Pharmacy bulletin 1ed 2015

PHARMACY PKDMT
PHARMACY BULLETIN
VOL UME 1,
ISSUE
1, YE AR
2015
Editorial Board
Advisor:
Dr. Rusdi bin Abd.
Rahman
Editors:
Lee Mei Lin
Chew Poh Chiong
Foo Swee Yen
Lim Bee Ping
Noorafinah Mohd
Zudin
Nursyahirah Abd
Raof
INSIDE THIS
ISSUE:
LEPTOSPIROSIS
1-5
PAINKILLERS
6-11
DRUG COMPARISON :
IBERET AND OBIMIN
12
MTAC DIABETES
13-16
MIKOSTAT
17
TRUTH @ MYTHS
18-22
LEPTOspirosis
ALERT
By: Siti Khatijah binti Mohd Saffian, Noor Adilah Md Yusoff
In the end of year 2014, heavy rain and flood happened in Malaysia
contribute to the increasing number of the human that can be affected by Leptospirosis.
L
eptospirosis can be defined as direct or indirect transmission from animals to
human by pathogenic spirochete bacteria of the genus Leptospira that can cause
the infectious disease toward human life.
Sporadic cases may occur throughout the year with outbreaks associated with extreme
changing weather events such as heavy rainfall and flooding.
The floods that hit Malaysia in late December are
considered epic- forcing 200,000 to evacuate in
several states. Northern and Eastern states of
Kelantan, Terengganu, Pahang, Perak and Perlis
in Malay Peninsula were hit by flash floods including
some areas in Sabah. Approximate two dozens
deaths were reported. Now after the floods subside
come the increase in infectious diseases
especially Leptospirosis.
1
LEPTOSPIROSIS
STATISTIC NUMBER
OF DEATH
1) 753 suspected leptospirosis infections with 126 confirmed cases were recorded from 1st
January 2015 in the flood-hit states according to Health Minister Datuk Seri S. Subramaniam.
[21 January 2015] (New straits times online: http://www.nst.com.my/node/70400#)
2) Cases: 134 Death: 7
Reported by Pengerusi Jawatankuasa Tetap Kesihatan, Pembangunan Usahawan, Sains,
Teknologidan Inovasi, Dr DaroyahAlwiIn on 26 of November 2013.
3) Cases : 3665 Death: 48
(Statistic from Health Indicator 2013) - table 1
Table 1: Number of cases and incidence rate of communicable diseases by state, Malaysia, 2012:
Other Infectious Diseases
2
LEPTOSPIROSIS
MODE OF TRANSMISSION
Skin, mucosa or conjunctiva with water or
soil contaminated with the urine of rodents, carrier or diseased animals in the
environment.
¨ Ingestion of contaminated water may also
cause infection.
¨
BUT no reports of transmission between human to human.
SIGNS & SYMPTOMS
3
LEPTOSPIROSIS
PREVENTION
TREATMENT
*
Early treatment with antibiotics is essential.
Adults
* Severe cases: IV C-penicillin (2 M units 6 hourly for 5-7 days).
* Less severe cases: Oral antibiotics such as doxycycline (2 mg/kg up to 100 mg 12-hourly for
5-7 days), tetracycline, ampicillin or amoxicillin.
Pediatrics
4
LEPTOSPIROSIS
REFERENCES
1. Guideline for the Diagnosis Management, Prevention and Control of Leptospirosis in Malaysia.
Disease Control Division Department of Public Health Ministry of Health Malaysia; 1st edition
2011.
2. World Health Organization. Report of the First Meeting of the Leptospirosis Burden Epidemiology Reference Group. Geneva; 2004
3. Health Indicator 2013. Indicators for Monitoring and Evaluation of Strategy Health for All.pg 73.
4. Centers for Disease Control and Prevention 17 June, 2011
5. Guideline for the Diagnosis Management, Prevention and Control of Leptospirosis in Malaysia.
Disease Control Division Department of Public Health Ministry of Health Malaysia; 1st edition
2011, pg 9
5
PAINKILLERS
PAINKILLERS
By: Victor Ong Sheng Teck
Syazreen bt. Arshad
What are painkillers?
