptor
block
O2 demand
Vasodilation
Decrease in
peripheral resistance
Decrease work load
and O2 demand
Antioxidant
property
•
improvement in
nitrate tolerance
Antiproliferative
•
Antiatherosclerotic
Cardioprotective
Adverse reactions
2.
Bradycardia
3.
Asthmatic episodes
4.
Patients with pre-existing high levels of blood lipids
Drug
Dose
Propranolol
(Inderal)
10 mg, 20 mg, 40 mg, 80 mg.
Can be given twice / thrice daily
Atenolol
(Aten)
25 mg, 50 mg, 100 mg
Depending on the need, once a daily dose
Carvedilol
3.125 mg, 6.25 mg, 12.5 mg, 25 mg
(Carvedil)
Twice daily
Esmolol
(Miniblock)
10 mg/ml, 250 mg/ml (injectable)
Used as injectable for the treatment of supraventricular
tachycardia, postoperative tachycardia and hypertension
Alpha blockers :
In general, b-blockers are well tolerated, but can cause bradycardia, can also
precipitate CCF by blocking sympathetic support to the heart. Carbohydrate
intolerance may be impaired and therefore can precipitate hypoglycemia. All
traditional b-blockers can precipitate variant Prinzmetals Angina due to
unopposed action on a-receptors which can precipitate constriction. This is
not seen with the new b-blockers such as Carvedilol. Similarly, there is no
bronchoconstriction with the newer b-blockers and cardioselective drugs like
Atenolol and Metoprolol. GI upset, lack of drive, nightmares, forgetfulness and
impotence can be reported.
Any degree of cardiac block.
Dose
•
•
1.
25-A
Types :
1.
Prazosin (Minipress) (1-4mg bd or td ), even Terazosin (Hytrin) ( 1-2mg bd
or td ) is being used
2.
Phenoxybenzamine ( 20-60mg /day oral and 1mg/kg by slow IV infusion
over an hour )
3.
Phentolamine ( 5mg IV , double the dose as required
25-B
Mechanism of action : Block of vasoconstrictor alpha 1 and 2 receptors reduces
peripheral resistance , this results in peripheral pooling of blood and diminished
venous return to the heart , resulting in fall in BP
Side Effects : palpitation, postural hypotension, nasal block, fluid retention
and impotence
Indications :
1.
Hypertension : Except prazosin, none of drugs are preferred since all of
them cause reflex tachycardia
2.
Pheochromocytoma : The adrenal medullary tumor which secretes
catecholamines such as adrenaline and noradrenaline. These drugs reduce
dangerous BP
3.
Shock with is associated with reflex vasoconstriction
4.
Peripheral vascular disease
5.
CCF
6.
Benign prostatic hypertrophy where prazosin or terazosin improve the
urinary flow
Classification
Drug
Dose range
Clinical evidence
Captopril
(Aceten)
12.5 mg - 50 mg BD
Better quality of life than
propranolol. Early onset of action
Enalapril
(Envas)
5 - 40 mg OD
Longer duration of action than
Captopril
Lisinopril
(Listril)
2.5 mg - 40 mg OD
Better reduction of BP in
hypertensive patients
Perindopril
(Coversyl)
2 mg - 8 mg OD
Greater diastolic BP reduction
than Captopril
Ramipril
(Ramace)
12.5 mg - 10 mg OD
Compared to Lisinopril, Ramipril
produced better response in more
number of patients
Fosinopril
(Fosinace)
10 mg - 40 mg OD
Significantly reduced systolic
hypertension better than other
ACEI
Trandolapril
500 mcg - 4 mg OD
Significant reduction of BP better
(Zetpril)
7.
Migraine :Prazosin can terminate acute attacks
Quinapril
10 mg - 40 mg BD
or
80 mg OD
Clinically better reduction than
Captopril
Moxepril
7.5 mg - 30 mg OD
Effective in all grades of
hypertension
ACE INHIBITORS
Angiotensin converting enzyme inhibitors
Newer drugs :
Delapril
Spirapril
Temocapril -
26-A
than Captopril
26-B
Improved quality of life
comparable to Enalapril
Mechanism of Action
1.
2.
complications. They reduce proteinuria, and slow the progression of
nephropathy in type 1 diabetics.
Inhibition of angiotensin II production leads to :
■
Vasodilatation as the vasoconstrictor action of ANG II is removed.
Major drug interactions
■
Decreased stimulation of aldosterone, hence no Na+ and H2O
retention.
●
Lithium levels can increase 3-4 times after 2-4 days of ACEI initiation,
reduce lithium dose and monitor lithium levels
■
Lesser sympathetic activity.
●
■
Less ventricular hypertrophy, so no extension of infarct.
Potassium supplements, potassium sparing diuretics, potassium
retention, potential severe hyperkalemia
●
Diuretics - Increased risk of first-dose hypotension if patient is hypovolemic
●
NSAIDs -sodium and water retention, decreased effect of ACEI, and
increased risk of nephrotoxicity.
ACE is like enzyme kininase, the levels of kinins are raised following use
of ACEI :
■
Vasodilatation, improvement in endothelial dysfunction and hence
inhibition of atherosclerosis.
■
Improvement of diastolic function of ventricles.
Adverse effects
●
Symptomatic hypotension
●
Dizziness, fatigue, headache
●
Dry, non-productive cough (> 10%)
Indications
●
Angioedema - rare but serious side-effect (~ 0.1%)
1.
●
Hyperkalemia (with drug interactions / renal insufficiency)
●
Taste disturbance - more common with captopril (2%)
●
Rash - the incidence varies between 1-7%
3.
Restoration of parasympathetic tone which is reduced in CCF.
4.
Reduces insulin resistance and therefore better protection to myocardium.
2.
3.
4.
Hypertension : When used as monotherapy, ACEI control BP in 50% of
patients. When used in combination with diuretic, calcium channel blocker
and additional 30% control is obtained.
CCF : The ACEI are useful in patients with low ventricular ejection and
reduce mortality. They are used in lower doses initially and further
uptitration is done later.
Following myocardial infarction : ACEI have shown to reduce the
progression of CCF and improve coronary circulation if given within 24
hrs.
Diabetic nephropathy : ACEI are beneficial in preventing renal
27-A
Contraindications
●
Pregnancy
●
Hypersensitivity to ACEIs
●
Bilateral renal artery stenosis (RAS) or RAS of a solitary kidney
●
Severe hyperkalemia
●
Hypotension (SBP < 90 mm)
27-B
Angiotensin II receptor antagonists
Adverse effects
Federal pharmacy and therapeutics committee meeting have reviewed Sartans
as the beneficial drugs and as the first line in the management of hypertension
In clinical trials sartans are well tolerated The incidence of cough is much lower
than ACE inhibitors, since they don't potentiate bradykinin , which can locally
produce pharyngeal irritation.
Mechanism of action
The sartans exert their pharmacological action by binding to the angiotensin II
receptor subtype 1 (AT I ) ATI is located in vascular and cardiac tissue and in
kidney the location is at zona glomerulosa where aldosterone is also secreted
The role of AT II receptors located in brain, is not clearly known.
Feature
Losartan
Candesartan Irbesartan
(Alsartan-4) (Candez)
(Irovel)
Valsartan
(Diovan)
Telmisartan
(Telsar)
Bioavailability
33%
42%
80%
23%
43%
T-max (hr )
1.0
3-5
2
2
1.0
Active
metabolite
+
+
--
--
--
Not Reqd
Not Reqd
Monitored
Not reqd
Not required
Not required Starting dose
halved
Hepatic
impairmentModerately
severe
Starting dose Starting dose
halved
halved
Renal
impairmentModerately
severe
Not reqd
Dose/day
Frequency
For the management of mild to moderate hypertension either alone or if required
can be combined either with ACE inhibitors , calcium antagonists or diuretics
in cases of moderately severe hypertension
Sartans are found to reduce left ventricular hypertrophy and possibly reduced
mortality in patients.
Pharmacokinetic properties and dose :
Dose adjustment Not Reqd
in old patients
Indications
Evaluation of Losartan in the Elderly study ( ELITE) has revealed that the
decrease in mortality in CCF patients is due to reduction of arrhythmias due to
blockade of renin release.
Losartan was more effective in reducing renal albuminuria in diabetic
hypertensives as compared to amlodipine or felodipine. Losartan is generally
combined with hydrochlorthiazide for better efficacy.
Contraindications
Use in pregnancy is to be avoided because of the potential risks to the foetal
growth and development
Starting dose
halved
Not Reqd
50-100mg
8-16mg
150-300mg
Once or
Once a twice Preferentially
twice
Not reqd
Not reqd
Conclusion
OD
80-320
80mg
Once or
Preferentially
twice
OD
28-A
Sartans are safe drugs and they have proven efficacy in all grades of hypertension
given alone or in combination. Choice remains with physician so as to choose
the best possible for his patient
28-B
• Preoperatively
reduces anaesthetic
requirement
• Prevents vasomotor
symptoms of
menopausal
syndrome
• Controls loose
motions in diabetic
neuropathy
Methyldopa
250 mg twice
or 4 times a
day
Clonidine
• Moderate
hypertension,
• Reduces
noradrenaline
release from
peripheral nerveendings by
inhibiting α-II
receptors. The
decrease in
sympathetic
outflow results in
fall in BP and
bradycardia
• Sedation
• Hypersens
itivity to
the drug
and
sudden
discontinu
ation of
the drug
• Reduces
noradrenaline
synthesis as it
forms false
transmitter which is
responsible for
hypotensive effect
• Sedation and
lethargy
• Mild to moderate
hypertension
29-A
29-B
• Reduces elevated
systolic and diastolic
pressure by reducing
peripheral vascular
resistance
• Direct acting
peripheral vasodilator
• Weight gain and
impotence
• Severe hypertension
i.e. symptomatic and
is not associated
with target organ
damage
• Postural
hypotension
• Vasodilatation,
results fall in BP.
This leads to
compensatory
increase in renin
release which can
lead to oedema and
hence it should be
used carefully and in
combination with
other drugs
• Pheochrom
ocytoma
• Moderate to severe
hypertension
• Hypertensive
emergencies where
iv form is used
• CCF where it is used
because it dilates
arteries
• Hypertrichosis
(the body here
becomes thicker
and hence used
topically as 2%
scalp lotion for
baldness)
• Temporary
oedema
•
•
Palpitation,
dizziness and
hypotension
Lupus like
syndrome on
prolonged usage
Muscle cramps
and peripheral
neuritis
• Constipation
• Pheochromocyt
oma
• Aortic
aneurysm
• Acute
myocardial
infarction
• Angina
• Myocardial
infarction
• Older patients
Contraindication
• Impotence
Mechanism
• Mental
depression
Indications
• Hypertensive
emergencies where
IM dose can also be
used
•
Contraindica
tion
Side effects
Side effects
5 mg initially
and then the
dose is
increased to
10 mg / day
• Opiod withdrawal
Mechanism
Minoxidil
100 mcg 300 mcg
OD/BD
Indications
Hydralazine
25 - 50 mg
once or thrice
a day or 10 20 mg iv
(Arkamin)
Drug & Dose
Drug & Dose
Vasodilators
Central sympatholytics
• Pheochromocyt
oma
• Hypotension
• Hyperglycemia
• Acute
myocardial
infarction
• Oedema
Old drugs
●
Veramapil (1962 - Ingelhiem, Germany)
●
Nifedipine (1975 - Bayer, Germany)
●
Diltiazem
New drugs
• Potent vasodilator
acting as potassium
channel opener acting
for a longer duration
(24 h)
• Pain in abdomen
Classification
●
Amlodipine (Amlogard)
●
Felodipine (Plendil)
●
Lercanidipine (Lerka)
Mechanism of Action
These drugs interfere with the calcium movement within the cell involving
contraction of the heart by binding to enzyme troponin which allows interaction
of myosin and actin which are the cardiac proteins. The inhibition of calcium
channels leads to dilatation of arterioles which is required in case of hypertension
and in cases of exertional angina.
50 - 100 mg
iv
Diazoxide
• Malignant
hypertension
50 mg in 5 ml
inj
• Hypertensive
emergencies
• Nervousness
• Disorientation
• Aortic
aneurysm
• Dilates both arteries
and veins quickly and
no tolerance develops
to nitroprusside
action
Sodium
nitroprusside
• Palpitation
Mechanism
Indications
Drug & Dose
Vasodilators
Side effects
Contraindication
Calcium channel blockers
30-A
30-B
Comparative features
Features
■
Nifedipine
Diltiazem
Veramapil
+++
+
++
No effect
Less delayed
Much delayed
+++
+
++
■
ACE inhibitors
Angina
Angina
Angina
■
Angiotensin receptor antagonists
Arrhythmia
Channel blocking potency
Channel recovery rate
Vascular and smooth muscle
Clinical indications
To prevent the complications such as stroke, CCF, peripheral vascular
disease and renal insufficiency associated with raised blood
pressure.
Hypertension Hypertension
2.
Drugs of choice
■
Calcium channel blockers
Unit dose
10 / 20 mg
30 - 60 mg
40 - 120 mg
■
b-blockers
ADR profile
Palpitation
Palpitation
Nausea
■
Diuretics
Constipation
++
++
Flushing
Flushing
++
++
Ankle edema Ankle edema
+
3.
Preference for drugs
Bradycardia
■
(High incidence)
+
(Nifedipine = Adalat, Diltiazem = Dilcal, Ionozem, Verapamil = Calaptin)
Short acting calcium channel blocker
Nimodipine
■
(Nimotop, Bayer)
It is a short acting dihydropyridine like Nifedipine and Amlodipine, but being
lipophilic enters brain very efficiently and hence it is used in the cases of
subarachanoid haemorrhage. The dose used is 30-60mg, 4-6 hourly for 3 weeks.
■
Management of hypertension
1.
Aims
■
■
To reduce mortality and morbidity associated with persistently raised
blood pressure
31-A
ACE inhibitors and angiotensin receptor antagonists :
a)
Diabetics with nephropathy
b)
Co-existing ischemic heart disease
c)
Patients with lipid disorders
d)
High renin cases
Calcium antagonists
a)
Elderly patients
b)
Systolic hypertension
c)
Asthmatic patients
b-blockers
a)
Young patients with anxiety
b)
Co-existing ischemic heart disease
c)
Pregnancy
Diuretics
a)
31-B
Elderly patients
4)
5)
b)
Renal disease with sodium retention
c)
Isolated systolic hypertension
6) Choice of anti hypertensive in clinical situations :
Drugs to be avoided in pregnancy
■
Diuretics
■
ACE inhibitors and angiotension receptor antagonists (ARA)
■
Sodium nitroprusside
In 30-50% of patients there is need for drug combination, particularly in
cases of moderate to moderately severe hypertension so as to prevent
the organ damage to raised blood pressure. The following can be
combined:
a)
Diuretics with ACEI or ARA.
b)
ACEI or ARA with calcium channel blocker
c)
ACEI or ARA with b-blocker
d)
b-blockers with diuretics
Three drug therapy is required in cases of severe hypertension and generally
calcium channel blocker + ACEI or ARA with diuretic is used. Patient has to
be re-evaluated from time to time and causes of secondary hypertension are to
be excluded.
Drug
Preferred use
Avoid in situations
Diuretics
Isolated systolic
hypertension, advanced
age, CCF
Glucose intolerance, lipid
disorders, gout
Beta blockers
bradycardia,
vascular disease
Angina, Myocardial
Bronchospasm,
infarction, peripheral
Calcium
antagonists
Advanced age, Isolated
systolic hypertension,
General use
Oedema, heart block,
constipation
ACEI
CCF, LVF, diabetic
nephropathy.
Same as below
ARA
Same as in ACEI,
patients having
persisting cough
Renal artery stenosis,
pregnancy, hyperkalemia,
angioedema
Alpha blockers
Young males,
hyperlipidemia, prostatic
enlargement, aortic
dissection
Orthostatic hypotension
The two drugs belonging to the same group are to be avoided because they do
not cause any significant improvement in blood sugar control as they act by
similar mode of action.
Peripheral arterial disease
Peripheral arterial disease is a prevalent manifestation of atherosclerosis which
correspondingly increases with age. The symptoms being intermittent
claudication ie cramping pain in legs while walking. The basic reason being the
narrowing of the peripheral arteries.
32-A
32-B
Drugs Used :
Features
Cilostazol
Pentoxifylline
Derivative of
Quinolinone
Methylxanthine
Action
Phosphodiesterase III
inhibitor, suppresses cAMP
degradation with increased
levels of cAMP thus having
Just a hemorrheologic agent
which modifies the shape of
RBC`s so that they can pass
from even narrowed vessel
Features
Cilostazol
Pentoxifylline
Formulation
Regular
Sustained release
Contraindications
Congestive cardiac failure
•
Cerebral hemorrhage
•
Hypotension
•
Peptic ulceration
•
Coronary artery disease
•
Hypertension and angina
•
Headache, dizziness,
insomnia and palpitation
Side effects
•
Anti platelet activity
•
Anti thrombotic activity
•
Anti proliferative
Drug interactions
Effects on Lipids
Favors lipid reduction
No action on Lipids
Smooth cell proliferation in
arteries
Favored and hence reduces
atherogenesis
Not Favoured
Half life
Long ( 13 hours )
Short ( 6 hours )
Dose
100mg bd s or 50mg bds
400mg tds
Uses
Intermittent claudication
secondary to chronic occlusive
vascular disease
•
Intermittent claudication
•
Cerebrovascular
insufficiency
•
Transient ischemic attack
•
Raynaud`s disease
•
Venous ulceration
33-A
33-B
•
Headache, dizziness,
palpitation
•
diarrhea
Beneficial when aspirin is
combined
Can lead to more bleeding
when used along with aspirin
Contrast :
Antiarrhythmic drugs
These drugs are intended to be used for preventing and treating the cardiac
rythm irregularities.
Classification :
Class
I.
Memberane stabilizing agents :Quinidine (Natcardine)
Procainamide (Pronesty)
Lignocaine (Gesicard)
Flecainide
II.
Adrenergic blockers :
Propranolol
Atenolol (Tenormin, Aten)
III.
Agents widening action potential duration :
Aminodarone (Amiodar)
Bretylium
IV.
Calcium channel blockers :
Verapamil, diltiazem
34-A
Quinidine (Quininga)
Procainamide
(Pronestyl)
Lignocaine (Oxylocard)
1. Cardiac effects :a. Effective refractory
period of antrioventricular node-Equivocal
b. Action potential
duration increases
c. Automaticity
decreases
d. E.C.G. :Increases PR and QT.
intervals.
1. Cardiac effects :a. There is no change
1. Cardiac effects :a. There is no change or
there is decrease
b. Increases
b. Decreases
c. Decreases
c. Decreases
d. Similar to Quinidine
d. QT interval shortens
2. Side effects :1. Sino atrial block
2. Hypotension
3. Arterial embolism
4. Cinchonism
5. Vomiting
6. Hypersensitive
reactions
2. Side effects :1. Paradoxical
increases in ventricular response
2. Systemic lupus
erythematous
syndrome
2.
1.
2.
3.
Quinidine
Procainamide
Lignocaine
3. Contraindications
1. Intolerance or
Idosyncracy
2. Heart block
3. Hypotension
4. History of embolism
1. Hypotension
2. Hypersentivity to
the drug
1. Hypersensitivity
to the drug.
2. Hypotension
4. Drug interactions :
a. Quinidine increases
plasma concentration
of digoxin.
It can reduce the antimicrobial effects of
the sulpha drugs.
Cimetinide and propranolol increases halflife
(tra) of lignocaine.
34-B
Side effects :Paraesthesias
Drowsiness
Respiratory arrest
Quinidine (Quininga)
Procainamide
(Pronestyl)
Lignocaine (Oxylocard)
b. Synergistic cardiac
depression seen with
potassium salts.
c. Phenobarbinote, an
enzyme inducer
reduces the duration
of action of quinidine.
Arrhythmias
5. Uses :
1. Prevention of
recurrent supraventricular tachycardias
(Verapamil
2. Suppresses ventricular arrhythmias
5. Uses :
1. Venticular
arrhythmias.
2. Arrhythmias following
digitalis (Phenytoin
preferred)
5. Uses :
1. Prophylactic for
primary ventricular
fibrillation.
2. To prevention arrhythmias which follow
infarction.
6. Dose :
Oral or slow I.V.
200 mg, T.D.S.
6. Dose :
0.5 to 1 gram
oral or I.M.
6. Dose :
I.V. bolus is
50-100 mg
Amiodarone : (Amiodar) benzofaran derivative broad spectrum antiarrhythmic
agent with class II, III & IV activity.
Drugs of choice for arrhythmias
35-A
Drug of choice
Alternatives
Remarks
Arterial fibrillation or
flutter
Diltiazem or a betablocker to slow
ventricular response
Digoxin, quinidine,
procanamide so as
to slow ventricular
response. Drug like
Ibutilide for
termination of
arrhythmia
Digoxin, diltiazem
are dangerous
for patients with
W olff Parkinson
W hite Syndrome
Other supra
ventricular
tachycardias
Adenosine or
diltiazem for
termination
Esmolol, digoxin for
termination
Beta-blockers or
digoxin are
effective for long
term suppression
Ventricular premature
complexes
No drug therapy for
asymptomatic
patients
For symptomatic
patients use betablockers
Beta-blockers
prevent sudden
cardiac death
and are useful for
post myocardial
infarction patients
where the
treatment with
flecainide or
moricizine gives
good results
Sustained ventricular
tachycardia
Lignocaine for acute
treatment
Procanamide or
amiodarone
Beta-blockers are
also effective for
long term
prevention
Ventricular fibrillation
Lignocaine
Amiodarone,
procanamide
Defibrilator or
radio frequency
catheter, ablation
procedures are
used
Cardiac glycoside
induced ventricular
tachycardias
Digoxin – Fab
antibody fragments
Lignocaine,
phenytoin
Stops digoxin.
Use phenytoin at
early stage
Torsades de pointes
Magnesium
sulphate
Cardiac pacing,
isopreneline
Magnesium
sulphate in a
dose of 1 gm i.v.
should be given
repeatedly and
the potassium
should be coadministered so
as to raise serum
potassium
between 4-5.5
meq/l
35-B
1.
Supraventricular tachyarrthymias.
2.
Prophylactic control of life threatening ventricular tachyarrthymias following
myocardial infarction or CCF.
3.
Prophylaxis of recurrent paroxysmal atrial fibrillation, even during open
heart surgery.
4.
Recurrent ventricular tachycardia following ischaemic heart disease.
The efficacy of amiodarone is 80% for most supraventricular tachyarrthymias
and 60% for ventricular tachyarrthymias.
The dose is 1200-1600 mg/day is 3 divided doses orally for week & then 800
mg /day subsequently.
36-A
36-B
Thiazides :
Chlorothiazide
Hydrochlorothiazi
de
Bendrofluazide
Cyclopenthiazide
Chlorthalidone (a
diuretic
sulphonamide –
similar properties
to thiazides)
Diuretic
Slowly absorbed
Action persists 48 h
All effective orally
Pharmacokinetics
•
•
•
•
•
•
•
•
•
Hypokalaemia
Hyponatraemia
Hypovolaemia (esp.
elderly)
Hypomagnesaemia
Uric acid retention
and gout
Diminished calcium
excretion
Reduced glucose
tolerance
Raised blood lipids
Contraction of
extracellular volume
and secondary
polycythaemia
Toxicity
•
•
•
•
Chronic oedema,
especially cardiac
Hypertension
Diabetes insipidus
Idiopathic
hypercalciuria
Uses
Diuretics are the drugs which quantitatively increase the amount proeduction. They eliminate water and salt from the body and
hence are also called as "Saliuretics"
5. Diuretics
Indications :
Rapidly absorbed
from gut. Also given
i.v. Actions persist
upto 6 h (Bumetanide
a little shorter)
Pharmacokinetics
Hydrochlorthiazide (Esidrex), Frusemide (Lasin)
Diuretics:
Frusemide
Ethacrynic acid
Bumetanide
Diuretic
Hypokalaemia
Hyponatraemia
Hypovolaemia
Hypomagnesaemia
Uric acid retention
and gout
Ototoxicity with high
doses
Nephrotoxicity with
high doses, especially
when given with
gentamicin or
cephaloridine
PLUS :
• For ethacrynic acid :
alimentary
disturbances and
haemorrhage
• For Bumetanide :
muscle pain
•
•
•
•
•
•
•
Toxicity
1. Urgent reduction of
pulmonary oedema
2. Chronic oedema,
especially low output
cardiac failure;
chronic renal failure
3. Hypercalcaemia
4. Hypertension
Uses
Newer Diuretics
(Natrilix)
Methycl
othiazid
e
37-A
Diuretic
Onset (
hours )
Peak (
hours )
Duration
( hours )
Equivale
nt dose
(mg )
Percenta
ge
absorbe
d
T1/2
(hours )
Type
Indicati
on
preferr
ed
Indapam
ide
1-2
2
36
2.5
93
14
Belongs
to
thiazide
class
Edema
associ
ated
with
CCF ,
with
renal
impaire
ment
2
6
24
5
Not
known
Not
known
Belongs
to
thiazide
class
Edema
associ
ated
with
CCF
Calciu
m
nephrol
ithiasis
Metolazo
ne
1
2
12-24
5
65
Not
known
Thiazide
like
diuretic
Diuresi
s in
patient
s
where
GFR is
low
Quineth
azone
2
6
18-24
50
Not
known
Not
known
Thiazide
like
Reduce
urinary
volume
by 3050% in
nephro
genic
diabete
s
insipid
us
37-B
4-6
1
96
Long
Loop
Diuretic
like
furosemi
de
Edema
associ
ated
with
CCF,
Hepatic
cirrohs
is and
nephro
tic
syndro
me
Torsemi
de
Within
1hour
Within 2
hours
6-8
5
80
Long
Diuretic
like
furosemi
de
Hypert
ension
& CCF
associ
ated
with
other
conditi
ons
Dichlorp
henamid
e
Within
1 hour
Within 2
hours
6
50mg
70
6
Like
acetazol
amide
Used in
glauco
ma,
drug
induce
d
edema,
epileps
y and
acute
mounta
in
sickne
ss
Methazol
amide
Within I
hour
Within 2
hours
6
25mg
65
8
Like
acetazol
amide
Basical
ly for
glauco
ma
38-A
38-B
Block off triglyceride synthesis and release by the liver; reduction in synthesis of LDL in patients
with type IIa, IIb and IV hyperlipoproteinaemia
Nicotinic acid also
Diarrhoea, flatulence,
nausea, abdominal pain
Itching, flushing,
fainting, diarrhoea,
nausea, cholestatic
jaundice.
Hyperuricaemia and
gout.
Hyperpigmentation
Gallstones, Pulmonary
emboli, Cardiac
arrhythmias, Nausea
Dyspepsia, Myositislike syndrome, Rashes
Impotence
Bloating of abdomen.
Constipation.
Impairs absorption of :
Vitamins D and K
folate,
Phenylbutazone,
Thiazides, Warfarin,
Antibiotics, Thyroxin,
Cardiac glycosides
The most potent statin is Rosuvastatin with highest efficacy on LDL-cholesterol and triglycerides.
Probucol
Increases conversion of cholesterol to bile salts
Decreased synthesis and release of cholesterol by the liver; decreased release of triglycerides into
the circulation; increased excretion of neutral sterols (lowers LDL); HDL rises due to mobilisation
of tissue cholesterol; decrease in fibrinogen levels; increase in fibrinolysis
Clofibrate Group (Benzafibrate, Fenofibrate,
Clofibrate, Gemfibrozil)
Nicofuranose and Acipimox)
Anion exchange resin which can exchange chloride for bile salt anions. The bound bile salts cannot
be absorbed from the gut and the complex is passed in the faeces. As bile salts are lost from the
body, more synthesised cholesterol is diverted into the bile salt pool and less enters the circulation.
Reduction in bile salt reabsorption also results in increased oxidative removal of cholesterol
Drug
Resins (Cholestyramine, Colestipol)
(Dytor )
Toxicity
Within 1
hour
Mode of action
Within
30
minute
s
Actions of some lipid-lowering drugs
Bumetan
ide
Elevation of hepatic
liver enzymes,
headache, myalgia,
arthralgia.
Diarrhoea and
fatigue.
Benefits
Hepato-selective
Presence of a polar methane-sulfonamide
group
Decrease in cholesterol in the liver also leads to decrease in synthesis of VLDL.
This drug has to be used with statins for better effect and is useful particularly in
those who cannot adjust with dietary restrictions
Appears to act at the brush border of the small intestine and inhibits the absorption
of both dietary and biliary cholesterol, which results in decrease in delivery of
intestinal cholesterol to the liver.
Feature
Enhanced affinity to HMG CoA reductase
enzyme
Better efficacy
lesser incidence of adverse effects compared
to other statins particularly Rhabdomyolysis
Once a dose.
Long half-life of 20 hours
Can be taken anytime of the day
Food delays but doesn’t hamper extent of
absorption.
Can be safely given along with food.
90% of Rosuvastatin is not metabolized.
Metabolism is through CPY 450 2C9 & 2C19
isoenzyme
Can be safely co-administered with others
drugs
More patients’ achieves NCEP target goal.
Significantly reduces LDL-C compared to
Atorvastatin, Simvastatin and Pravastatin at
starting dose.
Patient’s reaches the goal faster.
Well tolerated and hence lesser chance of
withdrawal from therapy.
Ezetimibe (Ezzicad 10 mg)
Nausea
Lower triglycerides
Raise HDL
Reduce blood coagulability
Myositis,
Gastrointestinal
disturbances
Block rate – limiting step in cholesterol synthesis. Lower LDL
HMGCoA reductase inhibitors
(Simvastatin and
Pravastatin fish oils
(Omega-3 marine triglycerides)
Toxicity
Mode of action
Drug
Features & Benefits of Rosuvastatin
39-A
Significantly reduces triglyceride, non HDL-C
and ApoB level and increases HDL level and
Apo1
Reduces the risk of CAD.
Exerts anti-inflammatory effects
Additional vasoprotective effect
39-B
Say True or False
1.
Nicorandil sodium has similar mode of action as nitrates ?
2.
Glyceryl trinitrate relieves angina by liberating nitrous oxide ?
3.
Amlodipine acts by decreasing trans membrane Calcium influx ?
4.,
Source of Digoxin is Digitalis Lanata ?
5.
Candesartan is Angiotensin converting enzyme inhibitor ?
6.
Quinine is antiarrhythmic , where as quinidine is anti malarial ?
7.
Frusemide acts for longer period of time ?
8.
Lovastatin is effective lipid lowering drug , since it reduces LDL, TGL but
raises HDL ?
9.
Main side effects of spironolactone therapy are hyperkalemia and
gynaecomastia ?
10. The important medication for peripheral arterial disease is cilostazol ?
Answers
1.
False
2.
True
3.
True
4.
True
5.
False
6.
False
7.
False
8.
True
9.
True
10. True
40-A
40-B
CENTRAL NERVOUS SYSTEM
3
The neuronal effects produced are :1.
2. They produce a rise in threshold of action potential. (because they inhibit
increased in Na+ permeability).
1. Pre-anaesthtic Medication
Objectives
1.
To reduce apprehension.
2.
To supplement the action of anaesthetics.
3.
To have good antiemetic action post-operatively.
No change in resting potential
Types :1.
Inhalational :A)
Halogenated hydrocarbons :- Halothane, (Fluothane)
Methoxyflurane, Nitrous oxide
Drugs :1.
2.
3.
4.
B)
Diazepam 10 mg oral or I.M. (Calmpose) or lorazepam 2 mg oral of I.M.
(Ativan) produce transquillizing effects and also have central antiemetic
action.
2.
Atropine 0.6 mg I.M. is used to reduce salivary and bronchial secretions.
It prevents bradycardia during surgery.
Chlorpromazine 25 mg I.M. (Megatil) prevents anxiety, has antiemetic
action but in children ite use is not advocated as it can lead to involuntary
movements specially dystonias.
Opiate drug like pethidine 100 mg I.M. though effective can cause fall in
blood pressure and can precipitate bronchial asthma.
Note :
Non-haloganted : - Cyclopropane, ether
Intravenous :1.
Barbiturates :- Thiopentone (Pentothal), methohexitone
2.
Propandid
3.
Althesin
4.
Ketamine (Ketalor)
5.
Benzodiazepines : - Flunitrazepam, diazepam
1) Inhalational Anesthetics
A typical anesthetic sequence for major surgery is induction with an intravenous
anesthetic (like thiopentone), maintenance of unconsciousness with an
inhalational anesthetic (like nitrous oxide with oxygen), and production of muscle
relaxation with a neuromuscular blocker (like d-tubocurarine).
Sedatives are given on night before surgery.
Atropine is given ½ hour before surgery.
2. General anaesthetics
General Anaesthesia is state fo unconsciousness in which subject is not
arousable by external stimuli.
The inhalational anesthetics include gases and volatile liquids. Both types
enter the circulation rapidly on absorption from the alveoli of the lungs. From
the blood, the agent is transferred to the brain. Eventually, most inhalational
Central Nervous System
41-B
41-A
agents are returned to the lungs and excreted in exhaled air mostly unchanged.
A frequently used measure of anesthetic potency is the minimum alveolar
concentration (MAC). It is defined as the concentration of anesthetic in the
pulmonary alveoli which prevents response to painful stimuli (e.g. incision in
50% of patients. The lower the MAC, the more potent is the anesthetic drug.
4)
It is a poor muscle relaxant
5)
Due to lack of potency, it can induce only a very light plane of anesthesia
6)
It cannot elicit sufficient depth of anesthesia to allow surgical procedures
when used alone
Given below is a tubular form of the salient characteristics of inhalational
anesthetics.
7)
It results in hypoxia if used in concentrations higher than 80% and so
atleast 20% oxygen has to be provided in the inhalation mixture
8)
It is used in balanced anesthesia in concentrations of 50-70% to prolong
anesthetic state and reduce the amount of other general anesthetics
required
9)
It is used as a component of balanced anesthesia, as a supplement to
more potent inhalational anesthetics for maintenance of anesthesia and
for production of analgesia for minor surgical or dental procedures.
Drug
Inflammability
(MAC)%
Onset of
Muscle
anesthesia
relaxation
Gases
Nitrous oxide
Non-inflam.
>100
Rapid
Fair
Cyclopropane
Inflam+Explo
10
Rapid
Fair
Ethylene
Explosive
80
Rapid
Poor
Cyclopropane :
Volatile Liquids
Halothane
Non-inflam
0.75
Rapid
Fair
Enflurane
Non-inflam.
1.68
Rapid
Good
Isoflurane
Non-inflam.
1.2
Rapid
Good
Methoxyflurane
Non-inflam
0.16
Slow
Fair/Good
Ether
Inflam + Explo
2.0
Slow
Excellent
1)
It has a rapid onset of action
2)
It produces satisfactory analgesia and skeletal muscle relaxation
3)
It is explosive and so needs to be administered in closed rebreathing
system with oxygen
4)
It causes sensitization of myocardium leading to arrhythmias and malignant
hyperthermia (sudden drastic elevation of body temperature) leading to
death.
5)
It needs to be used with great caution because of its explosive nature
Gases
Of the gases available nitrous oxide is most extensively used.
Nitrous oxide
1)
It is a non explosive insert gas
2)
It has a rapid onset of action
3)
It has a short duration of action
Volatile Liquids
They are administered by inhalation of the vapours given off by the liquid, along
with adequate amounts of oxygen. These agents are generally short acting and
recovery begins as soon as the drug is stopped, because most drugs are
excreted through the lungs.
42-A
42-B
The first volatile liquid to be used was ether, which suffered from the following
drawbacks.
a)
Noxious odour
b)
Slow and unpleasant induction
c)
Respiratory irritation
d)
Prolonged emergence
e)
Extreme flammability
f)
Increased salivary and bronchial secretions
g)
High incidence of post-operative nausea and vomiting
Currently, ether is obsolete as more potent, more rapid acting and safer
anesthetics are now available.
Halothane :
1)
It is one of the most used anesthetics
2)
It is potent, non-flammable and pleasant smelling
3)
It is non irritating to lungs
4)
It does not increase salivary or bronchial secretion
5)
It sensitizes the myocardium causing arrhythmias
6)
It is used concomitantly with either oxygen or a mixture of nitrous oxide
and oxygen
7)
It is widely used today for many surgical procedures
3)
It causes rapid induction and rapid recovery
4)
It is non flammable
5)
It produces better muscle relaxation than halothane
6)
It sensitizes the myocardium causing arrhythmias
7)
It is used in combination with nitrous oxide
8)
It is to be used with caution in impaired renal function, epilepsy and cardiac
arrhythmias
Isoflurane :
1)
It is structurally similar to enflurane but with several advantages
2)
It has a rapid onset and produces rapid recovery
3)
It does not sensitize the myocardium
4)
It produces good muscle relaxation
5)
It is used in combination with nitrous oxide for maintenance
6)
It is to be used with caution in patients with respiratory or cardiac failure
Methoxyflurane :
It is contraindicated for obstetrical anesthesia (because it is a uterine
relaxant) and in hepatic and biliary disease
Enflurane
1)
2)
1)
It is the most potent anesthetic available
2)
It has a slow onset and recovery
3)
It produces fair muscle relaxation
4)
It produces significant analgesia at light levels of anesthesia.
5)
It causes minimal sensitization of myocardium and the incidence of
arrhythmias is low
It is a potent anesthetic
43-A
43-B
6)
3)
Should produce analgesia at subanesthetic concentrations
4)
Should produce minimal central nervous system and respiratory depression
5)
Should have no emetic effects
6)
Should not cause excitatory phenomena (e.g. coughing, hiccup) on
induction.
7)
Should not produce emergence phenomena (e.g. nightmares)
8)
Should have no interaction with neuromuscular blocking drugs.
Intravenous anesthetic agents are used commonly to induce anesthesia, as
induction is usually more rapid and smoother than that associated with
inhalational agents. In some circumstances intravenous anesthetics are used
also for maintenance, either alone or in combination with nitrous oxide; they
may be administered as repeated bolus doses or by continuous intravenous
infusion. Other uses of intravenous anesthetic agents include sedation during
regional anesthesia and sedation in intensive therapy unit (ITU)
9)
Should not cause pain on injection
Properties of an ideal intravenous anesthetic agent :
14) Should have a long shelf life
7)
Its use is associated with the problem of nephrotoxicity and liver damage
due to the accumulation of free fluoride ion as a by-product of
methoxyflurane and this limits its usage.
It is used for maintenance of surgical anesthesia of less than four hour
duration usually with nitrous oxide and oxygen and for production of
analgesia in obstetrics and minor surgical procedures.
2. Intravenous Anesthetic Agents
10) Should be safe if injected inadvertently into an artery
11) Should produce no toxic effects on other organs
12) Should not produce hypersensitivity reactions
13) Should be a water soluble formulation
A number of intravenous anesthetic agents have been developed but no
single agent represents the 'ideal' drug in terms of potency, efficacy, stability
and safety. Thus the practice of general anesthesia usually involves use
of two or more drugs in combination to take advantage of their desirable
effects (e.g. speed of induction, skeletal muscle relaxation) while
simultaneously minimizing their undesirable effects (e.g. respiratory
depression, hepatotoxicity).
Following are the properties of an ideal intravenous anesthetic agent
1)
Should have a rapid onset. This is achieved by an agent which is mainly
unionized at blood pH and which is highly lipid soluble. These properties
permit penetration of the blood brain barrier.
2)
Should cause early recovery. Early recovery of consciousness is produced
usually by rapid redistribution of the drug from the brain into well perfused
tissues, particularly muscle. The plasma concentration of the drug
decreases and the drug diffuses out of the brain along a concentration
gradient.
The quality of the later recovery period is related more to the rate of
metabolism of the drug; drugs with slow metabolism are associated with
a more prolonged 'hangover' effect and accumulate if used in repeated
doses or by infusion for maintenance of anesthesia.
44-A
Classification Of Intravenous Anesthetics
a)
Ultra short acting barbiturates (thiopental, metholhexital, thiamylal)
b)
Imidazole compounds (etomidate)
c)
Dissociative agents (ketamine)
44-B
d)
Alkylphenols (propofol)
e)
Benzodiazepines (diazepam, midazolam)
f)
Opioids (fentanyl)
4)
Solubility of the drug in lipid
High lipid solubility enhances transfer of drug to the brain
5)
Speed of injection
Rapid IV administration results in high initial concentrations of drug. This
increases speed of induction and also the extent of cardiovascular &
respiratory side effects.
Use of IV Anesthetic agents :
Intravenous anesthetic agents are used for
1)
Induction of anesthesia
Distribution of IV anesthetic agents to other tissues :
2)
As the sole agent for operation (TIVA - Total intravenous anesthesia)
3)
To supplement volatile anesthesia or regional anesthesia
The anesthetic effect of all IV anesthetic drug is terminated predominantly by
distribution to other tissues. Fig. Below shows the distribution for an IV
anesthetic agent thiopentone. In this figure, the percent of injected dose which
gets distributed in each of the four body compartments as time elapses after IV
injections is shown.
Pharmacokinetics of IV Anesthetic Drugs :
After IV administration of the drug, there is an immediate rapid increase in the
plasma concentration followed by a slower decline. Anesthesia is produced by
diffusion of drug from arterial blood across the blood brain barrier into brain.
The rate of transfer into brain and therefore the anesthetic effect is regulated by
1)
Protein Binding
Only unbound drug is free to cross the blood brain barrier. Protein binding
may be reduced by low plasma protein concentrations or displacement
by other drugs resulting in higher concentration of free drug and an increased
anesthetic effect. Protein binding is also affected by changes in blood
pH.
2)
Blood flow to brain
Reduced cerebral blood flow (CBF) results in reduced delivery of drug to
brain.
3)
Extracellular pH and dissociation constant of the drug :
Only non-ionized fraction of the drug penetrates the blood brain barrier.
Thus potency of the drug depends on the pH of the extracellular fluid and
dissociation constant of the drug.
45-A
The 4 body compartments are (1) Viscera (2) Muscle / Lean tissue (3) Fat (4)
others
A large proportions of the drug is distributed initially into the well perfused
organs (termed the vessel rich group or viscera: predominantly the brain, liver
and kidneys).
Distribution into muscle (lean) tissue is slower because of its low lipid content
but is quantitatively important because of its relatively good blood supply and
large mass. Despite their high lipid solubility, IV anesthetic agents distribute
slowly to adipose tissue (fat) because of its poor blood supply. There is also a
small amount of redistribution to areas with a very poor blood supply e.g. bone.
After a single IV dose, the concentration of drug in blood decreases as distribution
occurs into viscera and particularly muscle. Drug diffuses from the brain into
blood along the changing concentration gradient and recovery of consciousness
occurs. Metabolism of most IV anesthetic agent occur predominantly in the
liver. As IV anesthetic drug have a large volume of distribution, total elimination
takes.
45-B
1. Inducing agent in poor
risk patients and
asthmatics.
2. General anaesthetic in
out patient surgery.
3. General anaesthetic
where inhalational
anaesthesia is impossible.
Allergy, nausea
restlesness,
shock
raised intracranial pressure
vivid dremas
Orally or I.M. I.V. Anaesthesia
in 30 seconds lasts for 5-10
minutes. Hepatic metabolites
are active.
Mechanism of action: :-
Given I.V. or even rectally.
Anaesthesia within 10 seconds
lasting for 5-15 minutes.
Action short lived.
1. Induction of general
anaethesia.
2. General anaesthetic for
short surgical procedures.
3. Status epilepticus.
Definition :- Drugs which block nerve conduction in the regional areas without
causing loss of consciousness. At the cellular level they have same action as
general anaesthetics.
Permeability of the nerve membrane to Na+ ions which produce depolarization
is prevented; also K+ conductance is reduced. This is a membrane stabilizing
effect and is also seen with drugs like antihistaminics, antiarrythmics and the
B blockers.
Classification:Amides
Benzoic acid esters
Para-amino benzoic acid esters
Lignocaine
(Gesicain)
Cocaine
Procaine
Priolocaine
Piperocaine
Amethocaine
Mild Stimulation
There is tachycardia and blood
pressure rises.
Benzocaine
Bupivacaine
(Sensorcaine)
In contrast to general anaesthetics:-
2. Ketamine
(Aneket)
Depression of respiration and bronchospasm.
Mepivacaine
Cardiac output
and blood
pressure falls.
1. Thiopentone
sodium
(Pentothal)
Uses
Toxicity
Pharmacokinetics
Respiratory system
CVS
Drugs
Commonly Used Intravenous anaesthetics
3. Local anaesthetics
46-A
1.
Cardiac output and stroke volume are not much altered.
2.
No change in plasma cortisol or epinephrine levels.
3.
Low incidences of morbidity and mortality.
4.
Easier ambulation.
5.
There is less requirement for post operative analgesics.
46-B
Desirable properties in an local anaesthetic:"
a)
Non irritative.
b)
Low systemic toxicity.
c)
Should be effective whether injected or applied topically.
d)
Short induction time.
Addition of vasoconstrictor : Use of adrenaline I : 100,000 or phenylephrine
decreases the rate of absorption of local anaesthetic agents leading to its
prolonged effects and also reduces its systemic toxicity.
3)
Opthalmic anaesthesia:- used where tonometery is to be performed or a
comeal ulcer is very painful.
4)
Infilteration anaesthesia i.e. injection of local anaesthetic into tissues which
are to be excised. Adrenaline containing solutions are not injected to the
tissues supplied by end arteries (fingers, toes; ears) as it may cause
gangrene.
5)
Nerve block anaesthesia i.e. injection of local anaesthetic into a individual
nerve or plexus used in upperlimb surgery distal to the deltoid muscle
where the brachial plexus can be blocked. Pudendal block is another
example.
6)
Spinal anaesthesia: - i.e. injection of local anaesthetic below 2nd lumbar
vertebra. The level of block is 2 segment below the site of injection.
Side effects : These are basically due to systemic absorption.
1.
CNS
: Tremors; convulsions.
2.
CVC
: Conduction and force of contraction are reduced,
arteriolar dilatation can occur.
3.
Hypersensitivity : Methaemoglobinaemia
Addition of 10% glucose solution to that of local anaesthetic produces a
fluid heavier than cerebro spinal fluid and it is termed hyperbaric.
Complications of spinal anaesthesia :-
Metabolism :-
1.
Loss of sympathetic tone due to arteriolar and venous dilatation.
The esters are metabolised in plasma by plasma pseudocholmesterase; whereas
the amide compounds undergo enzymatic degradation in liver.
2.
Headaches and temporary palsy of abducens nerve.
3.
Forced expiration is impaired; due to paralysis of abdominal
musculature.
4.
Pain and infection at the site of injection can occur.
P.A.B.A. which is formed during the hydrolysis of esters can antagonize the
actions of sulphonamides.
7)
Therapeutic uses :1)
Surface anaesthesia is used for mucous membranes of upper respiratory
or the genito urinary tract . Lignocaine, cocaine and tetracaine are used.
Cocaine by virtue of its vaso-constrictive actions improves surgical visualization.
2)
Topical anaesthesia in the form of cream is effective in relieving anal and
Epidural anaesthesia: e.g. injection of local anaesthetic into epidural space
from lumbar to thoracic region in order to produce paravertebral nerve
block. This procedure is utilised to control the pain during labour.
genital pruritis. Hexylcaine and pramoxine are used.
47-A
47-B
Contrast :
4. Non narcotic analgesics
Lgocaine
Cocaine
Procaine
These drugs have analgesic, antipyretic and anti-inflammatory properties
(NSAIDS) by virtue to antagonise the prostaglandin (PG) synthesis.
(Xylocaine)
1. Pharmaco- Absorbed from injeckinetics
Not injected me-
Injected destoryed
ted sites and meta-
tabolized by este-
by serum choli-
Chemical Classification:Derivatives of -
bolized by liver
rases. Effective
nesterase. Not
amidases.
when applied to
effective when
Rapid absorption
mucosa and
applied to
from mucosa
considerable
mucosa.
Salicylic acid : Acetyl salicylic acid (Aspirin, known as generic was Bayer
discovery >100 years ago)
Paraminophenol: Paracetamol (Calpol)
Propionate: lbuprofen, ketoprofen, naproxen
Fenamates : Mefanamic (Brufen), fenfenamic acid
Oxicams: Piroxicam (Meftal), Meloxicam
Ethanoic acids: Diclofenac, Aceclofenac (Movon)
Coxibs : Celecoxib, Rofecoxib (Voveran), Valdecoxib (Valz), Etoricoxib
(Etrobax)
absorption occurs.
2. Action
No significant effect
Vasoconstriction
Vasodilatation.
Not much; but rarely
Too toxic to be
More toxic than
on blood
vessels
3. Toxicity
can cause CNS stimu- injected, cardiac
ligonocaine but
lation; fits and respi-
arrythmias and ce- less toxic than that
ratory failure, hypo-
rebral stimulation
failure, hypotension
due to block of
and cardiac arrest.
inhibitory
of cocaine.
(A) Salicylates:- (Aspirin)
Pharmacological actions:
pathways
4. Lenght
of action
Injection of 1% of
Prolonged surface
solution, lasts for
anaesthesia.
1 hour.
5. Vasocon-
Adrenaline
Injection of 1-2%
1.
solution, lasts for
½ hour.
No vasoconstric-
strictor
tor required as it
used to
blocks re-uptake
prolong
of endogenous
Adrenaline
The other postulated mechanisms for anti-inflammatory action.
NE
6. Clinical
use
Subcutaneous sub-
Local anaesthesia:- Subcutaneous and
mucus and topical
Applied to cornea
submucus infiltra-
anaesthetia.
cornea and nose
tion anaesthesia.
Analgesic and anti-inflammatory actions: uUeful in headache,
rheumatic and muscular pain arising from integumental structures. Not
effective in acute visceral pain. The peripheral analgesic action depends
on reducing the production of PG present in inflammatory process. There
is also an- tibradykinin action which is reflected as elevation of pain
threshold.
48-A
48-B
i)
Interference with oxidative phosphorylation.
ii)
Intereference with migration of leucocytes.
2.
Antipyretic:
7.
Hepatic and renal:
Salicylatcs have antipyretic action and reduce elevated body temperature.
This is due to inhibition of synthesis and release ofPG in the hypothalmus.
3.
Antirheumatic:
Elevation of enzymes SGOT/SGPT.
Shredding of renal tubular epithelium leading to analgesic nephropathy.
8.
Platelets:
The pain and fever are reduced. It is suggested that salicylates stimulate
endogenous cortisone. They also prevent release of lysosomal enzymes
which destroy cartilage of rheumatic joints.
4.
Antiaggregatory action on platelets. Therefore aspirin now finds its use in:
1.
Stroke
2.
T.I.A. (Transient ischaemic attacks)
Respiration and acid base balance:
3.
Prophylaxis of myocardial infarction.
There is increased respiratory rate and volume:
4.
Intermittent claudication. (Peripheral vascular diseases)
a)
By direct stimulation of respiratory centre.
5.
Pre-eclampsia.
b)
By uncoupling oxidative phosphorylation.
The efficacy of aspirin can be enhanced, if it is combined with clopidogrel
since both of them act synergistically.
As a secondary effect respiratory alkalosis occurs. In very high doses
respiratory centre is depressed and salicylates can cause central
respiratory paralysis.
9.
Metabolic:
a) Carbohydrate: Large doses can lead to hyperglycemia and glycosuria
and depletion of liver and muscle glycogen. In diabetics there is
increased peripheral utilization of glucose and therefore blood sugar
decreases.
Salicylate induced sweating can cause water and electroyte unbalance.
High doses lead to K+ depletion.
5. Gastrointestinal:
b) Fat: Reduce lipogenesis.
Gastric erosion is caused by:
6.
a)
Precipitating protective glycoprotein component of gastric mucus,
thereby allowing H+ ions to attack mucosa.
b)
Reduction in mucosal PG levels.
c) Nitrogen: Negative nitrogen balance, aminoaciduria.
10. Uricosuric:
Low doses decrease urate excretion, whereas large doses cause uricosuria.
Cardiovascular:
11. Pregnancy:
Peripheral vessels dilate in large doses.
No teratogenecity. It can prolong normal parturition.
49-A
49-B
Pharmacokinetics:
●
mostly absorbed from upper small intestine.
●
peak : 2 hours.
●
t ½ increases with dose
●
considerably bound to plasma proteins.
Uses:
(1)
Analgesia : Therapeurically useful in cases of myalgia, neuralgia, toothache, dysmenorrhaea, backache, and premenstural tension.
(2)
Antipyretic : In acute rheumatic fever dose is 5-8 g/day. In rheumatoid
arthritis it is 2.4 g/day
(3)
Gout : Due to uricosuric action aspirin is used in doses of >3g /day.
Toxicity : 1.
Salicylism characterised by tinnitus, ana (uzziness,
2.
Haemorrhage from gut.
3.
Wheezing.
4.
Hypersensitivity reaction.
5.
Hepalotoxity.
Drug interactions:
i)
Potentiates effects of oral hypoglycaemic agents and oral anticoagulants.
ii)
Gastric irritation potentiated when used with alcohol.
(B) Paracetamol:
1.
It is major metabolite of phenacetin
2.
It has no anti inflammatory or anti-rheumatic activity.
3.
It has no effect on platelets.
50-A
50-B
●
6.
Half life of drug is 2 hours.
7.
There is less gastric irritation than aspirin.
8.
The drug abuse leads to liver damage, particularly in glutathione
deficient individuals.
9.
Toxicity treated by giving N-acetylcysteine 150 mg/kg I.V.
51-A
51-B
11
17
Celecoxib
Rofecoxib
86 L
91 L
400 L
0.2L/kg
0.36 L/Kg
Volume of
distribution
3
2
3
9
1.5
Peak
effect
(Hrs)
10mg, once
for PD
20mg ,
twice
50mg, once
100mg ,
twice
500mg750mg ,
once or
twice
400mg,
twice
Dose &
Frequency
Pain, RA, OA
RA, OA
Pain , RA, OA
Analgesic and anti
Pain, OA,
inflammatory / High efficacy RA,PD
but causes edema in few
individuals
Pain, OA,
Analgesic and anti
inflammatory / High efficacy RA,PD
but causes hypertension in
few individuals
Potent analgesic / Moderate
efficacy and reasonable
safety
Potent anti inflammatory /
Moderate efficacy and
reasonable safety
Good analgesic effect for
long duration /Moderate
efficacy and reasonable
safety
Special Features / Efficacy
RA = Rheumatoid arthritis, OA = Osteoarthritis , PD = Primary dysmenorrhoea
11
2
Nambumetone
Half
life
(Hrs)
7
Valdecoxib
There is diumal variation in absorption.
Indications
5.
Newer Non Steroidal Anti inflammatory Drugs
The antipyretic effect is due to actions on central prostaglandins.
Etodolac
Drug
●
4.
52-A
52-B
Toxicity
Releases sulphapyridine +5 aminosalicyclate
(5AS)
Well absorbed orally and given at low dose once
per week.
Well absorbed
Sulphasalazine
Methotrexate
Leflunamide
Acute opiate poisoning
c. Production of sleep.
congeners
Naloxone is tried.
present.
increased.
piratory depression is
5. Muscle tone throughout the gut is
substitute. If acute res-
to give methadone as a
patient airway and then
codeine appears to be superior.
6. Treatment of cough, where
5. Biliary, renal or ureteric colic.
4. Diarrhoea.
3. Preanaesthetic medication.
reduced
work load on hear is also
rature also falls. Treatment is to establish a
causes vascular pooling, the
ventricular, failure and as it
2. To reduce pain in acute lef
during post operative period.
1. Pain of myocardial infarction or
Therapeutic uses
4-6 hourly
repeated
I.M. can be
10 mgs.cor
Dose
Alopecia, diarrhoea, increased cough
abdominal pain.
Myleosuppression. GI intolerance and oral
ulceration, Shock
Sulphonamide injury
Retinal injury.
volume and body tempe-
ressed respiration, urine
pinpoint pupils and dep-
4. Peripheral arteriovenous dilatation.
induced.
3. Stimulation of CTZ and vomiting is
centre
2. Depression of respiratory and cough
d.Liberation of endorphins
b.Changing emotional reaction to pain.
hold
in characterised by coma,
1. Analgesic action :a.Elevation of pain perception thres-
Toxicity
Pharmacological actions
ant it's
morphine
alkaloides-
Opium
Drugs
Pyrimide synthatise inhibitor with
antiproliferative activity
Inhibits folate metabolism
5AS scavenges toxic oxygen radicals from
leucoytes
5. Narcotic Analgesics
Given as a loading dose of 100 mg for 3 days,
followed by 20 mg subsequently for 4 weeks,
Well absorbed from gut; concentrated in tissues;
t1/2 3-7 days.
HydroxyChloroquine
Not analgesic or anti-inflammatory.
Stabilises lysosomal membranes.
damage. Mammary hyperplasia. Haemolytic
anaemia. Mucous membrane ulceration. SLE.
immune complexes.
Penicillamin (β
Myasthenic syndrome.
Nausea. Vomiting. Abdominal discomfort.
Rashes. Bone marrow depression. Renal
Dissociates macroglobulins. Inhibits
release of lysosomal enzymes. Chelation of
Well absorbed from intestine. Tight binding to
plasma proteins. Slow excretion.
dimethylcysteine)
Rashes. Renal damage. Blood dyscrasias.
Stomatitis. Diarrhoea with oral gold.
tissue metabolism.
Actions
excretion
Pharmacokinetics
Inhibits PG synthesis. Inhibits lysosomal
enzymes. Binds to immunoglobulin and
complement. Possibly modifies connective
Gold salts
Given by i.m. injection or orally (less well
absorbed). Bound to plasma proteins.
Concentrated in inflammed areas. Very slow
Drug
Drugs used in rheumatoid arthritis
Contrast :
Analysis of Drugs used as analgesics :
Morphine
Pethidine
1. Introduction
Isolated by Serturner in 1806
Introduced in 1939.
2. Source
Natural from Poppy
Synthetic
3. Potency
More potent
1/10th as morphine.
Features
Chemistry
I.M
5. Pupils
Miosis (constriction of pupil)
Mydriasis (dilatation of
pupils)
6. Cough
Anti-tussive activity
No anti-tussive effects.
7. CVS
Arterio-venous pooling
Only decreased
peripheral arterial
resistance.
i. Acute pain of any etiology.
i. Moderate or sever
pain due to coronary
occlusion.
ii. Left ventricular failure
ii. Renal or biliary colic.
iii.Diarrhoea.
iii. Obstetrical analgesia.
+++
Fentanyl citrate
Phenyl piperidine
derivative ,
chemically related to
pethidine
Midazolam
It is an
imidazobenz
odiazepine
Acts as an agonist by
acting on mu
receptors & the
antagonist activity is
mediated by delta
receptors
Acts on mu and delta
receptors producing
good supraspinal &
spinal analgesia
The action is
mediated
through
GABA , at the
mesolimbic
system of the
brain
Onset is within 30
minutes & can remain
for 6 hours
Onset is within 15
minutes and remains
for 2 hours
Moderate to severe
pain
Post operative pain
Pre operative &
perioperative
analgesic
As an adjunct to
General anesthesia
Side effects
Constipation
Tachycardia
Vertigo
Dizziness
Unit Dose
Injectable
50mg and
oral 50mg
Confusion
Hypotension
Miosis
Respiratory
depression
Injectable 0.3mg and
sublingual tablet
0.2mg
Respiratory
depression
No significant
histamine release
unlike morphine
Each injectable dose
contains 50mcg
Onset is
within 30
minutes and
remains for
about 4 hours
Pre
anesthetic
medication
Maintenance
of anesthesia
Procedural
sedation
Sedation in
critical care
settings
Drowsiness
Coughing
Nausea &
vomiting
Kinetics
Indications
iv.Biliary, renal or ureteric
colic.
9. Dependence
liability
Buprenorphine
Synthetic partial
opiate agonist
Mode of
action
4. Route of
S.C. or I.M.
administration
8. Uses:-
Tamadol
Synthetic
compound ,
not
chemically
related to
opiates
Opiate
agonist
activity by
acting on mu
receptors and
also inhibit
the reuptake
of
catecholamin
es
Onset is in 1
hour &
analgesia
remainsfor 24 hours
Postoperative
pain
Chronic Pain
++
53-A
53-B
Each
injectable
dose
contains 1mg
54-A
54-B
arise from the process
of fementation. Distillation can incrase the
alcohol concentration.
1. Neutral spirit
water yeast and warm
atmosphere are
present, alcohol is
produced Sugar can be
obtained from fruits,
and brandy.
from ethylene.
4. Beer 3-12% alcohol
alcohol
3. Wine 10-22%
alcohol whisky, rum
2. Vodka 40-55%
trial use its produced
sugarcane. For indus-
90-95% alcohol
All alcoholic brevages
When molases (sugar)
grains, potatoes and
Alcoholic
brevages
Production
driving are 0.10%
tion of alcohol for
of blood concentera-
acetate. Legal limits
is then converted to
to acetaldehyde which
Alcohol is oxidised
reaches rapidly.
of alcohol in brain
2 hrs. Concentration
Peak level attained ½-
Rapidly absorped
Pharmacokinetics
is dementia, fits
and impairment
of motor skills.
secretions.
5. ADH releae is
inhibited.
drome where there
5. Marchiafava syn-
4. Can increase salivary and gastric
pathy and retrobulbaneuritis.
and flushing.
4. Peripheral neuro-
impairment.
there is memory
psychosis where
3. Korsakof's
and nystagmus.
there is confusion
phalopathy where
2. Wemicke's Ence-
activities
terest in daily
changes i.e. disin-
1. Behavioural
Chronic
cutaneous vasoli-
it leads to
3. In moderate doses
trasmission.
reduce synaptic
tion of alcohol can
2. Lower concentera-
judgement.
learing and
concentration,
stem. It impairs
formation of brain
acting at reticular
1. CNS depressant,
Actions
effects
6. Alcohol
CNS depressants.
2. Synergistic action with other
colitis
1. Hyperacidity or ulcerative
Contraindications
5. Methanol poisoning.
to suppress premature labour.
4. I.V. alcohol is sometimes used
neuraligia.
in cases of trigeminal
3. Local anaesthesia, is injected
2. Appetizer.
in bed ridden patients.
1. Topical in prevention of sores
Therapeutic uses
55-A
55-B
not produce drowsiness.
(valium)
electrically stimulated
seizures.
Nitrazepam
(Nitravet)
+
+
--
Zopiclone
Zolpidem
Phenobarbitone
--
+
Lorazepam
Chloral hydrate
+
Diazepam
--
+
Alprazolam
Promethazine
Capacity
to
improve
GABA
activity in
brain
Drug
+
+
+
++
++
+
+
+
Onset
O2 demand is reduced.
improved and mycardial
5. Coronary flow is slightly
receptors in spinal cord.
stimulation of glycine
effect is obtained due to
4. Skeletal muscle relaxant
for chemically induced or
acid)
amino butyric
(Gamma
G.A.B.A.
action of
facilitate the
pathway and
neuronal
polysynaptic
tively on
BDZ act selec-
action
Mode of
12
14
11
3
6
10-20
20-60
9-20
Half life
(hours )
1 gram
25mg
15-30mg ,
thrice daily
10mg
7.5mg
0.5mg-1mg
5-10mg
0.5mg
Usual dose (
Oral )
syndrome.
8. Alcohol withdrawal
7. Tetanus
Moderate
Moderate
Moderate to
Severe
No
No
Mild
Mild
Mild
Less safe for
insomnia
Less safe for
insomnia
Less safe for
insomnia
Yes
Yes
Yes
Yes
Yes
Safety
compared to barbiturates.
4. Drug dependence is less as
underlying lung disease.
sion in patients with
3. Cardiorespiratory depres-
photosenstivity.
2. Fixed drug erruption and
day time terrors.
incoordination, diplopia,
wsiness, ataxia, motor
1. CNS :- Dose dependen dro-
Side effects
Hangover or
day time
effects such
as sedation
or sensation
of heaviness
in head
vertebral disc prolapse
6. Muscle spasm due to
neuron leisons.
with upper motor
5. Spasticity associated
anaesthesia.
4. Permedication for
ful in status epilepticus.
diazepam are very use-
3. Clonazepama and
doses produce sleep.
2. Insomnia : where larger
1. Anxiety
Therapeutic uses
7. Anxiolytics
3. They can raise the threshold
viour
(Ativan)
Lorazepam
Prazepam
2. Can reduce aggresive beha-
anxiety in doses which do
epoxide
Oxazepam
limibic system, reduce
1. Benzodiazepines (BDZ)
Chloridiaz-
2-40 mg
Diazepam
Pharmacological Actions
exert more specific effect in
dose range
drugs
(calmpose)
Total daily
Name of
7. Anxiolytics
56-A
56-B
Phenytoin stimulates
Na+ K+ AT Pase, reduces
Na + conductance in
membrane and also limits
membrane permeability
to calcium ions thus
reducing post tetanic
potentiation (PTP). It
has antiepileptic activity
without causing generalised CNS depression. It
can cause complete
remission of tonic and
clonic seizures.
1. Hydantoin :
Diphenylhydantoin
(Dilantin)
1. Sedation and
drowsiness.
2. Nystagmus,
ataxia personality changes
3. Megaloblastic
anaemia
4. Can precipitate
acute intermittent prophyria
in susceptible
individuals.
Abolishes clonic
seizures, Tonic
component is reduced
only is large doses.
Dizziness,
eosinophilia, SLE
Well absorbed.
Toxicity
1. Abscence seizures.
2. Abinetic epilepsy
3. Myoclonic spasms
Terporal lobe epilepsy
Grandmal epilepsy
Abscence seizures.
Myoclonic spasms.
Trigeminal and glosso
pharyngeal neuralgia.
6. To treat cocaine addiction.
1.
2.
3.
4.
5.
Therapeutic uses
1. Its used in cortical focal epilepsy and in grandmal epliepsy,
(50-100 mg orally, 2-3 times a
day.)
2. Used I.V. to treat status
epilepticus.
4. Ethosuximide
(Zarotin)
Pharmacokinetics
8. Antiepileptics
Well absorbed on oral and
I.M. administration. It can
cause induction of hepatic
microsomal enzymes. Less
bound to plasma proteins.
Peak levels in 6 hours.
Estimation of plasma levels
in 6 hours. Estimation of
plasma levels (therapeutic
drug monitoring) may
become necessary.
1. Used alone or in combination
with phenobarbitone for treatment of grandmal epilepsy,
psychmotor epilepsy and
symptomatic convulsions.
2. Status epilepticus
3. Atypical fascial pain.
The usual dose is 300 mg.
daily
4. Treatment of digitalis cardio
toxicity.
Therapeutic uses
Drug is slowy, but completely 1. Sedation, ataxia
absorbed from the gut.
giddiness,
Plasma levels fluctuate
nystagmus
widely.
2. Can cause fatal
aplastic anaemia.
3. Hyponatraemia
Mode of action
1. Hyperplasia of
gurms.
2. Yeaning vertigo
3. Drug fever
4. Acne
5. Nystagmus
6. Thickening of
fascial muscles
Toxicity
3. Metabolised by hydroxylation and is genetically
determined.
4. Control of seizures occurs
with plasma levels of
(HYDANT)
10 mg/ml.
1. Absorption from gut is
slow and peak is reached
8 hrs after drug administration.
2. Absorption is erractic
after I.M. administration.
Pharmacokinetics
3. Carbamazepine It inhibits maximal
(Tegretol)
electroshock seizures,
abolishes focal brain
discharges. It has only
slight inhibitory effect
on PTP in spinal cord
Drug
2. Phenobarbitone It limits the spread of
(Gardinal)
seizures activity and also
elevates seizures threshold. It also auguments
the postsynaptic inhibitory effects of GABA.
(Gama amino butyric
acid)
Mode of action
Drug
8. Antiepileptics
NEWER ANTI EPILEPTIC DRUGS
Drug
Mechanism of
action
Kinetics
Toxicity
Therapeutic
use and doage
Gabapentin
Its analogue of
GABA ( direct
action ) which
reduces
convulsive
threshold.
•
Less bound
to plasma
proteins
•
Somnolence
•
•
Nausea ,
vomiting
Plasma
clearance is
in a week
•
Pruritis
•
Ataxia ,
nystagmus
Partial and
generalize
d
secondary
epilepsy
•
Neuropathi
c pain
•
300mg
thrice daily
, available
as 300mg
capsules
•
Partial
seizures
•
Lennox
Gastaut
syndrome
where
convulsion
isan
associated
feature
( Neurontin )
•
•
Felbamate
It has weak
affinity to
GABA receptor
and open K+
channels to
reduce
excitatory
threshold
•
•
Interacts
with
antacids ,
H2blockers
Quick
abosption
and
excretion so
no
cumulation
Clearance
of drug
after
multiple
dosing after
24 hours
•
Insomnia,
headache,
dyspepsia
•
Diplopia
•
Electrolyte
imbalance
•
400mg
tablets or
600mg
tablets
twice a
day
57-A
Drug
Mechanism of
action
Kinetics
Toxicity
Therapeutic
use and doage
Lamotrigine
(Lamictal )
It has anti
serotinergic and
pro GABA
action in brain
•
Rapidly
absorbed
•
•
Parial
seizures
•
Immediate
proper
concentratio
ns are
achieved
•
Generalise
d tonic
clonic
seizures
•
•
Fast
elimination
Bipolar
depression
•
50-100mg
thrice
daily,
available
as25mg
and 100mg
tablets
The other newer drugs include :
●
Levetiracetam
●
Primidone
●
Tiagabine
●
Topiramate
●
Oxcarbazepine
●
Zonisamide
●
Topiramate
The above second line drugs should only be used as the second choice if the
primary anti epileptic medication fails.
57-B
100 mg, B.D.
2.
What happens after the release of neurotransmitters ?
The neurotransmitter after release at the synapse may meet with one of
the following fates :
virus
2. Prophylaxis of influenza A2
litic parkinsonism.
1. Idiopathic and post encepha-
Example : Noradrenaline, Serotonin / 5-HT, Acetylcholine, Dopamine,
GABA, etc.
Livedo reticularis
Nervous excitement, ataxia.
What are neurotransmitters ?
Neurotransmitters are chemicals released by the nerve ending which act
selectively on the receptors situated on post synaptic membrane bringing
some physiological change.
3.
■
Act on postsynaptic receptors after release
■
Reuptake into presynaptic neuron
■
Destroyed by enzymes (MAO, COMT)
■
Diffusion into surrounding tissues
What are mood and affect ?
Mood is the sustained internal emotional state of a person. Mood may be
normal (euthymic), elevated or depressed.
Affect is the external expression of the present emotional state.
transmission in CNS
Potentiates dopaminergic,
3. Amantadine
1.
Depressive and bipolar disorders are referred to as mood or affective
disorders.
4.
Which neurotransmitters play a role in depression ?
Norepinephrine / Noradrenaline, Serotonin and Dopamine are important
neurotransmitters associated with depression.
(Amantrel)
b. Acromegaly
therapy are :
lactation.
prolactin.
hallucinations
3. CNS :- Confusion, dreams,
dopamine receptors and
also reduces high levels of
Proctinal)
(parlodel,
a. Used in small dose to suppress
50-100 mg
is comparable with Levo dopa
1. It is used in parkinsonism and
1. GIT :- Nausea, vomiting
2. CVS :- Hypotension.
It is dopamine agonist act-
ing on part post synaptic
tine
2. Bromocrip-
*Dopa Decarboxylase inhibitor
of levodopa.
dopamin available to the brain.
carbidopa thus making more
hallucinations
2. G.I.T. : Nausea, anorexia
10mg. of carbi-
dopa with 100 mg
rently administered with DDCI*Peripheral neuropathy,
Eldopa)
Sinement contains
athetoid movements.
95% of levodopa is decarboxy1. CNS :- Dyskinesia choreoIt restores the nigrostriatal
(Levopa,
1. Levo-dopa
deficiency of dopamine
latesd and therefore it is concur-
Dose
Therapeutic uses
Side effects
Mode of Action
Drug
9. Antiparkinsonian Drugs
CONCEPTS - DEPRESSION AND ANXIETY
5.
What is depression ?
Depression is a common and disabling mental disorder with a lifetime
58-A
58-B
prevalence in the community estimated at around 15%. Women are twice
as more commonly affected than men. Depression limits daily functioning
and well being considerably.
Definition
Depression is defined as one or major depressive episode lasting for at
least 2 weeks. It is a result of imbalance between affect (feeling), cognition
(thought) and conation (action).
6.
8.
■
Psychomotor agitation or retardation
■
Fatigue
■
Feelings of worthlessness or guilt
■
Diminished ability to think or concentrate
■
Suicidal ideation
What causes depression ?
Depression is considered to be a multifactorial disorder
What is a major depressive episode ?
■
Major depressive episode is defined as a depressed mood on a daily
basis for a minimum duration of 2 weeks. An episode may be characterized
by sadness, indifference or irritability. It is usually associated with change
in sleep patterns, appetite and weight, motor agitation or retardation, fatigue,
impairment in concentration and decision making, feelings of shame or
guilt and thoughts of death or dying.
7.
Genetic : Genetic factors play an important role in making an
individual vulnerable to mood disorder. The lifetime risk for children
of one parent with depression is 27% and of both parents with
depression is 74%.
Biogenic amines / neurotransmitters Studies have indicated that
norepinephrine (NE) and / or serotonin (5-HT) levels are decreased
in depression.
How is depression diagnosed ?
Depression is diagnosed with the help of ICD-10 (International Classification
of Diseases - 10th revision, 1992) or DSM-IV (Diagnostic and Statistical
Manual of Mental Disorders - IV edition, 1994, which is an American
Psychiatric Association's classification of mental disorders).
According to DSM-IV classification, the diagnostic criteria for depression
are five or more of the following 9 symptoms present during the 2-week
period.
■
Depressed mood.
■
Diminished interest or pleasure
■
Weight loss / gain
■
Insomnia / hypersomnia
59-A
Biological factors
■
Psychosocial factors
Stressful life events, loss of a parent / spouse is among the stress
factors associated with the onset of depression. Failures in life or
marriage, loss in business, etc. can lead to depression.
9.
59-B
What is the course and prognosis of therapy in depression ?
■
1st episode
:
occurs before 40 years of age
■
Untreated episode
:
lasts for 6-13 months
■
Treated episode
:
lasts for 3 months
■
25% relapse
:
in 6 months
■
30-50% relapse
:
in 2 years
■
50 - 75% relapse
:
in 5 years
■
Prophylactic therapy
:
relapse rate is low
■
OTHERS
Nefazodone, Bupropion, Mirtazapine
10. What is the duration of therapy for depression ?
12. What is anxiety ?
■
Acute phase : 6-12 weeks
■
Continuation phase : 4-6 months therapy after resolution of symptoms
(WHO recommendation)
Anxiety is a diffuse, unpleasant, vague sense of apprehension, often
accompanied by autonomic symptoms such as headache, tightness of
chest, perspiration, restlessness, etc. the source of the fear or uneasiness
being unknown.
11. What drugs are used for the treatment of depression ?
Having understood that the low levels of NE and serotonin in the brain are
responsible for depression, drugs that increase their levels are used in
the management of depression. These drugs are called antidepressants.
Anxiety is an alerting signal; it warns of impending danger and enables a
person to take measures to deal with a threat.
13. What are anxiety disorders ?
Anxiety disorders are the most common of all psychiatric illnesses,
present in 15-20% of all patients.
Other modalities of treatment include psychotherapy and electroconvulsive
therapy (ECT). The important classes of antidepressants based on the
mechanism of action are :
■
Anxiety disorders as a group is classified into the following conditions
(DSM IV) :
Tricyclic Antidepressants (TCAs)
Imipramine, Amitriptyline, Clomipramine, Desipramine, Nortripytline,
Doxepin, Dothiepin, Amoxapine.
■
Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine, Sertraline, Fluvoxamine, Paroxetine, Citalopram and
Escitalopram
■
Generalised anxiety disorder (GAD)
■
Panic disorder with / without agoraphobia
■
Social / specific phobias
■
Obsessive compulsive disorder (OCD)
■
Post-traumatic stress disorder (PTSD)
Serotonin Noradrenaline Reuptake Inhibitors (SNRIs)
14. What are the peripheral manifestations of anxiety ?
Venlafaxine, Duloxetine
■
■
Anxiety is accompanied by a variety of peripheral manifestations such
as :
Noradrenaline Reuptake Inhibitors (NARIs)
Reboxetine (Reboxxin)
■
■
Diarrhoea
Palpitations
■
Dizziness
Pupillary dilatation
■
Excessive sweating
Restlessness
MAO Inhibitors (MAO-I)
Phenelzine, Tranylcypromine, Moclobemide
60-A
60-B
■
Hyperreflexia
Syncope (fainting)
■
Hypertension
Tachycardia
■
Tingling in the extremities
Tremors
■
Bowel / Bladder disturbances
are associated with anxiety. These are norepinephrine, serotonin
and GABA.
Neuroanatomical centres : Abnormalities have been reported in the
cerebral cortex (frontal, occipital and temporal areas) and in parts of
the limbic system in patients with anxiety.
15. What is the etiology of anxiety disorders ?
16. What is the difference between panic disorder and GAD ?
Like depression, anxiety too is multifactorial in its etiology. These factors
include :
■
Psychological theories
Different psychologists have proposed different psychological factors
that may contribute to the development of anxiety features. Anxiety
may be the result of conflicts between unconscious wishes and
external reality (psychoanalytic theory), as a learnt (conditioned)
response to specific environmental stimuli or an internal anxiety
response imitating those in parents (behavioral theory) and because
of distorted / counterproductive thinking patterns that accompany or
precede maladaptive anxiety states (cognitive theory).
■
Panic disorder is an anxiety disorder characterized by the presence of
panic attacks with or without agoraphobia (fear of being in situations from
which escape is difficult). A panic attack is a period of intense fear with
anxiety symptoms developing abruptly and reaching a peak in 10 minutes.
GAD is a common condition described as excessive anxiety and worry
about several events / activities for a majority of days for at least 6 months.
The patient finds it difficult to control the worry.
17. What is social anxiety disorder (SAD) ? How is it caused ?
SAD is also called as social phobia. It is a type of an anxiety disorder,
where people have excessive fears of humiliation or embarrassment in
various social / performance settings. When generalized, there is phobic
avoidance of most situations. The fear is recognized as excessive and
situations are avoided of endured with intense distress. The condition is
chronic and disabling. Although common (lifetime prevalence is 3 - 13%),
a large number of patients do not seek help to overcome their phobias.
Females are affected more than males.
Biological theories
Genetic : Studies suggest that atleast some genetic component
contributes to the development of anxiety disorders. Upto 25% of
first degree relatives of patients with GAD also suffer from the same
illness. With panic disorder, the risk is almost 4 to 8 fold.
Autonomic nervous system : Stimulation of the ANS causes certain
symptoms of anxiety. ANS of patients with anxiety disorders
especially those with panic disorder exhibit an increased sympathetic
tone, adapt slowly to repeated stimuli and respond excessively to
moderate stimuli.
Multifactorial in etiology like other anxiety disorders, specific causes
include; trait of behavioral inhibition in childhood, parents with panic
disorder, inconsistent parenting, neurochemcials (adrenergic /
dopamigergic activity), and genetic factors.
18. What is mixed anxiety depression (MAD) ? How is it caused ?
Neurotransmitters : There are three major neurotransmitters that
61-A
MAD is included in the DSM IV appendix. It describes patients with
61-B
symptoms of both anxiety and depression and who do not meet the
diagnostic criteria for either a mood or an anxiety disorder. The prevalence
in the general population may be as high as10%. Almost two-thirds of all
depressives have prominent anxiety 20-90% of patients with panic disorder
have episode of major depression.
19. What are the clinical features of MAD ?
The DSM IV research criteria for MAD includes symptoms of :
Persistant / recurrent dysphoric mood lasting atleast 1 month with (4 or
more of)
Concentration difficulties
being easily moved to tears
■
Sleep disturbances
fatigue
■
Irritability
worry
■
Hypervigilance
anticipating the worst
■
Hopelessness
low self-esteem
20. What are the treatment modalities available for anxiety
disorders ?
Pharmacotherapy for anxiety disorders includes the use of - alcohol
■
Barbiturates, Meprobamate (older)
■
Benzodiazepines (rapid onset of action)
■
Buspirone
■
MAO-inhibitors
■
SSRIs (Esc / citalopram, paroxetine, sertraline)
62-A
Tricylic antidepressants
■
Neuroleptics (very low dose)
■
Betablockers (for peripheral symptoms)
Pyschotherapy mainly includes cognitive and behaviour therapy, relaxation
techniques, exposure and response prevention, family and insight-oriented
therapy.
MAD is caused by etiological factors similar to anxiety and depression
namely, common genetic linkages, abnormalities of NE, 5-HT and GABA,
similar neuroendocrine findings and response to serotonergic drugs.
■
■
62-B
MAOI-A :Chlorgilin
MAOI-B:Deprenyl
2. Monoamine
inhibitor
(MAOI)
depressant
Impiramine
(Tofranil)
Desipramine
(Dapsonil)
Anti-
1. Tricyclic
Drug
Increased avialability 1. Interfere with hepatic metaboof sympathomimetic
lism of many drugs
amines and 5HT in
2. Supressor of REM sleep
in the CNS or
sympathetic nervous
system
2. Moderate depressive illness with
psychomotor and physiological
changes may show some
improvement.
3. Central and peripheral anticholinergic activity.
drug act by their
ability to increase
avialability of NE in
the synaptic cleft by
blocking the reuptake mechanism.
a. Endogenous depression.
1. Depression :-
Therapeutic uses and dose
1. Agitation, hallucina- 1. In depressive patients refraction hyperreflexia,
tory to other treatment.
hyperpyrexia,
2. Narcolepsy.
convlusions.
2. Orthostatic
hypotension.
2. Arrythmias.
b. Agitated depression.
3. Agranulocytosis
c. Phobic anxiety states.
4. Ataxia and convul2. Enuresis
sions
3. Chronic vague pain associated
5. Drug interactions
with mental instability
with
The dose range in between
a. anti-hypertensives
75-300 mg/day.
b. Cheese (particularly seen with
MAOI)
eff.
1. Anticholinergic side
1. Variable sedative effect not
different from phenothiazines
Toxicity
Pharmacological
estabhlished, these
Though exactly not
Mode of action
10. Antidepressants
Newer Antidepressants
63-A
Drug
Mode of action
Tetracyclics :
These drugs
increase post
synaptic alpha
adrenergic and
serotonin
activity at the
same time also
decrease
senstivity of
presynaptic
receptors
thereby
improving
neurotransmitte
r efficacy
Maprotiline
Mirtazapine
Trazodone
Bupropion
Venlafaxine
Nefazodone
Selective
serotonin
reuptake
inhibitors
Citalopram
Fluoxetine
63-B
•
Inhibit the
reuptake of
serotonin
and hence
leads to
mood
elevation
Pharmacologica Toxicity
l actions
• Anticholine
• Well
rgic side
absorbed
effectssuch
and have
as dryness
quick action
of mouth,
• Long half
blurring and
life and
palpitations
hence upto
2weeks are • Photosenstit
required for
ization ( sun
proper
light to be
clinical
avoided )
response
•
•
Quick relief
of
symptoms
ie in about
10 days
Day time
drugs as
produce no
sedation
virtually
•
•
•
Therapeutic
uses and dose
Besides
depression
these are also
tried in :
• Obstructive
sleep apnea
• Cocaine
withdrawal
syndrome
• Panic
dirorder
• Bulimia
nervosa
• Premenstru
al
symptoms
• Chronic
urticaria
50-225mg/ day
15-45 mg/day
150-600mg/day
200-450mg/day
75-375mg/day
200-600mg/day
Weight gain • Premenstru
al
Photosensiti
symptoms
ve
• Chronic
No
urticaria
increased
incidence of • These are
preferred as
impotence
day time
as reported
antidepressa
by tricyclics
nts
20-60mg/day
20-80mg/day
Side effects and kinetic profile of anti depressants
Drugs
Anticholinergic Sedation
side effects
Psychotherapy
Half life
(Hours)**
Steady
state**(days)
Imipramine
++
++
25
5
Amitriptiline
++++
++++
31
10
Desipramine
+
+
24
11
Maprotiline
++
++
25
10
Mirtazepine
++
+++
20
5
Trazodone
+
++++
9
3
Bupropion
++
++
24
1.5
Venlafaxine
--
--
11
4
Nefazodone
--
++
4
4
Citalopram
--
--
33
7
Fluoxetine
--
--
24
14
Cognitive-Behavioral and Behavioral Therapy
Research has shown that a form of psychotherapy that is effective for several
anxiety disorders, particularly panic disorder and social phobia, is cognitivebehavioral therapy (CBT). It has two components. The cognitive component
helps people change thinking patterns that keep them from overcoming their
fears. For example, a person with panic disorder might be helped to see that
his or her panic attacks are not really heart attacks as previously feared; the
tendency to put the worst possible interpretation on physical symptoms can
be overcome. Similarly, a person with social phobia might be helped to overcome
the belief that others are continually watching and harshly judging him or her.
●
Steady state is the situation where there are minimal fluctuations in plasma
levels of drug. It also signifies achievement of proper clinical response
●
Half life signifies that the concentration of the drug reduces to half in
biological tissues
●
Proper clinical response with most drugs is produced only after 2 weeks
Psychotherapy involves talking with a trained mental health professional, such
as a psychiatrist, psychologist, social worker, or counselor to learn how to deal
with problems like anxiety disorders.
64-A
64-B
(Orap)
Pimozide
Malindone,
Haloperidol,
Othe drugs :-
(Largactil)
Chlorproma-
derivative
Phenothiazine
Drug
psychosis)
portion prevents
gonism at mesolimbic
(Dopaminergic anta-
various central sites.
dopamine (DA) at
blocks the action of
Chlorpromazine (CPZ)
Mode of action
as amphetamin or L.S.D.
psychotomimetic drugs such
behaviour which is induced by
4. It prevents the abnormal
environmental changes.
3. There is indifference to the
is reduced.
2. Patient is tamed or aggression
emotional responsiveness.
1. It causes sedation and reduces
Pharmacological
4. Agranulocytosis
3. Hepatotoxicity
Hypotension
2. C.V.S.
d. Parkinsonism.
c. Dyskinesia
b. Akathesia
dyskinesia
a. Tradive
1. CN.S.
Toxicity
11. Antipsychotics
between 50 mg to 1500 mg/day.
The dose range of Largactil is
2. Anti pruritic
1. Shock.
B. Peripheral
7. Anti hiccough.
6. Antiemetic.
following opiate withdrawal.
5. Withdrawal symptoms
4. Hutington's disease.
3. Mania.
2. Anxiety neurosis.
1. Schizophrenia.
A. Central :-
Therapeutic uses dose
Newer Antipyschotics
15-225mg/day
65-A
Drug and dose
Mode of action
Kinetcs
Molindone
They act on
various
dopaminergic
receptors acting
as agonist and
antagonise
serotonin,
histamine and
nicotine
receptors
•
Loxapine 20250mg/day
Drug
65-B
Clozapine 300900 mg/day
•
Highly
lipophilic
and hence
remain in
tissues for
long periods
Extensively
metabolised
in liver
Olanzapine 520mg/day
Toxicity
Therapeutic
uses
•
Drowsiness
•
•
Hypertherm
ia
Elevate
prolactin
levels
•
•
•
•
Impotence
•
Convulsion
s
Glaucoma
GERD
•
•
•
Sedation Extra pyramidal Anticholinergic
symptoms
Besides in
pyschosis
where these
drugs
improve
association
and do not
produce
parkinsonia
n like
movements
Hutington`s
chorea
Spasmodic
torticollis
hemiballism
us
Quetiapine 500- Risperidone 4800mg/ day
16mg/day
Side effects of newer antipysychotics
Weight
gain
Molindone
++
++
+
--
Loxapine
+
++
+
--
Clozapine
+++
-+++
++
Olanzapine
++
-+++
++
Queitiapine
++
--+
Risperidone
+
--+
12. Harmful effects of Cigarette Smoking
13. Anti Migraine Drugs
1.
CVS : Rise in BP, tachycardia, vasoconstriction, angina, ischeamia of
myocardium
1. Serotonin -5HT I receptor agonists :
2.
Increased platelet aggregation
3.
Drug
Dose
Vomiting or emesis
Sumatriptan
(Suminat)
100mg
6mg
1 1/2 hour /
17 minutes
2 hours
96%
Oral
SC
4.
Antidiuretic effect as ADH is suppressed
Zolmitiptan
1.5 hours
3 hours
46%
Oral
5.
Reduced white cell engulfing property so that the invading organism is
active
2.5mg 5mg
Naratriptan
2.5mg
2 hours
6 hours
98%
Oral
Rizatriptan
(Rizact)
10mg
1 hours
2hours
50%
Oral
Almotriptan
12.5mg25mg
2.5 hours
4 hours
80%
Oral
Frovatriptan
2.5 mg40mg
3 hours
26 hours
30%
Oral
6.
Osteoporosis
7.
Delayed peptic ulcer healing
8.
Less fetal weight in smokers
Therapy to Relief Tobacco addiction :
1.
Council the patient - Persue, tell him the hazards of nicotine Keep this as
an ongoing aggressive activity
2.
Bupropion 75mg to 100mg , which prevents the withdrawal symptoms of
smoking such as anxiety, tremors and depression. It is basically dopamine
re uptake blocker and produces dose related stimulant effects
3.
4.
Nicotine patches : This is used as a part of comprehensive behavioral
smoking cessation program This can be used for the maximum duration
of 10 weeks ,where nicotine 14mg/24 hours is released slowly to prevent
withdrawal symptoms of tobacco
Family support to give up addiction
Onset of action Half life Bioavailablity Route
Indications :
1.
Acute treatment of migraine with or without aura
2.
Acute treatment of cluster headache episodes
Mode of action :
These drugs are selective 5 HT 1 receptor agonists. The 5HT 1 receptors are
basilar artery of the brain. The headache is due to the vasodilatation of the local
cranial nerve which is reversed by triptans
Contraindications :
66-A
1.
Angina, Myocardial infarction
2.
Severe hepatic impairment
66-B
Side effects :
3. Ergotamine tatarate or Dihydroergotamine mesylate
1.
Dizziness , vertigo
2.
Burning sensation in body
Indication :
3.
Palpitations and raised BP
Rapidly control vascular headaches such as Migraine , cluster headaches
2. Methysergide Maleate :
Mode of action :
Indication :
Reduction of the extracranial blood flow with improvement of the basilar flow to
the brain
Vascular headache ( Migraine )both as preventive as well during attack
Ergotamine is potent emetic, whereas the dihydro form is 12 times less active
as an emetic
Mode of action :
Semisynthetic ergot derivative preventing the actions of serotonin in the brain,
blood vessels. It also prevents the release of histamine from the mast cells
Contraindications :
Contraindications :
1.
Pregnancy
2.
Peripheral vascular disease
3.
1.
2.
Fibrotic process in the body
Side effects :
3.
Pregnancy
1.
Numbness and tingling of fingers
2.
Coronary vasoconstriction
3.
Raised BP
Side effects :
1.
Drowsiness, Dizziness
2.
Oedema, myalgia, weight gain
Contraindications :
3.
Increased hair loss
1.
Glaucoma
2.
Side effects :
Transient dizziness and rash
67-A
67-B
4.
Newer NSAID`s such as Diclofenac, Rofecoxib, Valdecoxib have
IM 25mg every 4 hours,
Orally 10-25mg 4 hourly
Promethazine
(Phenergan)
+
+
--
5-10mg thrice orally or
injected
Metoclopramide
(Perinorm)
+
--
--
10mg thrice or four times
orally or 5mg/ml
injectable
Dimenhydrinate
+
+
+
50mg every 6 hourly orally
Meclizine
+
+
+
12.5mg -25mg thrice day
orally
Hydroxyzine
(Atarax)
+
--
--
25mg IM parenteral
Domperidone
(Domstal)
+
--
--
5mg thrice a day
Ondansetron
used (Osetron)
+
--
--
4-8mg orally thrice or
as 2mg/ml injectable
Granisetron
injected (Granicip)
+
--
--
1mg twice orally or
Other drugs :
68-A
14. Antiemetic Drugs
Anti cholinergics :
68-B
As for
metoclopramide
Antiemetic e.g.
postoperative,
post radiation,
drug induced,
acceleration of
gastric and
intestinal
emptying.