Painkillers are drugs that help to reduce pain. We refer to these drugs as analgesics. There are two types
of analgesic; opioid and non-opioid.
A) Non-opioid analgesic
Non-opioid analgesics are the most common pain-killers prescribed. The common ones are paracetamol
and non-steroidal anti-inflammatory drugs (NSAIDs).
Paracetamol
·
Commonly used
as painkillers for mild
to moderate pain.
·
It can also be used
to reduce fever
(antipyretic).
NSAIDs
·
Help to reduce inflammation.
·
Classified based on their chemical structure or mechanism of action.
Acetic acids
Propionic
acids
COX-2
inhibitors
Fenamates
Oxicam
derivatives
Salicylates
Diclofenac
Fenoprofen
Celecoxib
Meclofenamate
Meloxicam
Aspirin
Etodolac
Flurbiprofen
Etoricoxib
Piroxicam
Diflunisal
·
Well tolerated
with few side effects.
·
Exceeding maximum dose of 4g per
day may harm the
liver.
·
Onset of action: <
1 hour.
Mefenamic
acid
Indomethacin
Ibuprofen
Magnesium
salicylate
Ketorolac
Ketoprofen
Salsalate
Nabumetone
Naproxen
Sulindac
Oxaprozin
Tolmetin
6
PAINKILLERS
Table: Comparison of common NSAIDs in PKDMT
Mefenamic Acid
250mg
Diclofenac Sodium 50mg
Indomethacin
25mg
Meloxicam 7.5mg
Mechanism of
action
Inhibits cyclooxygenase (COX)-1 and COX-2, thus inhibits prostaglandin synthesis
Prescriber
category
B
B — tablet
A/KK — injection
B
A/KK
Dosage
250-500mg TDS
50mg TDS
50-200mg daily in
divided dose.
OA: 7.5mg/day, may
increase to 15mg/day
RA: 15mg/day, may
reduce to 7.5mg/day
AS: 15mg/day
Adminstration
After food
After food
After food
Unaffected by food
Onset of action
Rapid
30 minutes
30 minutes
89 minutes
2.3—6.5 hours
1.67—2 hours
4.9 hours
(Not stated in product insert,
online drug monolog)
Tmax
2—4 hours
Indication
·
·
·
·
Relief mild to moderate pain
(muscular, traumatic and dental
pain, headache)
Dysmenorrhoea
Post-op and post
partum pain, pyrexia in children
Menorrhagia
·
Treatment of painful OA, RA, SA and other inflammatory conditions.
OA: Osteoarthritis RA: Rheumatoid Arthritis AS: Ankylosing spondylitis
COX-1 SELECTIVITY
1) Indomethacin
2) Diclofenac Na
More COX-1
selective
GASTROINTESTINAL SIDE
EFFECTS
1) Indomethacin
2) Diclefenac Na
More GI side
effects
CARDIOVASCULAR RISK
1) Diclofenac Na
2) Indomethacin
3) Mefenamic acid
3) Mefenamic acid
3) Meloxicam
4) Meloxicam
4) Meloxicam
4) Mefenamic Acid
More CVS
risk
7
PAINKILLERS
Table: Comparison of COX-2 inhibitors available in MOH
Etoricoxib 90mg (Arcoxia ® )
Celecoxib 200mg (Celebrex ® )
Mechanism of
action
Inhibits cyclooxygenase (COX)-2, thus inhibits prostaglandin synthesis.
(Does not affect COX-1 at therapeutic doses)
Prescriber
Category
A*
A
Dosage
OA: 30 0r 60mg od
RA & AS: 90mg od
Acute gouty arthritis, acute pain, primary
dysmenorrhoea: 120mg od
OA: 200mg od or 100mg bd
RA 100mg-200mg bd
AS: 200mg or 100mg bd. May increase to 400mg
Acute pain and primary dysmenorrhea: 400mg
initially followed by an additional 200mg if
needed
Low back pain: 100mg bd or 200mg od.
Adminstration
Unaffected by food
Indication
Treatment of primary dysmenorrheal, RA, OA and AS.
Minor dental procedures
Low back pain
Onset of
action
45 minutes
25—30 minutes
Tmax
3 hours
1.5 hours
Comment
Less GI side effect (due to inhibiting COX-1 causes less gastroprotective effect)
Linked to high CVS risk at high doses.
Long Term Adverse Effects of NSAIDs
Normal levels of PGE2 helps gastric mucosa maintaining its normal characteristics. Intake of NSAIDs for
prolonged duration blocks PGE2, leading to disturbance in the mucosal equilibrium which precipitates
inflammation of the gastric mucosa, resulting to gastritis.
Side effects occur when NSAIDs are taken in high doses or prolonged duration. Some are mild and reversible, while others are more serious and need medical attention.
Most frequently reported side effects of NSAIDs are
gastrointestinal symptoms, such as:
Feeling bloated
Stomach pain
Vomiting
Constipation
Nausea
Heartburn
Diarrhea
COUNSELING POINT
Þ Always take NSAIDs after a heavy meal or with antacid.
Þ If gastrointestinal symptoms persist, stop taking NSAIDs and contact your healthcare provider.
8
PAINKILLERS
B) Opioid analgesic
Opioids are the most potent analgesics and have been a mainstay in pain management for centuries.
Opioids refer to all drugs (natural and synthetic) that have morphine-like properties and act on the opioid
receptors [eg: receptor µ(mu), қ (kappa), and d (delta)] in the body. Opioid drugs include full agonists, partial agonists and antagonists.
Mechanism of Action
·
Opioids bind to opioid receptors, located throughout the CNS and in some other tissues.
·
Pharmacodynamic properties of specific opioids depend on which receptor is bound, binding affinity
and whether the receptor is activated.
·
Opioid receptor activation inhibits the presynaptic release and postsynaptic response to excitatory
neurotransmitters (e.g. acetylcholine, substance P) from nociceptive neurons.
Opioids available in MOH
Drug
class
Drugs
Indication
Dose
t½
(hr)
Duration of
action (hr)
Comment
Strong
opiods
Morphine HCL
10mg/10ml
Management of moderate to severe pain, especially that associated
with neoplastic disease
5-20 mg or more regularly every 4 hours in
terminal pain
4-5
2-4
Management of moderate to severe pain especially that associated
with neoplastic disease
Adult : SC or IM 10-20
mg every 4 hours as
needed.
Child:
<1month: 0.15mg/kg
1-2 mths : 0.2mh/kg
1-5 yrs : 2.5-5mg
6-12 yrs: 5-10mg
Metabolites can accumulate causing increased therapeutic
and adverse effects.
Both parent drug and
metabolites can be
removed with dialysis,
watch for “rebound”
pain effect.
Prolonged relief of
severe pain associated
with neoplastic disease
10-60mg bd depend
upon the severity of the
pain
Second line drug in
management of chronic
cancer pain
Available in transdernal
patch
3-4
0.5-1
Not to be used in
opioid naïve patients.
Restricted to pain
specialists palliative
medicine specialists
and oncologists.
Category: B
Morphine sulphate 10mg/ml
Category: B
Morphine sulphate 10mg,
30mg, controlled released
tablet
Category: B
Fentanyl
Fentanyl 12mcg/hr
Fentanyl 25mcg/hr
Fentanyl 50mcg/hr
Category: A*
9
PAINKILLERS
Oxycodone
Second line drug in the
management of opioid
responsive, moderate
to severe chronic cancer pain.
Management of moderate to severe pain
(medical and surgical),
pre- anaesthetic medication and obstetrical
analgesia
Adult: 0.5-2mg/kg SC
or IM q 3-4 hrs if necessary.
Post operative pain,
chronic cancer pain,
analgesia/pain relief, for
patient with impaired
renal
Adult: 50-100 mg q 4
hrs (Max 400mg daily)
Category: B
Weak
opioids
Tramadol
Nalbuphine
10mg/ml
Metabolites and parent drug can accumulate causing toxic and
CNS-depressant effects.
In severe hepatic impairment, the parent
drug may not be readily converted to metabolites.
3-4
3-4
Long term pethidine
usage may have a
higher risk of addiction compared to
morphine.
Child: by IM 0.5-2mg/
kg.