Treatment of
spasm and biliary
reflux in peptic
ulceration
Less CNS action than
metoclopramide
--
Domperidone
--
-
+
Extrapyramidal
effects including
tardive dyskinesias,
drowsiness,
convulsions in infants
following large doses
Chlorpromazine
(Megatil)
Mode of action
Anti dopaminergics :
Increased tone of
oesophageal (cardiac)
sphincter, increased
motility of stomach,
reduced transit time of
contents through small
intestine (due to increased
release of acetylcholine).
Central inhibition of
chemoreceptor trigger
zone on which it acts as a
dopamine antagonist
Same as
metoclopramide
Toxicity
Use in
Use in
Use in Dose and route
nausea
Motion Vertigo
and
sickness
vomiting
Drug
Drugs
Drugs acting on
CTZ and gut
- Metoclopramide
Antiemetic and Antivertigo agents :
•
Belladona alkaloids with pentobarbital are the traditional combinations
Pre-operative
medication, Motion
sickness
7.
Drowsiness, Dry
mouth, Blurred vision
Cyproheptadine a 5HT1 antagonist is proven useful in this condition
Antimuscarinic action on
the gut and central
inhibition of vomiting
centre
6.
Anticholinergic:
- Hyoscine
Beta blockers with or without anxiolytics such as diazepam or alprazolam
•
5.
Uses
been evaluated for headaches. They also relieve initial pain of migraine
69-A
69-B
Neuroleptics :
- Phenothiazine
s e.g.
Chlorpromazi
ne,
Prochlorperazi
ne
- Butyrophenon
es e.g.
haloperidol
Antihistamines
(H1):
- Cyclizine
(Marzine)
- Meclozine
(Ancolan)
- Dimenhydrina
te
(Dramamine)
- Promethazine
(Phenergan)
•
•
5HT3 antagonist
Ondansetron
Betahistine (Serc)
Drug
Mode of action
Blocks 5HT3 receptors in
gut and CNS
Partial agonist of
histamine – exerts
vasodilation like
histamine, but can relieve
histamine headache
Mode of action
Block dopamine
receptors in
chemoreceptor zone
Have an anticholinergic
hyoscine-like action
•
•
Drug
Constipation, headache
Aggravation of asthma
and peptic ulcer. Can
produce nausea
Toxicity
Postural hypotension,
extrapyramidal effects,
ataractic states
Drowsiness, dry mouth,
blurred vision
Toxicity
Reduces nausea
and vomiting
following
anticancer
chemotherapy
Reduces vertigo
and nausea in
Meniere’s disease
Uses
Antiemetic e.g.
postoperative, post
radiation, drug
induced
Motion sickness
and other forms of
labyrinthine
vomiting
Uses
15. Nootropics / smart drugs
The drugs which improve recall and cognition are termed nootropics . The role
of these drugs requires precise evaluation The important drugs include :
●
Acetylcarnitine
●
Adrafinil (Olmifon)
●
Almitrine-raubasine (Duxil)
●
alpha-lipoic acid
●
Amineptine (Survector)
●
4-Aminopiperidine analogues
●
Aniracetam (Draganon, Ampamet)
●
AMPA
●
Ampakines
●
Caffeine
●
Calcineurin-inhibition
●
Captopril (Capoten)
●
Centrophenoxine (Lucidril)
●
Cerebrolysin
●
Cholinesterase inhibitors
●
Citicoline
●
Clever mice
●
Clitoria Ternatea
●
Cognitive enhancers/CREB
●
Cognitive enhancers/memory
●
Curcumin
●
Cycloprolylglycine
●
Cytidinediphosphocholine
70-A
●
Depressed or demented?
●
Desmopressin (DDVAP)
●
Fipexide (Vigilor)
●
GABA(A) alpha5 receptor inverse agonists
●
Galantamine
●
Gilatide
●
Ginkgo biloba
●
Hydergine
●
Hyperforin
●
Idebenone (Mnesis)
●
Lecithin/phosphatidylcholine
●
Methylphenidate (Ritalin)
●
Metoprine
●
Milacemide
●
Minaprine (Cantor)
●
Modafinil (Provigil)
●
Molsidomine
●
Nefiracetam (Translon)
●
Neotrofin
●
Nicergoline (Sermion)
●
Nicotine
●
Nimodipine (Nimotop)
●
Nitric oxide
●
Nomifensine (Merital)
●
Oestrogens
●
Ondansetron (Zofran)
●
Oxiracetam (Neuromet)
70-B
●
PDE4 inhibitors
●
Phenserine
●
Phosphatidylcholine/lecithin
●
Phosphatidylserine
●
Piracetam (Nootropil)
It also seems to enhance some forms of protein syntheses in the brain.It's
been proven that protein synthesis is an essential step in laying down longterm memories.
Perhaps the most intriguing aspect of piracetam is that it has been proven to
increase the flow of information between the right and left hemispheres of the
brain.
Piracetam is the best known nootropic drug.
It's mechanism of action is unknown but most would describe it as facilitating
learning in ways that are hard to quantify. It seems to awaken a noticible
improvement in creativity and lucidity, but it is not a simulant or sedative.
The scientific record on piracetam is quite extensive.It does not seem to be
metabolized by the body, and it's effect is minimal on the dopaminergic and
serotonergic neurotransmitter systems. It does seem to lower acetylcholine
levels slightly.This decline is reversed when choline is given with piracetam.
(Many people report that choline potentiates piracetam.)
As a result of experiments with human subjects one researcher concluded that
piracetam causes the hemispheres to become superconnected.
Since there's increasing evidence that high level brain states are a product of
the integrated and synergistic functioning of both hemispheres simultaneously
we might suspect that piracetam enhances not only simple learning and memory
but creative or syntheses thinking.
●
Piribedil (Trivastal)
●
Pramiracetam (Neupramir)
Piracetam also seems to have neuroprotective properties, for example, it seems
to block the action of some sedative drugs. This action is fairly easy to measure
and has been studied extensively.Research on piracetam has been controversial.
Piracetam has been found to be particularly useful in alcohol withdrawal and in
treating age-related mental decline and some forms of drug-resistant depression.It
is inexpensive and available over-the-counter in Mexico.Although it has virtually
no toxicity and it's benefits are well documented, it is not available in the US.
Piracetam has been proven to boost learning and memory in normal subjects
as well as those who suffer cognitive deficits, and is also a cognitive enhancer
under conditions of hypoxia or too little oxygen. Recent expeditions to climb
Mt. Everest have included piracetam as an essential medication to treat frostbite
and memory lapses causes by altitude.
●
Pregnenolone
●
Propranolol (Inderal)
●
Pyrrolidone derivatives
●
Rivastigmine (Exelon)
●
Rolipram
●
Selegiline/l-deprenyl (Eldepryl)
●
Sildenafil (Viagra)
●
Tacrine (Cognex)
●
Testosterone
In fact it selectively stimulates the anterior or frontal part of the forebrain, that
part of the brain that has evolved most recently rapidly and remarkably in the
course of our evolution from ape to human and which is the seat of our higher
functions.
●
Tropisetron (Navoban)
●
Tyrosine
71-A
71-B
●
Vasopressin (Pressyn, Diapid)
Statement is Correct or incorrect
●
Venlafaxine (Effexor)
1.
●
Vincamine
The objectives of pre anaesthetic medication are to make patient
sedated ?
●
Vinpocetine (Cavinton)
2.
Phenytoin reduces post tetanic potentiation ?
3.
Ether is very explosive ?
4.
PABA esters are : Procaine, Amethocaine, Benzocaine ?
5.
Aspirin has anti aggregatory action ?
6.
Pethidine is derived from poppy ?
7.
Benzodiazepines act on polysynaptic neuronal pathways ?
8.
Amantadine is antiviral and also used in parkinsonism ?
9.
Chlorpromazine has anti psychotic action ?
Biological approaches to Memory improvement
1.
Mental Techniques such as solving problems, direct conversation
2.
Physical state such as proper sleep, rest , excersize, limited tea , tobacco
or coffee
3.
Emotional relaxation
4.
Self motivation
10. Methyl alcohol is used to treat alcohol poisoning ?
Answers
1.
Incorrect
2.
Incorrect
3.
Correct
4.
Correct
5.
Correct
6.
Incorrect
7.
Correct
8.
Correct
9.
Correct
10. Incorrect
72-A
72-B
4
Toxicity or poisoning leads to lacrimination, salivation, bronchoconstriction,
twitchings, confusion, ataxia, tremors and convulsions. The cause of death is
respiratory failure.
AUTONOMIC NERVOUS SYSTEM
1. Cholinergic system
Treatment of poisoning:-
Drugs that act like acetylcholine (Ach) or mimic the effects of vagus or other
parasympathetic nerves are called as cholinomimetics. The drugs like methacholine, bethanechol and carbachol are comparable to Ach but are longer
acting.
Cholinergic agonists are therapeutically used in :1.
Paralytic ileus
2.
Congenietal megacolon (Hirshsprung's disease)
3.
Post operative abdominal distention.
4.
Post operative urinary retention.
5.
Glaucoma, (condition with raised intra occular pressure)
6.
To treat d-tubocurarine poisoning and myasthenia gravis,neostigmine
15 mg, 4 hourly, is used.
i)
Remove the patient from contact site eg. wash skin with soap and tannic
acid (This removes the contact with most insecticides).
ii)
Atropine sulphate 2-4 mg I.V. till pupillary dilatation occurs. Maximum of
50 mg I.V. can be given.
iii)
Paraldoxime 1-2 mg I.V.
Cholinergic agonists are not be used in cases of :-
Side effects:- sweating, salivation, lacrimation, cramps, urinary urgency.
Choline esterase inhibitors inhibit the metabolising enzyme that hydrolyses
Ach. Their duration of effect is 4 hours.
i)
Peptic ulcer.
ii)
Asthma
iii)
Hyperthyroidism
iv)
Coronary insufficiency
Anti-Cholinergic drugs
The drugs which block the actions of Ach. are Belladona alkaloids namely
atropine, scopolamine and homatropine.
Atropine is given in dose of 0.6 mg -2 mg. For children the dose is 10 µg/kg.
Drugs are: Physostigmine (acts centrally and peripherally)
Use of atropine :-
Neostigmine (acts peripherally)
Their uses are similar to cholinergic agonists.
A)
Poisoning due to Tic 20 is common. This is a organophosphorous compound
and is irreversible enzyme inhibitor. The other drugs are:-
B)
Malathion
Parathion
used as insecticides
Autonomic Nervous System
73-A
73-B
CNS :
1)
Parkinsonism
2)
Motion sickness
Preanaesthetic medication because it can :
a)
Reduce secretions of respiratory tract
b)
Prevention of vasovagal attacks.
C)
D)
E)
F)
G)
C.V.S :
1)
Stokes Adam's syndrome.
2)
Sinus bradycardia with nodal blocks.
3)
Wolf Parkinson White syndrome.
4)
Ventricular premature beats with slow atrial rate.
Side effects :-
Respiratory:-
G.I.T.:
1)
Acute rhinitis due to hay fever.
2)
Bronchial asthma (Atropine substitute ipratropium is
used).
1)
Peptic ulcer disease
2)
Cardiospasm and pylorospasm.
3)
Various colicky pains.
Dryness of mouth
2)
Blurring of near vision.
3)
Dilatation of pupil.
4)
Increased heart rate
5)
Dry skin
6)
Large doses can lead to memory disturbances, slurred speech and
delerium.
2. Adrenergic system
Genitourinary :1)
Dysmenorrhoea (combined with NSAID'S)
Drugs that partially or completely mimic the effects of sympathetic nerve
stimulation or adrenal medullary discharge are called as sympathomimetics.
2)
Ureteric colic
Drugs are:-
3)
Nocturnal enuresis.
1.
Cathecholamines:
Adrenaline, nor adrenaline, dopamine, isoprenaline
2.
CNS Stimulants:
Amphetamines, ephedrine, phenylpropanolamine
3.
Vasodilator:
Nylidrin (Arlidin)
4.
Nasal decongestants:
Xylometazoline (Otrivin), naphazoline (Nasivion), oxymetazoline
Eye:
Atropine 1% drops or homatropine ½% drops are useful in fundoscopy
and to prevent adhesions between iris and lens in cases of iridocyclitis.
H)
1)
Poisonings:1)
Organophosphorous poisoning.
2)
Amanita muscaria poisoning (mushroom)
Contraindications for use atropine :-
Adrenaline :-
1)
Glaucoma
1.
2)
Prostate enlargement
3)
Partial pyloric obstruction.
74-A
74-B
It increases the force of contraction, cardiac output and increases blood
pressure and therefore it is used with caution in patients with angina or
hyperthy-roidism.
2.
Side effects:-- Palpitation, substemal pain, headache, tremors
2.
The drug is used in cases of:"
1.
Status asthmaticus
2.
Angioneurotic oedema
3.
Cardiac arrest
4.
Prevention ofepistaxis from nose
5.
Added to local anaesthetic to prolong its action
Phentolamine (5 mg I.M.)
Tolazoline (25 mg, four times a day, orally)
Uses:
Dopamine :-
1.
Diagnosis and treatment of pheochromocytoma.
2.
Shock.
3.
C.C.F. with pulmonary oedema.
4.
Peripheral vascular disease where there is digital spasm of small arteries.
5.
Prevention and treatment of hypertensive reaction when anti-depressants
such as MAO inhibitors and cheese are taken together. This is a food
drug interaction.
As the duration of action of the drug is short it is given as I.V. infusion in dose
of 3 µg/kg/minute.
Side effects:- Sedation, miosis (constriction of pupil), failure of ejaculation, postural hypotension.
It is used in cases of:1.
Cardiogenic or septic shock.
2.
Low cardiac output syndrome following coronary bypass surgery.
3.
To induce forced diuresis in cases of barbiturate intoxication.
b - blockers e.g. - Propranolol is a classcial b blocker basically used as
antihypertensive or used to reduce the tremors in hyperthyroidism
3. Peripherally acting skeletal muscle relaxants
Ephedrine:-
The drugs are:"
Besides its infrequent use in bronchial asthma, it is also tried in cases of:"
1.
Narcolepsy.
2.
Nocturnal enuresis.
3.
Nasal decongestant.
4.
Mydriatic
d-tubocurarine given as 10 mg/ ml injection.
2.
Succinylcholine (Scoline) 500 mg/IO ml injection.
Uses:1.
They are used as adjuvants to the general anaesthetics and therefore
helpful during abdomino-thoracic surgeries, endoscopies or for orthopaedic
manouveres.
2.
During electro convulsive therapy for psychosis or endogenous depression,
they can reduce the trauma to the patient.
a and b blockers: These drugs block the actions of adrenaline, noradrenaline
at respective receptor sites.
a - adrenergic blocking drugs :Phenoxybenzamine (I mg/kg I.V.)
1.
75-A
75-B
Early 20th Century
Mechanism
Competitive to Ach,
Open sodium channel,
thereby decrease the
leading to the failure of
amplitude of contractions muscle action potential
Potency
More potent
Less potent
Dose after anesthesia
Reduced
Same
Duration of action
Long > 30 minutes
Short > 3 minutes
Histamine release
Minimal
None
Vagal block
Minimal
None
BP
No change
Fall or rise
Indication
Most surgeries
Endotracheal intubation
76-A
76-B
Irriation, bradycardia, worsens
pre-existing
asthma.
Conjunctival
flush browache.
Lacrimation.
Decreases, in patients
with narrow angle gall
coma
Itching
Irritation
Photophobia
Increases in patient with
narrow angled glaucoma
Decreases in patient with
wide angled glucoma
No ciliary muscle
spasm
Early 19th century
No miosis
Discovery
5. Timolol maleate
(0.25%-0.5%)
(b-blocker)
Depolarizers
Spasm of accommodation. Duration
2 hours.
Competitive blockers
Miosis
Peak - 15 minutes
Duration - 4 to 8 hours
Features
4. Pilocarpine
(0.5%-4%)
(Cholinergic drug)
Neuromuscular Blockers
Cycloplegia (par
alysis of accommodation) Duration:1 to 3 days.
Scoline is a very short acting drug and therefore toxic effects wear off
rapidly. Thus, only supportive measures (e.g. artificial respiration) are
necessary.
Mydriasis
Peak-1 hour
Duration - 1 to 3 days
4.
3. Homatropine
(!%)
(Cholinergic drug)
Neostigmine is never used to reverse toxicity due to Scoline.
No effect
3.
No effect
Fresh plasma infusion can only prevent toxicity of Scoline.
Mydriasis
Peak - 10 minutes
Duration - 2 hours
2.
2. Phenylephrine
(2.5-10%)
(Adrenergic drug)
Neostigmine 15 mg, Q.I.D. reverses d-tubocurarine induced paralysis
Decreases in normal subjects
and also in patients with
wide angled glaucoma
1.
4. Ocular drugs
Antagonists :-
No effect
Flushing and fall in blood pressure with d-tubocurarine.
Mydriasis
Peak 10 minutes
Duration - 1 hours
2.
1. Adrenaline
(0.25%-2%)
(Adrenergic drug)
Respiratory apnoea with succinylcholine.
Accomodation
1.
Effects on pupil and
duration
Side effects:-
Intra ocular pressure
Other effects
Diagnostically they are used in case of spinal cord compression.
Drug
3.
ERECTILE DYSFUNCTION ( ED)
These drugs are contraindicated in cases of :
" The inability to achieve or maintain penile erection sufficient for satisfactory
sexual performance "
52 % of the men above the age of 40 years suffer from ED
Atherosclerosis
2.
Diabetes
3.
Pelvic trauma
4.
Alcoholism
5.
Spinal cord injury
6.
Depression, stress
2.
■
Patients on Nitrate therapy
Most of the time a proper pyschotherapy is required and the patient has to be
made aware of his own self
DRUGS USED IN OBESITY
Oral Medications :
Magnitude :. India, though developing country has also currently seen the up
spurts of weight gain more common in urban cities where nearly 6 % of population
is overweight . Obesity is more abundant in southern part of India, due to genetic
reasons and where there is a higher incidence of truncal obesity .
Sildenafil (Viagra, Penegra 50mg ) Vardenafil (Levitra 10mg ),
Tadalafil (Cialis, Apcalis 10 mg)
Pharmacotherapy :
Drugs used in ED are :
1.
Hypersenstivity
The Extraoral medication is used , provided the oral medication is not responding.
Councelling of the both partners is required. Patients show hypersentivity, and
patients do resist oral medications. The drug has to be injected in the penile
muscle
The causes are :
1.
■
Extra oral medications :
Papaverine, Phentolamine, Apomorphine, Alprostadil
Sildenafil is a Phosphodiesterase 5 inhibitor which increases levels of
cyclic GMP , causing more blood flow through penile vasculature leading
to erection. The most selective enzyme inhibitor is Vardenafil which is
more potent, has quicker and longer duration of action. Tadalafil , since
the half life of the drug is long, it can be used even on the alternate day,
but the relative incidences of side effect such as backache can be
disturbing
77-A
Lifestyle modifications such as altered diet , decreased caloric intake & increased
exercise are the mainstay for the therapy of obesity . Ideal body weight for
most is unrealistic target & hence lowest weight the patient can attain is a
more realistic target . Weight loss of 10% of the initial body weight can lead to
lowered BP , glucose & lipid levels with reduction in the cardiovascular risk .
Even the intentional weight loss leads to 20% reduction of overall mortality .
Weight loss management requires commitment from dietician , doctors ,
psychologists and even the patient
1.
77-B
Dietary fiber supplements as Methylcelluose reduce weight loss as they
produce sensation of fullness in stomach, thereby reducing afferents to
the satiety center . There is no clear documentation for their significant
benefit
2.
Thyroxine in high doses, although tried reduces lean body mass rather
than fat . Acarbose & Metformin are also been evaluated & tried in diabetic
obese patients where the weight reduction over a period of months is
about 2-3.5 Kg
3.
Fluoxetine a day time antidepressant is used in treatment of obese
patients , including the binge eaters
4.
The long term use of certain anorectic agents such as dextro amphetamine,
fenfluramine and dexfenfluramine have been associated with an associated
increased risk of primary pulmonary hypertension and valvular heart
disease
5.
Phentermine is a centrally acting agent with nor adrenergic activity with
mild stimulant properties . Since it has no dopaminergic activity it has no
abuse potential . Adverse effects of phentermine include headache,
insomnia, nervousness and irritability
6.
Sibutramine is a noradrenaline and serotonin reuptake inhibitor, like any
selective serotonin reuptake inhibitor anti depressant . Adverse effects
include dry mouth, constipation, insomnia, dizziness and headache . The
cause of the concern are raised BP and mild increase in heart rate .
Sibutramine in doses of 10, 20 & 30mg for 26 weeks led to good reduction
of basal weight about 12% in men and 9% in women . The dropout in the
clinical study of 173 patients had been about 15 %
7.
Adverse effects with Orlistat are common but are reversible on stopping
the therapy . Loose stools, diarrhoea, abdominal pain, flatulence are fecal
incontinence are observed . Most of the national guidelines do not
recommend the use of any drug for the reduction in weight for more than
1 years . The summary of the product characteristics states that decrease
in bodyweight was less in type 2diabetic patients than in non diabetic
patients The orlistat treated patients had also shown the improvement in
the blood glucose levels , although thiswas not statistical significant .
Deficient lipoprotein lipase in patients explains the increased incidence of
insulin resistance in some patients where there are also associated high
lipid levels
8.
ALT 962 is the new compound with similar activity as Orlistat, but has no
serious ADR reported . In Phase 1a trial , 24 subjects received 4 doses
and 8 subjects received placebo with reasonable safety . In 140 healthy
volunteers phase IIIa trials have also shown reasonable efficacy . The
weight reduction is about 12 % from the basal The multicentric trials with
this compound are now being planned
9.
Compounds under evaluation include : Leptin and Leptin analogues ,
Cholecystokinin agonists are under evaluation . Satiety reduction is potent
and these compounds rarely lead to rebound increase in weight . Some of
the drugs with beta 3 agonist activity are also under evaluation , since
these drugs act on brown adipose tissue , the value in human is non
conclusive as there is minimal brown tissue in humans
Pancreatic lipase is an enzyme that causes lipid breakdown in the
gastrointestinal tract and hence absorption of the digested fats . Orlistat
the drug developed by Roche and evaluated at Sahlgren`s Hospital in
Gothenborg, Swaeden in a dose of 120mg 3times a day prevents and
inhibits fat absorption and about 30% of the ingested fat is excreted in
feces . The drug should be started in those with BMI of 28 with associated
risk factor and should be discontinued if the weight loss is not more than
5 % in 4 months . In general the basal weight reduction is about 10%.
78-A
78-B
Statement given below is correct or wrong
1.
Atropine is used in preanesthetic medication because it reduces secretions
of respiratory tract and prevents vasovagal attacks ?
2.
Adrenaline is the drug of choice in status asthmaticus ?
3.
Neostigmine increases d- tubocurarine induced paralysis ?
4.
Timolol increases intraocular pressure in wide angle glaucoma ?
5.
Common organo phosphorus compounds are malathion, parathion, tabun,
di iso propyl phoshofluridate ?
6.
Dopamine is used in cases of nocturnal enuresis ?
7.
Ephedrine is used in cases of cardiogenic shock ?
8.
B blockers can be easily used in cases of broncho constriction ?
9.
Succinylcholine is metabolized by pseudo cholinesterase ?
10
Phentolamine is alpha blocker , given IM ?
Answers
1.
Correct
2.
Correct
3.
Wrong
4.
Wrong
5.
Wrong
6.
Wrong
7.
Wrong
8.
Wrong
9.
Correct
10. Correct
79-A
79-B
2.
GASTROINTESTINAL SYSTEM
5
H2 receptor antagonists :
■
Histamine receptor on parietal cell is blocked which is responsible
for acid secretion
Management of acid peptic disease (APD)
■
Twice a day dosing, since complete 24 hour inhibition is not possible
The goals of peptic ulcer management are :
■
Quick onset of action and hence immediate symptomatic relief
●
Inhibit acid secretion and control pain
■
Significant drug interactions, with warfarin, theophylline and phenytoin
●
Protect G.I. mucosa
■
Longer duration of ulcer for ulcer relief
●
Prevent complications and recurrence
●
Eradicate H. pylori from stomach
Drugs used :
The way to treat APD is :
General management : This includes life style changes.- Avoid stress, have a
good night sleep, eat regularly on time and don't indulge in excessive alcohol or
spices. Give smoking or tobacco in any form
Drug therapy :
1.
Antacids :
Features
Ranitidine
Famotidine
Nizatidine
Duodenal ulcer
+
+
+
Gastric ulcer
+
+
+
Heart burn (GERD)
+
+
+
Bioavailability
60%
45%
> 90%
Onset of action
1 hour
1 hour
30 minutes
Healing rates
77% at
4 weeks.
Healing rate
about 90% at
8 week
77% at
4 weeks
Healing rate
about 90%
8 week
81% at
4 weeks
Healing rate
about 95%
8 week
■
Provide temporary symptomatic relief
■
Do not help in ulcer healing
■
Have to be given more frequently
■
Can reduce serum concentrations of various concomitant drugs
Minimal duration
2-4 weeks
2-4 weeks
2-4 weeks
■
Can cause constipation- aluminium salts or diarrhoea- magnesium
salts
Dose
10-40mg BD
75-150mg BD
■
Eg : Aluminium magnesium salts, calcium carbonate, sodium
bicarbonate
150-300mg
BD or 1mg/m
l injectable
Gastrointestinal System
80-A
Cimetidine is not much preferred as it interferes with the metabolism of
theophylline, warfarin and phenytoin and can produce oligospermia (reduce
sperm count, leading to infertility ) and impotence
80-B
3.
Features :
Prostaglandin analogues :
■
Inhibits HCI secretion and promotes mucus and bicarbonate secretion
■
Cytoprotective action ( Reduces acid damage )
■
TDS or QDS administration
■
Less effective in reliving pain and relapses
Eg : Misoprostol
4.
Ulcer protectives:
■
5.
Form protective coat covering the ulcer and prevent aggression of
acid and pepsin , thereby ensures healing of an ulcer
■
Delayed symptom control
■
■
1.
Proton pump ie H+ K+ATP ase is final step in acid secretion which is
inhibited
2.
Prolonged inhibition of acid secretion for full 24 hours and hence OD dosing
3.
Faster relief of pain
4.
Rapid ulcer healing
5.
Lesser incidences of recurrences
6.
Mantainence of intragastric acidity >4 for longer time thereby relieving
associated symptoms such as belching, bloating, abdominal discomfort
7.
Good tolerance. Nausea, headache, dizziness ,rashes are reported.
Features
Omeprazole
Pantoprazole
Esomeprazole
Can be useful even those who are smokers
Onset of action
30 minutes
1 hour
30 minutes
BDS or TDS dosing
Duration of action
< 72 hours
>24 hours
24-72 hours
Eg : Sucralfate ( leads to constipation ) , Colloid bismuth subcitrate
( black stools )
PH>4
16 hours
18 hours
24 hours
Mantainence of
alkaline pH
4.0
3.7
4.7
Healing rate in
erosive esophagitis
87 % after
8 weeks
90% after
8 weeks
94% after
8 weeks
H.pylori eradication
using triple therapy
which includes,
metronidazole with
> 90%
eradication
and good
symptomatic
> 90%
eradication and
and good
symptomatic
> 90%
eradiation
and good
symptomatic
amoxicillin or
clarithromycin
relief
relief
relief
NSAID induced
ulceration
+
+
+
Proton Pump inhibitors :
First generation drugs :
■
Omeprazole (Omez)
■
Lansoprazole (Lancibay)
■
Pantoprazole (Pantodac)
Second generation drugs :
■
Esomeprazole (Nuloc, 20 mg - 40 mg OD)
■
Rabeprazole (Peptard, 10mg - 20mg OD)
81-A
81-B
Documented
for 1 years
82-A
82-B
Contains glycosides which are
hydrolysed by colonic bacteria to
sennosides A and B. These are
absorbed and then stimulate colonic
peristalsis by acting on mural nerve
plexuses. Enters milk
Documented
for 6 months
SENNA
Documented
for 6 months
Digested in small intestine to
ricinoleic acid. Can stimulate
uterine contractions at full term
Safety on long term
administration >6
months
CASTOR OIL
0.5%
Chemical stimulants of
colonic action (irritants)
2%
Griping and diarrhoea.
Diarrhoea in suckling child.
Melanosis coli. Red or
yellow colouration ofurine
8
Hepatocellular failure
Hepatocellular failure
Excessive loss of water and Obsolete
electrolytes (incldg.
Potassium)
Contraindicated in
galactosaemia
Magnesium can be
absorbed and be of clinical
significance in renal failure
2
48
1.5%
Is a disaccharide which is split by
bacteria in colon to organic acids
which are unabsorbed and act
osmotically to increase bulk of
stools. Gas formation is increased
Rash
LACTULOSE (Duphalac)
6%
2
5%
Acts like sodium sulphate but in
addition magnesium ion stimulates
peristalsis by liberating
cholecystokinin
6.9%
MAGNESIUM
SULPHATE
Headache
2
3%
Increased bulk of water in lumen
stimulates peristalsis
2.5%
SODIUM SULPHATE
3%
Special uses
Diarrhoea
Toxicity*
Esomeprazole
Largely unabsorbed from gut and so
osmotically active
Approximate dose
effect interval (h)
Pantoprazole
Osmotic purgatives
Pharmacological properties
Side effects:
Omeprazole
Drug
2. Constipation
Features
83-A
■
Lubricants contents of colon. Not
digested.
Surface acting agent which allows
water to enter inspissated colonic
contents
15% absorbed from gut, excreted in bile
and undergoes an enterohepatic
circulation – resulting in a prolonged
effect. Active fraction produced in
liver and undergoes further
modification in colon
Deacetylated in gut, absorbed,
glucronidated in liver and enters
enterohepatic circulation. Has a direct
action on gut wall to stimulate
peristalsis. Also absorbed into
circulation and reaches gut wall in
arterial blood
Detergent action alters
Faecal impaction
intestinal mucosa permeability
Interferes with absorption of
Obsolete
fat soluble vitamins.
Aspiration lipid pneumonia.
Anal leakage. Absorption into
tissues (e.g. after intestinal
operations). Can cause
granuloma formation.
Possible carcinogenicity
24
24
Obsolete
Can be given by suppository
Special uses
4% develop a fixed drug
eruption. Other rashes. SLE
– like syndrome. Alkaline
urine coloured pink
Toxicity*
8-10
10
Approximate dose
effect interval (h)
all can give rise to purgative abuse syndrome : dilated, atonic colon; sodium depletion; potassium depletion;
enteropathy and weight loss; osteomalacia.
LIQUID PARAFFIN
DIOCTYL SODIUM
SULPHOSUCCINATE
(DSS; DIOCTYL)
Lubricants and stool
softeners :
PHENOLPHTHALEIN
BISACODYL
Drug
3. Diarrhoea
Symptomatic treatment of diarrhoea as follows :-
(1)
(2)
83-B
Drugs which increase intestinal transit time
A)
Opiates e.g. Codiene, diphenoxylate. (Lomotil)
B)
Anticholinergics e.g Atropine
C)
Loperamide (reduces acetylcholine release)
D)
Racecadotril
Racecadotril is a novel antidiarrheal agent as it reduces
hypersecretion of water and electrolytes into the intestinal lumen by
preventing the degradation of enkephalins. Racecadotril is a potent
and specific inhibitor of enkephalinase. This antisecretory
mechanism of action differs from that of loperamide, which reduces
intestinal lumen motility.
The indications of drug are :
1.
Acute watery diarrhoea
2.
Acute diarrhoea of bacterial and viral etiology
Dosage
Adults - 100 to 300 mg three times a day
Children - 1.5 mg / kg three times a day.
Side effects
Nausea, thirst, vertigo, constipation, headache and vomiting.
The drug should be used with caution in patients with renal insufficiency
Drugs which increase bulk and viscosity of gut contents.
e.g. Pectin, bran, kaolin, methylcellulose.
84-A
By its anticholinergic
action, it blocks that
afferent impulses to the
CNS.
Blocks cental 5 HT receptors
& the afferent impulses to
the CNS
5. Ondensetron
(Ondem)
Vomiting centre is located in lateral reticular formation in the brain.
Chemoreceptor trigger zone (C.T.Z.) on stimulation induces vomiting. Distension
of viscera can also to afferent pathway stimulation which can lead to emesis.
4. Scopolamine
(Vesprax)
4. Antiemetics
Besides inhibiting CTZ it
has also antihistaminc
Pinch of salt, fist of sugar in a glass of water so as to give about 1½ litres
of oral intake (6-7 glasses full).
84-B
1 tablet to be given twice or
thrice daily as required
0.6-1mg subcutaneously or a
post auricuar patch is applied.
25 mg T.D.S. Side effects are
the same as above.
Oral rehydration therapy : Easiest procedure to control diarrhoea in
developing countries where it prevents fluid electrolyte imbalance
(dehydration).
3. Prochlorperazine
(Stemetil)
Antibiotic induced enterocolitis.
25 mg. thrice daily. Children
1/2-1mg/kg bod weight
Side effect are :- Extrapyramidal symptoms dystonia,
drowsiness, tardive dyskinesias, cardiac toxicity etc.
5.
It has a stabilizing action
CTZ i.e. it blocks the
release at the site.
Crohn's disease
2. Chlorpromazine
(Largacil)
4.
Most effective drug in reducing vomitting due to any
etiology
Most effective drug in reducing vomiting due to
motion sickness.
Useful in vomiting induced by motion sickness,
Meineres disease. (endolymphatic hydrops).
The nausea and vomiting due to drug toxicity,
radiation, sickness, controlled.
Used in
1. Drug induced vomiting.
2. Post operative vomiting.
3. Used in radiology to speed the barium meal
examination.
4. Treatment of gastro-oesophageal reflux.
5. Hiccups.
6. Can be used in pregnancy with caution to
prevent the severe bouts of vomiting.
7. Vomiting asscoiated with migraine.
8. It is the drug of choice where vomiting is dut to
gastrointestinal disturbances.
Cholestyramine is effective in diarrhoea due to excess unabsorbed bile
salt. This is seen in clinical conditions like :
10 mg, three times a day
Side effects are :- Drowsiness,
dystonias, stimulation of
lactation, extra pyramidal
symptoms.
Ileal resection.
1. Blocks the dopamine
receptors in CTZ.
2. Reduces the afferent
impulse input from GIT.
3. It improves peristalsis of
intestines.
3.
1. A. Metoclopramide
(Perinorm,
Reglan)
B. Domperidone
(Dromstat)
(O)
Post vagotomy.
Comments
2.
Dose and effects
Diabetic neuropathy.
Mechanism
(4)
1.
Drug
(3)
These are used to enhance the digestion of food e.g. HC1, pepsin, papain, diastase and pancreatin.
6. Digestants
5. Carminatives
These are used orally for dyspepsia e.g. Sodium bi-carbonate and peppermint oil.
1. Vomiting due to motion sickness.
2. Hyperemesis is gravidarum.
This is a labrynthinc
sedative.
5. Diphenhydramine
(Benadryl)
Trimeprazine
25 mg tablet thrice daily.
10 mg tablets thrice daily.
Side effects are :- Sedation,
lack of concentration. These
drugs are to be avoided when
concomittant antidepressant
therapy is given.
Mechanism
Drug
Dose and effects
Comments
State whether you agree or not
1.
The best drugs to neutralize acidity in peptic ulcer disease are the proton
pump inhibitors
2.
The healing rates with H2 blockers in reflux esophagitis are better than
proton pump inhibitors
3.
Magnesium sulfate can lead to cerebral excitation when used as a purgative
4.
Loperamide and imodium can be used in pallative therapy of diarrhoea in
children
5.
Antibiotics should never be used in cases of viral diarrhoea
6.
Metoclopramide can be used in cases of drug induced vomiting
7.
Digestants enhance the digestion of food such as pancreatin
8.
Esomeprazole has similar efficacy than omeprazole
9.
Potency of the molecule is not reflected as efficacy as both pantoprazole
and lansoprazole have similar efficacy
10. Domperidone does causes pyschotic reactions like metoclopramide
Answers
1.
Agree
2.
Don't agree
3.
Don't agree
4.
Don't agree
5.
Agree
6.
Agree
7.
Agree
8.
Don't agree
9.
Agree
10. Don't agree
85-A
85-B
1.
RESPIRATORY SYSTEM
6
Given subcutaneously I : 1000 solution, 0.2 - 0.5 ml slowly (Hurst-method).
The action lasts for ½ to 2 hours.
1. Bronchial Asthma
Used in :- (1) Acute bronchospasm. (2) Management of status asthmaticus.
Asthma is characterized by narrowing of the peripheral airways leading to
decreased forced expiratory volume and mean expiratory flow rate and is
manifested as breathlessness. Extrinsic asthma is allergen induced due to
reagenic lgE antibodies, whereas in intrinsic asthma exercise, pollution and
infection plays an important role. At the cellular level there is decreased level of
cyclic adenosine monophosphale (C-AMP) and increased level of cyclic
guanosine monophosphate (C-GMP) which cause bronchoconstriction.
Adrenaline (subcutaneously), isoprenaline
2.
Aminophylline (intravenously)
3.
Corticosteroids (IV/IM)
Disadvantage :-
1.
Short acting drug.
2.
Can be oxidised easily to adrenochrome.
Advantage :- Potent, quick acting drug.
Isoprenaline: (Isoprin, Neo-epinine)
Given sublingually or orally 5-20 mg, 3-6 times a day.
I.V. solution (I : 5000) and metered aerosol 20 mg (µ) (microgram)/day.
Disadvantages:-
Drugs in chronic attack:1.
Side effects :- Palpitations, arrhthymias and angina and therefore to be avoided
in old patients. CCF and hypertension are contraindications.
2.
Drugs in acute attack:1.
Adrenaline:-
Oral sympathomtics:" Ephedrine, salbulamol, orciprenaline, terbutaline
2. Deriphylline
Drugs in status asthmaticus (persistent acute attack).
Drugs:- Aminophylline, hydrocortisone, salbutamol
1
High incidence of arrhthymias.
2.
Tachyphylaxis (Response decreases with subsequent dosing).
Advantages:1.
Potent and rapid acting drug.
2.
As it is a pulmonary vasodilator it decreases pulmonary hypertension.
3.
Ephedrine (Ingredient in Asmapax)) :-
Prophylactic drugs:-
1.
Obtained from plant (Ma Huang).
Aerosol of disodium chromoglycate and montelukast, zafirlukast
2.
Relieves moderate bronchospasm.
3.
It has lesser cardiac side effects.
4.
It has a longer duration of action and therefore it can be given orally.
Respiratory System
86-A
86-B
Respiratory System
5.
6.
Side effects:- Tachycardia, glaucoma, urinary retention, and
tachyphylaxis, insomnia (therefore combined with sedatives).
2.
It reduces cardiogenic pulmonary oedema.
3.
In management of status asthmaticus it is given in dose of 500 mg
diluted in ½ litre of normal saline given slow I.V.
4.
It is oral derivative deriphyiline can be used in any form of asthmatic
attacks.
5.
Side effects:- Gastro-intestinal irritation, insomnia, tachycardia,
tremors.
Used in:1.
Chronic asthma.
2.
Prophylactic nianageraent of mild to moderate asthma.
Dose :- 15-50 mg, 4-6 times a day.
4.
5.
Salbutamol (Asthalin) :-
6.
1.
It acts by stimulating formation of C-AMP in bronchial musculature
resulting in bronchodiladon (due to preceptor stimulation).
2.
Lesser cardiac side effects.
3.
Improves pulmonary ventilation by stimulating respiratory centre.
4.
Acts for 4-6 hours.
5.
Potent drug.
6.
Can cause tremors.
7.
Dose is 4 mg three times a day.
8.
Uses
7.
Hydrocortisone:1.
For acute attacks dose is 40 mg to 4 grams/day whereas in status
asthmaticus it is given as 4 mg/kg I.V. bolus, followed by I mg/kg/
hour.
2.
It acts by decreasing mucosal oedema, antagonize inflammatory
mediators like prostaglandins and stabilize most cells.
3.
Side effects include:- Cushingoid effects (moon face, buffalo hump),
steroid dependency and impairement of immune status.
Disodium chromoglycate (Intel)
1.
It is only a prophylactic drug, not useful in acute attack.
2.
It is given in spinhaler as 20mg of micronized preparation out of
which only 2% reaches alveoli.
a)
Allergen induced acute asthma.
b)
Chronic asthma.
3.
It can be tried in allergic rhinitis and alveolitis.
c)
Excercise induced asthma.
4.
Side effects:- dryness of mouth, urticaria
d)
In conditions where there is broncho spasm such as : chronic
bronchitis, eosinophilic lung and pneumoconiosis (industrial lung
disease).
5.
It acts by stabilising the mast cells.
Aminophylline:- (Minophyl)
1.
It decreases bronchospasm by stimulating C-AMP formation (due
to action on phosphodiesterase enzyme).
Respiratory System
87-A
87-B
Respiratory System
Newer Anti asthmatic Drugs
Drug
Mechanism of
action
Kinetics
Toxicity
Indications
and dose
Zafirlukast
It is selective
and competitive
leukotiene
receptor
antagonist,
which also
antagonises
slow release
substance A ,
preventing
airway edema
and smooth
muscle
constriction
•
•
•
Same as above
•
Montelukast
•
•
•
•
Respiratory System
Rapidly
absorbed
Food
reduced
bioavailabil
ity
High
volume of
distribution
Interacts
with aspirin
and
erthromycin
•
Rapidly
•
absorbed
with
•
bioavailabli
•
ty of 64 %
Linear
kinetics ie
the serum
concentratio
ns increase
with the
dose
Headache,
dizziness,
nausea
Urticaria
•
•
Headache,
dizziness
Dyspepsia
Urticaria
•
•
Drug
Mechanism of
action
Kinetics
Zilueton
Same as above
•
Prophylaxi
s and
chronic
treatment
of asthma
in adults
and
children
Chronic
urticaria
10mg20mg
tablets as
required
by the
patient
•
Toxicity
•
Gets
converted to
an active
metabolite
which is
responsible
for drug
activity
The
baseline
peak
expiratory
peak flow
values
improve
Indications
and dose
Dyspepsia,
nausea,
headache
Same as
above. Used as
600mg tablets
as required by
the patient
All above
drugs are not
bronchodilator
s and hence in
no way acute
episode of
asthma should
be treated with
them
Prophylaxi
s and
chronic
treatment
of asthma
in adults
and
children
10mg
tablet as
required
by the
patient
88-A
88-B
Respiratory System
2. Cough
Codeine
The drugs used in cough increase the threshold of cough centre or decrease
the flow of impulses from the cough centre to periphery (Anti-tussives).
1.
Cough can arise due to:-
a)
Allergic phenomenon.
b)
Upper or lower respiratory tract infection.
c)
Chronic pulmonary disease.
d)
Acute left ventricular failure.
2.
Centrally acting anti-tussive:-
3.
Dextromethorphan
(Romilar) (Zedex)
1. It depresses cough
centre in medulla
1. Potent drug similar
to codiene
1. Synthetic powerful
anti-tussive agent.
2. It has anti-tussive
effect similar to
morphine
2. It can cause drowsiness, headache,
nausea and rhinitis
2. Low addiction
liability.
3. It can cause dependance, euphoria and
bronchospasm.
3. Side effects are:drowsiness,
dizziness
4. It never depresses
respiration.
Codiene (Phensedyl)
:
10-15 mg, 4-6 hourly.
Noscapine (Noscopax)
:
15-30 mg, 4-6 hourly.
Dextrometholphan (Clistin)
:
10 mg, 4-6 hourly.
Bromhexine is a mucolytic which reduces the viscosity of sputum. It can be
used in any patient suffering from respiratory distress resulting from thick
tenacious sputum eg. bronchitis, emphysema and alelectasis.
Expectorants increase secretions from the respiratory tract and hence reduce
the stickiness of sputum.
Peripherally acting anti-tussive:-
They are:- Cresotes, tincture benzoin Co., volatile oil of Anise or Eucalyptus
(corex) and saline expectorants which reflexly stimulate gastric reflexes,
increasing the respiratory secretions, e.g.:- Ammonium, potassium iodide,
vasicine (from leaves of Vasaca)
Benzonatate (Tessalon)
Bromhexine (Solvin expectorant) 8-16 mg, thrice daily.
4.
Respiratory System
Noscapine
89-A
89-B
Drug causing bronchospasm:i)
b-blocker eg. propranolol (used as antihypertensive).
ii)
D-tubocurarine (drug used in anaesthesia.)
iii)
Morphine (used for pain)
iv)
Colloids (used for shock).
v)
Cholinergic drugs (aracholine)
Respiratory System
5.