Up to 1 yr : 1-2mg/kg
IM,
1-5 yrs :12.5-25mg IM
6-12 yrs 25-50mg IM
NOT RECOMMENDED FOR USE
IN CHRONIC PAIN
4-6
4-6
Elderly: start at lowest
dose (50 mg) and maximum 300 mg daily
Interaction with TCA,
SSRI and SNRI.
Risk of seizures in
patients with history
of seizures and with
high doses.
Management of moderate to severe chronic
pain
Adult : 30-60mg q 46hrs
Child : over 4 yrs: 0.51mg/kg q 4-6hrs
2-4
4-6
Management of moderate to severe pain, and
perioperative pain
SC, IM or IV: 10-20 mg
every 3-6 hours
4-6
4-6
For the complete/
partial reversal of narcotic/respiratory depression induced by
opioids
Initially : IV 0.4-2mg repeated at intervals of 23mins according to pt’s
needs
1-1.5
0.5-1
Category: B
Partial
agonist
opioids
3-4
Child : not recommended
Category: A/KK
Dihydroxycodeine
2-4
Oxycodone HCl 10mg,
20mg Prolonged Release
Tablet:
Adult, elderly, child
>18 y/o : 10mg bd
Renal/hepatic impairment: 5mg bd, titrate
dose carefully once a
day if necessary to
achieve pain relief
Category: A*
Pethidine
50mg/ml,
100mg/2ml
injection
Oxycodone HCL 5mg
Immediate release :
Initially 5mg every 46hrs, increased according to severity of pain.
Max 400mg daily.
Do not use in dialysis,
hepatic dysfunction
and renal dysfunction
patient.
Category: B
Opioid
antagonist
Naloxone HCl
0.4mg/ml
Category: B
Treatment of
methadone overdose
10
PAINKILLERS
Long-term use of opioid analgesics can lead to
physical dependence. The body adapts to the presence of the substance and if one stops taking the drug
abruptly, withdrawal symptoms occur. Besides that,
the body can build up tolerance to the drug, meaning
that higher doses is required to achieve the same effects.
Symptoms of withdrawal include restlessness, muscle
and bone pain, insomnia, diarrhea, vomiting, cold
flashes with goose bumps (known as “cold turkey”),
and involuntary leg movements.
One of the serious risks of opioids is respiratory depression—high doses can cause breathing to slow
down to the point it stops and the user dies.
Mental and physiological effects
of painkillers
Constipation
Nausea
Vomiting
Dizziness
Confusion
Addiction
Unconsciousness
Respiratory depression
Increased risk of heart attack
Coma
Death
References
1.
MIMS 109th ed 2007
2.
3.
Medscape
Non-steroidal anti-inflammatory drugs (NSAIDs): Making safer treatment choices;BPJ
55:9-18
Ong CKS, Lirk P, Tan CH, Seymour RA. An Evidence based Update on Nonsteroidal Anti-inflammatory Drugs. CM&R 2007;5(1):19-34
Painkillers (Analgesic) [Online]. Arthritis Research UK. Available from: URL: http://
www.nhs.uk/ipgmedia/national/Arthritis%20Research%20UK/Assets/Painkillersanalgesics.pdf
Susan Jeffery. Risk for CVD Events With NSAIDs Can Be Predicted [Online]. 2013 May 30 [cited 2015 Feb 27]. Available from: URL: http://
www.medscape.com/viewarticle/804976
Perry LA, Mosler C, Atkins A, Minehart M. Cardiovascular Risk Associated With NSAIDs and COX-2 Inhibitors. US Pharm. 2014;39(3):3538.
4.
5.
6.
7.
8.
Essentials of Medical Pharmacology 6th edition 2008.
9.
Basic and Clinical Pharmacology 10th edition 2007
10.
11.
Pain Management Handbook 2013
http://www.intechopen.com/books/gastritis-and-gastric-cancer-new-insights-in-gastroprotection-diagnosis-and-treatments/new-approaches-ingastritis-treatment
11
Drug Comparison: IBERET & OBIMIN
Comparison of
IBERET and OBIMIN
by Nor Shalizah binti Sazali
IBERET
OBIMIN
Indication
Treatment of anemia due to iron deficiency in
pregnant women.
Nutritional supplements for pregnant women.
Prescriber
Category
A/KK
B
Cost per
tablet
0.63
0.13
Contents
Ferrous sulfate
525mg
(elemental iron………………………105mg)
Ferrous Fumarate
30mg
(elemental iron ……………………………....10mg)
Vitamin C
Niacinamide
Folic Acid
Vitamin B1
Vitamin B2
Vitamin B6
Vitamin B12
Calcium Pantothenate
Vitamin C
Niacinamide
Folic Acid
Vitamin B1
Vitamin B2
Vitamin B6
Vitamin B12
Calcium Pantothenate
Vitamin A
Vitamin D
Calcium Lactate
Copper
Iodine
Dosage and
administration
500mg
30mg
0.8mg
6mg
6mg
5mg
25mcg
10mg
100mg
20mg
1mg
10mg
2.5mg
15mg
4mcg
7.5mg
3000iu
400iu
32.5mg
100mcg
100mcg
Þ 1 tablet daily
Þ 1 tablet daily
Þ To be taken on empty stomach.
Þ To be taken with meals for better absorption or
if gastrointestinal discomfort occurs.
Þ Do not chew or crush, to be swallow
whole.
12
MTAC DIABETES
by Khairunnisa Zuradi
Diabetes mellitus has become a major healthcare burden in almost every country in the world, including
Malaysia. A survey conducted by the Ministry of Health in 2011 – National Health and Morbidity showed a rise
from 8.3% (1996) to 20.8% (2011) in the prevalence of diabetes among Malaysian age over 30 years old. This alarming figure urges us to be more aggressive in treating and managing diabetic patients in order to prevent further increasing trend.
DMTAC is a service offered by pharmacists in collaboration with clinicians. It aims to help diabetic patients to
achieve a better medication adherence level and glycemic control. Patients who involve in this service will have to
attend a minimum of 8 visits where in each visit, patients will receive medication adherence assessment, identification and management of drug related problems, medication counselling, monitoring of clinical outcomes and diabetes education from the pharmacists.
Patient Selection Criteria:
1. All uncontrolled DM:
FBS
>6.1 mmol/L
2HPP >8.0 mmol/L
HbA1c >8.0%
2. Diabetes with co-morbodities or multiple medications
3. Patients with complications (macrovascular and microvascular)
4. Non-compliant with medications
First visit
13
MTAC DIABETES
Subsequent visits
Education Outline for Diabetes Patients in Each Visit
Visit 1
Visit 2
Visit 4
Visit 5
Visit 3
Subsequent visits
14
MTAC DIABETES
Glucometer Set
Pamphlets
Drug Identification File
Counseling
Tools
Insuman Pen
DM Modules
Documentation
All relevant data are to be recorded using the DMTAC/F2 – Patients’ Pharmacotherapy Review Form and stored
in each individual’s file.
15
MTAC DIABETES
References:
1. Protocol Medication Therapy Adherence Clinic: Diabetes Second Edition 2014, Pharmaceutical Service Division,
Ministry of Health Malaysia
2. Clinical Practice Guidelines Management of Type 2 Diabetes Melitus 4th Edition May 2009, Ministry of Health
Malaysia
3. Practical Guide into Insulin Therapy in Type 2 Diabetes Melitus 2011
16
MIKOSTAT
MIKOSTAT
Oral Suspension
by Tan Chen Jie
INDICATION:
CONTENT:
Prophylaxis or treatment of oral cavities and
perioral candidiasis, as well as intestinal candidiasis for children (2-12 years) and adult.
Nystatin ……………………………… 100,000iu /mL
Mikostat oral suspension is safe for children aged 2 to 6 years but not recommended for use in children below 2 years
due to the ethanol content in the products.
Ethanol is a central nervous system (CNS)
depressant. Alcohol metabolism varies with age.
Most literature relates to acute poisoning in children. Hypoglycaemia, hypothermia and coma are
the signs of ethanol intoxication in children (1, 2).
Ethanol USP …………………….…. 0.03g /mL
ALCOHOL CONTENT IN RELATION TO
SAFETY PROFILE
Mikostat Oral Suspension contains approximately
3% of ethanol
Þ FDA recommend OTC liquid preparation
should not more than 5% ethanol(3, 4).