Drugs depressing respiration;i)
Narcotic analgesics e.g. : Morphine
ii)
Hypnotics: Phenobarbitone
Drug
Dose
Sedation
Anticholi
-nergic
activity
Antiemetic
effects
Special
features
Minimal
Anti –
histaminic
activity
+++
Cetirizine
10mg, once
+/-
+/-
120-180mg ,
once
Minimal
++
+/-
+/-
10mg, once
Least
+++
+/-
+/-
Best efficacy,
Long duration
of action , acts
on initial and
late phase of
allergy
Good efficacy,
Safe, acts
better on initial
phase of
allergy
Moderate
efficacy, actson
initial and late
phase of
allergy
(Allegra)
Loratadine
(Incid-L)
Anti histaminics
These agents are used for the relief of manifestations of immediate type of
hypersensitive reactions. Antihistamines are reversible, competitive H1 receptor
antagonists that reduce or prevent most of the physiologic effects of histamine,
normally at H1 receptor site. Most of the drugs such as Cetirizine, Fexofenadine,
Loratadine, Azelatine, Ebastine and Levo cetrizine are used in cases of perennial
allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, urticaria, angioedema,
adjunctive anaphylactic therapy, allergic reactions to blood & plasma and in
cases of insect bites. They cause lesser sedation as compared to older drugs
Dose/day
Chlorpheniramine 4mg, tds
Sedation
+
(Lorfast)
The sedation produced by these drugs could be increased by alcohol and
antipyschotic drugs
First Generation Drugs :
Drug
Fexofenadine
Anti
Antichol-
histaminic
inergic
effects
activity
++
++
Anti emetic
Advantages of the Second generation drugs :
●
●
--
●
(Avil)
●
Promethazine
25 mg, tds
+++
+++
+++
++++
●
(Phenergan)
●
Hydroxyzine
25mg-
(Atarax)
100mg ,tds
+++
++
++
Rapid onset of action
Early onset of action
Sustained action for longer time
Least interaction with alcohol
Convinience of administration
Minimal sedation
+++
Side effects include drowsiness, confusion and even hallucinations. There is
Cyproheptadine (Periactin) has antihistaminic, antiserotoninergic and anticholinergic properties. The dose is 2-4 mg T.D.S. It is specially useful
inconditions as :1. Anorexia
2. Migraine headache.
dryness of mouth, diplopia & symptoms of urinary retention
3.
Diphenhydramine 25mg-
+++
++
+++
+++
50mg ,tds
Respiratory System
90-A
90-B
Drug and serum hypersensitivity reactions.
Respiratory System
8.
Hiccough:Injection or oral chlorpromazine (Largactil) in dose of 25-50 mg is useful.
Do you confirm or reject
HAEMATINICS
7
Hematopoietic growth factors
1.
Advantages of salbutamol are potency, effective bronchodialtion and in
any stage of asthma ?
2.
Monteleukast is for the prevention of asthmatic attacks and is given orally?
3.
Adrenaline is given IV in cases of status ashtmaticus ?
4.
The mode of action of disodium chromoglycate is similar to Zafirleukast ?
5.
The side effects of aimophylline are insomnia, tachycardia, tremors and
gastrointestinal irritation ?
6.
The therapy of cough is purely symptomatic ?
7.
The cough becomes productive in cases of infections ?
8.
Better centrally acting anti tussives is dextromethorphan ?
9.
The newer antihistaminics are less sedating antihistaminics ?
1. Erythropoietin
Introduction
The mature red blood cells have relatively short life span and hence there is
need for continuous replacement of blood cells. The growth factors are used to
regulate proliferation and differentiation of hematopoietic cells in the bone marrow.
a)
Erythropoietin : Glycoprotein hormone produced mainly by the peritubular
cells in the proximal tubule of kidney and has molecular weight of 34,000.
b)
Thyroxin growth hormone, testosterone, prolactin, prostaglandins stimulate
erythropoietin production
10. Loratadine and Fexofenadine are the least sedating antihistaminics ?
c)
Erythropoeitin acts by binding to a receptor on the surface of erythroid
precursor cells.
Answers
d)
Available commercially by using recombinant DNA technology and has
half-life of 6-8 hrs.
e)
50 units / kg i.v. or s.c., three times weekly for a period of 3-4 months is
sufficient to keep haematocrit upto 36%.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Confirm
Confirm
Reject
Reject
Confirm
Reject
Confirm
Confirm
Confirm
Confirm
Indications
91-A
a)
Anaemia in patients with AIDS or with cancer chemotherapy.
b)
Aplastic anaemia or bone marrow failure.
c)
Myeloproliferative or myelodysplastic disorders
91-B
cells. Studies also demonstrate B12's ability to reduce high
homocysteine serum levels, which has been linked to arterial injury.
Methyl B12 has exhibited beneficial effects against brain aging,
regular sleep patterns and reducing high homocysteine serum levels.
It may also support immune function, and promote no cellular growth.
Further, methyl B12 represents one of the best values for the nutritional
products, given its comparably least side-effects and wide range of
potential benefits.
Side-effects
1.
Thrombotic episodes hypertension, convulsions.
2. Granulocyte colony stimulating factor
a)
GM-CSF is indicated in patients with neutropenia secondary to
neoplasia, myelodysplasia, aplastic anaemia, congenital cyclic
neutropenia, hairy cell leukemia, chronic bone marrow malignancies,
AIDs, neutropenia associated with chemotherapy an autologous bone
marrow transplantation
b)
Following iv administration, there is rapid increase in bone marrow
cellularity
c)
The toxic side-effects include fever, malaise, myelgia, fatigue,
arthralgias, skin rashes, gastrointestinal distress, peripheral oedema
and plural effusion
d)
Given in a dose of 5 mcg / kg / day
3. Mecobalamin
a)
Mecobalamin occurs as dark red crystals or crystalline powder. It is
sparingly soluble in water, slightly soluble ethanol, and practically
insoluble in acetonitrile.
b)
Methylcobalamin (methly B12) is the neurologically active, most
bioavailable and best utilised form of vitar B12. Methyl B12 is more
effective than traditional forms of B12 for treating pernicious anaemia
(B deficiency) as there is no need for conversion by the body and is
better retained by the liver and other tissues. Clinical studies have
documented the efficacy of methyl B12 in slowing down or even
reverse the effects on nerve tissue. Methyl B12 also appears to play
a role in balancing brain chemicals by synthesising neurotransmitters,
which are the chemical means of communication between nerve
92-A
92-B
Haemitinics
93-A
93-B
Haemitinics
4. Malignancy
5. Worm infestations
6. During infancy,
pregnancy and
lactation.
ness stools.
fort and it dark-
Oral iron can
cause nause,
gastric discom-
3-6 months to
replenish iron
stores.
With oral
globin values
should reach
normal within
10 weeks and it
requires about
Iron as:Sulfate, ammonium, citrate,
gluconate,
fumarate,
ferrocholinate
salts.
therapy haemo-
Oral
acid, 10-30 mg
orally/day
Also known as pteryglutamic
acid, known to cure megaloblastic
only haematological disorder
its metabolic pathway and corrects
Folic acid utilizes Vitamin B12 in
Pernicious anaemia results due to
for absorption of extrinsic factor
which is vitamin B12 itself. By
For various other
conditions
15 µg/day.
anaemia.
Daily requirement : 1-5 µg.
Dietary sources of Vit.B12 are egg
mucosa also known as the intrinsic
increase in number of circulating
reticulocytes.
yolk, meat, cheese, liver, kidney
and peak (legumes).
giving Vitamin B12 there is
factor of Castle, which is essential
I.M. every 3 days
for 7-10 doses.
lack of glycoprotein in gastric
in the treatment of pernicious
anaemia. 100 µg
They are commonly employed
In pernicious
(Vitcofol)
egg and meat.
Cyanocobalamin (Vitamin B12)
advisable to give Vitamin B12
folic are liver, green vegetables,
prior to its administration.
can be aggregavated eg. subacute
degeneration of spinal cord. It is
50-100 µg. Dietary sources of
whereas the neurological damage
Synthetic folic
Folic acid (Folvite)
Importance
anaemia. Daily requirement is
Dose
Physiology
beans.
10% of iron whereas
anaemic absorbs 30%
4. Iron requirement ranges
between 0.5-10 mg/day
5. Diet rich in iron is spinach,
apple, liver, fish and dry
Microcytic anaemia
resulting due to :1. Severe or chronic
haemorrhage.
2. Malabsorption
syndromes
3. Achorhydria
Uses
haemoglobin
x 0.255 f
Total amount
iron required
in mEq=
standard
haemoglobin
- patient's
Iron Dextran
(Imferon)
which
contain 50mg
of elemental
iron/ml.
of elemental
alcoholic neuritis, tobacco amblyopia.
Trigeminal, neuralgia, diabetic and
c. Neurological conditions like :-
b. Psychatric disorders.
a. Malabsorption syndrome.
in :-
Besides pernicious anaemia, its also used
4. Chronic haemolytic states.
nitrofurantoin.
pyrimethamine, trimethoprin,
acid antagonists like:- Phenytoin,
3. In treatment of toxicity caused by folic
childhood and pregnancy.
2. Megaloblastic anaemia of infancy,
1. Nutritional megaloblastic anaemia.
stration.
DesferrioxamineB1-2g I.M., every
12 houry.
Abdominal discomfort haematemesis
cardiovascular
collapse may occur
occur following
parenteral adminiTreatment includes
Parenteral
Iron toxicity
preparation
Therpeutic uses
Folic acid / Cyanocobalamin
It takes place in
duodenum and
proximal jejunum
1. Essential for Hb formation
and for oxidative process
in tissues
2. Diet contains 10-15 mg of
iron/day
3. A normal man absorbs
Iron absorption
Physiology and
requirement
Iron
Opine positive or negative
1.
Iron can be given by any route and the maximal utilization is by
anemic ?
2.
Iron is used to treat any type of anemia ?
3.
Iron deficiency anemia is common in pregnancy ?
4.
Folic acid deficiency is caused by drugs like phenytoin, nitofurantoin &
trimethoprim ?
5.
Vitamin B12 is used in cases of pernicious anemia ?
Answers
1.
Positive
2.
Negative
3.
Positive
4.
Positive
5.
Positive
Haemitinics
94-A
94-B
Haemitinics
-
glycoprotein from the
venom of the Malayan
pit viper
ANCROD
- a hydroxycoumarin
WARFARIN
Anticoagulant
HEPARIN
- sulphated acid
mucopolysaccharide
prepared from beef lung
and intestine
Onset
Immediate
Effective after
24-36 h.
Rapid
Mode of action
1. Acts as an antithrombin
and thus prevents
conversion of fibrinogen –
fibrin
2. Inhibition of activated
factor, IX, X, XI
Also : Is active in vitro and in
vivo; activates lipoprotein
lipase; inhibits platelet
aggregation by fibrin (*These
actions require the presence of
antithrombin III, a plasma
factor)
Prevents the reduction of
vitamin K1 oxide to active
vitamin K1. This blocks the
synthesis of factors II, VII, IX
and X
Acts as an anticoagulant by
destroying fibrinogen. Any
fibrin formed is unstable
1. Comparison of three anticoagulants
Clinical uses
T½ = several days
Given i.v. for central retinal
vein thrombosis, priapism and
sickle cell crisis
T½ = 44 h (but much individual
variation)
Given orally prevent embolic
disease and in the treatment of
arterial and venous thrombosis.
Continuous or intermittent i.v.
administration for arterial and
venous thrombosis; low dose
subcutaneous administration for
prophylaxis of deep vein
thrombosis.
T½ = 90 min.
Antagonised by a specific
antivenom.
Treatment is monitored by
measurement of plasma
fibrinogen.
Reversal of action by water
soluble vitamin K
Prothrombin time is
prolonged and is the usual
guide for dose
Reversal of action by
protamine sulphate
Control of therapy
Thrombin time }
Clotting time
} all
Activated partial } prothromboplastin } longed
time (kaolin – }
cephalin time) }
8
HAEMOSTATICS
2. Anti thrombotic drugs
Drugs are :-
95-A
1.
Aspirin :- 300mg/day (Bayer's Aspirin)
2.
Dipyridamole :- 100mg B.D. (Deplatol)
3.
Sulfinpyrazone :- 200 mg Q.I.D.
4.
Vitamin E :- 200mg.(Evion, Evit)
5.
Clopidogrel (Clopid)
6.
Cloribrale (Astromids, Lipomid)
7.
Dextran70
These drugs are used for arterial thrombotic diseases in contrast to heparin
which is used for venous embolic disorders.
Uses:-
1.
Reduce reinfarction rate in post myocardial infarction patients.
2.
Transient ischaemic attacks.
3.
Coronary bypass implants.
4.
Prosthetic heart valves.
5.
Pre-eclampsia.
6.
Peripheral vascular diseases.
Actions:-
Aspirin acts by inhibiting the release of adenosine diphosphate from platelets
whereas dipyridamole inhibits phosphodiesterase and stimulates the production
of prostacyclins (PGI3). Thus platelet aggregation and addition is prevented.
These two drugs might complement the actions of each other.
95-B
Haemitinics
Parameters
Aspirin
Ticlopidine
Clopidogrel
Parameters
Aspirin
Ticlopidine
Clopidogrel
Category
Antiplatelet
Antiplatelet
Antiplatelet
Category
Antiplatelet
Antiplatelet
Antiplatelet
Thienopyridine
derivative
Drug interactions
Heparin, Coumarin
derivatives,
Methotrexate,
Probenecid,
Spironolactone.
Aspirin & Other
NSAIDs, Antacids,
Digoxin, Cimetidine,
Theophylline
NSAIDs, Heparin,
Warfarin.
Ticlid (Roche Labs)
Plavix (BMS)
Class of the drug
COX Inhibitor Thienopyridine
derivative
Strengths
available
50-350 mg tablets
250 mg Tablets
75 mg Tablets
Mechanism of
action
Non selective
inhibition of the
COX enzyme
Inhibits the ADP
induced Platelet
aggregation
Inhibits the ADP
induced Platelet
aggregation
Protein binding
80-90%
98%
85%
Onset of Action
30 min- 2 hrs
24-48 hrs
2 hours
Tmax
2 hours
2 hours
1 Hour
Effect of food
Delays the
absorption
Increase in AUC by
20%
No affect
Excretion
Renal elimination
60% in urine
23% in feces
50% Urine
46% in Feces
Half-life
15-20 minutes
Elderly patients:
12.6 hrs, with single
dose
4 to 5 days after
multiple dosing
Metabolite: 8 hours
Radiolabeled
molecule: 11 days
Primary and
Secondary
prevention of
Thrombotic stroke
(Fatal or Non fatal)
Reduction of
Atherosclerotic
events (MI, Stroke,
Vascular death)
Secondary events
caused by MI,
Established PVD.
Indications
Primary and
Secondary
Prevention of
Cardiac events
International
Disprin (R & C)
brand & company
Benefits of Clopidogrel
Feature
Advantage
Benefit
Onset of action is more rapid
than Ticlopidine
(2 hrs Vs 24-48 hrs)
Faster in achieving
antiplatelet action.
Useful alternative than
Ticlopidine
More selective inhibition of
ADP induced platelet
aggregation
Six times more potent than
ticlopidine
Superior to Ticlopidine
Greater blocking of ADP
receptors
Well tolerated than
Ticlopidine
Useful in wider subset of
patients like with secondary
ischemic events, Diabetes,
History of CABG, Stent
thrombosis.
Lesser incidence of TTP,
Agranulocytosis and
Neutropenia
No need for the repeated
blood testing
Safe and Convenient therapy
Dosage &
Admin.
50 mg to 325 mg
OD
250 mg BD
75 mg OD
No Effect on Protective
Prostaglandins
Offers better efficacy over
other anti platelet agents
Lesser incidence of GI
disturbances
Contraindications
Hypersensitivity,
Presence of
Bleeding disorders
Hypersensitivity,
Presence of
hematopoietic
diseases, Presence of
a hemostatic
disorder or active
clinical pathological
disease (Bleeding,
Ulcer).
Hypersensitivity,
Active pathological
bleeding conditions
No changes were observed in
the kinetics of the special
population
No dosage adjustments
required in the special
population
Better patient compliance
Extensively studied in large
groups of patients
Shown efficacy in the varied
types of patients
Well accepted over long term
Few reported Drug
interactions
No dosage adjustments with
other medicines except few
like other antiplatelet agents.
Can be considered for coprescription also.
No affect of Food on
absorption
No dose adjustments
required.
Excellent patient
convenience
Haemitinics
96-A
96-B
Haemitinics
Staphylokinase :
Thrombolytic agents
Streptokinase lacked fibrin specificity and was highly immunogenic, whereas
the bleeding diathesis were high with urokinase and hence the novel fibrinolytic
agent was produced by the selected strains of Staphylococcus aureus which
had136 amino acids without disulphide bridges. The recombinant staphylokinase
is produced by cystosolic expression
Staphylokinase is not an enzyme but forms complex with plasminogen. This
complex activates other plasminogen molecules to plasmin which is the
proteolytic enzyme capable of digesting fibrin and fibrinogen
This is infused as 10mg infusion over half hour or as a 20mg infusion . The
patients develop less bleeding and less titres of neutralizing antibodies are
produced
Newer derivatives of Staphylokinase are under development such as the
Polyethylene glycol complex to the Stapylokinase known as SY 161 -P5 having
a higher thrombolytic potency
97-A
Features
Streptokinase
Urokinase
Preparation
Purified preparation of bacterial
protein purified from group C betahaemolytic streptococci
Produced from human
neonatal kidney cells.
Mechanism of
action
Act on plasminogen to produce an
activator complex that converts
plasminogen to plasmin. Plasmin
degrades the fibrin clots as well as
fibrinogen and other plasma
proteins
Similar mode of action
Duration of action
24-36 hrs.
24-36 hrs.
Elimination half-life
23 mins.
12.6 mins
Metabolites
No metabolites, cleared very fast
by liver
Metabolites observed
Uses
Acute, transmural myocardial
infarction, Pulmonary embolism,
deep venous thrombosis, arterial
thrombosis and embolism
Lysis of acute massive
pulmonary emboli, acute
transmural myocardial
infarction
Contraindications
Active internal bleeding, recent
cerebrovascular accident, severe
uncontrolled hypertension, severe
allergy to the product.
Similar to streptokinase +
AV malformation
Dose
250 000 units over 30 mins. as a
loading dose followed by 100 000
units for 24-72 hrs.
4400 units / kg over a
period of 10 mins. followed
by continuous infusion of
2000 units for a period of
12 hrs.
Side effects
Bleeding, fever, shivering,
respiratory depression, pain at the
site of injection
Similar to streptokinase
97-B
Third generation Anti platelet Drugs
Feature
Source
Mode of action
Indications
Contraindications
Side effects
Dose
Abciximab
It is the Fab
fragment of human
murine monoclonal
antibody
Binds to GP IIb/III a
receptors and
prevent platelet
aggregation . It also
prevents monocyte
adhesion
Patients undergoing
coronary
intervention or those
having unstable
angina
Eptifibatide
It is cyclic
heptapeptide
History of bleeding
diathesis, severe
hypertension,
stroke, or any
intracranial
anuerysm
Bleeding at site of
arterial puncture
Thrombocytopenia
Hypotension
0.25 mg/kg bolus
followed by
0.125mg/kg/min for
12 hours
Same as Abciximab
Similar to
Abciximab
Acute coronary
syndrome and in
cases of
percutaneous
interventions
Tirofiban
It is a small
nonapeptide
molecule , with
tyrosine residue
Similar to
Abciximab
Patients of unstable
angina, not
responding to
conventional
medical treatment ,
since it has faster
action
Same as
Abciximab
Same as Abciximab
Same as
Abciximab
180 mcg/kg bolus
followed by 2 mcg
/kg/min , infusion
over 24 hours
0.4-0.6mg/kg of
body weight
followed by
infusion of 0.100.15mcg/kg/min
for 24-72 hours
98-A
98-B
3. Coagulants
4. Systemic Hemostatics
These drugs promote coagulation and are used in haemorrhagic states.
(These drugs prevent excessive bleeding)
Drugs are:1.
Human fibrinogen
2.
Adrenochrome monosemicarbazone (Styptochrome)
3.
Rutin or vitamin P (Styptomel)
4.
Vitamin K
5.
Gelatin foam
The Topical haemostatics (styptics) stop bleeding from wounds following dental
extraction, epistaxis bleeding piles. They can also be used in Neuro surgery
and during skin grafting.
1.
Gelatin foam:- It is moistened with saline or thrombin and is used for
packing wounds.
2.
Adrenochrome:" 0.5 1mg B.D. reduces capillary fragility.
3.
Rutin:- 60 mg twice or thrice daily also reduces capillary fragility
4.
Vitamin K:- Phytonadione 10 mg/ml. I.M. can be used in cases of:
a)
overdosage of oral anticoagulants.
b)
obstructive jaundice or malabsorption syndromes which can interfere
with the absorption of vitamin K.
c)
Long term use of anti inflammatory drugs can cause hypoprothrombinaemia. Here vitamin K is given prophylactically.
Haemitinics
99-A
1.
Aminocaproic acid is used in conditions where blood transfusions
contributes to bleeding, prevention of recurrence of subarachnoid
haemorrhage. Given as an initial dose of 5 gram IV, followed by 1 gram
hourly.
2.
Tranexamic acid is used for short term 2 to 8 days in haemophilia patients
to prevent haemorrhage. It is 10 times more potent than aminocaproic
acid. Given as 25 mg/kg orally 3-4 times a day.
3.
Aprotinin (Trasylol) used in CABG patients for reducing blood loss/need
for transfusion used parenterally with 2 million units IV loading dose, followed
by 50,000 units hourly.
99-B
Haemitinics
DRUGS REDUCING BLEEDING
Always or Never
1.
Heparin acts both in vivo and in vitro ?
Reduction of blood loss
following Coronary artery
by pass surgery
2.
Heparin has no antidote for its toxicity ?
3.
Oral anti coagulants are used as part of mantainence therapy ?
2 Million KIU IV loading
dose , followed by 50,000
KIU as constant infusion
4.
The antithrombotic which rarely cause neutropenia is clopidogrel ?
5.
The prime use of anti thrombotics is in transient ischemic attacks ?
Drug
Actions and kinetics
Use and dosage
Aprotinin ( Trasylol )
Protease inhibitor stimulates
clotting by intravascular
activation of coagulation
cascade
Rapidly distributed to all
body compartments
Phlebitis
Answers
Heamorrhage are main side
effects
Tranexamic acid
Competitive inhibitor of
plasminogen activation thus
facilitates coagulation
1.
Always
2.
Never
3.
Always
30% oral absorption
10mg/kg IV who do not
tolerate oral drug. Or
25mg/kg orally , available
as 500mg tablet
Eliminates after 24 hour
Haemophilia
4.
Always
Giddiness
Dental extraction bleeding
5.
Always
Hyotension are reported
side effects
Bleeding following ENT
procedures
Menorrhagia
EMERGENCY COLLOID INFUSION
Drug
Albumin ( Plasbumin 5%,
20% and 25 %
Features
Restores normal function
immediately
Applications and dosage
• Shock
• Burns
• Hypoproteinemia
• Acute nephrosis
• Renal dialysis
• Hyperbilirubinaemia
• 50-100ml vials
available, about 100ml
is required initially
100-A
100-B
VITAMINS
9
2. Vitamin-A
(Auasol)
1. Dietary source:
Vegetables, butter, eggs,
milk, fish liver oils
Fish liver oils, butter, eggs.
2. Daily requirement
5000 U
400 U
3. mode of action
1. Maintains the functional and structural integrity of epithelial cells
throughout the body.
2. Stimulates the synthesis
of nuclear RNA suggesting role in genetic
transcription.
3. Essential for the vision
in dim light (dark
adaptation.
Vitamin D itself is inactive
In the body it is converted to
calcifediol and 1,25 dihdroxychole calciferol which
are active products.
The primary action of Vit D
is to increase absorption of
calcium and phosphorous
from intestines.
4. Deficiency states
Night blindness or
nyctalopia, retarded
growth, susceptibility to
infection, hyperkeratosis
and xerophtalmia
(conjuctiva)
1. Rickets in children.
2. Ostemalacia in adults.
3. Hypoparathyroidism
5. Toxicity
Overdosage leads to
hypervitaminosis A
characterized by anorexia,
irritability, Periosteal
thickening, dry skin,
pruritis, desquamation,
fatigue, myalgia nystagmus
and hepatosplenomegaly.
Hypervitaminosis D results
in dearranged calcium
metabolism. There is hypercalcemia, fatigue, vomiting,
diarrhoea, calcium deposition in kidneys can lead
to nephrocalcinosis.
Introduction :The vitamins are essential micro constituents of diet which do not give energy
but are necessary for the normal metabolism in the body. Adequate amounts
can reach with a well balanced diet, which may not be true in developing countries
such as, the Indian sub continent.
Types :B complex group
1.
Water soluble vitmains :
Vitamin C,
2.
Fat soluble vitamins :
Vitamin A, D, E, K.
1. Vitamin-C (Ascorbic acid) :Uses
1.
A deficient intake of vitamin C, leads to scurvy. Vitamin C lack results in
disintegration of intracellular ground substance specially of capillaries,
connective tissues and the bones. Hence to prevent this state a dose of
50 mg is essential and in established case, a dose of 3 g/day is given till
patient is cured symptomatically.
2.
In idiopathic methaemoglobinaemia where it is used as reducing agent.
3.
Treatment of dental carries, pyorrhoea and gum infections.
4.
Prevention of upper respiratory tract infection.
5.
To promote healing of the wounds.
Palliative therapy
101-A
3. Vitamin-D
(Arachitol)
101-B
Vitamins
2. Vitamin-A
(Auasol)
6. Clinical use
3. Vitamin-D
(Arachitol)
1. Prevention and cure of
conditions resulting
due to deficiency as
hyperkeratosis, xeroph-
thalmia and nyctolopia.
2. During pregnancy,
lactation and infancy.
3. In Kwashiorkor
retinol palmitate 30,000
µ I.M. given as single
dose
VITAMIN
1. For prevention and treament of rickets.
2. Osteomalacia.
3. H y p o p a r a t h y r o i d i s m
Vitamin B complex group
(a)
(b)
Vitamin B1 simulates
conversion of carbohydrates to fats
4. Daily
Thiamine 0.6 mg for
requirements
700-1000 I.U. or 2-3 mg. for
adults, 1.5 mg for children. adults.
6.
Vitamin E (alpha-tocopherol) (E-Vit, Evion)
Features
1.
Source is from wheat germ oil, nuts and egg yolk.
2.
It has antioxidant property.
3.
It has antisterility actions in animals.
4.
Daily requirement is 10-30 mg/day.
5.
Indications for use :-
Vitamin B6 (Pyridoxine) - This is routinely given along with INH to
prevent preipheral neuropathy.
a)
Retrolental fibroplasia in cases of premature infants.
b)
In hypervitaminosis A to reduce toxicity of the vitamin.
Vitamin B12 (Cyanocobalamine) - See chapter on haematinics.
c)
In selected cases of haemolytic anaemias where tocopherols can
prolong erythrocyte survival time.
d)
In cases of intermittent claudication (peripheral vascular disease)
where it can be combined with aspirin.
e)
Habitual abortion.
VITAMIN
(c) B1 Thiamine
(d) B2 Riboflavin
1. Deficiency
syndrome
Beri-Beri, polyneuritis,
myalgia, anorexia and
retarded growth
Eye: Keratitis and photophobia; rhagades, cheilosis, sprue
and loss of hair.
2. Source
yeast, liver, kidney, pork
muscle, milk and egg.
Yeast, liver, kidney, milk, egg,
meat, and green vegetables.
3. Mode of action
For catabolism of carbohydrates. In deficiency there
is accumulation of pyruvic
and lactic acid.
For carbohydrate and protein
metabolism. As phosphoric
group of many enzymes for
tissue oxidation.
Vitamins
(d) B2 Riboflavin
where dihydrotachysterol agent of choice.
1 unit=0.025 µg of pure
calciferol.
At 6 month.... 400 U are
given
" 3 years.... 600 U
'' 8 years.... 800 U
> 12 year.......1000 U
and above.
4.
(c) B1 Thiamine
102-A
In all the above conditions, the dose requirement ranges from 200-600 mg/day.
6.
Vitamin K (Phytonadione)- See chapter on haemostatic drugs.
102-B
Viitamins
Say Yes or No
1.
The doses of the vitamins are as per the recommended dietary
allowance ?
2.
Vitamin C delays the wound healing ?
3.
The deficiency of Vitamin A causes night blindness ?
4.
Osteomalacia is seen in children ?
5.
Vitamin E is a potent anti oxidant ?
Answers
1.
Yes
2.
No
3.
Yes
4.
No
5.
Yes
Vitamins
103-A
103-B
Viitamins
2. Thyroid hormones
ENDOCRINES
10
The main function of thyroid gland is to synthesize, store and secrete thyroxine
(T4) and tri-iodothyronine (T3) which are under the control of thyrotrophic hormone
(TSH) from the anterior pitutory.
1. Introduction to hormones
Hormones are chemical substances produced endogenously by endocrine
glands and certain nerve cells and are released directly into the blood and have
action on distant tissue targets.
Actions :1.
Both T3 and T4 have calorigenic action which increase basal metabolic
rate. (B.M.R.).
2.
These hormones enhance glycogenolytic action of adrenaline.
3.
They mobilise blood lipids leading to fall in the circulating plasma lipids.
4.
They synergize the effects of catecholamines by enhancing sensitivity of
the beta receptors of heart.
5.
They are essential for the development of C.N.S.
6.
They regulate haemopoiesis.
7.
They mobilize calcium from bones and simulatneously facilitate calcium
clearance from kidneys.
There are two major groups of hormones in the body eg:- steroids and peptides.
Comparative differences :Steroids
Peptides
1. Biosynthesis
enzymes
From multiple
prohormones
From precursor
2. Storage of performed hormone
Minimal
Substantial
3. Half life (t½)
Long
Short
4. Binding protein
Present
Very rare
5. Peripheral
transformations
Common
Do not occur
6. Mechanisms of
action
Complex :Simple i.e. there is activation
A two stage process of adenyl cycalse enzyme.
7. Degradation
Retain activity
Inactive
8. Acid resistance
Not destroyed,
therefore can be
given orally
e.g. Prednisolone
Rapidly destroyed, therefore
not given orally e.g. Insulin
Preparations:1.
Thyroid extract:- an orally effective preparalion. Inexpensive and should
contain 0.20% of iodine by weight.
Dose :- 30 to 250 mg/day.
2.
Levothyroxine sodium:" a .sodium salt of synthetic thyroxine. Readily
absorbed, quick and persistent action.
Dose: 50 to 300 ug/day (Eltroxin)
3.
Liothyronine sodium, a synthetic salt of T3.
i)
Endocrines
104-A
104-B
Rapid onset.
Endocrines
ii)
Short duration of action.
Classification:
iii)
Used in emergencies like myxoetiema coma.
1.
Dose : 5-100 µg/day
Inhibitors of thyroxine synthesis :(Thioamides)
1.
Propyhylthiouracil
2.
Methylthiouracil
Therapeutic uses:-
3.
Mathimazole
1.
Thyroid deficiency states particulary in myxoedema or cretenism
4.
Carbimazole (Neo-mercazole)
2.
Hypothyroidism secondary to anterior pitutary destruction (Simmond's
disease)
2.
3.
Chronic thyroiditis (Hashimoto's disease)
3.
4.
Hyperlipedemia with hypothyroidism.
5.
Palliation in treatment of:- infertility, menstrual disorders, refractory anaemia
and hypogonadism.
4.
Thyroglobulin (Proloid) 65 mg tablet, ½ to 3 tablets per day
1131 (Radioactive iodine)
4.
Side effects :The toxicity of thyroid hormone manifests as hyperthyroidism e.g. irritability,
insomnia, nerovousness, polyphagia, arrythymias and tachycardia.
5.
3. Anti-thyroid drugs
In hyperthyroidism there is an excessive secretion and hyperactivity of the
thyroid hormones. The symptoms are due to increased basal metabolic rate,
neuromuscular activity and stimulation of sympathetic nervous system leading
to irritability, voracious appetite but there is loss of weight, palpitation and
hypertension. There may be exopthalmos and thyroid enlargement.
Drug that destroys thyroid tissue :-
1.
Inhibitors of iodine trapping
1.
Thiocyanates
2.
Perchlorates
Drugs with uncertain mode of action:
1.
Potassium and sodium iodide
2.
Lugol's iodine
Drugs producing hypothyroid state as their side effect :1.
Sulphonamides
2.
Amiodarone
Inhibitors of thyroxine synthesis :Side effects :-
Goitrogenic
Allergic rashes
Leucopenia and agranulocytosis
Drug fever sometimes seen.
Dose :- Propylthiouracil 75-100 mg every 8 hrly.
Uses : 1.
Endocrines
105-A
105-B
Hyperthyroidism in Grave's disease.
Endocrines
2.
2.
Preparation of thyrotoxic patient for surgery.
Therapy :-
Precaution :- Pregnancy (since these drugs cross placental barrier)
1)
Oral antithyroid drugs:Sodium iodide 1-2 g, slow I.V. infusion.
Radioactive iodine I 131 :-
2)
It acts by destroying the functional and regenerative capacity of thyroid
cells by emitting b radiations. The follicular cells are necrosed, the colloid
disappears, followed by fibrosis.
b-blockers to prevent sympathetic overactivity.
Atenolol (Aten) 50-100 mg O.D.
3)
Correction of relative adrenal insufficiency:Hydrocortisone 200 mg, I.V. (Wycort injection)
4)
Heart failure may require digitalization (dose titration essential).
Tepid sponging, O2, inhilation, I.V. glucose infusion forms supportive
therapy.
Dose :- 80 µ curies/g of thyroid tissue, spaced for 2 doses in a 6 weeks
duration.
Uses :- 1.
Selected cases of hyperthyroidism
2.
Thyroid carcinoma
3.
To diagnose various thyroid disorders
4. Sex steroids
Side effects :- Radiation thyroiditis
Bone marrow depression
Subclinical or clinical hypothyroidism
Late reactions include thyroid carcinoma and leukemias
Contraindication : Pregnancy & lactation.
3.
(A) Female sex hormones
1. Oestrogens :- This hormone plays a vital role in development of female
reproductive system. All sex hormones have acetate as their precursor. The
formation of oestrogens is by ovarian follicles. During pregnancy oestrogens an
synthesized in large quantities by the placenta.
Iodide :-
Types of oestrogen :-
If administered in hyperthyroid patients, there is reduction of vascularity
and the swelling of gland. This response reaches to maximum in 10-15
days. High iodide content probably inhibits thyroid hormone release.
1)
Dose :- 300-600 mg may be used.
2)
Use :- To prepare hyperthyroid patients for surgery.
Thyrotoxic crises is a condition of thyrotoxicosis where there is marked
fever, sweating, tachycardia and CCF.
3)
Endocrines
106-A
Natural oestrogen:
1.
Oestradiol (Disecron Forte, Kesnicetin antiozena)
2.
Oesirone
3.
Oestriol.
Semi synthetic oestrogens:
1.
Ethinyloestradid
2.
Mesaranol (Ch'ulen, Orthonovin)
Synthetic oestrogens
106-B
Endocrines
1.
Diethyl stilbesterol
2.
Dienosterol
3.
Hexosterol
from pregnant mares urine. There are mixture of sodium estrone sulphate and
sodium equilin sulphate. It contains concomitant components such as 17
alpha estradiol, 17-betadihydro equilin.
Side effects :-
Indications
A)
In females:
●
Common symptom is nausea; which can be avoided by gradually
decreasing the dose of oestrogen. Anorexia, diarrhoea and oedema,
withdrawal bleeding can also occur.
Treatment of moderate to severe vasomotor symptoms associated with
menopause
●
Prevention of osteoporosis where the case controlled studies have shown
an approx. 60% reduction in hip and wrist fractures in women whose
estrogen replacement was begin with few years of menopause.
●
Treatment of vulvar and vaginal atrophy
●
Treatment of hypoestrogenism due to hypogonadism, castration or primary
ovarian failure
●
Treatment of breast cancer (for palliation only) in appropriately selected
women and men with metastatic disease.
●
Treatment of advanced androgen-dependent carcinoma of the prostate
(for palliation only).
B)
In males :
Gynaecomastia, decreased libido, impotency
Therapeutic implications:1)
During menopause or climecteric.
2)
Senile vaginitis.
3)
Dysmenorrhoea where the relief is obtained by inhibiting ovulation.
4)
Endometriosis.
5)
D.U.B. (Dysfunctional uterine bleeding).
6)
Osteoporosis.
7)
Acne, i.e. by decreasing gonadotropins and androgen secretion.
8)
Hirsiutism.
9)
To accelerate the epiphyseal closure in tall girls.
Dose
Conjugated estrogen therapy (Espauz) may be given continuously with no
interruption in therapy or in cyclical regimens (regimens such as 25 days on
the drug followed by 5 days of drug). Tablet of 0.625 mg strength is used and
the repeated checks on lab. functions is done every 3rd month.
10) Vulvovaginitis in children.
Contraindications
Conjugated Estrogens
Conjugated estrogen tablets for oral administration contain a mixture of
estrogens obtained from natural sources, occuring as sodium salts of water
soluble estrogen sulphate mixed with average composition of material derived
Endocrines
107-A
1.
Known of suspected pregnancy.
2.
Undiagnosed abnormal genital bleeding
3.
Known or suspected cancer of breast
107-B
Endocrines
4.
Acute thromboflebitis
i)
Population explosion.
5.
Patients hypersensitive to the ingredients
ii)
To ensure a good health of mother by way of spacing.
II. Progesterone :-
Types of oral contraceptives :-
It is secreted from corpus luteum during the second half of menstural
cycle and secretion begins just before ovulation. After third month of
pregnancy the placenta starts secreting this hormone.
A)
Regular Pills :
1.
Weakly oestrongenic but strongly progestenic containing ethinyl
oestradiol in low concentration and nor ethisterone in higher
concentration.
2.
Weakly progestenic but strongly oestrogenic containing mestranol
in high concentration and ethynodrel diacetate in low concentration.
Types of progesterone :1.
2.
17 alpha compounds:1.
Ethisterone (Menstrogen, Orasecron forte)
2.
Norgestrel (Ovral)
3.
Medroxyprogeslerone (Farlutal)
B) Mini pills : They contain progesterone as :-Nor ethindrone and Norgesterel.
C)
Post coital contraceptives:- They can be given within 72 hours of coitus.
Drugs like ethinyl oestradiol or diethyl stilbesterol are given in high doses
for 5 days. (Evalon)
D)
Depot I.M. preparations:" Medroxyprogesterone acetate 150 mg, can/be
given 3 or 6 monthly. (Empeea)
19 - Nortestosterones;1.
Norethisterone (Regestrone)
2.
Ethynodriol diacetate (Ovulen-50)
Therapeutic implications:1.
D.U.B. (Dysfunctional uterine bleeding)
Procedure to administer oral contraceptives :-
2.
Dysmenorrhoea.
i)
3.
Endometriosis
4.
Pre-menstrual tension.
5.
Threatened and habitual abortion.
Given from 5th to 25th day of menstrual cycle
ii) Sequential therapy :OestrogenGiven from 5th to 20th day
Oestrogen+Progestin
Given 21st to 25th.day
III. Oral contraceptives :-
iii)
These are used in order to control
Endocrines
Combination therapy :Oestrogen+Progestin
(Novelon)
108-A
Serial therapy is similar to sequential method but after 25th day, placebo
is given.
108-B
Endocrines
Mechanism of action of oral contraceptives :-
Warnings :-
1.
Oestrogens inhibit secretion of follicular stimulating hormone, thus supressing ovulation. Progestins inhibits the release of leutenising hormone.
Undiagnosied vaginal bleeding
Pre-existing diseases as epilepsy, migraine, and asthma
2.
Stimulation of prolactin releasing factor.
3.
Cervical mucus becomes thick tenacious and less alkaline acting as
cervical barrier.
Uses of oral contraceptives :-
4.
Motility of fallopian tubes is altered.
5.
Endometrium becomes thin and hence not suitable for implantation
Side effects
1.
When pregnancy is to be avoided.
a)
Fertile females
b)
during rape or incest
2.
Endometriosis.
3.
Precocious puberty.
A) Immediate :
B) Gradual
4.
Primary amenorrhoea.
1. Mild:Nausea, vomiting, oedema,
psychological changes
Retinal thrombosis,
Alopecia.
Vaginal and uterine carcinomas
5.
Primary dysmenorrhoea.
6.
Dysfunctional uterine bleeding (D.U.B.).
Advantages :-
2. Moderate :Breakthrough bleeding, acne,
ureter dilatation
3. Severe:Thromboembolism,
hypertension,
cholestatic jaundice
1.
Dependable.
2.
Coitally independant.
(B) Male sex hormones
Sites of production :i)
Interstitial cells of Leydig of testis.
ii)
Adrenal cortex and ovary in lesser amounts.
Contraindications :Thromboembolism
Carcinoma of breast and genietals
Liver damage
Preparations :1.
Endocrines
109-A
Testosterone (Sustanon, Testanon) (25-50 mgl.M. daily or weekly)
109-B
Endocrines
2.
Methyl testosterone (25 mg O.D., sublingual)
3.
Refractory anaemias.
3.
Dromosterone
4.
Pitutary dwarfs.
5.
Certain cases of oesteoporosis.
Side effects :-
Precautions :-
(A) Males:
1.
Early closure of epiphysis
2.
Semiferous tubule degeneration
(B) Females :
1.
Increased libido
2.
Hirsuitism
Oedema
2.
Jaundice (Peliosis hepatitis)
Uses :1.
2.
3.
5.
Anabolic steroids:
These are synthetic derivatives of testosterone having a greater effect on
protein anabolism. Commonly abused drug by athelets but is ineffective
in persons having normal testicular functions. If used by females invariably
leads to virilising side effects.
2.
Acute and chronic renal failure.
Endocrines
Large doses are harmful and the total dose should not exceed 50 mg.
c)
Not to be used in hepatic diseases.
1.
Methandienone (Anabolex) (2-5 mg, O.D. B.I.D.) oral.
2.
Nandrolone
injectable.
3.
Stanozolol (Stromba, Menabol) (2 mg, T.D.S. before meals) oral.
(Decadurabolin)
1.
Pregnancy.
2.
Carcinoma of prostrate.
(10-50 mg once or twice weekly)
5. Diabetes mellitus
Diabetes mellitus is a metabolic disorder characterised by :a)
110-A
Hyperglycemia due to deranged secretion of proinsulins and insulin and
possibly of glucagon.
b)
Situational uses :In chronic illness so as to accelerate the rebuilding of tissues.
b)
Contraindications :-
Primary hypogonadism
Senile orteoporosis
Carcinoma breast in premenopausal women
1.
Always to be given for short time and then can be repeated.
Preparations :-
Other effects include :1.
a)
Vascular derangements characterised by the basement membrane
transformations of capillaries.
110-B
Endocrines
c)
Complications involving the glomerulus, rentina and peripheral nervous
system leading to renal failure, blindness and polyneurophathies.
d)
It can be inherited.
Drug Used
Hormone :e.g. Insulin
Mean Plasma Glucose (MPG) is a calculation that related % A1c (GHB)
levels to plasma glucose levels. Many diabetes patients now perform selfmonitoring of BG (SMBG) in the home setting, understanding plasma calibrated
meters. The relationship between A1c and PG can be useful in setting goals for
day-to-day testing.
How does A1c related to MPG ? The largest set of clinical data relating PG
to A1c comes from the DCCT. The study subjects performed quarterly, 24-hr, 7point capillary-blood glucose profiles. Blood samples were collected by subjects
in the home setting, pre-meal, 90 minutes post-meal, and at bed-time.
Analysis of data : Mean A1c (GHB) and PG were calculated for each study
subject (n=1439). Results demonstrated a linear relationship between A1c (GHB)
and PG:
Drug Used
(MPG = (35.6 x GHB) - 77.3) with a Pearson correlation coefficient (r) of 0.82
Hormone :e.g. Insulin
In summary, each 1% change in GHB represents a change of approximately
35 mg/dl MPG or 2.0 mmol/l. Note that this relationship applies only to A1c
(GHB) methods certified traceable to the DCCT reference (NGCP certified
methods), and that it is based on overall averages and may vary slightly in
dividuals.
111-A
Synthetic drugs :e.g. sulfonylureas (Gliclazide (Glycor),
Glipizide (Glynase), Glimepride
(Amaryl), Glibenclamide), (Daonil)
biguanides (Metformin), (Glyciphage)
Acarbose (Glucobay)
Glitazones (Pioglitazone) (Pioz)
Repaglenide
111-B
Synthetic drugs :e.g. sulfonylureas
biguanides
Acarbose
Glitazones
Repaglenide
Insulin
A . Insulin preparations :
It is a polypeptide with a molecular weight of 6000 released from the beta cells
of the pancreas. It has two amino acid chains which are linked to each other by
disulfide bridges.
Type
Short acting
Source 1) Natural :- Extracted from pancreas of pig or cattle
2) Synthetic :- Recombinant D.N.A. technique using E.Coli bacteria.
Intermediate
acting
Drugs affecting release of insulin
Onset of
action (hr.)
Peak activity
(hr.)
Duration of
action (hr.)
Time of
injection (hr.)
0.1 – 1
2–4
4–6
Before breakfast
Semilente
1–2
3–6
8 – 12
Before breakfast
Lente
3–4
10 – 16
20 – 24
Before dinner
Neutral Protamine
Hegedron - NPH
3-4
10 – 16
20 – 24
Before dinner
Preparation
Regular
14- 20
32
Release inhibitors
Protamine Zinc Insulin
– PZI
6–8
Release stimulators
Any part of the
day
1. Glucose
1. Catecholamines (e.g. Adrenaline)
Ultra Lente
6–8
14- 20
32
Any part of the
day
2. Glucagon
2. Diazoxide (Antihypertensive)
0.5
2 – 10
12 - 18
3. Sulfonylureas
3. Phenytoin (Antiepileptic)
4. Anti retroviral
4. Indinavir
To have the
normal insulin
release pattern
during the day
Long acting
Biphasic
Actions :1.
Facilitate entry of glucose and other sugars into the cells.
2.
Prevents the conversion of protein into glucose.
3.
Accelerates the transfer of amino acids.
4.
Stimulate lipogenesis i.e. synthesis of triglycerides in increased.
Pre-mixed (NPH +
Short acting)
Insulin administration : Most of the insulins used in India are available in
concentration of 40 units / ml and these are called U-40. In other countries,
especially US insulin is used as U-100, even U-80 insulins are available in few
countries.
Calculation of dose : The initial dose can be approx. 0.5 units / kg body weight
for type 1 diabetics and 0.2 units / kg body weight for type 2 diabetics. The
other approx. method to estimate the dose of intermediate acting insulin is
given as :
Fasting blood glucose -
50
10
B . Newer insulins
The purification of conventional insulin by iron exchange chromatography results
Endocrines
112-A
112-B
Endocrines
in monocomponent insulin, which has reduced antigenicity due to contaminants.
a)
Juvenile diabetics
1.
b)
Diabetic coma
Human short-acting insulin : Actrapid (Human), Huminsulin-R, Insuman
Rapid and Rapidica Human.