Blood alcohol concentration (BAC) of Mikostat
Oral Suspension is 0.000238g/L.
Þ EMEA references considers the rise of BAC of
0.01g/L to be safe for the children aged 2 to 6
years(5)
FOR PATIENT BELOW 2 YEARS OLD:
Dissolves 1 tablet of T. Nystatin 500,000iu in 5mL of water to produce Syr. Nystatin 100,000 IU/mL.
However, safety and efficacy study in such extemporaneous preparation is found lacking.
Reference:
1. Milap C Nahata et al. Safety of ‘‘inert’’ additives or excipients in paediatric medicines. Arch Dis Child Fetal Neonatal Ed November 2009 Vol 94 No 6.
2. Brothers E et al. Toxicity, ethanol. 2009. Available from: http://
emedicine.medscape.com/article/1010220-overview
3. Over-the-Counter Drug Products intended for oral ingestion that contain alcohol,
department of health and human services, FDA, vol. 58, No. 202, 1993. Available
from:http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/
DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/
UCM155028.pdf
4. American academy of pediatrics; Commitee on Drugs. Ethanol in Liquid Preparations Intended for Children. Pediatrics 1984; 73: 405-407.
5. Questions and Answers on Ethanol in the context of the revision of the guideline
on ‘Excipients in the label and package leaflet of medicinal products for human
use’ (CPMP/463/00) EMA/CHMP/507988/2013
17
TRUTH @ MYTHS
The Use of TRANEXAMIC ACID
for Beauty Purpose
by Suhaila Nur Rahman
Tranexamic acid (TA) is a synthetic analog of the amino acid lysine. Generally, it is indicated for
haemorrhage associated with excessive fibrinolysis.
However, have you ever heard of TA can be used for beauty purpose??
YES! IT’S TRUE!!
NOT A MYTH!!
It was recently reported that TA is used for treatment
of hyperpigmentation and also as whitening agents.
Topical TA is said to be an effective treatment for
ultraviolet-induced hyperpigmentation1,2 while intralesional
localized microinjection of TA can be used as a potentially new,
effective, and safe therapeutic modality for the
treatment of melasma2.
… HOW IT WORKS?
Tranexamic acid is a kind of protease inhibitor. It rapidly suppresses the activity of tyrosinase and melanocytes. After its entry into the dermis, it increases collagen synthesis directly and thoroughly cuts off the channel for
the formation of melanin due to ultraviolet irradiation. Thus, it can rapidly
and effectively whiten the skin. It helps eliminate black spots, prevents and
reduces pigmentation, leaving the skin white and pretty.
CLINICAL STUDIES FOUND….
A clinical study was conducted with 25 women from March to July 2010,
where volunteers were instructed to take two TA tablets three times a day and
apply a TA topical agent twice a day for 8 weeks. Skin pigmentation and
erythema was measured using a Mexameter during each visit and skin biopsies
were collected from eight subjects before and 8 weeks after treatment.
Result: Twenty-two subjects completed the study and the mean lesional melanin index (MI) scores decreased significantly. Histological analysis showed significant reduction of epidermal pigmentation, vessel numbers and mast cell
counts1.
18
TRUTH @ MYTHS
A total of 100 women with melasma were enrolled for a prospective open pilot
study of 12 weeks to evaluate the usage of TA injected intradermally into plasma
lesion by using the Melasma Area and Severity Index (MASI) and also patients
self assessment.
Result: Eighty-five patients completed the trial and significant decrease in the
MASI from baseline to 8 and 12 weeks was observed (13.22±3.02 vs 9.02±2.62 at
week 8 and vs. 7.57±2.54 at week 12; p<.05 for both). For patients' selfassessment of melasma improvement: 8 of 85 patients (9.4%) rated as good (51
–75% lightening), 65 patients (76.5%) as fair (26–50% lightening), and 12 patients (14.1%) as poor (0–25% lightening)2.
After 5-18 weeks of applying TA to their skin,
80% of women with melasma and 75% of
women who had freckles agree brown spots
appear less visible and skin tone looks more
even.
CONCLUSION...
TA is currently being widely used for beauty purpose. However, further research
need to be done to investigate the pro and cons of TA in cosmetic field, as well
as it’s long term effects.
To date, oral or injection TA is not approved by KKM as a whitening
agent. However, there are numerous skin products that contain TA are
available in the market and approved by BPFK.
References
1. J.I. Na, S.Y. Choi, S.H. Yang, H.R. Choi, H.Y. Kang, K.-C. Park. Jan 2012.
2. Effect of tranexamic acid on melasma: a clinical trial with histological
evaluation, Journal of European Academy of Dermatology and
Vereonology.
3. DOI: 10.1111/j.1468-3083.2012.04464.x
4. J.H. Lee , J.G. Park, S.H. Lim, J.Y. Kim, K.Y. Ahn , M.Y. Kim , Y.M. P.
(May 2006). Localized Intradermal Microinjection of Tranexamic Acid
for Treatment of Melasma in Asian Patients: A Preliminary Clinical
Trial. Dermatologic Surgery. Volume 32, Issue 5, pages 626–631.
DOI: 10.1111/j.1524-4725.2006.32133.x
5. Tranexemic acid. Available from: http://www.mcbiotec.com/
products/?type=detail & id=33. [Last accessed on 2013 Jun 17].
19
TRUTH @ MYTHS
by Satyavani A/P Radhakrishnan
METFORMIN IN
WEIGHT MANAGEMENT
??
METFORMIN is the first line oral glucose lowering Þ A randomized trial in 150 women with BMI
medication recommended by the American Diabe>30 kg/m2 evaluated sibutramine, metformin
tes Association for people with Type 2 diabetes
or orlistat for 6 months. [6]Weight, waist and
(T2D) and individuals with pre-diabetes and at
BMI were reduced in all groups . Small 7least one CVD risk.[2]
month studies in nondiabetic overweight (BMI
Despite its role in metabolic syndrome, metformin
>28 kg/m2) or morbidly obese subjects (mean
has been used off label for weight loss. Since the
BMI 43 kg/m2) demonstrated decreases in
only approved indication for metformin is T2D,
body weight with metformin, although only
thus most of the understanding of the effect of
the latter study demonstrated a reduction in
metformin on weight loss has been gained from
research in patients with T2D.
waist circumference.[7]
EFFECTS OF METFORMIN ON BODY WEIGHT IN Þ A systematic review of randomized, controlled
PATIENTS WITH OBESE/ABDOMINAALY OBESE
evaluations of metformin (duration 15 days to
PATIENTS :
1 year) in populations without diabetes or
Þ To date, the best study of metformin on body
polycystic ovary syndrome (PCOS) found insufweight comes from the Diabetes Prevention
ficient evidence to consider metformin as a
Program.[4]Within the first 3 years of this doupotential therapy for weight loss in overweight
ble blind randomized controlled trial, metor obese patients.
formin treatment of 1700 mg/day induced
weight loss of approximately 2.9 vs. 0.42 kg in
the control group. Impressively, this weight
loss effect persisted up to 8 years.
Þ Recent study demonstrated that 2g/day of
metformin for 3 months induced approximately 3 kg weight loss in obese adults with
prediabetes, with or without exercise, compared with placebo or exercise training alone.
Metformin administered at 2g/day was also
reported to induce greater weight loss in
obese insulin-resistant adolescents during a
lifestyle intervention compared with metformin alone, suggesting that metformin has
additive anorectic effects to exercise.[5]
20
TRUTH @ MYTHS
POTENTIAL WEIGHT LOSS MECHANISMS BY METFORMIN
There are evidences suggesting that metformin reduces weight through appetite regulatory pathways in
the brain, with additional influences on adipose and gut-derived signals as well as through the effects of
metformin on the interaction of fat metabolism and circadian clock genes.[2]
Decrease in meal size are noticed during initial metformin treatment, whereas reductions in meal number continue over time. It has been revealed that these actions of metformin are related to the activation of AMPK.[9]
NOTE!
Adenosine monophosphate (AMP) -activated protein kinase (AMPK), is a key molecular player in
energy homeostasis at both the cellular and whole-body levels.Generally, activated peripheral AMPK
enhances catabolic pathways and suppresses anabolic pathways.[10]
Metformin inhibit AMPK in the hypothalamus and activate AMPK in peripheral tissues. Hypothalamic AMPK activity is uppressed by leptin. Through metformin, low glucose-induced AMPK phosphorylation is inhibited, and the Messenger Ribonucleic acid expression of neuropeptide Y (NPY) is suppressed in the hypothalamus, leading to reduce in food intake.