2.
Human Intermediate acting insulin : Monotard (Human), Huminsulin-L/N,
Insuman Basal, Zinulin Human
3.
Pre-mixed human insulins - Mixtard Human, Huminsulin and Insuman (in
various ratios of regular and NPH), Rapimix Human
2.
Primary or secondary failure to oral antihyperglycemics
3.
Diabetics undergoing surgery
4.
Myocardial infarction (to observe the patency of vagotomy)
5.
Schizophrenia (to induce insulin coma)
Indications for newer insulins :
Early insulin initiation in type 2 diabetes
1.
Insulin allergy
Insulin therapy in type 2 diabetes should be given to the following clinical groups:
2.
Immunogenic insulin resistance (IIR)
1.
3.
Insulin lipodystrophy
Patients having a recent onset of diabetes with high postprandial blood
glucose levels
4.
Pregnant diabetic patients
2.
Resistant diabetics not responding to various oral medications
5.
Diabetic patients requiring temporary insulin therapy while undergoing
stress (surgery, illness, etc.)
3.
6.
Diabetic patients with angiopathies and renal damage
7.
Preferably all newly diagnosed insulin dependent diabetics
8.
Insulin antibodies and immune complexes interfere with measurement of
circulating plasma insulin levels. Use of the newer insulins eliminates
these complexes and thus permits a more accurate assessment of insulin
level, and thus, aids in the determination of an appropriate insulin dosage
Insulin should be started as early as possible in type 2 diabetics as per
consensus guidelines, when a patient has been given a trial of oral
antidiabetic drugs, fasting plasma glucose > 140 mg/dl and postprandial
plasma glucose > 180 mg/dl it is time to start insulin. The insulin is
initiated with 0.2 units / kg /day of premix insulin (30% short acting and
70% intermediate acting) and then the doses are titrated based on the
clinical judgement. The insulin should be continued at a dose that provides
a stable, fasting plasma glucose between 80-120 mg/dl.
9.
Diabetic vegetarians and diabetics who have 'religious reservations' to the
use of insulin of animal origin.
Indications for regular insulins :
1.
Problems with insulin therapy :
1.
Immunological : Insulin allergy, insulin lipodystrophy and insulin resistance
2.
Non-immunological : Hypoglycemia, insulin oedema which is due to fluid
accumulation resulting from ADH and sodium retaining action of insulin
Type 1 diabetes mellitus
Endocrines
113-A
113-B
Endocrines
2 mg TID
(Calcinol, Kalzana, Ossopan)
Miglitol
Total calcium content of body is 1-1.2 gm and 99% is in skeletal form. 10 mg%
is its blood concentration. It exists in two forms:
1-2 U/kg/day
Non-diffusable which is protein bound.
2.
Diffusable, a part of which is complexed with phosphates and bi carbonates.
1.
Ossification of bone and formation of teeth.
2.
Maintenance of integrity of intracellular cement
3.
To maintain cell selective permeability.
4.
In control of neuronal excitability.
5.
Control of rhythm, tonicity and contractility of heart, and tonicity of blood
vessels.
6.
Control of contraction of skeletal and smooth muscles.
Calcium metabolism is regulated by parathormone (PTH) which raises blood
calcium by increasing bone resorption, calcium reabsorption from kidneys and
by stimulating conversion of Vit D to its active metabolites. Calcitonin lowers
blood calcium by antagonizing the actions of PTH. It inhibits bone resorption.
Vit D metabolites raise plasma calcium concentration by promoting absorption
from gastrointestinal tract.
Cause of hypocalcemia are :-
Maximum
effective dose
proper
exercise for
30 min.
1.
The main functions of calcium are:
500 mg BID
25 – 50 mg TID
Acarbose;
25 mg TID
Pioglitazone
15 mg- 30 mg OD
(1) Calcium :-
½ mg
max or
1-2
double to 8
increase
mgstarting
for
Glimepride
None
weight gain,
oedema, anemia
None or decrease
Minimal
decrease
Decrease
modest
Decrease
TGL
Minimal
decrease
None
None
Increase
None
HDL
Minimal
decrease
None
Increase
Minimal increase
None
Increase
Decrease
None or increase
Decrease
Decrease
Modest decrease
Modest decrease
None
Minimal
decrease
Increase
Increase
Minimal decrease
Variable
LDL
Insulin
+1
+1 to 13
0 to –10
0 to –6
+3
Weight changes
(lb/year)
+1
+3
Yes
BID to QID
QD or BID
Rare
No
BID to TID
BID or TID
Rare
Yes
QD to TID
Yes
QD to continuous
Rare
Continuous
Dosing interval
Hypoglycemia
Good
Excellent
Good
Good
Moderate
Excellent
Good
Good
Good
Good
Excellent
Excellent
Good
Good
Postprandial
Fasting effect
β-cell
1-2%
0.5-2%
Muscle
Gut
0.5-1%
1-2%
Liver
β-cell
1-2%
1->2%
β-cell supplement
Variable
Muscle / Fat
Target tissue
HbA1c
monotherapy
Repaglinide
Thiazola
dinediones
“Glitazones”
α-Gluco
sidase inhibitors
Metformin
Sulfonylurea
Insulins
Lifestyle
Parameter
Comparisons of therapies for type 2 diabetes
6. Calcium, parathormone, calcitonin, vitamin D
114-A
1.
Malabsorption and inadequate intake.
2.
Hypoparathyroidism
3.
Chronic renal failure with hyperphosphatemia.
114-B
4.
Acute pancreatitis
Therapy indudes:-
5.
Ingestion of Na+ flouride which forms insoluble salts.
1.
Surgical removal of diseased gland.
6.
In hypocalcaemic state there is tetany, neuromuscular excitability, laryngospasm, muscle cramps and convulsions.
2.
I.V. saline to correct dehydration
3.
I.V. dibasic sodium phosphate to promote calcium excretion.
4.
E.D.T.A. as an emergency procedure.
5.
Mithramycin a cytotoxic agent
(Dose :- 25 µg/Kg I.V. slowly)
6.
Calcitonin.
7.
Glucocorticoids.
8.
Haemodialysis as last resort.
Treatment :Calcium gluconate as 1 g tablets or as 10% injection, I.V. slowly.
Hypercalcemic states results due to :1.
Hyperparathyroidism
2.
Milk-alkali syndrome
3.
Hyperthyroidism
Hypoparathyroidism :-
4.
Sarcoidosis and renal neoplasms
This may be due to:
Alternative drugs
1. Accidental removal of gland during thyroid surgery.
Treatment :-
2. Interrupted vascular supply.
Calcitonin or E.D.T.A. can be given.
3. Idiopathic.
(2) Parathormone:
Its a large polypeptide. The release of hormone from parathyroid glands is
regulated by the concentration of calcium in blood. Release is stimulated by
fall and inhibited by a rise in the ionized calcium levels of plasma.
Hyperparathyroidism :This may be due to :
The symptoms are basically due to hypocalcemia and finally result into tetany.
Therapy is aimed to raise the calcium levels by adopting following measures:
1.
Calcium gluconate 10-30 ml, 10% in 500 ml of isotonic saline.
2.
Parathyroid injection.
3.
Vitamin D.
4.
Calcium rich and phosphate poor diet.
(3) Calcitonin :-
Diffuse hyperplasia, adenoma and carcinoma of gland.
It is a small polypeptide, synthesized and secreted by the parafollicular cells of
the thyroid gland. The main action of calcitonin is to produce hypocalcemia by
Endocrines
115-A
115-B
Endocrines
inhibiting bone resorption and by promoting the urinary excretion of calcium. It
thus antagonizes the actions of PTH. The use of calcitonin in hypercalcemic
states is limited due to its short duration of action.
Dose :- 400 units to be dissolved in gelatin solution and injected I.M. or S.C.
(4) Vitamin D :The two sterols of greater therapeutic importance are ergocalciferol Vit D, and
cholecalciferol Vitamin D. Vitamin D occurs in fish liver oils, eggs and butter.
Sunlight is a good source as 7-Dehydrocholesterol is converted to cholecalciferol.
It undergoes 25-hydroxylation to form 25-OH calcifediol and later 1-25(OH)2,
calcitriol which are active compounds. The primary action of Vit D is to increase
the absorption of calcium and phosphorous from the intestine. Recently, Vitamin
D is considered as a hormone.
7. Drug acting on uterus
(A) Uterine stimulants :- "Ecbolics"
Therapeutic
Drug
Actions
Dose and
Side effects
Use
1. Oxytocin
(Pitocin,
synthocinon)
1. It increases force
and frequency of
uterine contractions.
2. Oestrogen can
can sensitize
uterus to the action
of oxytocin.
3. Fundus and body
of uterus are contracted while the
lower segment is
relaxed.
1. Unit = 2 µg of
pure hormone
Dose : 2.5 units
I.M.
Side effects :1. Water intoxication
2. Uterine contracture and rupture
of uterus.
3. Fall in the blood
pressure.
1. Indication of labour
2. Uterine inertia
3. Post partum
haemorrhage
4. Mid trimester
abortion.
2. Erogmetrine
and methyl
ergometrine
(Ingagen-M)
1. The force, frequency
and duration of
contraction is
increased
2. Pregnant uterus
is more sensitive
3. It involves the lower
segment stimulation
also
Erogmetrine 0.25
mg tablets and
0.5 mg/ml injectable
Side effects :1. Rise in blood
pressure
2. Milk secretion
as prolactin
release in
inhibited
1. Prophylactic as
well as therapeutic
control of post
partum haemorrhage.
2. Prevents uterine
atony
3. To have normal
uterine involution.
3. Dinoprostone
eg PGE2
Dinoprost
eg. PGF2a
Prostaglandins
contract human
uterus and soften
cervix making it
more compliant
PGE2 as 20 mg
1. Induction of labour.
vaginal suppository 2. Cervical priming
PGF2a 20 mg injec3. Intravaginal
Side Effects :administration for
1. Watery diarrhoea.
causing abortion
2. Uterine cramps
in first trimester.
3. Fall in blood
pressure
The deficiency states are rickets in children and osteomalacia in adults.
Endocrines
116-A
116-B
Endocrines
(B) Uterine relaxants:- "Tocolytics"
9. Danazaol (Danogen, Ladogal)
Features :-
Drug
Actions
Dose and
Side effects
Use
1. Salbutamol
(Asthalin)
These drugs reduce
uterine motility
4-8 mg thrice daily.
1. Prevention of
premature labour
2. Magnesium
Sulphate
6 mg as 10%
solution slowly
I.V.
2. Threatened
abortion.
3. Nifedipine
20 mg twice daily
daily
Except salbutamol
the other drugs
have variable effects
in relaxing uterine
tone.
4. Ibuprofen
1.
Testosterone derivative having androgenic, anabolic and progestational
actions.
2.
The dose ranges from 200 to 800 mg/day.
3.
Side effects are complete amenorrhoea, acne, hirsuitism, weight gain
and flushes.
4.
Uses :-
200 mg thrice daily
5. Progestrone
6. Isoxsuprine
(Duvadilan)
10 mg oral / I.M.
O.D. or B.D.
(C) Ovulating agents
Endometriosis.
2.
Chronic cystic mastitis.
3.
Menorrhagia.
4.
Infertility due to cornual block.
5.
Gynaecomastia.
6.
Hereditary complement (C3 mediated) angioedema.
10. Raloxifene (Evista, Fiona)
Drug
Actions
Dose and
Side effects
Use
1. Clomiphene
citrate
(Fertotab,
Fertomid)
50 mg oral, starting
from the 5th day of
menstrual cycle. If no
ovulation occurs
100 mg oral dose is
repeated in the next
cycle
Ovarian enlargement, hot flushes,
urinary urgency,
multiple pregnancy.
2. Human
menopausal
gonadotrophin
5000-10,000 units
I.M. for 3 days.
Hypertermia,
follicular cysts,
multiple prenancy
1. Induction of
ovulation in
anovulatory females
2. Oliogospermia and
importance in males.
3. Post pill amenorrhoea.
4. Polycystic ovarian
disease.
Induction of ovulation
promotion the production of gonadotrophins
Endocrines
1.
117-A
Mechanism of action : Raloxifene is the selective estrogen receptor modulator,
which improves bone mineral density so as to prevent spontaneous fractures in
women.
Indications : Prevention and treatment of postmenopausal osteoporosis in women
so as to reduce the incidence of fractures
Benefits of Raloxifene :
●
Significant reduction of LDL , TGL & fibrinogen levels
●
Reduces incidence of cardiac problems
●
Reduces incidence of breast and endometrial cancer
117-B
Endocrines
Side effects: hot flushes, vertigo, peripheral oedema and rarely
thromboembolism
Dose : 60mg tablet, once a day
The non-steroidal anti-inflammatory drugs act by inhibiting the cyclooxygenase
enzyme whereas steroids inhibits phospholipase A2, an immediate precursor
of arachidonic acid.
Uses :-
11. Corticosteroids
1.
These are the hormones of adrenal cortex. The zona glomerulosa layer secretes
aldosterone, whereas zona reticularis layer secretes corticosterone.
Aldosterone is a mineralcorticoid which has sodium retaining and potassium
depleting properties. Angiotensin is a stimulus for aldosterone production.
(a)
(b)
Compounds having aldosterone like activity are : Fludrocorstisone (0.05
mg to 0.5 mg/day) and deoxycorticosterone. These are therapeutically
used in conditions like Chronic primary adrenoscortical insufficiency and
Congenital adrenal hyperplasia.
2.
Spironolactone, which is used as a diuretic.
2.
Amphenone B
3.
Mitotane
4.
Metyrapone
5.
Aminogluthimide
(a)
Acute adrenal insufficiency
(b)
Addison's disease
(c)
Chronic adrenal hyperplasia.
Nonendocrinal uses :(a)
(b)
Bone disorders :
Osteoarthritis, ankylosing spondylitis, gouty arthritis and rheumatoid
arthritis.
(c)
Bronchial asthma
(d)
Pulmonary fibrosis (Interstitial oedema)
(e)
Cerebral oedema
(f)
Intestinal disease :
The glucocorticoids are :1.
Hydrocortisone (Wycort, Efcorlin) 50-100 mg i.v. infusion
2.
Cortisone (Corlin) 20-100 mg/day, oral
3.
Prednisolone (Deltacorti) 5-60 mg/day oral
4.
Dexamethasone (Decodron) 0.5-5 mg/day,
oral/I.M./I.V.
Betamethasone (Betnesol).
5.
Ulcerative colitis, Chron's disease and coeliac disease.
3.
Endocrines
Autoimmune diseases :
S.L.E., polyarteritis nodosa, dermatomyositis and nephrotic
syndrome.
The drugs having antagonistic activity to aldosterone are :
1.
Replacement therapy :-
118-A
(g)
Type I and Type III hypersentive reactions.
(h)
Eye disorders :
Keratitis, iridocyclitis and allergic conjunctivitis.
(i)
Malignancies :
Acute lymphoid leukemia and Hodgkin's disease.
Life-saving uses of glucorticoids :-
118-B
Endocrines
(1)
Acute adrenal insufficiency
(2)
Status asthmaticus
(3)
Side effects :
Acute episode of collagen disease
(A) Immediate :
(Within few months)
(B) Delayed
(More than 6 months)
(4)
Septicaemic shock
1. Weight gain
(5)
Pemphigus (Acute exacerbation)
1. Suppression of the pitutary
adrenal axis.
(6)
Nephrotic syndrome
2. Rise in blood pressure and
moon
2. Supraclavicular hump and
blood Sugar moon face
3. Susceptibility to non-specific
infections
3. Posterior subcapsular cataract
4. Delayed healing of wounds
4. Glaucoma
5. Psychosis and mild euphoria
5. Growth retardation
4.
In case of organ transplants and dermal allograft.
5.
To test adrenal pituitary axis function by performing dexamethasone
suppression test. Similar test with certain variations is performed to
establish diagnosis of endogenous depression.
Contraindications :(1)
Herpes simplex keratitis affecting eyeball.
(2)
Epilepsy and episode
(3)
Hypertensive episode
(4)
Diabetes mellitus
(5)
Peptic ulcer disease
(6)
Fungal infections
6. Osteoporosis, specially
involving the vertebral process.
7. Suppression of immunity.
Endocrines
119-A
119-B
Endocrines
Comparison of the Topical Steroids
Say true or false
Features
Clobetasol
Fluocinolone
Betamethason
e
Fluticasone
Mometasone
Administration
Twice daily
Twice or four
times daily
Twice daily
Twice daily
Once a day
Potency
Potent
Potent
Potent
Very potent
Very potent
Hpoyhalamic
pitutary axis
suppression &
skin atrophy
++
+++
++
+++
++
Pediatric
usage
Under 12 years
not
recommended
Not
recommende
d under 6
years
Not
recommended
under 12 years
Under 6 years
not
recommended
Under 12
years not
recommended
Atopic dermatitis,
Psoriasis , lichen
planus, stasis
dermatitis ,
photodermatitis
Also used
Also used
Also used
Also used
Uses
1.
Uses of the radioactive iodine are hyperthyroidism, thyroid carcinoma and
to diagnose various thyroid disorders ?
2.
The common side effect of oral contraceptive is thromboembolism ?
3.
Raloxifene is used in osteoporosis in males ?
4.
Anabolic steroids are used in refractory anemia ?
5.
Newer insulins have replaced the animal insulins ?
6.
The common side effects of insulins is hyperglycemia ?
7.
Side effects of pioglitazone are weight gain & anemia ?
8.
Acarbose is the first alpha glucosidase inhibitor used in therapeutics ?
9.
Treatment of hypercalcemic states is with Calcitonin & EDTA ?
10. Steroids should be used anytime when required ?
Answers
1.
True
2.
False
3.
False
4.
True
5.
False
6.
False
7.
True
8.
True
9.
True
10. False
Endocrines
120-A
120-B
Endocrines
Factors determining establishment of infection are :
CHEMOTHERAPY
11
INFECTION
Q1.
What is infection ?
A1.
Infection is the invasion and multiplication of an organism in the tissue of
a host.
Q2.
Mention the history of infection.
A2.
The concept of infection is present since biblical times. The connection
between the disease and micro-organisms was established by Louis
Pasteur. Further the concept that micro-organisms are responsible for
infection was established by Robert Koch.
Q3.
How infection occurs in man ?
A3.
Infections are preceded by colonisation on body surfaces, wound or hollow
viscera with infecting agents. The agent first colonizes at the site of
entry. Success there depends on quantity of large infecting dose.
Subsequent proliferation at site of entry increases opportunity for tissue
invasion. Pathogens can cause infection either by direct cell toxicity to
host or by production of toxic substances called toxins. For the
occurrence of pathogen has to overcome the host defence mechanisms.
Most infections present as primary infection at the site of entry, but it
can also be present as a generalised infection if spread of infection
occurred.
Micro-organisms causing infection are classified as :
Bacteria, Fungi, Viruses, Protozoa, Chlaymydia, Ricketsias
Chemotherapy
121-A
1)
Physical condition and resistance of host.
2)
Number of organisms present.
3)
Virulence of organisms.
4)
Therapy received.
Q4.
What are the methods for transmission of infection ?
A4.
1)
Contact - Direct or Indirect.
2)
Airborne
3)
Foodborne
4)
Inoculation
Q5.
What is Virulence ?
A5.
A wide variety, bacteria, fungi and protozoa, have been demonstrated to
infect humans. Virulence is the potential of an organism to produce
disease. The ability of a specific pathogen to cause disease depends
upon the interaction between virulence and defense mechanisms of host.
Organisms with low virulence can infect when immunity of host is low
and it is called opportunistic infection.
Q6.
What is the reaction of human body to infection ?
A6.
Human body reacts to infection by mobilizing the cells with phagocyctic
action (such as Polymorphonuclear cells, Macrophages or Natural
Killer cells) which engulf invading micro-organisms or any other foreign
body and destroys them.
Q7.
What are Polymorphonuclear cells ?
A7.
When infection occurs (PMN) Polymorpho nuclear cells (mainly
121-B
Chemotherapy
neutrophils) are released in large numbers from bone marrow - PMN
then cross the blood vessel and then migrate to the site of infection and
engulf the pathogen. The ingested pathogen is then killed by specific
microbicidal activities within PMN.
b)
If the bacterial cells appear to be red in colour due to safrin dye
they are said to be gram negative. The gram negative bacteria are
not stained by crystal violet.
Q12. What are the important differences between the cell wall of Gram
positive and Gram negative bacteria ?
Q8.
What are Macrophages ?
A8.
The monocytes (type of WBC) which have phagocytic action are termed
Macrophages.
There are specialized blood cell which circulate for short time in blood
and then establish residency in organs such as spleen, liver, lung and
play a role in removal of pathogen from blood stream. They have similar
microbicidal activities as PMN.
Q9.
What are antibodies ?
A9.
Antibodies are types of plasma proteins. The major plasma proteins
present in humans are albumin, globulin and fibrinogen. Globulins are
further divided into b and gamma globulins. Gamma globulins are also
called immunoglobulins. These immunoglobulins are of five distinct
classes viz., IgG, IgA, IgD and IgE. Antibodies can bind to microbial
antigens.
A12.
Features
Gram Positive Gram negative
Thickness
Thicker
Thinner
Sulphur containing amino
Thicker
Present
Q13. What are the different shapes of bacteria ?
A13. 1)
Cocci
-
spherical or oval
2)
Bacilli
-
red shaped
Q14. What is the classification of bacteria and what diseases are caused
by them ?
A14.
Gram-Postive Cocci
Bacteremia
Abscesses
Endocarditis
Q10. How bacteria are classified ?
Staphylococcus aureus
A10. The most common way of classifying bacteria is by using Gram staining
method. Using this technique the bacteria are classified into Gram
positive bacteria and Gram negative bacteria.
If the bacterial cells appear blue in colour due to crystal violet dye
they are said to be gram positive.
Chemotherapy
122-A
Pneumonia
Meningitis
Osteomyelitis
Cellulitis
Pharyngitis
Scarlet fever
Q11. With gram staining what colour the bacteria acquires ?
A11. a)
Diseases
Streptococcus pyogenes
122-B
Otitis media, sinusitis
Cellulitis
Chemotherapy
Erysipelas
Pneumonia
Bacteremia
Pseudomonas aeruginosa
Urinary tract infections
Pneumonia
Bacteremia
Streptococcus (viridans group)
Endocarditis
Bacteremia
Klebsiella pneumoniae
Streptococcus faecalis
Endocarditis
Urinary tract infection
Pneumonia
Otitis media
Sinusitis
Haemophilus influenzae
Otitis media
Sinusitis
Bronchitis
Epiglottitis
Pneumonia
Meningitis
Salmonettosis
Typhoid fever
Paratyphoid fever
Bacteremia
Shigellosis
Acute gastroenteritis
Gram - Negative Bacilli
Diseases
Acinobacter
Various nosocomial infection
Haemophilus ducreyi
Chancroi
Cholera
Gram Negative
Diseases
Neisseria gonorrhoea
Genital
Infections
Arthritis - dermatitis
Neisseria meningitidi
(meningococcus)
Meningitis
Bacteremia
Gram Negative
Diseases
Corynebacerium
diphtheriae
Pharyngitis
Laryngotracheitis
Pneumonia
Carrier state
Clostridium perfringens
Gas gangrene
Vibrio cholerae
Clostridium tetani
Tetanus
Campylobacter jejuni /
Helicobacterjejuni Diarrhoea
Gram - Negative Bacilli
Diseases
Escherichia coli
Urinary tract infection
Other infections (eg. LRTI)
Bacteroides species
(oral, pharyngeal)
Bacteremia
Enterobacter aerogenes
Urinary tract and other infections
Proteus mirabilis
Urinary tract and other infections
Chemotherapy
123-A
123-B
Sinusitis
Brain abscess
Lung abscess
Intra-abdominal abscess
Empyema
Bacteremia
Chemotherapy
Endocarditis
6)
Splenomegaly
:
Spleen can be enlarged.
Legionella pneumophila
Legionnaires disease
7)
G.I. upset
:
Nausea, vomiting, loose motions and loss
of appetite.
Acid - Fast Bacilli
Diseases
Mycobacterium tuberculosis
Pulmonary tuberculosis
Q16. What is the consequence of infections ?
Biliary, renal, meningeal, and other
tuberculous infections
A16. 1)
Eradication of infection
: The infection is eradicated with
Resolution) or without treatment,
depending upon the severity of infection
and host defence.
2)
Chronic infection
: Infection persisting more than 3 weeks.
Mycobacterium leprae
Leprosy
Miscellaneous Microbes
Diseases
Mycoplasma pneumoniae
Atypical pneumonia
Chlamydia trachomatis
(Types L1, L2 and L3)
Lymphogranuloma venereum
3)
Carrier state
Trachoma
Inclusion conjunctivitis
Nonspecific urethritis
: Prolonged shedding of infective agent
via stool, sputum etc. and this is called
as the carrier state.
4)
Latent infection
: An infection which is not clinically
evident but still persists in host tissue
in dormant state. Reactivation of this
will again lead to infection.
Pneumocystis carinii
Pneumonia in imunocompromised
host, common in patients with
AIDS.
Q15. What are the clinical features of infection ?
Q17. What are the common Lower Respiratory Tract Infections and their
features ?
A15. 1)
Fever
:
Fever is invariably present in infection
A17. Respiratory tract infections :
2)
Chills
:
Patient is shivering
3)
Myalgia
:
Generalised muscle ache
4)
Photophobia
:
Inability to tolerate light
5)
Lymphadenopathy
:
Swelling of lymph glands. This is a
protective phenomenon to restrict the
spread of infection.
1)
Pneumonia :
It is defined as inflammation of the lungs with exudation (fluid
protection) and consolidation (hardening of portion of lung).
Common causative organisms are :
Chemotherapy
124-A
Streptococcus pneumoniae
124-B
(38%)
(16%)
Chemotherapy
b haemolytic streptococci
Staphylococci
2)
(6%)
(4%)
complaints of cough, fever, chills, expectoration of purulent material
(pus).
The patient complains of fever, cough with expectoration,
hemoptysis (blood in sputum), chest pain, breathlessness and
bodyache.
It can be primary or secondary, primary is mainly because aspiration
of vomitus in unconscious patient and secondary is due to bronchial
obstruction as with foreign body or malignancy.
Bronchopneumonia :
It is a condition in which there is inflammation and infection of lung
tissues including terminal and respiratory bronchioles. It is more
common in infants, young children as well as aged, debilitated
individuals.
Anaerobic bacteria
Klebsiella
Pneumococci
H. influenzae
Streptococci
5)
Streptococcus pneumoniae
Beta Haemolytic streptococci
Staphylococci
H. influenzae
Anaerobic bacteria
3)
It is a condition characterised by permanent and abnormal dilation
of one or more bronchi due to destruction of elastic bronchial walls.
It can be due to hereditary, congenital or mechanical factors, which
predisposes to infection. These patients are prone to get repeated
infections and present with chronic productive cough.
Empyema :
Empyema signifies presence of pus in pleural cavity. The most
common predisposing factors are : complications of pneumonia or
post operative contamination.
Staphylococci
Streptococci
Gram - ve organisms
4)
Q18. What are common Upper Respiratory Tract Infections and their
features ?
A18. Tonsilitis
Pharyngitis
Sinusitis
Laryngitis
Tracheatis
Otitis media
The upper respiratory tract infections are associated with fever, pain (due
to inflammation), production of exudates and sometimes the associated
complications can occur, such as the retro pharyngeal abscess if the
sore throat is left untreated.
Lung abscess :
It is a localised formation of pus in lung tissue. The patient
Chemotherapy
Bronchiectasis :
125-A
125-B
Chemotherapy
is caused by Salmonella typhi. Patients manifest with prolonged fever,
diarrhoea, etc. The major problems in therapy are the increasing incidence
Streptococcus (Pneumoniae, Beta haemolytic, Faecalis)
Staphylococcus (Aureus, Epidermidis)
H. influenzae
of resistance to conventional antibiotics, high frequency of relapse, high
incidence of side-effects and a more frequent occurrence of carrier state.
Bacillary dysentery is manifested by fever, passage of blood-stained
stools, crampy abdominal pain, etc.
Q19. What are the features of Urinary Tract Infections ?
A19. Urinary tract infection can be acute, chronic or recurrent. It can be either
lower urinary tract infection such as urethritis, cystitis and prostatitis or
it can be upper urinary tract infection such as pyelonephritis, nephritis or
pyelitis.
The efficacy of antibacterial therapy in therapy GI infection is of undoubted
value. The major problems encountered are :
E. Coli (75 - 80%)
Proteus
Klebsiella
Enterobacter
Serratia
Pseudomonas
N. gonorrhoea
Staphylococcus
Streptococus
2)
Bacillary dysentery by Shigella
3)
Diarrhoeas due to E. coli, Staphylococcus, Campylobacter
(Helicobacter), etc.
Antimicrobial resistance has developed to many agents and has
been progressively increasing.
3)
Clinical response to therapy has been unsatisfactory.
4)
Currently used antimicrobial agents disturbs the normal intestinal
flora, resulting in colonization and/or infection with resistant bacteria.
Meningits :
The patient presents with severe headache, vomiting, pain in neck
or back, rigors in children and sometimes convulsions.
The complications of meningitis are septicemia, arthritis, cerebral
oedema, myocarditis and acute circulatory failure.
Streptococci
Staphylococci
Pneumococci
H. influenzae
Mycobacterium tuberculosis
Typhoid is more a systemic infection than a gastrointestinal one which
Chemotherapy
2)
A21. 1)
A20. The major gastrointestinal infections are :
Typhoid by Salmonella typhi
No single agent is effective against all enteric bacterial pathogens.
Q21. What are the features of CNS infections ?
Q20. What are the features of Gastrointestinal infections ?
1)
1)
126-A
126-B
Chemotherapy
2)
Encephalitis :
Q23. What are the features of Bone & Joint infections ?
Acute inflammation of brain and spinal cord caused by viral infections.
There can be superadded bacterial infection which has to be
adequately treated by using a broad spectrum drug.
A23. 1)
Osteomyelitis :
It is an infection of bone in which bacteria invades the bone and
destroys it. The route of entry of organism is either by blood or
directly open wounds or fractures.
The patient presents with restlessness, stiff neck, puplillary changes
and sometimes inability to speak. The complications of
encephalitis are :
Staphylococcus
Salmonella
Pseudomonas
Anaerobic organisms
Parkinsonism, sleep disturbances, general intellectual impairment
and convulsions.
Q22. What are the features of infective endocarditis ?
Bone infections are difficult to treat and may become chronic.
Therefore, penetration of most antibiotics is not adequate, due to
poor vascular supply.
A22. Infective endocarditis is an illness caused by microbial infection of the
cardiac valves or myocardium. Acute bacterial endocarditis is caused
by virulen organisms and runs its course over days to weeks. Subacute
bacteria endocarditis is caused by organisms of low virulence and runs
its course over weeks or months. Sterile vegetations are labelled as
non-bacterial thrombotic endocarditis.
2)
Septic arthritis :
It is mostly pyogenic (pus forming) infection of the joint. The entry
usually is from blood but can occur directly following needly
aspiration procedure.
Signs of infection are fever, anaemia, clubbing of finger and toes,
splenomegaly and arthralgia.
Gonococci
E. coli
Salmonella
H. influenza
Pseudomonas
Streptococcus viridans
Streptococcus faecalis
Staphylococcus epidermidis
The complications of endocarditis are :
Acute valve perforation
Embolism
Renal failure
Chemotherapy
Q24. What are the features of Skin & Soft Tissue infections ?
A24. Skin and soft tissue infections are very common, most of which are
caused by Staphylococcus.
127-A
127-B
Chemotherapy
1)
2)
Cellulitis :
Acute inflammation of skin and subcutaneous tissue causing pain,
erythema, fever and regional lymph node enlargement.
E. coli
Chlamydia
Klebsiella
Mycoplasma
Pseudomonas
Group B haemolytic streptococci
Actinomyces
Entercococci
Staphylococci
Gonococci
PID may lead to sterility
Pyoderma :
Commonest bacterial skin infection associated with pus containing
vesicles in skin mostly found in children. It may be multiple. It most
commonly involves lower limbs and hands.
3)
Abscess :
Abscess is localised formation of pus which can be formed
anywhere in the body. It is extremely painful and may be associated
with fever and chills.
2)
4)
Gonorrhoea :
Infected burns :
It is commonest sexually transmitted disease caused by Neisseria
gonorrhoeae. In female it may manifest as urethritis, increased
vaginal discharge, andocervicitis, abnormal menstrual bleeding,
abdominal discomfort and salpingitis.
In patient with burns infection is the commonest major cause of
death. The problem with burns patient is that the wound is open
and rarely sterile.
Q26. What are the features of Intra-abdominal infections ?
E. coli
Klebsiella
Enterobacter
A26. Intra-abdominal infections may take several forms. Infections may be
within peritoneal cavity or outside peritoneal cavity.
1.
Inflammation of peritoneum as a result of contamination of peritoneal
cavity with micro-organisms. Infective peritonitis may be -
Q25. What are the features of Gynaecological infections ?
A25. 1)
Pelvic inflammatory disease (PID) :
The commonest gynaecological infections are salpingitis (infection
of the fallopian tube), endometritis (infection of uterus) or pelvic
inflammatory disease in which there is widespread inflammation of
pelvic organs through ascending infection from vagina of covering.
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Infective Peritonitis
128-A
128-B
a)
Primary
b)
Secondary in which primary focus is not within the peritoneum
e.g. : ruptured appendix organisms causing peritonitis are :
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3)
E. coli
S. Pneumoniae
Group A Streptococcus
Anaerobes
N. Gonorrhoeae
S. aureus
2.
Cholecystitis is an inflammation of gall bladder. It can be either
acute or chronic. It is usually associated with gall bladder stone.
E. coli, Klebsiella species
Streptococcus
Staphylococcus
Clostridium
Intra-abdominal abscess
a)
Visceral abscesses
These abscesses are located in various different organs such
as liver, spleen, pancreas, kidney, etc. The route of entry of
organism is blood borne but can be due to infection adjacent
to the organ.
Q27. What are the features of post surgical infections ?
A27. Post surgical infection is common and is a serious problem, which is
very commonly faced as surgery creates an ideal environment for the
lodgment and multiplication of bacteria. The post surgical infection can
invade host either from air (if the operation theater is not properly sterilized)
and instruments.
Staphylococcus, Streptococcus, E coli, Klebsiella, Enterobacter
and anaerobes such as Fusobactericum.
b)
Cholecystitis
Surgical prophylaxis :
The incidence of post surgical infections is very high. To avoid this,
treatment with antibiotics are started prior to surgery. This is called
surgical prophylaxis. The ideal antibiotic or antimicrobial should act
throughout the period of surgery so that the causative organisms are
adequately suppressed.
Intra - peritoneal abscess
Source of infection in intraperitoneal abscess can be either
primary peritonitis or appendicitis, biliary tract infection,
pancreatitis, abdominal surgery or penetrating wound.
Anaerobes (60-70%)
E. coli
Klebsiella
Enterobacter
Proteus, S. aureus and enterococci
Streptococcus spp.
Staphylococcus spp.
E. coli
Proteus spp.
Pseudomonas spp.
Chemotherapy
129-A
129-B
Chemotherapy
5)
Q28. How do the serious infections manifest ?
A28. 1)
Secondary infection
Septicemia
infection, a new organism sets up an
infection, it is called secondary infection.
A condition in which pathogenic organisms or their toxins circulate
in blood. There is systemic proliferation of organisms which can
result in organ or tissue destruction. Septicemia can cause septic
shock.
6)
Cross infection
: When in a patient already suffering from
an illness, an infection is set up from
another host or another external source it
is called cross infection.
7)
Focal or localised
: A condition where infection is localised to
well defined anatomic sites such as
appendix or tonsil.
8)
Nosocomial infection : Infection acquired by a patient during his
stay in the hospital which was not present
on admission.
Mortality due to septicaemia is very high and can lead to progressive
failure of target organs e.g. liver, kidney.
Patients with gram negative septicemia are more prone for metabolic
complications, such as acidosis or alkalosis which can be fatal.
2)
Infections in immunocompromised host
Patients who lack resistance to infection are called Immunocompromised hosts.
Major risk factors for the development of
Noscomial infection include :
Factors leading to immuno compromisation are congenital disorders,
acquired diseases (such as AIDS). They can also be induced due
to diabetes, patients on corticosteroid therapy, malignancy or
malnourishment.
Q29. What are the terms used commonly to discuss infection ?
A29. 1)
Host
: Host is one in whom the organism lodges
itself and multiples to cause infection.
2)
Normal flora
: Organisms normally present within the
body.
3)
Primary infection
: Initial infection with an organism in a host
is called primary infection.
4)
Re-infection
Chemotherapy
: Recurrence of an infection generally with
another organism or with a different strain
of the same organism.
130-A
: When in an infected host, whose
resistance is lowered by a pre-existing
130-B
a)
Invasive
procedures
instrumentation.
&
b)
Very young age and very old age.
c)
Surgical procedures especially
thoracic or abdominal surgery.
d)
Antibiotic misuse.
e)
Underlying conditions like diabetes
mellitus,
cancer
or
any
immunocompromised state.
f)
Poor nutritional status.
g)
Patients on prolonged corticosteroid
therapy.
Chemotherapy
9)
Iatrogenic infection
: It refers to infection resulting from
diagnostic, or therapeutic procedures.
10)
Exogenous infection
: When the source of infection is outside
the body of the host.
11)
Endogenous infection
: When the source of infection is within the
host.
12)
Mixed infection
: When infection is caused by two or more
(Polymicrobial) different organisms it is
called mixed infection. The mixed infection
is more commonly encountered in clinical
practice.
13)
Superinfection or Supra
infection
Pyaemia
: Is a condition where pyogenic bacteria
produce septicaemia with multiple
abscesses in internal organs such as
spleen, liver, kidney, etc.
19)
Opportunistic
: Infections in patients with infection
impaired host defences caused by
infectious agents that do not ordinarily
produce disease in healthy individuals.
Q30. What are the terms commonly used for the treatment of
infections ?
A30. 1)
: Normal flora of the gut exists in a state of
Suprainfection equilibrium. When this
balance is disturbed, such as by
antibiotics some organisms from normal
flora can overgrow and cause infection. This
is termed as superinfection or supra
infection.
14)
Pathogen
: Pathogen is an organism that is capable
of causing disease.
15)
Incubation period
: It is a period taken by a pathogen to
multiply and cause effects (infection) after
entering a host.
16)
Bacteraemia
: Circulation of a bacteria in the blood stream
is called bacteraemia.
17)
Septicaemia
: Is a condition where bacteria circulate and
multiply in the blood, form toxic products
which cause high swinging type fever.
Chemotherapy
18)
131-A
131-B
Chemotherapy
: Use of chemical substance (synthetic) to
treat an infectious process.
2)
Antibiotics
: Substances produced by micro-organisms
used to kill other micro-organisms in low
dilutions.
3)
Antimicrobials
: Any substance used to kill microbes.
4)
Bacteriostatic drug
: Bacteriostatic drug is the one which
inhibits growth of the bacteria but does not
kill it.
5)
Bactericidal drug
: Bactericidal drug is the one which kills the
bacteria particularly in multiplication phase.
6)
MIC
: Minimum Inhibitory Concentration (MIC) is
the minimum concentration required of a
drug to inhibit or kill the bacteria after 1824 hours of incubation.
Interpretation of
antimicrobial agent
: MIC values reflects the activity of the
antimicrobial agent. The effectiveness of
the microbial agent is inversely proportional
Chemotherapy
to the value of MIC. Lower the MIC value,
higher the efficacy of the antimicrobial
agent.
7)
8)
MBC
Antibacterial
Spectrum
MIC90
1)
: Minimal Bactericidal Concentration is the
lowest concentration of an antimicrobial
that sterilizes the medium or results in a
99.9% decline in bacterial numbers.
: It is the spectrum of bacteria which are
2)
susceptible to the antibacterial agent.
: It is the Minimum Inhibitory Concentration
required to inhibit the growth of 90%
bacteria of same strain and is nearly
equivalent MBC of an antimicrobial.
Mutational resistance :- It is the change in the code of genetic
material which leads to change of bacterial characteristics.
a)
Multistep mutations : Series of small step mutations lead to
it eg. B-lactams.
b)
Single step mutation : Where the resistance develops rapidly
as the single genetic loci is involved eg. Sulfonamides,
Streptomycin.
Plasmid mediated resistance : - The extrachromosomal bodies
in the bacteria are called plasmids. These plasmids contain R
factor which can transfer resistance.
Plasmid resistance is seen :
B-lactams
Aminoglycosides
Plasmid resistance is not seen with :
Quinolones (Ciprofloxacin)
Q31. What is inflammation ?
A31. Inflammation is a vascular and cellular response to any injury to the
tissues.
Injury could be caused due to trauma, micro-organisms by physical and
chemical factors.
Inflammation could be acute or chronic.
Inflammation could be specific or non-specific.
(Hence during infection, inflammation is mostly an important associated
phenomenon).
Q32. What is the bacterial resistance ?
A32. It is temporary or permanent capacity of an organism or its progeny to
remain viable or multiply even in presence of drug.
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132-A
132-B
Chemotherapy
A33.
Mutational Drug Resistance
A34. 1)
Chemotherapy
Plasmid Mediated Drug
Resistance
1 Resistance to one .
drug at a time
1 Simultaneous resistance to
multiple drugs.
2 Degree of resistance low.
2 Degree of resistance high.
3 Overcome by high drug
dosage.
3 High drug dosage are ineffective
4 Prevented by treatment
with combination of drugs.
4 It cannot be prevented with
combination of drugs.
5 Resistance does not
spread.
5 There is spread of resistance to
other cells.
6 Resistant mutants are .
usually metabolically
defective
6 Resistant mutants are
metabolically normal.
7 Virulence low.
7 Virulence not decreased.
Q34. Mention the history of infection control or briefly indicate the
chronology of the antimicrobial development ?
Paul Ehrlich discovered arsenical compounds 1910.
2)
Sulphonamides discovered in 1935.
3)
Penicillin discovered by Sir Alexander Fleming in 1940.
4)
Macrolides discovered by Mc Guire in 1952.
5)
Quinolones discovered by Sterling in 1971
6)
Oxazolidinediones (Linezolid) in 1996
133-A
133-B
IM / IV
3rd Generation
Cephalosporins
• Minocycline
• Doxycycline
100 - 200 mg
12 hrs.
1-2 gm / day PO qds.
100 mg 12 hrs.
IM / IV
2nd Generation
Cephalosporins
Tetracyclines
• Oxytetracycline
PO / IV
Dosage
Given Parenterally
1-4 gm / day
3-5 mg / kg / day
1 mg / kg / day
7.5 mg / kg / day
4 gm / day
1st Generation
Cephalosporins
Cephalosporins
Drug
Aminoglycosides
• Streptomycin
• Gentamycin
• Tobramycin
• Amikacin
• Neomycin
G -ve, aerobic
bacilli
Limited G + ve
spectrum
Spectrum
Nephrotoxicity
Ototoxicity
Neuromuscular
blockade
Side effects
Inhibit bacterial
IM / IV
30S ribosomal
inhibited.
Bacteriostatic
Chlamydia
Rickettsia
Broad spectrum
synthesis,
sub-unit G + ve, G - ve.
Cholestatic syndrome
Staining of teeth
protein Nephrotoxicity
Nephrotoxicity
By selectively inhibiting the Good G + ve
synthesis of mucopeptide in
the bacterial wall of
multiplying G bacteria Good against - ve modest Hypersensitivity,
(Bactericidal)
against G + ve.
rashes
antiabuse reaction.
Very less against + ve
Encephalopathy
Very good against - ve
Action on 30S
Ribosomal subunit
leading to abnormal
protein formation &
bacterial cell death.
Mechanism of Action
Q 35. What is the mechanism of action, dosage, spectrum and side-effects of the various
antimicrobials ?
Q33. What is the difference between mutational and plasmid mediated
drug resistance ?
Chemotherapy
Chemotherapy
134-A
134-B
Chemotherapy
PO / IV
• Cotrimoxazole
(contains
sulfamethoxazole
and trimethoprim
Ciprofloxacin
(Reference Standard)
• Quinolones
Erythromycin
Broad spectrum
Spectrum
Aplastic anaemia.
Grey baby syndrome
Side effects
Mechanism of action
Affects
protein
synthesis by inhibiting
50S ribosomal sub unit,
bacteriostatic
Wide spectrum
Spectrum
Gram positive cocci
H. influenzae
Corynebacterium
Chlamydial
Myco. pneumoniae
Mild GI side effects,
arthralgia
Side effects
Abdominal colic
diarrohea
Interferes with
Mainly aerobic
Urticaria
normal cell wall synthesis & G + ve organism
Bronchospams
function
& spirochaetes
Anaphylaxis
Bactericidal
Mainly aerobic G + ve Rashes (common)
organism spriochets
Arthralgia
Interferes with normal cell
wall synthesis & function
Mainly aerobic G + ve
organism spriochets
Bactericidal
Rashes (common)
Arthralgia
Interferes with normal cell Mainly aerobic
Diarrhoea
G + ve but also
Skin rashes
Bactericidal
• Proteus
• E. coli
Interferes with normal cell Mainly aerobic G + ve
Diarrhoea
Abdominal
but also
discomfort
• Proteus
Bactericidal
• E. coli
Allergy, nephro
Inhibits cell metabolism by Broad spectrum
toxicity & blood
inhibiting folic acid synthetase
& dihydrate reductase
dyscrasias
Affects protein
Synthesis by inhibiting
50S ribosomal sub unit,
bacteriostatic
Mechanism of action
Inhibits DNA gyrase or
PO / Infusion
500 mg twice daily topoisomerase II
after meals
250-500 mg QDS
parenteral
Dosage
PO
250 - 500 mg qds
• Amoxycillin
PO
PO / IM / IV
250 - 500 mg qds.
• Ampicillin
Drug
• Macrolides
500 mg 6 hrly.
6-20 million
units/d. IM/IV
125 - 500 mg
tds/qds
IM / IV not oral
2-4 gm / day
PO / IV
Dosage
• Cloxacillin
• Methiciline
• Penicillin V
Penicillins
• Penicillin G
Drug
Chloramphenicol
Q36. What should be the requirement of an ideal antimicrobial
agent ?
A36. 1)
9)
10) Instead of using antibacterial combinations in cases of mixed
infections, a single antibacterial drug is preferable with higher potency
and wider spectrum of activity.
The drug should be a broadspectrum anti-microbial agent;
The drug should have antibacterial activity to cover wide range of
micro- organisms.
2)
11) The drug should be well tolerated within the therapeutic range.
The drug should be bactericidal;
12) The drug should have good post antibiotic effect (PAE) for quinolones
it is 2-6 hours, which means that after discontinuation of therapy
the bactericidal effect persists for desirable time so as to eradicate
any reamining pathogen and also delays the chances of clinical
relapse.
Bactericidal (one that kills the bacteria) drugs are preferable to the
bacteriostatic (one that just inhibits the bacteria).
Since bacteriostatic drugs are unable to kill bacteria, this gives an
opportunity to form resistance by various mechanisms.
3)
13) The drug should be cost-effective. It should justify its existence in
terms of efficacy, compare to the existing drugs.
The drug should be effective in all degrees of severity;
Severity of infection and general condition of patient is important :
An antibacterial selected should be useful in all forms of severity
e.g. mild to serious infection.
4)
The drug should have low incidence of adverse effects.
Q37. Why antibiotics are combined ?
A37
Reasons :-
The drug should have LOW MIC.
1.
To treat mixed bacterial infections. (crush injuries and peritonitis)
Lesser the minimum inhibitory concentrations required for the
inhibition of growth of bacteria, more potent is the drug. A drug
with least MIC is preferred.
2.
Bacteraemic shock.
3.
To delay the emergence of resistant
4.
Infections of doubtful etiology.
5)
The drug should have MIC and MBC very close to each other.
Drawbacks of combination :-
6)
The drug should have high penetration into the tissues;
1.
Increased incidence of side effects and more chances of super
infections (e.g. Candidiasis)
2.
Increased cost of drug therapy.
A drug which has high penetration into the tissues is preferred.
7)
The drug should have minimum protein binding;
Minimum protein binding of a drug enhances the availability of the
free drug.
8)
The drug should be effective against organisms resistant to other
antibiotics.
Chemotherapy
135-A
135-B
Chemotherapy
2. Sulphonamides
haemolytic anaemia in patients with G-6PD deficiency, crystalluria (therefore
high water intake is essential).
Types :1.
Co-trimoxazole :-
Short-acting drugs :
Sulphamethizole (2-3 grams/day orally)
Sulphafurazole
Trimethoprin 80mg and 400 mg of sulphamethoxazole (Septran, Bactrium) has
advantages :
2.
Medium acting drug : Sulphadiazine (Aubril, Trimozin)
1.
Bactericidal combination, sulphonamides only are bacteristatic
3.
Long acting drug : Sulphamethoxpyridazine (1-2 gram orally/day)
2.
Potency is more.
4.
Topically applied drug :
Sulphacetamide (Albucid, Locula eye drops - 10-20-30% strength)
Silver sulphadiazine cream 1% w/v (Silvirin)
It should be avoided during first trimester of pregnancy and in children under 2
years of age.
Mechanism : Sulphonamides inhibit synthesis of DNA as these are competitive
antagonists of paramino benzoic acid (PABA), which is an essential fuel of
bacteria. Hence in the presence of pus, which contains large amounts of PABA,
sulphonamides are ineffective. They are bacteriostatic drugs.
Uses :
Uses :
Doses :
1.
Shigellosis dysentry.
2.
Venereal diseases.
2 tablets B.D. for 5 days, followed by course of ampicillin for a week in cases of
enteric fever.
3.
Trachoma and inclusion conjunctivitis.
4.
Urinary tarct infections.
5.
Respiratory tract infections
Sources :- Obtained from fungal mould be penicillinium notatum.
6.
Meningococcal meningitis
7.
Resistant strains of malaria
Chemistry : It is chemically 6-aminophenicillanic acid which has a b-lactam
ring and a 5 membered thiazolidine ring.
8.
Burns cuts and skin disorders.
It has similar uses as of sulphonamides
It has been used with varying degree of success of typhoid fever.
3 . Penicillins
Side effects :
Rashes eg. Stevens Johnsons syndrome, dizziness, headache, kernicterus,
Chemotherapy
136-A
136-B
Chemotherapy
Test for hypersensitivity muse be carried out in the
following way before administration of penicillins.
Classification of b -lactam antibiotics
(A) Conventional Drugs
No resistance to penicillinase
enzyme elaborated by bacteria
Good oral
absorption
Penoxymethyl
- penicillin
(Penicillin-V)
Phenethicillin
Poor oral
absorption
Penicillin-G
(Benzylpenicillin
These are mainly effective against
gram positive cocci and
ineffective against staph, aureus
and bacteriodes fragilis
Scratch test with solution of 5 units/ml
if negative
Resistance to penicillinase
enzyme elaborated by bacteria
Acid labile
Methicillin
(never given
orally)
Scartch test with solution of 10,000 units/ml
if negative
Acid Resistant
Oxacillin
Dicloxacillin
Floxacillin
Cloxacillin
(Oral administration
possible)
Intradermal 0.02 ml of 100 units/ml solution
if negative
Administer penicillin cautiously
1.
These have extended spectrum of
antibacterial action
2.
Haematological reactions :- Though haemolytic anaemia is uncommon;
there is development of Coomb's positivity where the antibody globulin is
adsorbed on RBC's.
The cell wall of bacteria is essential for their normal growth and development.
Penicillin, a bactericidal drug, inhibits cell wall synthesis thus inhibits the
bacterial growth.
3.
Its a multi-step pattern of bacterial resistance which leads to progressive
ineffectiveness of penicillins.
Relatively safe
Sterile abscesses.
Phlebitis.
Therapeutic implications :It is essential to know that :a)
137-A
Local reactions :- The effects due to local irritation may follow after an
I.M. injection.
a)
b)
Drug resistances :
Chemotherapy
Hypersensitivity reactions :- Allergic reactions can occur. This is due to
sensitization by the b-lactam ring. The important immediate type of
reactions are uriticaria and analphylaxis (Precaution - A tray containing
injection adrenaline, hydrocortisone and antihistamin must be kept ready
before administration of penicillins)
Serum sickness, eosinophilia, fever and skin reactions can also be present.
Jarisch Herxheimer reaction due to massive kill of spirocheates (Syphilis).
Mode of action:
Toxicity of penicillins :-
(This is routinely done in
wards but eventually may
cause severe reactions.)
These antibiotics are most active against the bacteria in the log phase of
137-B
Chemotherapy
growth and have little effect in log phase (rapidly multiplying bacteria).
b)
Presence of pus protein, does not decreases the ability of b-lactam
antibiotics to kill bacteria.
c)
These antibiotics are active when pH or oxyen tension is low. This is not
seen with bacteriostatic drugs.
1.
Respiratory system :- All acute and chronic respiratory disorder particularly
in cases of lung abscess and bronchiectasis. Patients who are allergic to
penicillins they can be given cephalosporins which have nearly same basic
chemical structureand and are drugs of choice for klebsiella pneumoniae.
endocarditis can occur
5.
Prevention of infections during caesarian section.
6.
Agranulocytosis
7.
Rheumatic involvement of the heart :- Benzathine penicillin 1.2 megaunits I.M. every month.
Amnopenicillins or broad spectrum drugs :
2.
Infective endocarditis
These are bactericidal for both gram positive and gram negative bacteria; but
being less active on gram positive bacteria than penicillin-G. Highl effective
against micro-organisms like Strept. viridans; H-influenzae; E.coli and gonoccoi.
3.
Skin infections of staph, epidermidis causing :- abscess, furuncle and
carbuncle
These drugs undergo enterohepatic circulation in bile and an appreciable amount
are excreted in stools. e.g. Ampicillin (usual dose is 500 mg Q.D.S.)
4.
Urinary tract :- Acute and chronic infectious of urinary tract, except those
caused by obstruction.
Amoxycillin (Novamox, Nodimox)
5.
Acute and chronic osteomyelitis is due to staphylococcus aureus.
a)
Less effective than ampicillinin cases of shigellosis.
6.
Although they can be used in gonorrhaea; they are only drugs after sulphas
and 4-aminoglycosides. They are the drugs of choice forthe syphlitic
infections.
b)
Peak concentrations 2½ times greater than ampicillin.
c)
For rest of the micro-organisms; the amoxycillin is far superior.
d)
It can be combined with clavulanic acid and hence is effective against
b-fargilis and proteus group of micro-organisms.
Prophylaxis :1.
Streptococcal infections :- 1.2 mega-units of penicillin G is known to reduce
the carrier state specially in patients with burns and deep wounds.
2.
Recurrences of rheumatic fever is due to b-haemolytic streptococcus, the
recurrent episodes where the cariac injury occurs is prevented penicillin
G-200, 000U-12 hrly; till blood culture is negative.
3.
Venereal diseases.
4.
During dental extraction; where in 25% cases subacute bacterial
Chemotherapy
These drugs can interfere with platelet function and bleeding episodes
can occur because of abnormal aggregation of platelets.
b -lactamase inhibitors :- These enzyme inhibitors for e.g. clavulanic acid and
sulbactum can be combined with b lactam antibiotics that are destroyed by blactamase enzyme e.g. Pencillin G and V.
Pencillin alternatives :- If patient is allergic to penicillins other broad spectrum
antibiotics can be gives according to results of culture-sensitivity test.
138-A
138-B
Chemotherapy
1. Penicllin-G
Preparation
1) Sodium penicillin
Dose (many times
depends on the severity
of infections)
400,000 units orally, I.M.
2) Potassium penicillin 4 times a day.
3) Procaine penicillin
300,000 units every 24
hours I.M.
4. Cephalosporins
These are bactericidal drugs with mode of action and other characteristics
similar to penicillins. Cephalosporins have :
1.
7 structure ring, instead of 6 structure ring of penicllins.
2.
They are used mainly for penicillin resistant staphylococcal infections,
urinary tract infections, syphilis and gonorrhoea.
3.
Allergic skin rashes and genietal pruritis are common.
4.
They do not penetrate will into sputum and are less active the ampicillin
and chloramphenicol against Haemophilus influenzae.
5.
Penicillins are mainly effective against gram positive micro-organisms.
Cephalosporins in addition, also have action against some of the gram
negative micro-organisms.
4) Benzathine penicillin 1.2 mega units every month.
2. Acid resistant
penicillin
Preparations
Dose
1. Phenoxymethyl
penicillin
125-250 mg Q.I.D. orally
2. Phenoxyethyl
penicillin
Same dose as above
Types :1.
Cephalexin (Sporidex) 250-500 mg, 6 hourly orally.
2.
Cephamandole 500mg-2 gram, 6 hourly I.M./I.V.
B) Newer penicillins
3.
Cephazolin ½-1 gram 6-12 hoursly IM/IV.
These penicillins have advantages of either being resistant to b-lactamase
enzyme or extended spectrum of antibacterial actions or both.
4.
Cephalothin IV, IM deep 4-12 gram, 8 hourly
5.
Moxalactum - Inj 4 grams T.D.S.
1.
Indanyl penicillins : - Carbenicillin (Pyopen)
2.
Amidinopenicillin :- Ticarcillin, piperacillin
5. Erythromycin (Erythrocin)
These are effective against pseudomonas, proteus, enterobacteriacae and
klebsiella group of micro-organisms.
3.
4.
Broad spectrum pencillins : - Ampicillin, amoxycillin, bacampicillin,
cyclacillin, talampicillin.
Ureidopenicillins :- Alzocillin, mezlocillin
Chemotherapy
139-A
1.
Erythromycin is macrolide antibiotic. Even though it is a bacteriostatic
drug, in high concentration it has bactericidal action.
2.
Side effects are :Gastrointestinal: nausea, anorexia, diarrhoea, stomatitis, headache skin
rashes. Estolate salts can cause elevation of hepatic enzymes and hence
any liver disease is contraindication for its use.
139-B
Chemotherapy
3.
Dose :- 250-500 mg, 6 hourly (Ethyl succinate or sterate salts are used).
Urticardial rashes
4.
Uses :-
Brown staining of teeth and deposition in bones, because it bounds to
calcium in the body, forming "chelates" (therefore contraindicated in
pregnancy and during childhood).
5.
1.
An alternative to penicillin allergic patients.
2.
Alternative to tetracyclines for Mycoplasma pneumonia therapy,
relapsing fever, pertusis (whooping cough) and carrier state for
diphtheria.
3.
Effective drug against Campylobacter diarrhoea.
4.
Leigonella pneumophilia infection.
2.
3.
Depresses prothrombin systhesis.
Ataxia and vertigo
Other macrolide antibiotics are :-
4.
Dose:- 250-500 mg, 6 hourly orally/IM/IV.
5.
Uses :- As a broad spectrum antibiotic, it has many applications.
1.
Spiramycin.
1.
Drug of choice
2.
Alternative Therapy
2.
Roxithromycin.
1.
Non specific urethritis
1.
Chronic bronchitis
3.
Azithromycin
2.
Rickettsial infections
2.
Syphilis
4.
Clarithromycin
3.
Brucellosis
3.
Anthrax
4.
Acne
4.
Meningococcal carriers
5.
Lymphogranuloma venerum.
6. Tetracyclines
1.
Nephrogenic diabetes insipidus.
These are bacteriostatic drugs which act by inhibiting protein synthesis in
bacterial ribosomes.
7. Chloramphenicol (Paraxin)
Types :- Tetracycline derivatives are :-
1.
It is a broad spectrum antibiotic, bacteriostatic, and inhibits bacterial protein synthesis.
2.
Side effects :-
1)
Oxytetracycline (Terramycin)
2)
Minocycline
3)
Doxycycline (Doxy-1), (has long life and almost complete absoption)
4)
Rotitetracycline
5)
Demeclocycline
Side effects :-
Superinfection, gastrointestinal upset.
Bone marrow depression :- Pancytopenia and aplastic anaemia.
Angioedema and urticaria, Jarisch Herxheimer reactions.
'Gray baby syndrome' in neonates and premature infants.
3.
Dose :-
Gastrointestinal upset
Adult dose varies between 1½ to 3 gram/day or it is 50 mg/kg.
Superinfection
Ophthalmic preparations -
Chemotherapy
140-A
140-B
Chemotherapy
4.
9. Antimalarial drugs
i)
drops 0.5%
ii)
ointments and applicaps :- 1%
Malaria is parasitic disease caused by plasmodium, enters the human body
via the bite of female anopheies mosquito.
Uses :1.
Typhoid fever (Enteric fever or Salmonellosis - drug of choice)
2.
Meningitis
3.
Rickettsia
Drug
Side effect
Therapeutic use
Comments
4.
Plague
1. Chloro-
Vertigo, blurring
1. Acute attack of
1. Chloroquine
qine
of vision, nerve
plasmodium vivax
5.
Lymphogranuloma venerum
(Lariago,
deafness, hallu-
malaria. 4 tablets
an prevents DNA from
6.
Mycoplasma infections.
Resochin)
cinations, rarely
initially (600 mg),
acting as tempelate.
psychotic episodes
then 2 tablets after
Drug used :-
6 hours and then 2
8. 4-Aminoglycosides
Side effects
tablets for 2 days.
Therapeutic
Dose
2. Suppression of
Specific Features
malaria
application
intercalates with DNA
2. In liver, spleen, skin
and kidney, it gets 200700 times concentrated
than plasma concentration
3. Hepatic amaebiasis.
1. Streptomycin
2. Gentamycin
(Genticin)
Vestibular and
auditory damage, neuromuscular block,
rashes
Vestibular
damage,
nephrotoxic,
skin rashes
1. Primary drug for
tuberculosis.
2. Effective against
gram-negative
infections
Broad spectrum
bactericidal drug
effective against
pseudomonas
and proteus
1/2-2g/
I.M.
given
daily
3-5 mg/
kg IM/
IV, 8
hourly
Ototoxicity
(irreversible
deafness),
malabsorption
of nutrients,
skin rashes
1. Sterilization
of bowel prior to
surgery
2. Bacterial
diarrhoeas
3. Cover skin
pathogens
Half life is 2 hours
and gets concentrated in the
kidneys. In old patients the dose to
4. Rheumatoid arthritis.
5. Lupus erythematosis.
2. Quinine
maximal
oral dose
is 1 gram
in a day
The drug is too toxic
for systemic use and
therefore it is given
orally for local action
(not absorbed)
e.g. Hepatic coma
(derived
tinnitis,blurred
vision and wet
Cinchona
bark)
skin.
2. In patients with
G6PD deficiency
there is
1. Relapsing vivax
malaria
2. Plasmodium falciparum malaria
resistant to chloro3. Nocturnal leg
1. It inhibits DNA replication.
2. Highly bound to plasma
proteins.
3. Mainly absorbed from
small intestine
cramps.
haemolysis
3. Bone marrow
depression.
3. Primaquine
Disturbances in
Radical cure for re-
vision, methae-
lapsing in malarias.
It is never given I.V.
as it can produce fall in
moglobinaemia,
15 mg base given
blood pressure and cause
abdominal cramps,
daily for 14 days.
E.C.G. changes.
headache.
topically
Chemotherapy
1. Chichonism :-
from
be reduce to 2/3rd
infection
3. Neomycin
(Renokab)
Permanent resistance to streptomycin can develop.
It is poorly bound
to plasma protein
141-A
141-B
Chemotherapy
prim,
malaria.
7. Meflo-
quine
Chemotherapy
plasmodium falciparum
Epigastric pain
Radical cure of malaria. It was developed by
Hypokalemia
Effective against
Walter Reed Institute
resistant strains of
P. vivax.
Vietnam war.
142-A
142-B
1 gm
(Dara-
15-20 mg
•
of chloroquine resistant
Streptomycin (S)
used for prophylaxis
tion
Inhibits
arabinogalactan
synthesis and
interferes with mycolic
acid in corporation to
bacterial cell wall
Tuberculocidal, but
less effective than INH
or Rifampicin and acts
only on extracellular
bacilli
combina-
•
week for 6 weeks. It is
1.2 gm
sulphadoxine every
pain.
15-25 mg
rashes, epiastric
haddoxine
Ethambutol (E)
and Sulp-
It inhibits mycolic acid
synthesis with
different encoding
gene
half life of 9 days.
•
Sulphadoxime has a long
mine and 1 gram of
2 gm
50 mg of pyrimetha-
anaemia, skin
20-30
Megaloblastic
thamine
Pyrazinamide (Z)
6. Pyrime-
Hepatotoxicity
Hyperuricemia
Arthralgia
Flushing
Hyperglycemia
Loss of visual acuity
Optic neuritis
Nephrotoxicity
Emergence of resistance
•
•
Hepatitis
Cutaneous syndrome
Flu syndrome
Abdominal syndrome
•
•
•
•
•
•
•
•
•
•
•
weekly.
•
metabolism.
prim)
600 gm
Interferes with folic acid
malaria. 25 mg orally
10-15
Pyralfin)
•
•
•
•
•
•
•
•
•
Useful in early clearance
of bacilli from tubercular
cavities
Well tolerated
Delays emergence of
resistance
Bactericidal
Rapid acting
Efficacious when
combined with other
antitubecular drugs
Shortens duration of
treatment
Lessens the risk of
relapse
Bactericidal
Acts on resistant T.B.
bacilli
Well tolerated
Long half life of 4 days.
Rifampicin (R)
suppressive cure of
(Malaranaemia
For prophylaxis and
•
thamine
Megaloblastic
•
•
daily for a week.
Peripheral neuritis which is
due to interference with
pyridoxine metabolism
Hepatitis, arthralgia
5. Pyrime-
•
in red blood cells.
100 mg salt is given
Inhibition of synthesis
of mycolic acid which
is in cell wall of
mycobacteria. It also
inhibits catalase
peroxidase enzyme to
inhibit the metabolic
activity
Inhibits DNA
dependent RNA
synthesis
of malaria.
proteinuria
•
haematuria,
10-20
It is mainly concentrated
Isoniazid (INH)
Chemoprophylaxis
Advantages
Epigastric pain,
Side-effects
4. Progu-
Mechanism of action
Comments
Dose in adult
mg/kg (>50
kg)
450 gm
Therapeutic use
Dose in child
mg/kg
Side effect
Drug
Antitubercular drugs
anil
Drug
Chemotherapy
For the treatment of tuberculosis, the therapies are included as per different
categories :
Inhibits DNA
dependent RNA
synthesis
•
•
Gastrointestinal intolerance
and turns secretions red
•
•
•
Delays emergence of
resistance
Well tolerated
Quick sterilising activity
Used in typical and
atypical mycobacterium
•
Abdominal discomfort
Inhibits DNA gyrase
●
Category 1 (New untreated smear positive pulmonary tuberculosis, new
cases of extra pulmonary tuberculosis)
●
Category 2 (Smear positive failures, relapse and interrupted treatment
cases)
●
Category 3 (New cases with less severe forms of extra pulmonary
tuberculosis)
●
Category 4 (These are the multidrug resistant cases of tuberculosis)
300 mg
TB category
Initial phase
Continuation
Total duration
phase
(months)
4H3 R3
6
5H3 R3 E3
8
I
2H3 R3 Z3 E3
I
2H3 R3 Z3 E3 S3+1H3 R3 Z3 E3
III
2H3 R3 Z3
4H3 R3
6
IV
2H 2Q R3 Z3 E3
H3R3Q
12
* prefix indicates the duration of the drug in months whereas suffix indicates
no. of doses per week.
-
1.5gm
•
•
•
Epigastric pain
Goiter
Tubercular static
Chemoprophylaxis in tuberculosis
Rifabutin
30mg
12 gm
Para
aminosalicylic
acid (PAS)
Ciprofloxacin (Q)
200 mg
•
•
•
Delays emergence of
resistance, but is a weak
drug
Slows the development of
resistance
•
Anaemia
Loose motions
•
•
Tubercular static with
long half life
•
10 mg
Thiacetazone
(TZN)
The first line drugs are INH, rifampicin, pyrazinamide, ethambutol and
streptomycin whereas second line drugs are thiacetazone para aminosalicylic
acid, ciprofloxacin and kanamycin.
143-A
1.
Contacts of open cases who frequently show mantoux conversion
2.
Children with positive mantoux test
3.
Child of tubercular mother
4.
Patients with leukemia, diabetes or with HIV infection
143-B
5.
Patients who have received inadequate therapy and hence are old inactive
cases
The drug generally used for prophylaxis is INH along with rifampicin and
pyrazinamide which are given initially for 2-3 months followed by INH and
rifampicin for 6-12 months
Drug
Use and dose
Side effects
Corticosteroids
1. To control drug hypersentsitivity
reactions
2. Seriously ill and moribund patients.
3. Where adhesions are formed :Meningeal adhesions, pericardial
adhesions, genieto urinary fibrosis
and peritoneal adhesion.
4. Addison's disease caused by
tuberculosis.
20mg of hydrocortisone (Efcorlin)
or 2 mg of fludrocortisone can be
given in above conditions.
1. Moon face or
buffalo hump.
2. Muscle weakness
3. Emotional changes
4. Glycosuria
5. Oedema due to
retention of salt and
water.
Chemotherapeutic regimens
Name
1. Optimal
Combination
Comments
Streptomycin 1g/day, isoniazid
1. Development of
primary
150 mg B.D., rifampicin 15 mg/kg.
resistance of relapse
treatment
This combination is given initially
is less.
for 3 months (streptomycin can be
given 6 times a week) followed by
2. Patient compliance
can be poor, because
isoniazid and rifampicin for :-
drug treatment is for
9 months - if lesion is minimal
long period.
12 month - if lesion is moderate
6. Elevation of blood
pressure.
7. Osteoporosis
8. Dyspepsia and
peptic ulcer.
9. Decreased
resistance
to an intercurrent
illness.
Prophylactic chemotherapy :-
15 month - if there is extension
cavitation.
Anti tubercular drugs may be indicated in persons considered to be at special
risk of contracting active disease.
Rifampicin is a must, isoniazid is
sometimes substituted with ethambutol or pyrazinamide.
2. Intermittent
Streptomycin and Isoniazid are
1. Relatively cheap.
Primary prophylaxis :-
given once weekly or twice weekly.
2. Can be more easily
Giving INH to protect a non immune person at risk of early infections.
regimens
3. Short
easily supervised.
Streptomycin - 8 weeks
Best patient compiance,
course
Isoniazid, rifampicin, pyrazinamide
lesser incidence of
therapy
The other 3 drugs are continued for
side effects.
Child can also be given BCG vaccin along with isoniazid.
Secondary prophylaxis :-
a period of 6 months.
144-A
1.
Child under 3 years of age who has never had BCG and reacts strongly to
tuberculin.
2.
Any individual known to have been exposed and assumed to be recently
infected.
144-B
3.
Individuals with minimal tuberculosis of doubtful activity. patients ca eb
given Iosnizd or Rifmapicin for period of 6 months.
11. Anti-leprotic drugs.
12. Therapy for worm infestations
Drug
Actions
Uses and dose
Side effects
1. Dapsone
(Diamino
DiphenylSulphone)
1. It is primary
bacteriostatic
drug.
2. It undergoes
enterohepatic
circulation and
remains in
plasma for
12 days
Maultibacillary and
Paucibacillary
leprosy. (50-100 mg
of dapsone daily for
multibacillary
leprosy as a
life long treatment).
(For paucibacillary
leprosy 2 year
treatment).
Gastro-intestinal
upsets, cholestatic
jaundice, peripheral
neurophathy.
Sulphone syndrome
characterized by
methaemoglobinaemia.
Haemolysis in patients
with G-6-PD deficiency.
Lepra reaction with
inadequate doses.
2. Clofazimine
Drug
Clofazimine 100 mg + Rifampicin 600 mg for 3 months followed by :
Clofazimine + Rifamipicin + Isoniazid + Pyrazinamide for 2 years
Paucibacillary leprosy, where the patient become almost bacilli free.
Introduction :- Helminthiasis is one of the major public problems in tropical
countries, where the sanitation is poor. The worms can cause various general
and gastrointestinal symptoms. in addition some of them can cause blood
loss; nutritional deficiencies, uriticaria; and intestinal obstruction.
Drug therapy :a)
Drug therapy of round worm (Ascaris lumbricoides)
1.
Piperazine citrate (Antepar) :- This drug constitutes the mainstay of
therapy. Cure can be achieved in nearly 100% of cases.
1. Bacteriostatic
1. Patients showing
Abdominal pain and
drug with antisulphone resistance skin pigmentation
inflammatory
2. Useful in patients
action.
of leprosy showing
2. It accumulates in
erythema nodosum
various tissues
leprosum 100300 mg orally.
Actions
Uses and dose
Side effects
3. Rifampicin
1. The action of
(Rimactane)
Rifampicin is
more rapid.
2. Not very
effective though
it penetrates
cells and
nerves well.
It is used in dose of
600-1200 mg daily
for tuberculoid
leprosy. It is most
effective.
Discused with antitubercular drugs.
Piperazine causes paralysis of Ascaris lumbricoides muscle and decreases the production of succinic acid by worms. The paralytic action of
piperazine occurs because the drug blocks the stimulating effects of ACH.
at N.M. junction of ascaris. Since worms are alive when passed; disintegration products do not accumulate in the intestines.
Side effects
1.
Mild reactions :- nausea, abdominal pains;
2.
Rare but serious :- erythema multiforme difficulty in focussing, precipitation of grandmal or petit mal seizures.
Combination therapy :-
Caution is to be taken in presence of renal disease, since the drug is
cumulative.
1.
Useful in prevention of emergence of resistant organisms.
Dose :- 5 gm since dose in evening or 3.5 gm on alternae days.
2.
Useful in paucibacillary leprosy.
Chemotherapy
This drug is also effective against pin worm (Entrobius vermicularsis)
145-A
145-B
Chemotherapy
2.
3.
Pyrantel pamote (Numantel) :- is effective alternative. The drug is depolarising agent resulting in spastic paralysis of the worm. It is given in from
of a oral suspension in dose of 11 mg/kg. Transient G.I. upset; headache
and dizziness are the only effects which are observed.
1.
Mebendazole (Mebex) :- This drug was introduced for treatment of roundworm infections as a result of research carried out in Belgium. Its a
yellowish powder which is very slightly soluble in water.
Side effects :-
The drug inhibits glucose uptake by the worm irreversibly. Parasite immobilisation and death occurs slowly and clearance from G.I. tract is only
after 3 days.
Only a small portion of drug is absorbed.
Bephenium hydroxynaphthoate (Alcopar) :Bephenium is a chlolinergic agonist. Hookoworms in the G.I. tarct loose
their attachement in the presence of drug and are expelled.
●
Drugs has low toxicity,
●
Vomiting is more common in children.
●
Cramping abdominal pain.
Caution is to be takein in hypertensive patients bacause drug causes marked
fall in blood pressure.
Side effects :- Abdominal pain; diarrhoea; teratogenic effects in
animals.
Dose :- Single dose : 5 gm on empty stomach.
Dose :-
100 mg tab - 1st week :
1.
Thiabendazole
100 mg tab - 2nd week
2.
Pyrantel pamoate
The drug is a broad spectrum antihelminthic and is effective against :
3.
Tetrachloroethylene
Pin worm; hook work; thread worm; and is drug of choice for creeping
eurption caused by larva migrans.
c)
Drug therapy of Thread or Pin worm (E. Vermicularis):-
The other less commonly used drugs are:4.
Tetramisole or Levamisole (Dewormis)
5.
Thiabendazole
b)
Drug therapy for hookworms (Ankylostoma duodenale)
The other alternative drugs are :-
The drug of choice for thread worm infestation is either pyrivinium or piperazine. Pyrivinium is a cyanine dye and acts by inhibiting cellular metabolism of worms. The stools are red coloured. The drug is given orally in
a dose of 5 mg/kg.
The other drugs are :Hexylrescorcinol, thiabendazole, gentian violet.
Aims of therapy are two fold :a)
To restore haemoglobinc values to normal.
b)
To expel the intestinal parasites (Vermifuge).
Chemotherapy
Pruritis in perianal and peiroral region is very severe and scratching
may cause secondary infection. An antihistaminic cream should be
applied to prevent itching.
146-A
146-B
Chemotherapy
d)
Drug therapy of Tape worms (T. Solium) :1.
tract caused by nematode parasite. The other indications are in the
treatment of Onchocerciasis caused by Onchocerca volvulus and
Wucheria bancrofti and in cases of cutaneous larvae migrans. It acts by
accelerating the GABA activity and increasing the permeability of chloride
channels thereby causing death of the worms. The kinetics of the drug
are non-linear (concentration in plasma is not proportionate to the dose)
and the drug is excreted from the body over a period of 12 days. The
important side-effects are diarrhoea, nausea, dizziness, pruritis and
urticaria. Single dose of 3 mg tablet is for child whereas 2-4 such tablets
are given in a day to adult. The course is repeated after a month.
Niclosamide (Niclosan) :- very little drug is absorbed from gut. High
concentration locally inhibits anaerobic metabolism of worms. Both
scoleces and proximal segments are rapidly killed and it may be
difficult to recognise the putrid material.
Side effects :- Nausea, vomiting, colics.
Dose :- 4 tablets (2 gm) taken after meal.
The tablets should be chewed thoroughly and swallowed with water. A purge is
given after 2 hours in order to isolate scolex.
Many times purgatives are given following administration of anthelmintics
to expell dead worms from the intestines.
Other drugs used are :- Mepacrine, dichlorophen, dihydrochloroquin,
paramomycin.
e)
Drug therapy of filariasis :- (Wuchereria bancrofti, W. malayi and
O. volvulus).
Diethylcarbamazine citrate (Hetrazan, Banocide):- It is piperizine derivative. The drug appears to sensitize the microfilaria so that they become susceptible to phagocystosis by the fixed macrophages of the reticulo
endothelial system. The durg do not kill microfilariae in nodules or even in
hydrocoele.
The drug is readily absorbed from G.I. tract and drug concentration falls to
zero within 48 hours.
Side effects :- Farily frequent but not severe anorexia, weakness, joint
pains. Caution :- If a pateint has a recent history of malaria an antimalarial
treatment is advised. This is to prevent relapses that might be provoked
by the systemic response to therapy by diethylcarbamazine.
Dose :- 6-14 mg/kg as a daily dose, (50,100 mg tablets) given three times
a day for two weeks.
13. Antiamoebics
Entamoeba histolytica causes amoebiasis. It invades gastrointestinal mucosa,
liver and to other tissues. The asymptomatic patients are cyst carrier where as
in infulminating dysentry there are basically vegetative froms of E.histolytica.
Drugs :A)
Nitroimidazoles : Metronidazole, Tinidazole, Orinidazole.
1.
Metronidazole is universal amoebicide, acts on intestinal and at
extraintestinal sites.
2.
More effective against vegetative froms than cysts of E. histolytica
3.
Side effects :Metallic taste in mouth, Anorexia, Leucopenia
4.
Not to be taken with alcoholic breverage as it can cause severe
vomiting and abdominal cramps. (Antibuse effect).
Ivermecetin : It is indicated in cases of strongyloidiasis of the intestinal
Chemotherapy
147-A
Contraindications :-
147-B
Chemotherapy
5.
Dose :- 200-400 three times a day for 5 to 7 days.
●
Lesser antabuse (diculfiram) like reaction
6.
Indiations :
●
No neurological toxicity
1.
Amoebic dysentry and liver abscess
●
2.
Giardiasis
3.
Trichomoniasis
The haematological picture is not much altered. The reasons for safety
are that it is not acetylated to active metabolite within liver, which can
produce the above problems
4.
Acute ulcerative gingivitis
●
5.
Anaerobic infections
The dose is 300 mg bd for 3-5 days and is effective in giardisis, ameobiasis
and in cases of trichomoniasis.
6.
Hypoxic malignant tumors as a radiosensitising agent.
Secnidazole
Tinidazole (Tiniba) :
The drug has long half-life and has good bioavailability and the plasma
concentrations achieved with the single dose are high enough to eradicate
vegetative forms of amoebiasis, giardisis. It is also used in cases of trichomonal
vaginitis. The total single dose is 2 gm.
1.
It has longer duration of action.
2.
It is more effective against cystic forms.
3.
Consumption of alcoholic beverages may be permitted as the antabuse
reactions is less severe.
4.
Dose :- 150 mg twice daily for 5 to 7 days or 500 mg B.I.D. for 2 or 3 days
(Fasign).
Ornidazole
The activity is similar to metronidazole , but can rarely lead to hypersensitive
hepatitis . It has a longer half life & the incidences of antabuse reaction ( fall of
BP, flushing etc , when given along with alcohol ) is less . 500mg tablet is given
thrice daily for the patients of amoebiasis, giardiasis for a period of 5-10 days
for clinical cure
B)
Diloxanide furoate (Mobitide-S, Dyrade-M) :-
1.
Effective in cystic intestinal amoebiasis (carrier status).
2.
Used in mild forms of dysentry.
3.
Side effects :- Flatulence, albuminaria.
4.
Dose : 500 mg three times a day for 5 to 10 days.
C)
Emetine hydrochloride :1.
It is alternative drug for hepatic amoebasis
2.
Dose :- 65 mg/day for 10 days.
3.
Side effects :- Toxic, therefore used only in hospitalized
patients. Projectile vomiting, hypotension and arrhtymias occur
frequently.
Satranidazole
The advantages over the traditional imidazoles are :
●
Better tolerability (no metallic taste in mouth and no significant elevation
of hepatic enzymes).
Chemotherapy
148-A
D)
Diiodohydroxyquine, Iodochlorohyroxyquin (Enteroquinol)
148-B
Chemotherapy
These drugs are effective against entamoeba, giardia, trichomonas and
some anaerobic bacteria. They kill the cyst forming trophozoites in the
intestine, but do not have tissue amboebicidal action. The 8hydroxyquinolones are well tolerated, can produce goiter, iodiosm and in
certain races sub-acute myelo optic neuropathy has been reported. This
is seen mostly in South-East Asian population mainly due to the genetic
susceptibility to metabolise these drugs slower. The dose of medications
is thrice daily for a period of 5-7 days.
E)
Antibiotics : (1) Tetracyclines (2) Paromomycin.
■
Norfloxacin (Norflox)
■
Ciprofloxacin (Baycip)
■
Pefloxacin (Pelox)
■
Ofloxacin (Oflo)
■
Sparfloxacin (Sparx)
■
Lomefloxacin (Mahaquin)
Features :
14. The Quinolones
1.
Good gram negative coverage. Sparfloxacin has additional gram positive
coverage
Classification :
2.
Long half life and hence twice or Once administration
1.
3.
Good tissue penetration, eliminating most of micro organisms easily
First generation compounds
■
Nalidixic acid
4.
Ciprofloxacin has good coverage against Pseudomonas aeruginosa
■
Piromidic acid
5.
Major Indications :
■
Pipemidic acid
a)
Respiratory tract infections (Upper and Lower)
■
Oxolinic acid
b)
Skin and soft tissue infections (Mild and Severe)
■
Cinoxacin
c)
Urinary tract infections (Uncomplicated and Complicated)
d)
Typhoid fever
e)
Bone and joint infections
f)
Chancroid and gonococcal infections (Single or Multiple dose)
g)
Obstetrical and Gynecological infections such as Pelvic inflammatory disease
Features :
1.
Active against enterobacteria only
2.
Poor to moderate tissue penetration
3.
Used in UTI and Shigellosis ( diarrhoea )
2.
Second generation compounds :
Chemotherapy
6.
149-A
Interactions with theophylline and warfarin
149-B
Chemotherapy
4.
Third generation quinolones :
quinolones is associated with lesser incidence of resistance but a more favorable
clinical response
■
Levofloxacin
■
Gatifloxacin
Tolerability :
■
Moxifloxacin
■
Gemifloxacin
Clinical adverse effects associated with the use of quinolones occur in 5-10%
of cases. Nausea, abdominal discomfort, diarrhoea are GI side effects where
as some CNS side effects such as headache, insomnia, dizziness can occur.
Features :
Severe adverse effects such as nephrotoxicity, hepatotoxicity, hypoglycemia
and sometimes prolongation of QTc interval is seen in ECG
1.
Activity against gram positive organisms, anaerobes and atypicals, retaining their gram negative activity
2.
Long half life and hence truly once a day administration
●
G 6PD deficiency in children
3.
Excellent tissue penetration due to high volume of distribution and
lipophilicity
●
Convulsive disorders or CNS disorders
4.
No interactions with theophylline
●
Cardiac arrythymias
5.
Lesser incidence of development of resistance
Precautions :
6.
Sequential therapy (switch from IV to oral form of same molecule) is also
available
7.
Major indications as second generation drugs
Contraindications :
●
To be used in children under 18 years of age as the arthropathy may be
more evident in young children (joint pains or impairment in cartilage
development). In certain conditions quinolones have been used safely
such as cystic fibrosis, shigellosis and in cases of typhoid fever not
responding to other antibiotics.
●
Patients should refrain from exercise as tendon rupture or tendinitis can
occur
●
Phototoxicity : Patients who are exposed to sunlight can develop reactions in term of patches , with drugs such as Lomefloxacin and Sparfloxacin
●
Patient should take large amount of fluids with these drugs to prevent
crystal formation in kidney, resulting in damage
Mechanism of action for quinolones :
Quinolones act by inhibition of bacterial topoisomerase II (gram negative bacteria)
and topoisomerase IV (gram positive bacteria) thus uncoiling bacterial DNA,
leading to disruption of cell
Resistance :
There is no plasmid mediated resistance with quinolones, in fact plasmid is
destroyed by it. Mutational resistance is sometimes seen. Regular use of
Chemotherapy
150-A
150-B
Chemotherapy
Nadifloxacin
16. Cancer Therapy
It is a broadspectrum topical bactericidal quinolone effective against various
gram positive and gram negative bacteria including pseudomonas aureginosa
and E. coli. It is effective in clinical cases of folliculitis, impetigo contagiosa,
secondary wound infections where the medication is applied for 7-14 days.
The cancer cells cycle
15. New Antimicrobials
S - This is the DNA replication phase (Methotrexate, 5-fluorouracil, 6Mercaptopurine, Cytosine arabinoside).
1. Aztreonam :-
G2 - Post replicative phase where the cells are dividing to initiate the formation
of daughter cells (Actinomycin, Bleomycin).
1.
It is a monobactam antibiotic
2.
Effective against gram negative bacteria.
3.
Effective in patients who are allergic to penicillin.
4.
Intramuscular 1 gram I.M. along with probenecid is effective as a single
dose in gonococcal and in non-gonococcal urethritis.
G0 - Here the cells are non-dividing, quiescent. This is also called as the
resting phase.
G1 - This is called as pre-replicate phase (Platinum compounds)
M - Mitotic phase (the cells are actively dividing to form many subsequent
cancer foci). (Vinca alkaloids, Taxols),
Some Principles of Cancer Chemotherapy
1.
Cure probably requires complete eradication of tumour cells
2.
A given dose of drug kills a given precentage of malignant cells in unit
time. Thus number of cells before therapy determines the number of cells
surviving therapy. The earlier treatment is started and the smaller the
tumour, the better the result.
2. Imipenems :Features :1.
Effective against gram positive and gram negative organisms which are
resistant or sensitive to aminopenicillins.
3.
Clinical manifestations of cancer occur at a time of considerable tumour
burden. Thus treatment may need to be prolonged if cure is intended.
2.
Useful in urinary tract infections, sexually transmitted diseases and against
meningococcal meningitis.
4.
Treatment is a balance between the toxic effects of the drugs (particularly
on the bone marrow) and their efficacy.
Antibiotics once started must be given in adequate doses and for the
defined length of time. Inadequate doses and irregular therapy leads to
development of resistance to the administered antibiotics.
5.
Curative chemotherapy must reduce tumour cells to nail or to such low
numbers that body defences can kill the rest. Aim is to allow more rapid
recovery of normal cells whilst killing cancer cells by pulsed therapy.
6.
Adjuvant therapy (cytotoxic drugs given after primary tretment of cancer
by surgery or radiotherapy) to eradicated seedling metastases is undergoing clinical evaluation. Of value is some patients with breast cancer.
Chemotherapy
151-A
151-B
Chemotherapy
Cytotoxic chemotherapy is potentially curative is leukaemia, lymphoma, testicular tumours, choriocarcinoma an embryonal childhood tumours. Other
chemoresponsive but not usually chemocurable tumours include small cell
lung cancer, ovarian cancer and myeloma. Chemotherapy has a palliative role
in breast cancer.
Aklylating Agents
Group
Drug
Use (examples)
1. Mustards
Mustine
Chlorambucil
Lymphomas
Chronic lymphatic
leukaemia and
lymphomas
Myelomatosis
Lymphomas
Leukaemias
Carcinoma of breast,
Sarcoma
Melphalan
Cyclophosphamide
Ifosfamide
(activated by liver to
alkylating
metabolites)
2. Ethyleneimmonium
3. Dimethyl
Sulphonates
Chemotherapy
Thiotepa
Busulphan
3. NewerAntimicrobials
OXALODINONES
Drug
Mechanism of
action
Linezolid
It binds to a site •
on the bacterial
23S ribosomal
RNA of the 50
S subunit and
thus inhibits
•
protein
synthesis
Malignant pleural effusion
compounds (chemical
pleurodesis) - little used
now
Chronic myeloid
leukaemia
152-A
152-B
Kinetics
Rapidly
absorbed
with
bioavailabli
ty of 100%
Quick
bactericidal
concentratio
ns are
achieved in
1 hour
Toxicity
Therapeutic
uses and dose
•
Thrombocyt
openia
•
•
Taste
alteration
•
Nosocomial
pneumonia
due to gram
positive
organisms
Tongue
discolourati
on
•
Community
aquired
pneumoniad
ue to gram
positive
organisms
•
Vancomyci
n resistant
Enterococc
us
infections
•
The
recommend
ed dose is
400-600mg
IV every 12
hourly for 2
weeks
Chemotherapy
LINCOSAMIDES
Drug
NEWER AMINOGLYCOSIDES
Mechanism of
Kinetics
Toxicity
action
•
Hypotension
the 50 S subunit
concenter
•
Neutropenia
of bacterial
ation is
•
Agranulocyto
They bind to
Clindamycin
•
ribosomes and
achieved
suppress
protein
Drug
Mechanism of
action
Kinetics
Toxicity
•
50mg500mg
Aminoglycosid
es are
•
Short half
life but
•
IM/IV per
day for
dactericidal .