In peripheral tissues, activated AMPK inhibits 3-hydroxy-3- methylglutaryl-coenzyme A and suppresses fatty acid synthase
expression, resulting in a decrease in fatty acid and cholesterol synthesis. AMPK also controls hepatic gluconeogenesis by
inhibiting phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Additionally, metformin stimulates AMPK in
muscle and induces glucose uptake.[10]
IS METFORMIN APPROVED FOR TREATMENT OF OBESITY?
According to Clinical Practice Guidelines on Management of Obesity 2004, metformin is
not approved for the treatment of obesity (BMI ≥ 30.0 kg/m2), but, may induce weight
loss when used for patients with diabetes, pre-diabetes, polycystic ovarian syndrome
(PCOS), and impaired glucose tolerance.[8]
In the Diabetes Prevention Trial (DPT), metformin-treated group lost 2.5% of body weight.
The effect of metformin on weight loss (~ 5%) is not large enough to meet FDA requirements for a weight loss drug. [9]
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TRUTH @ MYTHS
REFERANCES:
SPECIAL PRECAUTION!
Care should be taken with its use in patients with
cardiac, renal or hepatic decomposition as it may
result in lactic acidosis.[8] Side-effects include nausea, flatulence; bloating and diarrhoea should be
monitored while on metformin therapy.[8]
1.
2.
3.
4.
CONCLUSION
Metformin is a viable pharmacological agent for 5.
promoting modest weight loss in overweight people with cardiometabolic risk factors through multilevel effects on neuronal appetite pathways and 6.
peripheral fat metabolism. However, although the
quantity of weight loss following metformin treat- 7.
ment is clinically relevant for metabolic health, it
is minimal (1–5 kg) relative to the amount needed
for most overweight and obese people to achieve 8.
healthy weight status.
Thus, metformin is unlikely to be a sole
antiobesity agent for patients who need to lose
significant weight (e.g. >25 kg), and metformin
should only be considered as an adjunctive
therapy to initiate weight loss in obesity-related
diseases. Combining metformin with either
exercise or other antidiabetic drugs can promote
greater weight loss. However, further study is
warranted to elucidate the effect of metformin on
appetite regulation, as this will help us to understand how metformin can be optimally use for the
prevention and reversal of obesity in addition to
T2D.
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012.
JAMA. 2014;311:806-814
Steven K. Malin and Sangeeta R. Kashyap.Effect of metformin
on weight loss.1752-296X 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE. Metabolic effects of metformin in non-insulin-dependent diabetes
mellitus. N Engl J Med. 1995;333:550-554.
The Diabetes Prevention Program Research Group. Long-term
safety, tolerability,and weight loss associated with metformin
in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35:731–737.
Malin SK, Nightingale J, Choi S, et al. Metformin modifies the
exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. obesity 2012; 21:93–
100.
Levri KM, Slaymaker E, Last A, Yeh J, Ference J, D'Amico F et al.
Metformin as treatment for overweight and obese adults: a
systematic review. Ann Fam Med 2005; 3: 457–461.
Masako Nakano and Akio Inui.Metformin and incretin-based
therapies up-regulate central and peripheral Adenosine monophosphate-activated protein affecting appetite and metabolism.Indian J Endocrinol Metab. 2012 Dec; 16(Suppl 3):
S529–S531.
Clinical Practice Guidelines on Management of Obesity2004,
Ministry of Health Malaysia; pg: 32
9. Komori T, Yoshida F, Nakamura J, et al. Metformin ameliorates
treatment of obese type 2 diabetic patients with mental retardation; its effects on eating behavior and serum leptin levels.
Exp Clin Endocrinol Diabetes 2004; 112:422–428.
10. Kim HJ, Zhang XH, Park EY, et al. Metformin decreases meal
size and number and increases c-Fos expression in the nucleus
tractus solitarius of obesemice. Physiol Behav 2013; 110–
111:213–220.
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