They
irreversibly
bind to 30 S
subunit of
achieves
high tissue
•
Ototoxicity
concentratio •
n
usage and dose
Good
Lincomycin /
Therapeutic
•
Short half
life of 4- 6
hours
•
Maximum
hepatic
extraction
less
•
Serioud
bacterial
infections
due to gram
sis
in CNS
synthesis
•
positive
Vertigo
cocci
•
Amikacin
and
100mgIVfo
r Netilmicin
300mg IV
every 12
hourly or
500mg as
bacterial
ribosomes ,
blocking
protein
synthesis
•
Dose
titration is
required in
cases of
renal
impairment
Nephrotoxi
city
Therapeutic
usage and dose
•
Complicate
d UTI
Interactions
•
Septicemia
with drugs
like
digoxin,
methotrexat
e and
•
Complicate
d skin and
Vitamin A
•
soft tissue
infections
infections
an oral
•
capsules
amount is
Intraabdomi
nal
Lower
respirtatory
tract
infections
due to gram
negative
organisms
handled
by
kidneys
153-A
153-B
MACROLIDES
AMINOGLYCOSIDE ANALOGUE
Drug and
dosage
M echanism of
action
K inetics
Toxicity
Therapeutic
uses
Azithromycin
500mg talettablet
given once daily
for 3 days
They bind to
the 50S
ribosomal
subunit and
inhibit RNA
dependent
protein
synthesis
•
Quick onset
of action
•
•
•
Remain in
body for
long time
due to
lipophilicity
Abdominal
pain,
diarrhoea
Community
acquired
pneumonia
•
Headache
•
•
Pruritis
•
Increased
elevation of
hepatic
enzymes
Acute
bacterial
exacerbatio
n of chronic
obstructive
pulmonary
disease
Clarithromycin
250mg 500mg
tablets given
twice or once
daily for 7- 10
days
Dirithromycin
500mg tablet
given for 5-10
days
Roxithromycin
150mg or
300mg given for
5-7 days
•
•
Most
undergoes
hepatic
metabilism
Interacts
with
antacids,
antifungals,
rifampicin,
buspirone,
carbamazep
ine,
digoxin,
steroids,
antivirals
•
Atypical
pneumonias
•
Skin and
soft tissue
infections
•
URTIpharyngitis,
tonsillitis
•
Prophylaxis
of atypical
mycobacteri
a such as
Mycobacter
ium avium
complex
•
Pelvic
inflammator
y disease
•
Eradication
of
Helicobacte
r pylori
infection
•
Uncomplica
ted
gonococcal
infections
154-A
Drug
Mechanism of
action
Kinetics
Toxicity
Therapeutic
uses and
dosage
Spectinomycin
Site of action is
30 S ribosomal
subunit so as to
•
•
Acute
gonococcal
urethritis and
inhibit protein
synthesis in the
bacterial cells
Good
concentratio
ns achieved
in the
genital
tissue
Reduction
in urine
output
•
Reduction
in
heamoglobin
concentration
•
Elevation of
Hepatic
transaminases
154-B
proctitis where
400mg is
diluted in
normal saline
and given IV
MALARIA
Q.2. What is the standard recommended dose of chloroquine ?
Q.1. Mention some antimalarial drugs with their biological activities ?
A.2.
No. Class
Drug
Biological
ActivityTissue
Blood
Schizonticide
Schizonticide
1.
4-Amino quinolones
Chloroquine
2.
Arylamino-alcohols
Quinidine
++
-
Quinine
++
-
Mefloquine
++
-
Halofantrine
++
-
Proguanil
+
+
Chlorproguanil
+
+
Pyrimethamine
+
-
Sulfadoxine
+
-
Sulfalene
+
-
Tetracyclines
+
+
Doxycycline
+
+
-
+
3.
Phenanthrene
++
-
OR
The drug of choice is chloroquine (Resochin). Give 16.7 mg/kg body
weight (10 mg base/kg) immediately followed by 8.3 mg/kg (5 mg base
/ kg) at 6, 12, 24 and 36 hours to reach a total dose of 50 mg / kg (30 mg
base / kg).
methanlol
4.
Antimeta-bolites
Q.3. What is the antimalarial chemotherapy in chloroquine sensitive
falciparum malaria ?
A.3.
Dapsone
5.
Antibiotics
8-Amino-quinolone
Primaquine
7.
Artemisinin
Artesunate,
derivatives
Artemether,
Q.4
8.
Mannich base
++
-
Pyronaridine
++
-
What are the common adverse effects of chloroquine ?
A.4.. Adverse effects related to chloroquine are rare and mild, when the drug
is given orally.
Arteether,
Artelinic acid
The intramuscular doses for adults and children are 3.5 mg/kg every 6
hours or 2.5 mg/kg every 4 hours to a total dose equivalent to 2.5 mg of
base / kg body weight.
If given i.v., chloroquine 10 mg base / kg in isotonic fluid by constant i.v.
infusion over a period of 8 hours, followed by 5 mg / kg body weight
during next 24-hours.
Minocycline
6.
Chloroquine - a 4-aminoquinoline is usually given orally in a 3 day course
for the curative treatment of chloroquine-sensitive P. falciparum and P.
malaria and for termination of an acute attack of P. vivax or P. ovale
malaria. The standard regimen consists of 10 mg base per kg of body
weight followed by 5 mg/kg 6-8 hours later and 5 mg/kg on each of the
second and third days.
compound
155-A
155-B
■
Nausea and vomiting on empty stomach.
■
Headache and difficulty in visual accommodation.
■
Pruritus of the palms, soles and scalp in about 20% of Africans
and Asians, more in adults than children. It is not relieved by
antihistaminics.
■
Photoallergic dermetitis, pigmentation of the skin, leukopenia,
bleaching of hair and aplastic blood disorders are rare.
There is a degree of cross resistance between quinine and mefloquine,
suggesting that, the wide - scale use of quinine might influence the
future efficacy of the other valuable drug.
Q.5. Management of severe malaria in pregnancy ?
A.5.
In general Chloroquine is contraindicated in pregnancy , if required only
then it should in Pregnant women with malaria must be treated promptly
Q.7. What are the common toxicities and limitations of quinine ?
A.7.
Mortality is 2-10 times higher than non-pregnant women. They are more
susceptible to hypoglycemia, acute pulmonary oedema and severe
anaemia.
■
Pregnant women with severe malaria should be transferred to
intensive care if possible.
■
Monitoring of uterine contractions and foetal heart rate may reveal
asymptomatic labour and foetal tachycardia, bradycardia or late
deceleration in relation to uterine contractions, including foetal
distress.
■
Anorexia, nausea and vomiting may occur after the few doses, although
these may be difficult to distinguish from the symptoms of acute malaria.
Diarrhoea and abdominal pain.
ECG changes consisting primarily of delayed A. V. conduction,
bradycardia etc. and rarely A. V. block.
Quinine may potentiate orthostatic (postural) hypotension.
Drug fever.
Once labour has started, foetal or maternal distress may indicate
the need to shorten the second stage of labour by forceps or vacuum
extraction, or cesarean section.
Hypoglycemia due to malaria may be aggravated by oral treatment even
with low doses of quinine as a result of stimulation of insulin secretion.
Q.6. What is the status of quinine today ?
A.6.
The extension of chloroquine resistant P. falciparum has prompted an
increase in the need for quinine for the management of patients. It is
administered orally or by injection at a dose of 10 mg salt/kg of body
weight given 3 times a day for a period upto 10 days.
Certainly quinine is one of the most valuable antimalarial drugs available
because of its rapid schizonticidal action in most malarious areas.
Less frequent but more serious side effects include urticaria, asthma,
thrombocytopenia, haemolysis, oedema of eyelids, mucous membranes
and lungs. These may occur following a single dose, necessitating
immediate discontinuation of drug.
Q.8. What are the conventional dosages of primaquine in clinical
practice ?
A.8.
Decreasing sensitivity to quinine has occurred particularly when therapy
is given in an unsupervised and ambulatory setting and involved regimens
longer than 3 days.
All dosages are described in terms of the base.
Radical treatment of P. vivax and P. ovale malaria :
Adults : 0.25 mg/kg or 15 mg daily for 14 days following standard
chloroquine therapy or if G6PD deficiency is known or suspected
0.75 mg/kg weekly for 8 weeks.
Prolonged courses give rise to high frequency of side effects.
156-A
Cinchonism occurs in many patients taking quinine : giddiness, lightheadedness, transient hearing loss, tinnitus, blurred vision etc. may
appear at therapeutic blood concentrations of 5-10 mg/ml.
156-B
Children : Over 1 year of age, 0.25 mg/kg daily for 14 days after standard
chloroquine therapy.
Gametocytocidal therapy :
Q.11 What is the dosage of pyrimethamine / sulfadoxine combination
A.11 Adults : Pyrimethamine 75 mg plus sulfodoxine 1.5 g (i.e. 3 tablets
each of 25 mg pyrimethamine & sulfadoxine 500 mg) in a single dose.
(b)
Adults and Children : 0.5 - 0.75 mg/kg in a single dose.
Children :
Q.9. What are the symptoms of overdosage of primaquine ? How is it
treated ?
Weight in kg
31 - 45
2
A.9.
21 - 30
1.5
Symptoms of overdosage of primaquine are :
dose in tablets
■
Gastrointestinal symptoms
11 - 20
1
■
Weakness
5 - 10
0.5
■
Methhaemoglobinaemia
■
Cyanosis
■
Jaundice
■
Bone-marrow depression etc.
■
There is no specific antidote and treatment is consequently
symptomatic.
A single dose usually suffices to eliminate infection, but quinine should
additionally be given for 1-3 days in P. falciparum malaria to severely
infected patients, in whom quinine may accelerate reduction of
parasitaemia and clinical improvement.
Q.12. How artemisinin derivatives are classified ?
A.12 Artemisia annua
Q.10 What is the rationale of pyrimethamine / sulfadoxine
combination ?
:
Chinese herbs
Alkaloid
:
Artemisinin
Derivatives
:
Artemether (Paluther, Rhone- Poluenc)
Arteether (Artesunate (Arnate, Mesco;
Falcigo, Cadila HC)
A.10 A combination product containing two compounds that are presumed to
act synergistically to inhibit folic acid metabolism : a dihydrofolate
reductase inhibitor, pyrimethamine and a dihydropteroate synthase
inhibitor, sulfadoxine. The combination has blood schizonticidal activity
against P. falciparum and to a lesser extent, P. vivax..
Q.13. What is the mechanism of action of artemisinin compounds ?
A.13. Destroys erythrocytic forms of P. vivax and P. falciparum.
Toxic to parasites.
The two constituents were first used in combination, following rapid
development of resistance to pyrimethamine alone, to treat P. falciparum
infection unresponsive to chloroquine. Strains of P. falciparum and P.
vivax resistant to this combination are now widespread.
157-A
Destroys cell membrane of parasites.
157-B
Authorised only for hospital usage.
Q.14. What are the strengths and weaknesses of artemisinin
compounds ?
Q15
A.14 Strengths
A.15 Quick parasite clearance.
■
Resistance low.
■
Rate of parasite clearance equal to Chloroquine.
■
WHO recommended for Chloroquine resistant malarial.
■
Well tolerated
Ease of administration is a distinct advantage in remote rural areas.
Effective in multidrug resistant falciparum malaria.
Weaknesses
■
■
What are the distinct advantages of artesunate ?
Chances of development of drug resistance are low
Artemether i.m. only.
160 mg initially 1st day, then 80 mg x 4 days.
Q.16. What are the strengths and weaknesses of Mefloquine
5 day treatment
A16. Strengths
Injection painful - cost.
■
Effective in single dose 15 mg / kg body weight (3 tabs. for adults).
Expensive medication given in a form of injection.
■
Effective against Chloroquine resistant malaria.
1 b.d. x 3 days
■
Mefloquine is distributed extensively in the tissues, and because
of its longer half life, it is cleared slowly from the body. This increases
its efficacy.
WHO recommendation is for 5 days.
■
in serum transaminases.
Weakness
ECG abnormalities
■
Probability of inducing resistance very high.
■
Resistance increasing world-wide.
■
No parenteral formulation.
■
High propensity to cause adverse effects such as nausea, vomiting,
diarrhoea, abdominal pain, bradycardia, dizziness, light
headedness (starts in 4-6 hours and resolves in few days).
Potentiation of side-effects of Mefloquine.
Nausea, vomiting, dizziness, itching, convulsions.
■
Recrudescence rate very high.
Artesunate oral (Arnate) and iv/im (Falcigo)
Parenteral only for severe malaria
Oral dose 100 mg bd on day 1, then 50 mg bd x 6 days.
Q.17. What is halofantrine ? What are its characteristics and dosages ?
If given less than 7 days, a dose of Mefloquine to be given
A.17. Halofantrine, a phenanthrenemethanol is water soluble and fat soluble
antimalarial registered in 1988 in France.
Prolonged duration of therapy
■
Indicated only for severe and Chloroquine resistant malaria, cerebral
malaria.
158-A
■
158-B
It is a blood schizonticide with an activity comparable to that of
mefloquine.
■
It appears to have activity against some but not all mefloquine
resistant isolates in these models.
■
The drug is marketed as tablets containing 250 mg halofantrine
hydrochloride (233 mg base) and as a suspension containing 100
mg hydrochloride in 5 ml (93 mg base).
■
Dose for adults is two 250 mg tablets given 3 times at 6 hour intervals.
■
Dose for children is 8 mg/kg of body weight in 3 doses at 6 hours
interval.
■
Irregular absorption and variable peak levels are likely to affect the
clinical effectiveness.
■
It can be useful compound for the treatment of chloroquine resistant
falciparum malaria.
159-A
159-B
NEWER ANTIMALARIALS
Drug and
dosage
Mechanism of
action
Kinetics
Toxicity
Therapeutic use
Mefloquine
Structural
derivative of
quinine It raises
intravesicular pH
of the malarial
parasite leading
to its inhibition,
acts as a blood
schizonticide
•
•
•
250mg , 5 tabs
stat or 1250mg
For prophylaxis
250mg once
weekly for 4
weeks
Halofantrine
500mg every 6
hourly for 3
doses
Atovaquone
250mg
Atovaquone and
100mg proguanil
. Given as 4
tablets initially
Blood
schizonticide but
has quicker
action than
mefloquine but
lesser cure rates
Generally used
along with
proguanil .
Atovaquone
inhibits parasitic
mitochondrial
transport
whereas
proguanil
inhibits the folate
metabolism of
parasite
•
•
•
Long
terminal half
life of 14
days
Extensive
volume of
distribution
Long half
life of 10
days
Produces
active
metabolite
which is
responsible
for action
•
Intermediate
half life of 3
days
•
Good
volume of
distribution
•
Dietary fat
increases the
absorption
•
•
Vomiting,
dizziness,
syncope and
extrasystoles
Emotional
pyschiatric
disturbances
Prolongation
of QTc
interval,
chest pain,
hypotension
•
Arthralgia
•
Abnormal
vision
•
Raised
Hepatic
enzymes
•
Abdomial
pain,
diarrhoea,
vomiting
•
Elevation of
hepatic
enzymes
Treatment of
acute
malarial
infectionsdue
to P.
Falciparum
•
Moderate
parasetemia
with P.Vivax
and P.
Falciparum
resistant to
choroquine
•
Mechanism of
action
Kinetics
Toxicity
Therapeutic use
Artemisinin
They act against
blood parasites
including the
sexual forms of
plasmodiaand
reduce
transmissibility
•
Long half
life in blood
•
•
•
High volume
of
distribution
Prolongation
of PR and
QTc interval
•
Hypotension
•
Ischemia of
lower
extrimities
Analouges
Prophylaxis
of P.Vivax
and P.
faciparum
strains
resistant to
chloroquine
•
•
Drug and
dosage
Artesunate
Artemether
Arteether. These
are soluble
derivatives of
artemisinin from
Chinese herb
Artemisia annua
Less
emergence of
resistant
strains
NEWER TOPICAL ANTIFUNGALS
Drug , strength
and duration
of application
Mechanism of
action
Kinetics
Toxicity
Therapeutic
usage
Bifonazole 1%
(Mycospor)
cream to be
applied for 3
weeks only,
once a day
Dual mode of
action . Inhibits
HMG-COA
reductase and
ergosterol
synthesis
•
Highly
lipophilic
•
•
Tinea
corporis
•
Mild anti
inflammator
y action and
hence useful
in fungal
inflammation
•
Tinea cruris
•
Tinea
versicolor
•
Candidial
infections
of skin and
glans penis
•
Erythrasma
Prophylaxis
of P.
falciparum
malaria
where
chloroquine
resistance is
reported
Treatment of
acute and
uncomplicate
d P.
Faciparum
malaria
160-A
•
Treatment of
acute and
complicated
P. falciparum
malaria
160-B
Local
irritation on
the skin
Anti acne Drugs
Features
Retinoic acid
receptor subtype
Comedolytic action
Adapelene
Specific action
Topical modalities for psoriasis
Tretinoin
Modalities
Non specific action , also
binds to cellular retinoic acid
binding proteins
Dose related action
as has good anti
inflammatory action
involving lipo
oxygenase & cyclo
oxygenase enzymes
Detachment of cornified cells
Absorption
Less
More
Side effects
Erythema, pruritus,
scaling , burning
Reddening, blistering and
crust formation
Dose
Efficacy
Gel applied once a
day , for 8-12 weeks
Better
Advantages
Disadvantages
Remarks
Emollients
No side effects
Low efficacy
Mainly useful as
an adjuvant
Occlusive
dressings
• Useful for palmo
• Folliculitis
• Plantar psoriasis
• Miliaria
Useful as an
adjuvant
Tar
• Quite effective
• Messy, odor, folliculitis
• Long remissions
• Irritant dermatitis
• Photosensitivity
• Skin pigm entation
• Tim e tested
therapy
• Useful in
com bination
with UV light
• Not usitable for face
and flexural areas
Diathranol
• Effective
• Short contact
therapy
Corticosteroids
Gel , cream or liquid , once a
day , for 6-12 weeks
• Suitable for face,
flexures and
genitalia
• Easy to apply
• Cosm etically
acceptable
Vitamin D
analogue
(calcipotriol)
• Irritant and allergic
dermatitis
• Staining of clothes and
skin
• Tachypylaxis
• Rebound flare
• HP axis suppression
• Skin atrophy
• Pigmentary changes
• Non-irritant
• Telangiectasia
• Non-messy
• Irritant
• Non-staining
• Hypercalcaem ia
• Hypercalciuria
Relatively less
Useful in
com bination
with UV light
• Intralesional
steroids for
nail psoriasis
and resistant
plaque type
• Can be used
in combination
with other
agents
• Can be used
in combination
with steroids
• Should not be used
with salicylic acid as
this gets inactivated in
acidic medium
Tazarotene
• Quite effective
• Once daily
application
• Pregnancy category X
drug
• Mild irritation
• No evidence of
accumulation in any
tissue
Topical
methotrexate
Useful for
palm oplantar pustular
psoriasis
• Percutaneous
absorption is not
satisfactory
• Contact irritant
dermatitis
161-A
161-B
• Useful as
monotherapy
as well as in
com binations
• Useful if
dispensed
with
penetration
enhancers
Drug , strength
and duration of
application
Mechanism of
action
Ornidazole 1%
cream to be
applied for 3-4
weeks, once or
twice daily
Inhibits
ergosterol
synthesis of the
fungi
Kinetics
•
•
Terbinafine 1%,
applied once
daily for 2
weeks. Allyl
amine derivative
Inhibits squalene
epoxidase
enzyme , thus
blocking the
fungal synthesis
of ergosterol
Butanefine 1%
applied once
aday for 2 weeks
Allyl amine
derivative
Potent inhibitor
of squalene
epoxidae enzyme
•
•
•
Good
penetration
in the dermal
layers of the
skin
Toxicity
•
Local
irritation of
the skin
Remains in
skin for
considerable
period of
time
Good dermal
penetration
Eliminates
resistant
fungal strains
Resistant
strains are
eliminated
•
Local
irritation of
skin
•
Pruritis
•
Local
irritation of
skin
•
Pruritis
Therapeutic
usage
•
Tinea
corporis
•
Tinea cruris
•
Tinea
versicolor
•
Erythrasma
•
Drug, dose and Mechanism of
duration
action
Ornidazole
500mg , twice
day for 5-7
days
Tinea cruris
•
Tinea
versicolor
•
Tinea
corporis
•
Tinea cruris
Secnidazole
500mg tablets ,
One gram as
stat dose
Causes
breaking of the
DNA strands
Tinea
versicolor
Paromomycin
25mg/kg /day
in three divided
doses
Chemotherapy
Cause breaking
of DNA strands
Kinetics
Toxicity
Therapeutic
usage
•
Good
absorption
Lesser metallic
taste in mouth
•
•
Eliminated
by liver
Lesser
incidence of
antabuse
reaction
Amoebiasis
both
intestinal
and hepatic
•
Trichomoni
asis
•
Anaerobic
bacterial
infections
•
Giardiasis
•
Amoebiasis
both
intestinal
and
extraintestin
al
•
Trichomoni
asis
•
Acute and
chronic
amoebiasis
•
Hepatic
coma
•
Parasitic
infections
of GI tract
Tinea
corporis
•
•
NEWER ANTIAMOEBICS
162-A
162-B
Causes
disruption of
cell membrane
of amoeba
•
Slow
•
absorption
achieves
high
concentratio
n in 12
hours
•
Preferential
elimination
by liver
•
•
•
Poor GI
absorption,
•
100%
recovered in
stool
Moderate
GI
irritation,
nausea,
headache
and metallic
taste in
mouth
Leucopenia
Diarrhoea
Abdominal
cramps
Chemotherapy
ANTIVIRAL AGENTS
Drug and
dosage
Mechanism of
action
Kinetics
Toxicity
Therapeutic
usage
Foscarnet
sodium available
as 24 mg /ml
injection . The
total dosage
given is 90mg/kg
Inhibits activity
of viral
transcriptase
•
•
Fever,
nausea,
anaemia
•
•
Hypertension
and
palpitations
•
Acyclovir
resistant viral
infections
•
Elevation of
hepatic
transaminases
•
Hepatitis
sero
infections to
reduce viral
load
•
Hypertension
•
•
Abnormal
vision
•
Gancyclovir
available
as500mg
capsules and
injectable
Inhibits activity
of viral
transcriptase
enzyme
Cidofovir given
as intraocular
injection
75mg/ml
Inhibits activity
of viral
transcriptase
enzyme
Chemotherapy
•
Dose to be
reduced in
renal
impairment
Achieves
high
concentratio
n in most
tissues
Quick
inhibition of
viral
replication
•
Quick
achievement
of the steady
state
•
Good
concentratio
n in ocular
tissues
•
Taste
changes
•
Hypertension
•
Migraine
•
Electrolyte
disturbance
•
Insomnia
•
Cytomegalov
irus
infections
Cyomegalovi
rus
infections.
The recent
introduction
in this group
is
Valganciclov
ir which is
given
as450mg
tablet, twice
daily for
about 2
weeks
Drug and
dosage
Mechanism of
action
Kinetics
Toxicity
Therapeutic
usage
Ribavirin
200mg capsules
twice or thrice
daily or aerosol
preparation
Inhibits activity
of the viral
transcriptase
enzyme
•
•
Hypotension
•
•
Bronchospasm
•
Insomnia
•
Elevation of
hepatic
transaminases
Chronic
hepatitis C
infection or
those who
have
relapsed
following
interferon
therapy
High tissue
concentratio
n due to
large volume
of
distribution
•
Vomiting,
diarrhoea,
bronchitis
•
•
Insomnia
Prophylaxis
and
treatment of
influenza
infections
•
Verigo
More free
drug acts
since it is
poorly bound
to the plasma
proteins
•
Elevation of
hepatic
transaminases
Oseltamivir
available as
75mg capsule to
be given twice
daily
•
Inhibits the
activity of the
viral
transcriptase
enzyme
•
•
Long tissue
retention and
also has long
half life
Can induce
hepatic
isoenzymes
and therefore
many
interactions
Specially for
cytomegalic
viral
infection of
the eye
163-A
163-B
Chemotherapy
CEPHALOSPORINS
Drugs and
dosage
Mechanism of
action
Kinetics
Toxicity
Therapeutic
usage
First
Generation :
Cephalosporins
inhibit
mucopeptide
synthesis in
bacterial cell
wall making it
osmotically
unstable and
are effective in
bacterial
multiplication
stage
•
•
•
•
•
Cephradine
500mg
twice daily
as injectable
or capsule
Cefadroxil
250mg 500mg
twice daily
tablets
Second
generation :
•
Cefuroxime
250mg 500mg
twice daily
as
dispersable
tablets
•
Cefotetan 1
gram
injectable as
IM or IV
•
Loracarbef
500mg
capsules
Chemotherapy
Bactericidalsame as above
•
•
•
•
•
Good oral
absorption
and tissue
distribution
Effective
mostly
against
gram
positive
organisms
Resistance
develops
frequently
Effective
against
gram
negative
organisms
too
Resistance
develops
less
frequently
•
Nausea,
vomting,
diarrhoea
Angioedema
•
Lower
respiratory
tract
infections
Upper
respiratory
tract
infections
•
Chills
•
Malaise
•
Urticaria
•
Otitis media
•
Hypotension
•
Skin and
soft tissue
infections
•
Vertigo,
headache,
insomnia
•
Urinary
tract
infections
•
Same as
above
•
Same as
above
•
Antabuse
reaction
•
Typhoid
fever
•
Nephrotoxic on long
term use
•
Shigellosis
•
Bone
infections
•
STD due to
Chancroid
Drugs and
dosage
Mechanism of
action
Kinetics
Toxicity
Therapeutic
usage
Third
generation :
Bactericidal
•
•
Same as
above
•
•
Phlebitis at
injectable
site
Severe
respiratory
tract
infections
•
Septicemia
•
Peri
operative
prophylaxis
•
Bone
infections
•
Bacterial
meningitis
•
Typhoid
fever
•
Pelvic
inflammatory disease
•
•
•
Cefixime
200mg once
or twice
daily as
required
Cefotaxime
IM or IV
500mg
twice daily
Ceftriaxone
IM or IV
500mg
twice daily
•
•
Wider
coverage of
micro
organisms
Least
propensity
for development of
resistance
Excellent
tissue
distribution
high
concentrations in
CNS
Excellent
tissue
distribution
in order to
eradicate
tough
organisms
164-A
164-B
Chemotherapy
NEWER PENICILLINS
D rug
M echanism of
action
K inetics
Toxicity
Indications
A m oxycillin
(A ugm entin,
Clam ox)
500m g+
Clavulanate 125
m g, given tw ice
daily for 5-10
days
U nique
bactericidal .
A m oxycillin is
am inopenicillin
w ith w ide
coverage
w hereas
clavulanate is for
inactivating beta
lactam ase
enzym es
produced by
bacteria and
hence there is no
virtual
developm ent of
resistance
•
G ood tissue
distribution
•
•
•
Excellent
concenterations in gall
bladder
Ticarcillin 3
gram and
clavulanate
100m g used as
IV infusion
given 6 hourly
Chemotherapy
Sam e as above.
Ticarcillin has a
w ider range of
activity and there
is lesser
incidence of the
developm ent of
resistance even it
is used alone
•
•
G ood
concenterations in all
tissues
Effective
against
various
strains of
Pseudom onas
aeruginosa
•
•
N ausea
vom iting ,
diarrhoea
Skin rashes
•
Sam e as
above
Low er
respiratory
tract
infections
Severe
upper
respiratory
tract
infections
•
Skin and
soft tissue
infections
•
U rinary
tract
infections
•
Typhoid
fever
•
Still
rem ains the
best choice
for m any
infections
•
Septicem ia
•
Low er
respiratory
tract
infections
•
Bone and
joint
infections
•
G ynecologi
c infections
•
Intra
abdom inal
infections
•
U rinary
tract
infections
•
Streptococcal
infections
165-A
Drug
Mechanism of
action
Kinetics
Toxicity
Indications
Piperacillin
sodium, 2 3gram given 12
hourly. Can
also be
available with
250mg
tazobactum
Bactericidal- acts
on cell wall
•
Good tissue
distribution
•
•
•
Pseudomonas
aeruginosa
Intra
abdominal
infections
•
Urinary
tract
infections
•
Gynecologi
c infections
•
Septicemia
•
Bone and
joint
infections
•
Gonococcal
infections
•
Acute and
chronic
infections
of upper
and lower
respiratory
tract
•
Urinary
tract
infections
•
Prostatitis
•
Preferred
drug for
pseudomonas
infection
Carbenicillin
382 mg and
Indanyl ester
118mg , given
every 12 hourly
165-B
Bactericidal- acts
on cell wall
•
Same as
above
•
Same as
above
Same as
above
Chemotherapy
ANTI-FUNGAL AGENTS
(C) Agents for urinary tract infections
Organism
Acute infection
Chronic infection Bacteraemia
1. Escheria coli
Cephalosporins
Cotrimoxazole
Nitrofurantoin
Ampicillin
Norfloxacin
Perfloxacin
Ciprofloxacin
Gentamycin
2. Enterobacter
Tetracycline
Nalidixic acid
Nalidixic acid
Gentamycin
3. Klebsiella
Nalidixic acid
Chloramphenicol
Nalidixic acid
Carbencillin
4. Proteus
Ampicillin
Cephalosporin
Cephalosporins
5. Pseudomonas Gentamycin
Ciprofloxacin
Polymyxin
Gentamycin
6. Entero coli
Ampicillin
Ampicillin
Ampicillin,
Tetracyclines
Drug
Use and dose
Toxicity
1. Nystatin
(Mycostatin)
Candidiasis of skin, mouth,
intestines and vagina.
Tablets - 5 lac units, B.D.
units
Cutaenous irritation
if applied locally,
mild gastrotinal
irritation.
2. Amphoterecin-B
(Fungizone)
Systemic fungal infection such
as Candidiasis, Histoplasmosis,
Cryptococcosis, Coccidioidomycosis. I.V. --2900 mg every
6 hourly or as 3% cream.
I.V. administration
causes : Nephrotoxicity,
anaemia, paraesthesia.
Difficulty in micturition.
3. Griseofulvin
(Idifulvin)
Rignworm infection of hair, skin
and nails, 1 g daily orally in
divided doses
Headache, thirst,
skin eruptions,
dysgeusia (perversion
of taste)
4. Clotrimazole
(Canesten)
Candidiasis, Trichomoniasis of
skin and vagina are effectively
treated. Vaginal tablets -- 100
to 200 mg 1% cream for skin.
Irritation, pruritis
Burning of skin
5. Miconazole
Systemic candidiasis can be
(Zole, Valbet) effectively treated. 2.5%
ointment, 250 mg, 4 times a day,
orally, 25 mg / kg I.V.
6. Tolnaftate
(Tinaderm)
Chemotherapy
166-A
166-B
Topical application
leads to irritation,
whereas systemic
administration leads to
diarrhoea and
hyperlipedemia
It is applied topically for the
treatment of Trichophyton
rubrum infection, which is in
general resistant to griseofulvin.
1% lotion, cream or powder,
which has to be rubbed for
2 to 3 weeks.
Chemotherapy
ANTI-VIRAL AGENTS
Vaccination Chart
The Government of India recommends, the following schedule for vaccinations:
Drug
Use and dose
Toxicity
1. Acyclovir
Herpes simplex keratitis. 3%
Mild local irritation
(Herperex,
ointment is used. Lotion (1-5%)
Zovirax)
is used with some success in
Age
Vaccine
Birth
BCG
6 weeks
Oral polio Vaccine (OPV) and Diphtheria, Pertussis
and Tetanus (DPT)
10 weeks
OPV, DPT
14 weeks
OPV, DPT
9 - 12 months
Measles
15 - 18 months
OPV, DPT
Hallucinations.
4 - 5 years
DT, Typhoid
10 - 16 years
Tetanus, Typhoid
Herpes zoster.
2. Cytosine-
Herpes * Simplex * Zoster
Bone marrow
arabinoside
* Hominis, Vaccina virus ½%
stomatitis.
and
opthalamic ointment,
Iododeoxy-
100 mg/kg I.V.
depression,
uridine
3. Amantadine
Influenza A, A1, A2 and C
and
viruses 150 mg/day, orally. It is
Difficulty in
Rimantadine
most effective when given
concentration.
within 24 hours of infection.
4. 3-Azadiedothymidine
5. Inter-feron
Probably effective against
Vomiting, fever, bone
AIDS virus.
marrow depression.
1. Viruses :- Measles, hepatitis,
Irritation, skin rashes
rabies and poliomyelitis
2. Tumors :- Ovarian bronchogenic carcinoma, malignant
melanoma. Route : IM/IV
Topical
Chemotherapy
167-A
167-B
Toxicity
Group
Cisplatin - nephrotoxic and ototoxic and causes severe nausea and vomiting
5. Nitrosoureas
CCNU, BCNU
Lymphoma, brain tumours
Carboplatin - well tolerated; myelosuppressive
6. Platinum
compounds
Cisplatin
Carboplatin
Testicular tumours;
ovarian cancer;
lymphomas
Durg
Mode of action
Inhibit cell replication of forming covalent bonds with bases in nuclear DNA and
bind to bases in opposite strands of the DNA double helix and thus prevent
strand separation prior to DNA replication. Also alkylate proteins and enzymes
to produce cellular dysfunction.
Uses
Mode of Action
Methotrexate
Irreversible inhibition of dihydrofolate
analogue of folic acid
reductase which blocks the reaction uridylate
→ thymidylate due to the failure of formation
of active folate to act as a methyl group carrier.
Antimetabolites
Group
Durg
Uses
1. Folic acid
antagonists
Methotrexate
Acute lymphoblastic
leukaemia
Lymphomas
Chorioncarcinoma
Solid tumours, e.g.
osteogenic sarcoma
G-mercaptopurine (6 MP)
analogue of adenine
6 MP is converted to the 5-phosphate
nucleotide (thioinosinate) which blocks purine
synthesis at several steps (including; IMP →
adenylosuccinate; synthesis of guanylate;
glutamine + PRPP → ribosylamine-5-phosphate).
2. Purine
antagonists
6-mercaptopurine
6-thioguanine
Acute leukamias
Acute leukamias
5-FLUOROURACIL (5FU)
analogue of uracil
3. Pyrimidine
antagonists
5-fluorodeoxyuridine
5-fluorouracil
Adenocarcinomas of the
gastrointestinal tract
Carcinoma of breast and
ovary
5 FU is converted to the 5'-phosphate
nucleotide (F-UMP) and then to the
deoxynucleotide (5-dUMP). The latter inhibits
thymidylate synthetase.
Cytosine arabinoside
Cytarabine is converted to the 5'-phosphate
(Cytarabine) analogue of
nucleotide (ara-CTP) which inhibits
cytidine
nucleoside diphosphate reductase and RNAdependent DNA polymerase (reverse transcriptase).
6-thioguanine
Incorporated into DNA in place of guanine.
6-azauracil
6-azauridine
Cytosine arabinoside
4. Diepoxides
Acute leukaemias
Acute myeloblastic
leukaemia
Ethoglocid
analogue of guanine
168-A
168-B
Plant Alkaloids
Uses
Vinca alkaloids (from periwinkle) : vincristine; vinblatine; vindesine
Wilm's tumour of kindey (children), chorioncarcinoma, embryonal rhabdomyosarcoma.
Mode of Action
Bleomcin (mixture of polypeptides)
Bind to microtubules and disrupt spindle formation so chromosomes do not
separate at mitosis. Affect other microtubular functions (e.g. membrane mobility and transport) and enyzme activity.
Vincristine
–
_
toxicity : mainly peripheral neuropathy
uses : leukaemia, lymphomas, neuroblastoma, sarcoma
Vinblastine
–
–
toxicity : mainly myelosuppression
uses : lymphomas, breast cancer, chorionepithelioma
Mode of action
Fragments DNA and inhibits thymidine incorporation into DNA.
Main problems : pulmonary fibrosis, acute flu-like illness after injection; pigmentation of skin.
Uses
Etoposide (from May Apple)
Lymphomas, testicular teratomas, cancer of head and neck.
Mode of action
Other Anti-Neoplastic Drugs
Spindle poision but not by binding to microtubules; blocks DNA synthesis.
Mitozantrone
An anthracenedine resembling and anthracycline which acts as an intercalating agent but has less cardiotoxicity, causes less alopecia, is less irritant but
is more myelosuppressive. Used in breast cancer.
Uses
Lymphomas, small cell lung cancer, leukaemia.
Antitumour Antibiotics
Anthracyclines
Procarbazine
Doxorubicin (Adriamycin); daunorubicin, epirubicin.
A weak MAO inhibitor
Mode of action
Mode of action.
Intercalate DNA helix thus uncoiling and preventing DNA and RNA synthesis.
Also damage cell membrane and form the free radicles which peroxides lipids.
Depolymerizes DNA – probable alkylating agent.
Main problems: locally irritant (if given outside vein by accident); alopecia; doserelated cardiotoxicity.
169-A
Uses
Hodgkin's lymphoma.
169-B
Etoposide
Uses
Epipodophyllotoxin (synthetic derivative of podophyllotoxin).
Acute leukaemia.
Hormones
Mode of action
May produce remission in some cancers but do not eardicate disease.
Causes single strand DNA breaks and inhibits replication.
1.
Toxicity
Oestrogen used for two cancers which are partially hormone–dependent
a.
Prostatic carcinoma–oestrogens e.g. diethylstiboestrol block androgen production with remission in 60% patients with advanced disease
b.
Breast cancer–oestrogens give remission in 30% women with advanced disease who are 5 years post-menopausal but may
exacerbate disease in younger women. Tumours with oestrogen
receptors 6 times more likely to respond (60%) than receptor negative
tumours (10%).
Myelosuppression dose limiting; alopecia
Paclitaxel is a taxane (taxolanalogue), a natural plant product
Mode of action :
Acts on micrtabules, prevents mitosis or multiplication of cells.
2.
Uses :
Anti-oestrogens for breast cancer
a.
Ovarian cancer
Has fewer side effects
Breast cancer
b.
Non-Hodgbin's lymphoma
Refractory prostatic cancer
Pancreatic cancer
Aminoglutethimide produces medical adrenalectomy by inhibiting
adrenal steroid synthesis and inhibits peripheral tissue aromatisation
of androgens to oestrogens.
Given with cortisone acetate (replaces cortisol) and fludrocortisone
alternate days (replaces aldosterone deficit). Produce sedation,
ataxia, dizziness (dose dependent and reduces with chronic therapy–
self–induction of metabolising enzymes). Used for breast and
prostatic cancer.
Polycystic kidney disease
L-asparaginase
An enzyme produced by E.coli.
Mode of action
3.
Some tumour (unlike normal) cells cannot synthesise asparagine.
Colaspase hydrolyses free tissue and plasma asparagine so depriving tumours
of exogenous amino acid.
Chemotherapy
Tamoxifen–competes with oestradiol for cytoplasmic receptor.
170-A
Progestogens, e.g. medroxyprogestrone acetate (Depo-Provera). May
produce remission in up to 30% breast cancer resistant to other hormones.
Also used in endometrial carcinoma. Few side-effects.
170-B
Chemotherapy
4.
5.
6.
Anti-androgens
Toxic effects of cancer chemotherapy
Cyproterone acetate, flutamide for prostatic cancer
Major problems due to inability of drug to differentiate normal from neoplastic
cells.
LHRH analogues
Leuproprelin, goserelin, buserelin. Equivalent in effectiveness to oesterogens
in prostatic carcinoma, with less toxicity
1.
Bone marrow: leucopenia; thrombocytopenia; rarely anaemia or total
aplasia. This leads to infection and bleeding.
Glucocorticoids
2.
GI tract : ulceration of mouth and intestine, diarrhoea
Inhibit lymphoid proliferation. Adverse effects numerous. Used in acute
and chronic lymphocytic leukaemia; multiple myeloma; Hodgkin's and
non-Hodgkin's lymphomas; breast carcinoma.
3.
Testis : azoospermia and infertility
4.
Ovary : infertility; premature menopause
5.
Hair follicles : alopecia
6.
Local irritation : some drugs cause ulceration if extravasated during injection
7.
Vomiting : major problem with some drugs. e.g. cisplatin, CCNU,
doxorubicin.
Biological Response Modifiers
1.
Imunotherapy
Specific antitumour monoclonal and polyconal antibody targeting. Under
intensive investigation for many tumour types.
2.
Lymphokines
Interferon–natural antiviral substances. Effective in hairy cell leukaemia;
also being investigated in renal carcinoma, CML and myeloma
3.
Longer term hazards to cancer chemotherapy
1.
Gonadal damage–alkylating agents, vinca, alkaloids, cytosine arabinoside. Azoospermia usual during treatment. Recovery often occurs but
may take several years (N. B. many patients have low sperm count before
treatment). Many women develop amenorrhoea after cytotoxic drugs but
periods restart when treatment stopped. Women may have premature
menopause.
Haemopoietic growth factors (G-CSF, CM-CSF, IL3) are being tested to
reduce myelosuppression with cytotoxic drugs
2.
Second malignancy e.g. after treatment of Hodgkins lymphoma with radio
and chemotherapy incidence of acute leukaemia increased.
Other
3.
Teratogenesis : avoid pregnancy for at least 4 months after end of treatment.
IL2 (± Lymphokine-activated killer (LAK) cells)
Modulation of the immune response under investigation in renal carcinoma. Toxicity due to vascular leak and multiple organ failure
4.
5.
Growth factors
Intensive search for specific growth factor receptor agonists and antagonist and antisense oligonulceotides to modulate individual tumour proliferation.
Chemotherapy
171-A
171-B
Chemotherapy
INTERFERONS
Agent
Action and kinetics Toxicity
Interferon alpha 2a
Antiproliferative
and have
immunomodulatory
activities
•
•
Headache,
depression,
irritability
Applications and
dose
•
Chronic
hepatitis C
•
Hairy cell
leukemia
•
Chronic
myeloid
leukemia
•
Tumors of
bladder,
ovaries
Anorexia
•
Agent
Action and kinetics Toxicity
Interferon alpha 2b
Same as above
•
Arthralgia
•
•
Musculoskeletal
pain
Hairy cell
leukemia
•
Flu like
symptoms
Malignant
melanoma
•
Follicular
lymphoma
•
Chronic
hepatitis B
•
Multiple
sclerosis
•
2 Million IU
SC thrice a
week
•
Chronic
hepatitisC
•
Renal cell
carcinoma
•
1mcg /kg/week
for a year
•
Therapy of
AIDS or
Kaposi
sarcoma
•
Various
metastatic
tumors
•
Supraclavicular
cancers
•
6 million
IU/week SC,
for 6months
•
•
3 Million
IU/vial ,SC
initial 4 units
followed by 1
unit as required
Peginterferon alpha
2b
Interferon beta
172-A
172-B
Same as above
Same as above
Applications and
dose
Depression
•
Headache,
insomnia,
dizziness
•
Alopecia
•
Migraine
•
Neuropyschiatri
c symptoms
•
Constipation
•
Injection site
reaction
HIV / AIDS
Say Yes or No
ACQUIRED IMMUNODEFICIENCY DISEASE (AIDS)
Drug
MOA
Resistance
Spectrum/
kinetics
Side effects
Zidovudine
AZT is converted
to nucleoside
triphosphate and is
incorporated to
infected virus
through DNA by
reverse
transcriptase
Ø
Ø
Patients
infected with
HIV
Ø
Ø
Ø
Ø
W ell absorbed
Short half life
Mostly
excreted in
urine
Didanosine
Zalcitabine
Stavudine
Lamivudine
Saquinavir
Ritonavir
Indinavir
Incorporated to
DNA chain ,
causing
termination of
chain elongation
Ø
Incorporated into
viral DNA & inhibits
viral transcriptase
Ø
Inhibits reverse
transcriptase to
cause DNA chain
termination
Ø
Inhibits reverse
transcriptase of
HIV & Hepatitis B
Virus
Ø
These are
aspartate protease
inhibitors which
suppress viral
replication
Ø
Efficacy
decreases
with time .
Resistant
strains have
lower affinity
for
transcriptase
Ø
Confined to
infection by
HIV-I
Ø
Given in
fasting state
Ø
More available
in CNS
Used when
AZT gives
resistance
Ø
HIV-1/II
infection
Used during
AZT
resistance
Ø
Used during
AZT
resistance
Ø
Continous ,
uninterrupted
therapy
prevents
resistance
Ø
Cross
resistance
with other
drugs not
reported
HIV-1/II
infection
Ø
Ø
Ø
Ø
Pancreatitis ,
which can be
fatal
Ø
Peripheral
neuropathy
Ø
Pancreatitis
Ø
Peripheral
neuropathy
If MIC/MBC is low, it signifies therapeutic inefficiency or bacteriostatic
action ?
2.
Bactericidal drugs give better clinical efficacy than bacteriostatic drugs ?
3.
Penicillins are still preferred in cases of Rheumatic fever and Sub acute
bacterial endocarditis ?
4.
Cefuroxime axetil is used in tuberculosis ?
5.
Erythromycin is a aminoglycoside ?
6.
Amikacin should be given twice daily parentally ?
7.
Rifampicin can turn all the secretions red ?
8.
Tinidazole and Metronidazole are both given twice a day ?
9.
Clotrimazole and Bifonazole are potent topical antifungals ?
10. Ciprofloxacin is the quinolone having broad spectrum as well many
indications ?
Answers
1.
Yes
2.
No
3.
Yes
HIV-1/II
infection
Ø
Pancreatitis
4.
No
Ø
Interacts with
Sulfonamides
5.
No
Resistant HIV
infections
Ø
Interaction
with various
drugs as
cytochrome
enzymesare
involved
6.
Yes
7.
Yes
8.
No
9.
Yes
Ø
Chemotherapy
Severe
anemia
Leukopenia
Seizures
Headache
NSAID`s, H2
blockers
increase
toxicity if
given
together
1.
Elevated liver
enzymes &
triglyceride
levels are
encountered
173-A
10. Yes
173-B
Chemotherapy
12
MISCELLANEOUS
Drug
Actions
Precautions
Applications
Chlorhexidine
gluconate
Persistent anti
microbial effect
even against
Pseudomonas
Hypersenstivity
Lactation
Skin cleanser
Acne vulgaris as
atopical lotion
2-4% solution
available
Oxychlorosene
sodium
Rapid action against
spores , viruses,
fungi and bacteria
Do not expose to
light
Used for treating
localised resistant
infections. Used as
0.4 % solution
1. Topical Anti Infectives
Drug
Actions
Precautions
Applications
Povidone Iodine
Water soluble
complex of iodine
with povidone It has
bactericidal activity
of iodine but is less
irritating to the
tissues
Should be avoided
in cases of iodine
hypersenstivity and
hypothroidism
Ointment, lotion,
solution, surgical
scrub available
Eradicates in vitro
HIV virus totally.
Commonly used
strength 10%
Germicidal,
effective against
bacteria, viruses and
fungi
Avoid in chemical
burns
Silver Nitrate
Strong caustic and
germicidal
Avoid contact with
eyes or with broken
skin
10% ointment and
solution to treat
indolent wounds,
ulcers, fissures and
following surgery
of warts
Benzalkonium
chloride
Cationic surfactant
which has rapid anti
infective properties
Should be avoided
in occlusive
dressings
Per and post
operative cleaning
of skin
Eye irrigation
Post episiotomy
care
Sodium
hypochlorite
0.25-0.5% as an
antiseptic solution
Enzymes are the biochemical catalysts in the living cells capable of producing
chemical changes in other substances without themselves being altered.
1.
Wet dressings
To protect metallic
instruments from
rusting
1% topical solution
available
Miscellaneous
2. Therapeutic enzymes
174-A
Hyaluronidase :Uses :- It increases absorption of fluids an therefore used to :1. Reduce absorption of haematomas.
2. To reduce post operative oedema.
3. When large volumes of fluids is to be given S.C.
Dose :- 150-1500 units/ml are available for injections.
2.
Chymotrypsin :Uses :i)
Traumatic andinflammatory states to reduce oedema.
ii)
In cases of cutaneous ulceration.
Dose :- 50,000 - 100,000 unit tables are available. 2-4 such tablets
are used per day.
174-B
Miscellaneous
3.
Firbinolysin :-
b)
Patients with sickle cell disease.
Use :-
c)
Dysfunctioning spleen.
Used in cases of thrombophlebitis, phlebitis and pulmonary embolism.
3.
Malarial antisporozoite and antimerozoite vaccine which just gives
9 months protection.
4.
Orally it aids digestion. Topically it digests fibrinoid and purulent discharges
in wounds. Given intravertebrally, it removes the nucleus pulposus in cases
of prolapsed intravertebral disc.
Hepatitis B surfacee antigen vaccine. The good antibody response is from
200th day after the 1st dose. It is indicated in medical personel coming in
contact with injectables and in male homosexuals. Routinely it should be
given to all susceptible population, since Asia and Africa are more prone
to get hepatocellular cancers.
5.
Dose :- Intra-coronary or I.V. administration 2 x 105 U as loading dose,
followed by 4 x 105 U every 90 minutes, or as directed by a cardiologist.
Influenza subunit H and N antigen vaccine. This is indicated in old
susceptible patients.
6.
Vaccine for congenietal cytomegalo virus.
7.
Vaccine for respiratory syncytial virus.
8.
Varicella zoster vaccine :- In children with chronic disease and in those
receiving cortisone or cytotoxic drugs. This vaccine gives good results.
9.
Contraceptive vaccines are under evaluation.
Dose :- 100,000 units/ml injectable solution.
4.
Papain :Uses :-
4. Vaccines and Sera
Immunity means a state of relative resistance which develops after exposure to
a specific agent which is responsible for infection. Vaccines and antisera thus
confer immunity. Active immunity develops following contact with pathogenic
organisms. It takes time to develop immunity. Active immunization therefore
includes the administration of a vaccine, live or killed, or toxoids. Passive
immunity develops by the production of anti bodies in one body and then it can
be given in a person requiring protection. It is mainly used for prevention. Though
it develops rapidly, has a short duration. It can be given through antisera or
immunoglobulins.
B) New Vaccines
1.
Whole cell vaccine for pertusis :- It has lower incidence of local reactions.
2.
Pneumoncoccal vaccine containing 14 serotypes. It basic indications are:a)
1.
Congenietal or acquired immune deficiency.
2.
Pregnancy except tetanus toxoid, which can be given.
3.
Skin conditions such as :- Pyoderma, dermatitis or chronic eczema.
4.
Severe anaemia or gross malnutrition.
5.
Blood disorders such as leukemia.
6.
Immunosuppressive therapy and ionising radiations.
7.
Febrile disorders.
Immunisation has relieved humanity from small pox and has reduced the
Patients over 50 years of age who are under risk.
Miscellaneous
Contraindications for the use of vaccine :-
175-A
175-B
Miscellaneous
incidences of many diseases. There still exists continuous antagonism between
man and microbes and hence the newer vaccines will continues to develop.
2.
Calcium disodium edetate (E.D.T.A) :Uses :-
Contraindications for the use of vaccine:-
1.
Lead poisoning (from chemical exhaust and by putting certain toys
in mouth).
Pregnancy except tetanus toxoid, which can be given.
2.
Useful in iron, zinc, copper and maganese poisonings.
3.
Skin conditions such as:- Pyoderma, dermatitis or chronic eczema.
Side effects :- Proximal tubular necrosis fever, fall in blood pressure
4.
Severe anaemia or gross malnutrition.
Dose :- 1 gram diluted in 200 ml given I.V. slowly.
5.
Blood disorders such as leukemia.
6.
Imunosuppresive therapy and ionising radiations.
7.
Febrile disorders
1.
Congenietal or acquired immune deficiency.
2.
3.
D-Penicillamine :Uses
1.
Copper, mercury, lead and zinc poisonings.
2.
Hepatolenticular degeneration (Wilson's disease).
3.
Rheumatoid arthritis
4.
Primary biliary sclerosis
5. Chelating agents
5.
Scleroderma.
These drugs from stable, non-toxic easily excreted complex and are used in
heavy metal poisonings.
Side effects :- Proteinuria, myasthenia gravis.
Immunisation has relieved humanity from small pox and has reduced the
incidences of many diseases. There still exists continuous antagonism between
man and microbes and hence the newer vaccines will continue to develop.
1.
Dermercaprol (British Anti Lewisite):-
Dose :- 20-40 mg after each meal orally to decrease absorption of copper.
4.
1.
Poisonings due to arsenic, mercury, gold, bismuth, nickel and
cadmium.
2.
As an adjuvant with calcium edetate in lead poisoning.
Side effects :- Rise in blood pressure, burning sensations in mucus
membranes.
Contraindications : Iron poisoning, because here toxic complex forms.
Desferrioxamine B:Uses :1.
Acute iron poisoning.
2.
Patients who undergo repeated blood transfusions who are under
risk of haemosiderosis.
Side effects:- Fall in blood pressure, rashes, dysuria.
Dose :- 1 gram/day I.M.
Dose :- 5mg/kg stat I.M., followed by 2 mg/kg for 2 days.
Miscellaneous
176-A
176-B
Miscellaneous
6. Autacoids
9. Acne vulgaris :-
These are chemical substances produced by cells of different tissues at the
site of action (local action). In constrast to hormones, they are not secreted by
specialised group of cells and are not released directly into the blood. In very
small quantities they have diverse and intense pharmacological actions.
This is a common skin condition seen in puberty due to excessive androgenic
stimulation, particulary on face. There is redness, pustule formation and large
amounts of sebum is extruded.
Important autacoids are :Histamine, 5-HT (Serotonin), prostaglandins, angiotension and bradykinin.
Antihistaminics (H1 blockers) e.g. Cetirizine (Incid-L), are used in treatment
of allergic disorders.
5-HT antagonists e.g. Cyproheptadine and methysergide are used to control
certain allergic disorders. Cyprohepatdine is also used as appetite stimulant
(especially in children who refuse to eat).
Prostaglandins i.e. PGE2 and PGF2a and prostaglandin synthesis inhibitors
(aspirin). These are proinflammatory mediators and are responsibl for most of
clinical disorders related to skin, bronchus and other parts of the body. Aspirin
act as prostaglandin Antagonists.
Angiotensin converting enzyme inhibitors (Ramipril) and angiotensin receptor
antagonist (Telmesartan) are used in treatment of hypertension.
7. Astringents :These exogenous substances precipitate the surface proteins. e.g. Tannic acid,
bismuth carbonate, aluminium sulphate and zinc oxide.
8. Counterirritants :These are topically applied drugs to releive pain originating from deeper organs
by rubbing them superficially on the skin.
e.g. Turpentine oil, camphor, methylsalicylate etc.
Miscellaneous
177-A
The drugs used are :i)
Topical
:- Retionic acid and benzoyl peroxide.
ii)
Systemic :- These are effective against propionibacterium acne e.g.
Tetracyclines, erythromycnand artinoids.
10. Bodylice:For pediculosis i.e. body lice, the drugs used are Sulphur, benzyl benzoate
(25%) and crotamiton. The lice itch is vector for typhus and relapsing fever.
11. Radioimmunoassay & Nuclear Medicine
In radioimmunassay (RIA), a fixed concentration of labeled tracer antigen is
incubated with a constant amount of antiserum such that the concentration of
antigen binding sites on the antibody is limiting, eg only 50% of the total tracer
concentration may be bound by antibody. If unlabeled antigen is added to this
system, there is competition between labeled tracer and unlabeled antigen for
the limited and constant number of binding sites on the antibody, and thus the
amount of tracer bound to antibody will decrease as the concentration of
unlabeled antigen increases. This can be measured after separating antibodybound from free tracer and counting either the bound fraction, the free fraction
or both. A calibration or standard curve is set up with increasing amounts of
known antigen, and from this curve the amount of antigen in the unknown samples
can be calculated
RADIOACTIVITY is the property of an unstable isotope throwing out or emitting
energetic particles and rays from its nucleus. The amount of radioactive material
177-B
Miscellaneous
is measured by how many nuclei decay each second. This is called the activity
and is measured in units of curies, abbreviated Ci. One microcurie is 1,000,000th
of a Ci and is equal to 37,000 disintegrations per second (DPS's) or 2,220,000
disintegrations per minute (DPM's). The I125 used as radioactive labeled antigen
i this lab emits gamma rays (photons). The solid sodium iodide crystals in the
gamma counters are scintillators, which give off a flash of yellow light when
they absorb gamma radiation. A photomultiplier, which is optically coupled to
the sodium iodide crystal, produces a pulse every time it "sees" a scintillation.
The pulse is then amplified and measured to see if it is of sufficient intensity
and of a certain discrete energy level characteristic of the isotope selected to
be measured. These measurements from the gamma counter are called counts
per minute (CPM's)
2.
RIA Kits are available for Drug & Hormone estimation and is the most
sensitive method of assay unlike bioassay
3.
Estimation of plasma levels of :
a.
Hormones
b.
Digitoxin or digoxin
c.
Abused drugs
d.
Hepatitis B surface antigen
e.
Anti-DNA antibodies in systemic lupus erythematosus (SLE).
Radioisotopes
NUCLEAR MEDICINE
This is a branch of medicine that uses radiation to provide information about the
functioning of a person's specific organs or to treat disease. The thyroid, bones,
heart, liver and many other organs can be easily imaged, and disorders in their
function revealed. In some cases radiation can be used to treat diseased organs,
or tumours.
178-A
What are radioisotopes?
Many of the chemical elements have a number of isotopes. The isotopes of an
element have the same number of protons in their atoms (atomic number) but
different masses due to different numbers of neutrons. In an atom in the neutral
state, the number of external electrons also equals the atomic number. When
a combination of neutrons and protons, which does not already exist in nature,
is produced artificially, the atom will be unstable and is called a radioactive
isotope or radioisotope.. Overall there are some 1800 radioisotopes.
DIAGNOSIS
Diagnostic techniques in nuclear medicine use radioactive tracers which emit
gamma rays from within the body. These tracers are generally short-lived
isotopes linked to chemical compounds which permit specific physiological
processes to be scrutinised. They can be given by injection, inhalation or orally.
Positron Emission Tomography (PET) which is a more precise and sophisticated
technique using isotopes produced in a cyclotron. A positron-emitting
radionuclide is introduced, usually by injection, and accumulates in the target
tissue. As it decays it emits a positron, which promptly combines with a nearby
electron resulting in the simultaneous emission of two identifiable gamma rays
in opposite directions. These are detected by a PET camera and give very
precise indication of their origin. PET's most important clinical role is in oncology.
It is also well used in cardiac and brain imaging.
Organ malfunction can be indicated if the isotope is either partially taken up in
the organ (cold spot), or taken up in excess (hot spot). If a series of images is
taken over a period of time, an unusual pattern or rate of isotope movement
could indicate malfunction in the organ.
A distinct advantage of nuclear imaging over x-ray techniques is that both bone
and soft tissue can be imaged very successfully..
178-B
RADIOTHERAPY
For PET imaging, the main radiopharmaceutical is Fluoro-deoxy glucose (FDG).
Rapidly dividing cells are particularly sensitive to damage by radiation. For this
reason, some cancerous growths can be controlled or eliminated by irradiating
the area containing the growth. External irradiation can be carried out using a
gamma beam from a radioactive cobalt-60 source, though in developed countries
the much more versatile linear accelerators are now being utilised as a highenergy x-ray source (gamma and x-rays are much the same).
THERAPEUTIC RADIOPHARMACEUTICALS
Internal radiotherapy is by administering or planting a small radiation source,
usually a gamma or beta emitter, in the target area.
●
●
Iodine-131 is commonly used to treat thyroid cancer, probably the most
successful kind of cancer treatment. It is also used to treat non-malignant
thyroid disorders.
In most cases, it is beta radiation which causes the destruction of the damaged
cells. This is radiotherapy. Short-range radiotherapy is known as brachytherapy.
●
Iodine-131 and phosphorus-32 are examples of two radioisotopes used
for therapy. Iodine-131 is used to treat the thyroid for cancers and other
abnormal conditions such as hyperthyroidism (over-active thyroid).
●
In a disease called Polycythemia vera, an excess of red blood cells is
produced in the bone marrow. Phosphorus-32 is used to control this excess.
●
A new and still experimental procedure uses boron-10 which concentrates
in the tumor. The patient is then irradiated with neutrons which are strongly
absorbed by the boron, to produce high-energy alpha particles which kill
the cancer.
Iridium-192 implants are used especially in the head and breast. Many
therapeutic procedures are palliative, usually to relieve pain.
Strontium-89 and samarium 153 , Rhenium-186 are used for the relief of
cancer-induced bone pain.
Reactor Radioisotopes (half-life mentioned )
●
Technetium-99m (6 h): Used in to image the skeleton and heart muscle in
particular, but also for brain, thyroid, lungs
●
Chromium-51 (28 d): Used to label red blood cells and quantify gastrointestinal protein loss.
●
Copper-64 (13 h): Used to study genetic diseases affecting copper
metabolism, such as Wilson's
●
Dysprosium-165 (2 h): Used as an aggregated hydroxide for synovectomy
treatment of arthritis..
●
Holmium-166 (26 h): Being developed for diagnosis and treatment of liver
tumours.
●
Iodine-125 (60 d): Used in cancer brachytherapy (prostate and brain),
also diagnostically to evaluate the filtration rate of kidneys and to diagnose
deep vein thrombosis in the leg..
DIAGNOSTIC RADIOPHARMACEUTICALS
Diagnostic radiopharmaceuticals can be used to examine blood flow to the
brain, functioning of the liver, lungs, heart or kidneys, to assess bone growth,
and to confirm other diagnostic procedures. Another important use is to predict
the effects of surgery and assess changes since treatment.
A radioisotope used for diagnosis must emit gamma rays of sufficient energy
to escape from the body and it must have a half-life short enough for it to decay
away soon after imaging is completed.
The radioisotope most widely used in medicine is technetium-99m Myocardial
Perfusion Imaging (MPI) uses thallium-201 chloride or technetium-99m and is
important for detection and prognosis of coronary artery disease.
179-A
179-B
●
Iodine-131 (8 d): Widely used in treating thyroid cancer and in imaging the
thyroid; also in diagnosis of abnormal liver function, renal (kidney) blood
flow and urinary tract obstruction. A strong gamma emitter, but used for
beta therapy.
●
Iridium-192 (74 d): Supplied in wire form for use as an internal radiotherapy
source for cancer treatment
●
Iron-59 (46 d): Used in studies of iron metabolism in the spleen.
●
Palladium-103 (17 d): Used to make brachytherapy permanent implant
seeds for early stage prostate cancer.
●
Phosphorus-32 (14 d): Used in the treatment of polycythemia vera
●
Potassium-42 (12 h): Used for the determination of exchangeable
potassium in coronary blood flow.
●
Rhenium-188 (17 h): Used to beta irradiate coronary arteries from an
angioplasty balloon.
●
Selenium-75 (120 d): Used in the form of seleno-methionine to study the
production of digestive enzymes.
●
Strontium-89 (50 d): Very effective in reducing the pain of prostate and
bone cancer. Beta emitter.
●
Xenon-133 (5 d): Used for pulmonary (lung) ventilation studies.
●
Ytterbium-169 (32 d): Used for cerebrospinal fluid studies in the brain.
●
Gallium-67 (78 h): Used for tumour imaging and localisation of inflammatory
lesions (infections).
●
Indium-111 (2.8 d): Used for specialist diagnostic studies, eg brain studies,
infection and colon transit studies.
●
Iodine-123 (13 h): Increasingly used for diagnosis of thyroid function, it is
a gamma emitter without the beta radiation of I-131.
●
Krypton-81m (13 sec) from Rubidium-81 (4.6 h): Kr-81m gas can yield
functional images of pulmonary ventilation, e.g. in asthmatic patients,
and for the early diagnosis of lung diseases and function.
●
Rubidium-82 (65 h): Convenient PET agent in myocardial perfusion imaging.
●
Strontium-92 (25 d): Used as the 'parent' in a generator to produce Rb-82.
●
Thallium-201 (73 h): Used for diagnosis of coronary artery disease other
heart conditions such as heart muscle death and for location of low-grade
lymphomas.
12. Gene Therapy
Human gene therapy involves delivery of nucleic acid to a somatic cell to correct
a debilitating condition, relieve suffering, and extend life. It does not cause a
change in the germ line of the individual, so any genetic corrections are not
passed to successive generations.
Cyclotron Radioisotopes
Gene correction therapy trials ( Chimeraplasty ):
Carbon-11, Nitrogen-13, Oxygen-15, Fluorine-18:
Gene therapy is hope in a vast sea of human suffering , since 22% of the
newborn deaths are due to genetic disorders. Researchers believe that the
gene therapy methods currently used are reasonably safe & the risk is similar
to any new drug under evaluation , but this still involves lot of ethical
considerations
These are positron emitters used in PET for studying brain physiology and
pathology, in particular for localising epileptic focus, and in dementia, psychiatry
and neuropharmacology studies.
●
Cobalt-57 (272 d): Used as a marker to estimate organ size and for in-vitro
diagnostic kits.
180-A
180-B
Say true or false
Condition
Adenosine deaminase
deficiency
Therapy
Target cells used
Adenosine deaminase
Lymphocytes, bone marrow cells
Melanoma
Tumor necrosis factor
Tumor-infiltrating lymphocytes,
autologous tumor cells
IL-2
Autologous tumor cells
Melanoma, glioblastoma,
renal cell cancer
Hemophilia B
Hypercholesterolemia
Melanoma, colorectal
cancer, renal cell cancer
Glioblastoma, AIDS,
ovarian cancer
Cystic fibrosis
Factor IX
Autologous skin fibroblasts
LDL receptor
Autologous liver cells
Histocompatibility locus antigen class
Tumor cells
I-B7 plus beta 2 microglobulin
HSV-TK
Cystic fibrosis transmembrane
receptor gene to correct
phenylalanine at deltaF 508 mutation
Multidrug resistance
GMCSF
IL-1 receptor agonist
Breast cancer
Melanoma
Arthritis
Amyotrophic lateral
Ciliary neurotrophic factor
sclerosis
Head and neck squamous
p53
carcinoma
Fanconi anemia
Fanconi anemia C
1.
Chymotrpsin is used in traumatic and inflammatory states to reduce
edema ?
2.
Streptokinase is still preferred in acute myocardial infarction to dissolve
intracoronary thrombus ?
3.
Hepatitis B vaccine is necessary for preventing the occurrance of
hepatoma ?
4.
Calcium di sodium edetate is used in cases of lead poisoning ?
5.
Cyprohepatadine is used as an appetite depressant ?
Tumor cells, T-cells
Nasal and airway epithelia
Blood CD34+ cells
Tumor cells
Autologous fibroblasts
Encaplulated transduced xenogeneic
cells
Answers
Tumor cells
Bone marrow cells
181-A
1.
True
2.
True
3.
True
4.
True
5.
False
181-B
13
systems of medicine
DRUGS AND LAW
Schedule F I includes vaccines and sera
Schedule FF includes standards for ophthalmic preparations
Drugs and cosmetic act , 1940 and Rule 1945, Second amendment rules 2002
The drugs and cosmetic act, 1940 is amended upto Act 22 of 1995, is to
regulate the import, manufacture, distribution and sale of drugs and cosmetics
Under the act, the standard of the quality of the drug has to be mantained,
misbranded drugs should be identified, which is defined as statement on label
making a false claim in terms of actions, ingredients etc. The adulterated drugs
are those which are packed under unhygenic conditions, have reduced quality
or strength, contains harmful or toxic substances. Spurious drugs are those
which are imitated, have label to conceal identity, have been substituted wholly
or partly by other substance.
Schedule G includes anti neoplastic agents
Schedule H includes prescription drugs and in primary and secondary packing
on left side a red vertical line should be drawn.
Schedule I includes proportion of cases in poisonous substances
Schedule J includes certain diseases where cure cannot be claimed such as
AIDS, Angina, Diabetes, High blood pressure, Improvement of vision, Power to
rejuvinate, Premature aging, Rheumatic heart disease , Sexual impotence,
Stammering, Stones, Varicose veins etc.
Schedule K includes certain drugs from homeopathic medicines
Schedule M includes Good Manufacturing practices for the manufacturer
Schedules under this act :
Schedule A is the memorandum to the central drug laboratory for the purpose
of test and analysis of the product
Schedule N includes the requirements for the dispensing pharmacy
Schedule O includes standards for the disinfectant fluids
Schedule B is the fee for test or analysis by the central drug laboratories
Schedule P includes the shelf life of the drugs as per the local recommendations
Schedule C includes tests on biological products and antitoxins
Schedule DI includes information and undertaken to be submitted by the
manufacturer of the drug, such as the information about the premises , this
needs to be registered, with a fee of 1500 USD
Schedule P I includes the pack sizes of drugs. The drugs can have strip size in
number of 10 tablets or capsules in most cases. For numbers above 10, it can
be in multiple of 5.The pack sizes for liquid oral preparations shall be 30ml
pediatric, 60ml , 100ml, 200ml, 450ml . The pack sizes for pediatric oral drops
can be 5/10/15ml. The pack sizes for ENT drops can be 3/5/10ml.The same
holds true for ophthalamic ointments.There are deviations in certain specified
cases.
Schedule DII includes the drug master file from the manufacturer. Per product
registration is 1000 USD
Schedule Q includes list of dyes , colours and pigments used in cosmetics
and soaps
Schedule E I includes poisonous substances under the Ayurvedic and Unani
Schedule R includes standards for rubber latex used for condoms, syringes,
catheters
Drugs and Law
182-B
Schedule C I includes digoxin, liver extract, hormones, vaccines etc
Schedule D includes powdered milk products, ginger, spices etc
182-A
Drugs and Laws
Schedule S includes all what is a cosmetic, such as Soaps, Creams, Shampoo,
Hair dye etc
Schedule T includes good manufacturing practices for traditional medicines
coming under Ayurveda, Siddha and Unani
possess magic qualities and to provide for matters connected therewith
The infant milk substitutes rules 1993
Schedule V specifies the quantities of vitamins in a commercial preparation as
per the recommended standards.
For all infant feeds it is important to have label that mothers milk is best for
your baby. Further the label should not contain words like humanised or
maternalised. No expressions such as energy food, complete food, health food
should be made
Schedule X includes drugs which require prescription filing. These can cause
addiction or have to used by particular group of medical specialists such as
phenobarbitone, meprobamate and Sildenafil
The Medicinal and Toilet preparations (excise duties) act
1955
Schedule Y is for the introduction of the new drug into the country. The Phase
III clinical trials in India are required for introduction of the international molecule.
These clinical trials are to be conducted with the guidelines which go in accord
to those published by the Indian Council of Medical Research ( ICMR )
An act to provide for the levy and collection of duties of excise on medicinal and
toilet preparations containing alcohol, opium, Indian hemp or a narcotic
Schedule U includes the particulars to be shown in Manufacturing records
Labelled and Unlabelled uses of drugs
Labelled use are those which are approved for the indication applied for, by the
innovator company were as, unlabelled uses are basically are on experience.
In life saving conditions, unlabelled use of drugs can be premitted
The Drugs Prices Control Order 1995
Here the prices of some vital drugs are controlled by government for betterment
of patients consuming therapy such as chloroquine for malaria, captopril for
hypertension, aspirin for angina, salbutamol for asthma, rifampicin for
tuberculosis, vitamin B1, B 2, Vitamin A , Vitamin E and Vitamin C ,erthromycin
for infection etc.
The Drugs and Magic Remedies (Objectionable advertisements) Act, 1954
The purpose of this act is to control the advertisement of drugs in certain cases
, to prohibit the advertisement for certain purposes of remedies alleged to
Drugs and Law
183-A
The Pharmacy Act 1948
This registers pharmacists qualified with a degree as B. Pharm, dentists as
BDS, medical graduate as MBBS in a state register to practice his discipline .
This is governed by the state council . Even the nursing degree comes under
this act. The qualified nurses have potential for the national employment and
with experience they can possibly opt for overseas, if the opportunity arises
Prenatal Diagnostic techniques, prevention of misuse act
1994
An act to have the diagnostic techniques to check malformations, sex linked
disorders in foetus so as to perform corrective actions. It prohibits sex
identification
Process of Drug storage
In major hospitals, nurses are entrusted with the responsibility of drug storage
since they are professionally competent. This is prudent, as there should be a
183-B
Drugs and Laws
proper check on medication issued to all the patients in the ward With the
medico legal systems gaining contingency worldwide the nursing staff should
be careful and should record all the inventories by date , time and the quantity
should be specified
Each ward should have basically 4 cupboards :
●
One for drugs, which can come as emergency medication
●
One for surgical equipment, bandages, catheters , disinfectants and
antiseptics
●
One for drugs which are routinely used in practice
●
One for all the reagents and chemicals
All medication should be kept under the lock and keys (Confidence and
responsibility are the basic aim to be kept in mind )
Some medication require refrigeration and hence should be stored according to
storage specifications. Light sensitive drugs such as adrenaline, ranitidine should
be protected from light All the cupboards should be ideally in center of the ward
if space permits so as to have proper and easier reach for the medication.
Drugs and Law
184-A
184-B
Drugs and Laws
14
●
●
●
●
●
PIVOTAL ROLE OF PHARMACIST/
NURSE IN DRUG ADMINISTRATION
The first step when the drug reaches the ward is to look for its labeling.
Check the manufacturing date and the date of expiry. If the date of expiry
is near then make a note so that it is not given after the due date if the
stocks still remain. No drug as a rule should be used after expiry date.
The practice of pouring liquid ingredient from one bottle to other should
avoided . This is to prevent contamination which can be risky . Freshly
prepared liquid formulations at the pharmacy of hospital with pharmacists
signature carry validity
Check always warning on the label. If the prescribing information is available
for the product , check the contraindications, precautions, interactions
and make note of it
Observe patient for local or systemic reaction . If the adverse drug reaction
occurs report it in a proper format putting the patient's name, drug
adminstered and the time of administration to attending doctor. Further
the nature of adverse reaction whether mild, or severe should be notified.
If the adverse drug reaction is life threatening , in consultation with doctor
suspend the offending drug immediately and report this to the manufacturer
and to the Drug controller General of India, Nirman Bhawan, Maulana
Azad Road, New Delhi 110011. Drug safety is mandatory responsibility of
the medical team, which includes a nurse
●
Beware also of delayed hypersensitive reaction
●
Keep drug antidote chat and drug interaction chart as a reckoner
●
Administer certain drugs IV in presense of doctor such as amphoterecin
B, drugs used in cancer, HIV, emetine hydrochloride etc
Pivotal Role of Nurse in Drug Administration
185-A
●
Intradermal testing of penicillins does not always assure that a
hypersensitive reaction would not result. Repeat intradermal testing
whenever any penicillin or cephalosporin is injected IV as patient can
become hypersensitive any time.
●
Keep emergency tray containing life saving drugs ready, whenever the
parenteral drugs are injected.
●
If patient refuses intradermal testing of certain drugs which on IV
administration results in anaphylaxis, take patient's signature or document
this in presence of a valid witness.
Drug Destruction
This is required for the following situations ;
1.
Clinical trial is over , and the balance medication is to be returned
2.
Drug withdrawal
3.
Drug expiry
4.
Counterfeit medication
5.
Substandard drugs
The drug is destroyed in prescence of quality assurance manager, regulatory
manager, the person incharge of incinerator and the drug inspector. After the
destruction , the destruction certificate is issued in a prescribed format
185-B
Pivotal Role of Nurse in Drug Administration
15
FILING OF NEW DRUG APPLICATION
CURRENT PRESPECTIVES
Registration of drugs in neighboring counties ( Dossier Management )
PATIENT PYSCHOLOGY
The counties in Indian subcontinent require the following documents from the
pharmaceutical companies in order to get their products registered
Steps towards healing by changing mindset :
Applications should be individualized and should be done as per the format. In
general the following is needed :
●
Explain the nature of the disease and medications given in simple language
(clear to understand either in English or in vernacular)
●
Tell in brief how fast the patient can recover. In most cases its difficult to
predict and the same time from the nurses end it cannot be a negative
approach. You would have to balance between patient and his relatives.
Have a heal in approach, smile at face and do not allow the patient to
dominate you
●
Name and address of the manufacturer of the drug
●
Generic name
●
Brand name
●
Packaging
●
Composition/ Formula
●
Manufacturing Instructions
●
Control data for active ingredient
●
Control data for other constituents which make volume of the product
●
Control data for finished product
PATENT SITUATION IN INDIA
●
Stability data
India is a vast country with all the resources to emerge as a biggest exporter of
bulk material . For finished new formulations almost every year there are about
50 approvals for the new molecules from the directorate of health services ,
Delhi . At the present the Indian companies file the patent situation in the world
and the name of company who searched the new molecule. The information ie
source for technical documentation , clinical documentation should be post 1st
January 1995 in order to have patent protection. The patent treaty had been
signed by the Indian Government to protect the rights of the intellectual property
and as 2005 approaches the scene in India would change as the innovators
would be allowed to have protection for their research molecules.
●
Accelerated stability data
●
Shelf life
●
Registration status in India and other countries
●
Product information in form of data sheet
●
Product Monograph containing all clinical studies
●
Certificate of pharmaceutical product or the free sale certificate
●
Certificate of analysis of the product
Current Prespectives
186-B
●
Always praise the patient , for his sincerity for his approach in taking
drugs or getting done any invasive procedures on him . Cheering the patient
would make your more than half battle won. Desire is an aid for a faster
win
186-A
●
WHO GMP certificate for the product
●
Summary of Phase I clinical trials
●
Selling price of the product ( India and country where it is to be sold )
●
Summary of Phase II clinical trials
●
Summary of Phase III clinical trials conducted worldwide
●
Bioequivalence studies to confirm the similar release pattern of the drug
within the body
●
Results of Phase III trials within the country , with the investigator report
signed
●
Certificate of Pharmaceutical product from country of origin
●
Marketing information worldwide
●
Draft of labels & cartons
●
Testing protocol & analysis of pure substance from Government laboratory
●
Status of worldwide patent of the drug
All this is compiled in form of the dossier and then is submitted to the regulatory
authorities. The papers submitted need to be attested by responsible drug
inspector from the Local FDA and then duly notarized , before the complete
submission is done
Registeration of drugs in India ( Dossier Management )
For all new drugs , which are intended to be registered in India , for market , the
phase III , clinical trials are mandatory , which are to be conducted as per
norms of the good clinical practice at minimum 3-4 centers , with 100 patients
atleast on active new medication
Application addressed to the Drug controller General of India, should contain
the following :
●
Therapeutic class , to which drug belongs
●
Chemical & Pharmaceutical information :
●
This is to be submitted to the Regulatory authorities for approval . In general the
presentation on the molecule is asked for . Once the authorities are satisfied ,
the approval is granted . For the new molecule approval along with the local
clinical trials the time duration depending on the protocol is averages between
15 months- 24 months
1.
Dosage form & its composition
2.
Specifications of active & inactive ingredients
3.
Tests for identification of active ingredient
Procedures for Registering Biological Products :
4.
Outline of manufacture of active ingredient
The following documents are generally required :
5.
Stability data
1.
Details of the Product
2.
Copy of Certificate to Foreign Government (Free Sale Certificate)
3.
Lot Release Exemption
4.
Ceritificate of Analysis
5.
Worlwide Registration Status
6.
Certificate stating that this product has not been withdrawn by health
Animal Toxicity data
1.
Local toxicity
2.
Mutagenicity
3.
Carcinogenicity
187-A
187-B
authorities in the U.S. or other countries
9.
7.
Letter of explanation regarding the address on the label.
10. Dose & Administration
8.
Virus safety certificate
11. Packaging
9.
Certificate stating that this product is marketed in the country of origin.
Over dosage
Glossary of regulatory terms
10. Labeling samples
11. Manufacturing Process
Short term
Explanation
ADE
Adverse Drug Event
ADR
Adverse Drug Reaction
AE
Adverse Event
AQL
Acceptable Quality Levels
AR
Assessment Report
BAN
British Approved Name
BPG
Best Practice Guide
Prescribing Information
CANDA
Computer Assisted New Drug Application
This is the manufacturers responsibility / liability to educate registered medicall
practitioners, hospital or a laboratory for all the new drugs introduced in the
Indian Market. It should have the following.
CCC
Country co-ordination clinical
CCDS
Company Core Data Sheet
CCT
Concentration Control (Clinical) Trial
1.
Name of product (Brand and Generic Name)
CDB
Core Database
2.
Composition
CFT
Conference Fast Track
3.
Chemical Structure
CMR
Centre for Medicine Research
4.
COSTART
Coding Symbols for a Thesaurus of Adverse Reaction
Terms
5.
Indications
CPL
Clinical Project Leader
6.
Contraindications
CPM
Clinical Project Manager
7.
Warnings & precautions
CR
Control Release
8.
Side effects
CRA
Clinical Research Associate
12. Product Specifications
13. List of assay methods
14. Viral inactivation data
15. Stability Data
16. Test specifications and procedures for plasma pool testing
17. Test specifications and test procedures for individual plasma donation.
18. Prescribing Information
188-A
188-B
CRF
Case Record Form
NDA
New Drug Application
CTA
Clinical Trial Application
OOS
Out of Specification
CTC
Clinical Trial Certificate
DS
Drug Safety
CTD
Common Technical Dossier
PI
Prescribing Information
CTN
Clinical Trial Notification
PL
Product Licence
CTX
Clinical Trial Exemption
QC
Quality Control
CV
Coefficient of Variation
RAC
Regulatory Affairs Committee
DIA
Drug Information Association
SOP
Standard Operating Procedure
DP
Data Processing
TQM
Total Quality Management
DRA
Drug Regulatory Authority
WHO-ART
WHO Adverse Reaction Terminology
DRF
Dose Range Finding
DRS
Drug Registration Strategy
EDS
Electronic Data Submission
EP
Ethical Products
FDA
Food & Drug Administration
FSC
Free Sale Certificate
GCP
Essential Documents for the conduct of a clinical trial (
ICMR )
●
Before the trial commences :
1.
Investigator Brochure ( gives drug details )
2.
Signed protocol & Case record form
Good Clinical Practice
3.
Copy of informed consent
HP
Health Policy
4.
Financial agreement
IBH
International Biometry Harmonisation
5.
Insurance agreement
ICQM
International Clinical Quality Management
6.
Submission of documents to ethics committee
IRASC
International Regulatory Affairs Steering Committee
7.
Protocol approval by the regulatory authorities
IRB
Institutional Review Board
8.
Resume of the investigators
MA
Marketing Authorisation
MOH
Ministry of Health
9.
Normal values for laboratories
NBD
New Business Development
10. Instructions given to handle the drug , including drug labels
11.
189-A
189-B
Certificate of analysis of the product
●
12. Randomization list
articles
13. Premonitoring of the site , in form of report
Inappropriate data analysis reported in 42-78%
During the conduction of the trial
1.
Update on Investigator brochure or signed protocol
2.
Updates on laboratory values
3.
Signed informed consent
4.
Source documents to be with investigator
5.
Notification to sponsor & institutional review board regarding adverse
drug reactions
6.
Subject screening log
●
Mean (average): sum of all the individual data values divided by the
number of values
●
Median: the middle of a set of ranked values, i.e., one-half data values
are less than median and one-half are greater than median
●
Range: largest minus smallest values, depends on number
●
Standard deviation: square root of sum of squared deviations divided by
(n-1)
Generally, 95% of values do not lie within 2 sd of mean
●
●
Outliers: values clearly separated from group
●
Skew : distribution of values shifted away from center
After the trial is over
1.
Drug accountability
2.
Document for drug destruction
3.
Trial closeout report
4.
Clinical study report duly signed by investigators
5.
Audit report on the trial
Outliers and skewness can make typical values and variability misleading
Graphical displays useful when there are significant outliers or skewness
●
Histogram:
Frequency represented by area
Class interval important
Concepts in Medical Statistics
●
●
●
Frequency Polygon:
Connect midpoints of tops of successive histogram bars
Statistics: gathering, describing, organizing, analyzing, and interpreting
numerical data
Cumulative Distribution Polygon:
Descriptive Statistics: numerical description of a group
Shows percentage of observations less than any value
Inferential Statistics: making inferences about a population from a
population sample
The all above are represented graphically
Statistical methods commonly used to analyze data in medical journal
190-A
●
Scatter diagrams : Each point determined by two values
Should provide a quick visual impression of the data
190-B
Transformations sometimes performed for skewed data
●
Bias : The systemic tendency of any factors associated with the design,
conduct, analysis and evaluation of the results of a clinical trial to make
the estimate of a treatment effect deviate from its true value.
●
Blind review : Checking and assessment of data during the course of the
study.
●
Content validity : The extent to which there is variable in the rating scale
measures.
●
Double dummy : A technique for retaining the blind when administering
supplies in a clinical trial, when the two treatments cannot be made identical.
Supplies are prepared for Treatment A (active and indistinguishable
placebo) and for Treatment B (active and indistinguishable placebo).
Subjects then take two sets of treatment; either A (active) and B (placebo),
or A (placebo) and B (active).
●
Dropout : Subject in a trial who for any reason fails to continue in the trial.
●
Intention to treat principle : The principle that asserts that the effect of a
treatment policy can be best assessed by evaluating on the basis of the
intention to treat a subject (i.e. the planned treatment regimen) rather
than the actual treatment given. It has the consequence that subjects
allocated to a treatment group should be followed up, assessed, and
analysed as members of that group irrespective of their compliance to the
planned course of treatment.
●
Interim analysis : Any analysis intended to compare treatment arms with
respect to efficacy or safety at any time prior to the formal completion of
a trial.
●
Meta-analysis : The formal evaluation of quantitative evidence from many
trials bearing on the same question. Here sometimes, the raw data is
combined.
Random sample variability is called random error
With sufficiently large samples, 95% of all sample means are within 2
standard errors (SE) of the mean:
SE =
●
●
s
n
Paired observations : Many observations are paired:
e.g., BP before (PA) and after (PB) treatment
Does the treatment make a difference?
The null hypothesis is PB = PA
Collect and compute d = PB – PA:
Test the null hypothesis
Regression
Regression : What is the influence of one factor on another, e.g., diastolic BP
on BP reduction after therapy
Clinical Trial Terminology
●
All randomised subjects : The analysis set that includes all subjects
who were randomised to treatment, within this subset the patients are
assigned to the treatment group.
●
Analysis plan : The strategy for analysis is predefined in the statistical
section of the protocol and or protocol amendments.
●
Bayesian approaches : Approaches to data analysis which can provide
a probability distribution for same parameter which includes treatment
effect.
191-A
191-B
Spearman rank
correlation
(Chap. 8)
Friedman statistic
(Chap. 10)
Contingency
coefficients†
Lon-rank test or
Gehan's test
(Chap. 11)
Survial time
Mann-Whitney
rank-sum test
(Chap. 10)
Ordinal
(Chap. 5)
contingency table
(Chap. 5)
Krushal-Wallis
statistic
(Chap. 10)
Wilcoxon singedrank test
(Chap. 10)
Cochrane Q†
Chi-square analysisof-contingency
Nominal
Chi-square
analysis-of-
McNemar's test
(Chap. 9)
Linear regression
and Pearson
product-moment
correlation;
Bland-Altman
anlaysis (Chap. 8)
Repeated measures analysis
of variance
(Chap. 9)
Analysis of variance
(Chap. 3)
Interval (and
drawn from
normally
populations)*
Scale of
measurement
upaired t test
(Chap.4)†
Paired t test
(Chap. 9)
Association between
two variables
Multiple treatments
in the same
individuals
a single
treatment in the
same individuals
Before and after
Three or more
treatment groups
consisting of
different individuals
Two
treatment groups
consisting of
different individuals
Type of experiment
Statistical Methods of Test Hypotheses
*If the asumption of normally distributed populations is not met, rank the observations and use the methods of data measured on an ordinal scale.
† Not included in this text.
192-A
●
Non-inferiority trial : A trial with a primary objective of showing that the
response to investigational product is not clinically inferior to a comparative
agent.
●
Superiority trial : A trial with primary objective of showing that the response
to the investigational product is superior to a comparative agent.
●
Surrogate variable : It is the variable that provides an indirect measurement
of effect in situations where the direct measurement of clinical effect is
not feasible or practical.
●
Treatment effect : This is an effect attributed to a treatment in a clinical
trial. Here, 2 or more than 2 treatments are compared.
Inference
1.
Always consider data analysis when designing research studies
2.
Perform the statistical analysis before collecting any data
3.
Consult a statistician, who is well versed with medical terms & understands
significance of it
MEDICAL INFORMATION
The new century has given us a fast access to computers and through net we
can go to various informative sites. One can use home PC or go to the cyber
café in quest of knowledge which has grown tremendously in these years
The important sites are :
■
■
■
■
■
■
www.pubmed.com
www.altavista.com
www.google.com
www.yahoo.com
www.cardiovalens.com (paid site , Rs 1200/annum, has all important
cardiac journals)
www.megaspider.com
192-B
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www.metaspider.com
www.starmail.com
www.rocketmail.com
www.pobox.com
www.juno.com
www.healthlibrary.com
www.dialog1.com (paid site, $ 1000/ annum , depending on usage. The
vast information is available on this site)
www.netmedicine.com
www.infomed.org
www.ppdnet.com
www.medlit.com
www.emedicine.com
www.bhj.com
www.merk.com
www.uspto.com (Gives the information on patents on all new drug
introductions, as approved by US, FDA)
www.disease-explained.com
www.fpnotebook.com
The medical information , now hence is not restricted to books but is available
for masses. Its important to download information which is relevant and authentic
, for which a proper expertise is necessary. Encourage yourself to net for self
learning and to know the recent advances.
CHIROCHEMISTRY
Introduction
Presumed advantage
S-Amlodipine
2.5mg dose instead of usual 5mg dose with advantage
of having no ankle oedema as side effect
S-Ibuporofen
400mg dose equates 800mg dose with lesser incidence
of GI irritation
Esomeprazole
S- isomer of omeprazole giving 15% additional efficacy
in cases of Gastro oesophageal reflux disease and
the incidence of relative side effects are lesser as
compared to omeprazole
Levocetirizine
Dose is 5mg as compared to 10mg dose of cetirizine
Whether it causes lesser sedation than cetirizine
needs to be proved
ORPHAN DRUGS
These drugs are used less frequently since either the clinical condition is rare
or the usage is specified
Drug
Actions
Indications and dose
Riluzole
Inhibits glutamate release
Amyotophic lateral sclerosis.
50mg every 12 hourly
Botulin toxin
Type A
Potent muscle relaxant
1-8ml, in cases of cervical
dystonia, spasmodic torticollis
and to remove wrinkles as in
cosmetic surgery
In the era when most of the drugs are going off patent and research pipelines
are dry as the introduction of entire new chemical entity. The chemists are
seperating the molecule called as racemate in Levo or Dextro forms and trying
to get the clinical advantage. This also comes as a new introduction to the
market with the advantage that the clinicians are already aware about the profile
of the parent compound
193-A
193-B
DRUGS USED IN ORGAN TRANSPLANTS
These drugs are immunosuppressants and are used in cases of organ
transplants so as to avoid rejection by the body itself
Drug
Actions
Indications and dose
Rapamune
Potent immunosuppressive Renal Transplantation, follow
against T-lymphocyte
up therapy with 5mg tablets
activation
with or without steroid
Mycophenolate
Mofetil
Potent and selective
immunosuppressive of
T and B cell
lymphocytes
Renal, hepatic or cardiac
transplants and in autoimmune
disorders which are life
threatening 500mg injectable
for initial therapy followed by,
250mg capsules twice daily
Orthoclone
(OKT 3)
Murine monoclonal
antibody acting as
immunosuppressant as
well improves the
availability of CD4
receptors on white cells
Renal, hepatic and cardiac
transplants
5mg/kg per day for 14 days,
followed by steroids.
Available as 5mg/5ml vial
194-A
194-B
TEXT CITED FROM
●
Clinical Pharmacology, P.N.Bennet, M.J.Brown, 2003
●
Essentials of Medical Pharmacology, 4th ed, K.D. Tripathi, 2001
●
Drug Facts and Comparisons 2004
●
The Pharmacological basis of medical practice , Goodman and Gilman`s,
10th ed , 2001
●
Martindale the extra pharmacopoea , 33rd ed, 2001
●
API textbook of Medicine , 7th ed, 2003
●
Drugs and Cosmetic act, 1940 , Vijay Malik, 14th ed., 2002
●
American Hospital Formulary Service Drug Information, 2004.
●
British National Formulary 47, March 2004.
●
Manual of Endocrinology and Metabolism, 3rd edition, Norman Lavin, 2002.
●
Emergency Medicine, 5th edition, David M. Clin, 2000
●
The use of Antibiotics A. Kacers, S. Crowe, J. Hog, 5th edition, 1997.
●
Diabetes in the new millennium, John R. Turtle, First published 1999.
●
Therapeutic Drugs and edition, Colin Pollery 1999.
●
Physicians Desk Reference, 58th edition, 2004.
Important Text From
195-A
195-B
Index
1.
4-A
2.
17-A
3.
39-A
4.
59-A
5.
66-A
6.
Respiratory System
73-A
7.
Haematinics
78-B
8.
Haemostatics
82-A
9.
Vitamins
88-A
10. Endocrines
91-A
11. Chemotherapy
107-A
12. Miscellaneous
155-A
13. Drugs and Law
160-A
14. Pivotal role of pharmacist/ Nurse in Drug Administration
163-A
15. CURRENT PRESPECTIVES
164-A
16
173-A
Text Cited Form
196-A
196-B

ESSENTIAL PHARMACOTHERAPEUTICS To all those who believe in Humanity First Edition

Transcription

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