adelfan blood pressure

Lecture №2
Adrenotropic drugs
(adrenomimetics,
adrenoblockers)
НА
Lector:
НА
Head of the pharmacology
department, doctor of medicine
Voloshchuk Nataliya Ivanovna
Adrenergic drugs medical substances
which act in adrenergic
synapses
Adrenergic synapse
Presynaptic membrane
Thyrosine
Phenilalanine
DOPA
Dopamine
Desamination
Ca2+
Noradrenaline
КОМТ
О-methylation
Thyrosine
Na+
Noradrenaline
-, -adrenoreceptors
postsynaptic membrane
Adrenergic receptor types
Name
Typical locations
α2
Postsynaptic effector cells of the smooth muscles
of small vessels of the skin, mucosal membranes,
kidneys, mesenterial vessels, muscle dilatator of
the pupil, myometrium, sphincters of the GI tract.
Presynaptic adrenergic nerve terminals, platelets,
lipocytes, smooth muscle.
β1
Postsynaptic
lipocytes.
β2
Postsynaptic effector cells, especially smooth
muscles of the bronchi, myometrium, vessels of
skeletal muscles.
α1
Especially – CNS on the brake neurons.
effector
cells,
especially
heart;
β -specific Liver (hepatocytes), lyposytes, skeletal muscles
Main effects mediated by alpfa and beta-adrenoreceptors
Alpha 1
Alpha 2
Vasoconstriction
Sedative
effect on
CNS,
decrease
BP
Increased
peripheral
resistance
Increase
blood
pressure
Mydriasis
Increased
closure of
internal
sphincter of
the bladder
Inhibition
of the
insulin
release
Beta1
Beta 2
Beta-specific
Increase of
Increase of the Bronchodilatation
the
all function of
Relax
methabolic
the heart
myometrium
processes in
(tachycardia
Relax smooth
the organism
increase BP,
muscles of
(glycolysis,
sleletal
myocardium
lypolysis,
muscles
contractility,
glycogenoIncrease muscle
Increase
and liver
lysis)
glycogenolyoxygen
sis
demands of
Increase release
the
of glucagonum
myocardium
Classification of adrenotropic drugs
І. Adrenomimetics
1. --adrenomimetics (Adrenalini hydrochloridum)
2. -adrenomimetics (Noradrenalini hydrotartras
Mesatonum, Naphtizinum)
3. -adrenomimetics (Salbutamol, Fenoterol,
Dobutaminum)
ІІ. Sympathomimetics (Ephedrini hydrochloridum)
ІІІ. Adrenoblockers
1. -adrenoblockers (Prasosinum, Doxasosinum,
Terasosinum)
2. -adrenoblockers (Propranololum, Atenololum,
Talinololum, Bisoprololum)
3. - і -adrenoblockers (Labetalolum)
ІІІ. Sympatholytics (Reserpinum, Octadinum)
Direct-acting adrenergic
agonists
These drugs act directly on α and β
receptors, producing effects similar
to those than occur following
stimulation of sympathetic nerves.
As a group these agents are widely
used clinically.
Adrenalini hydrochloridum
(Epinephrinum)
is a hormone of medullar
layer of adrenal glands which
is used in a form of a remedy
It is an adrenomimetic which
stimulates 1,- 2- and 1,- 2adrenoreceptors
Pharmacological effects of Adrenalinum
Cardiovascular system Constriction of the small vessels and
increasing the blood pressure (short effect – 5 minutes
only). Cardiac output increases, increasing oxygen
demands on the myocardium.
Respiratory system: Bronchodilatation (β2 receptors)
Hyperglycemia: Significant hyperglycemic effect because of
increased glycogenolysis in liver (β2 effect), and the
decreased release of insulinum. Thus it can be used in
causes of acute hypoglycemia.
Metabolic processes: Initiation lypolysis through agonist
activity on the β receptors of adipose tissue, which upon
stimulation, activate adenylatcyclase to increase 3,5cyclic
AMP levels. Cyclic AMP stimulates a hormone-sensitive
lipase, which hydrolyses fat. This process leads to secrete
of high quantity of energy.
Eye: The radial pupillary dilator muscle of the iris contains α
receptors; activation by adrenaline causes mydriasis. This
drug also can decrease the intraocular pressure.
Administration of adrenalinum
 Cardiac arrest, for example, during






surgical narcosis, electric trauma
Sudden cardiac death (intracardial
administration).
Shock and collapse conditions
Bronchial spasm
Hypoglycemic coma
For prolongation of anesthetics action
due to vasoconstriction and for
reduction of regional blood flow
is desirable for achieving hemostasis
in surgery.
Treatment of open-angle glaucoma
Contraindications for use
of adrenalinum
 Hypertension,
 Severe atherosclerosis,
coronarocardiosclerosis,
 Cardiogenic and
posthemorragic shocks,
diabetes mellitus,
 Thyreotoxicosis
Noradrenalini hydrotartras
(norepinephrine)
Is an adrenomimetic of direct action which
stimulates preferentially -adrenoreceptors
Administration
in cases of acute decreasing of blood
pressure
shock
and
collapse
conditions, surgeries, traumas
NB! The drug is absolutely
contraindicated for subcutaneous
and intramuscular introductions
Dopaminum
Drug of first
choice for
treatment of
shock
and
collapse
of
different ethiology, including
cardiogenic and hemorrhagic
Mesatonum (phenylephrin)
Is a synthetic a1-adrenomimetic drug of
direct action
Administration


acute hypotensive conditions,
prophylaxis of decreasing of blood
pressure in case of infectious diseases,
poisonings,
 decreasing of blood pressure during
narcosis with fluorothan and cyclopropan
 nose drops in case of rhinits
Naphtisinum
Xylometazolinum
are α2-adrenomimetics of direct action
Usage
for rhinitis in a form of nasal
drops – 1-2 drops 2-3 times a day
NB! It is not recommended to use
the drug in case of chronic
cold
Dobutaminum
Is a synthetic 1-adrenomimetic
Cardiotonic effects of dobutamin is
5 times stronger than action of
dopamine
Administration
some forms of acute and chronic
cardiac
insufficiency
intravenous
transfusion with the speed of
2,5-10 mkg / (kg.min)
Salbutamol
(ventolin)
selective
b2-adrenomimetic
of direct action
Administration
 inhalations
during
attacks
of
bronchial asthma and bronchial spasms
of other etiology,
 premature
child delivery, rapid
(vigorous) child delivery
Fenoterol (berotek,
partusisten)
Is stimulant of mostly 2-adreno
receptors. Posses broncholytic
and tokolytic activity
Sympathomimetics
Ephedrini hydrochloridum
It has indirect α-, β-adrenomimetic (sympathomimetic)
action
Administration
collapse conditions, for prophylaxis of decreasing of
blood pressure before spinal anesthesia, infection
diseases
 treatment of rhinitis (2%, 3% solution of nasal drops)
 prophylaxis and elimination of bronchial spasm
(inhalations 0,5%-1% solutions of drug)
SIDE EFFECTS

agitation, excitement, tremor, inconsiderable
euphoria, insomnia, seizures
 drug addiction
 tachyphylaxy

Classification of the adrenergic blockers
I.
Adrenoblockers
1) α - adrenoblockers –
Prazosinum,
Doxazosinum, Terazosinum
2) β – adrenoblockers
Systemic (non-selective) - Anaprilinum
(Propranololum)
Cardioselective - Metoprololum, Atenololum,
Bisoprololum
With intrinsic sympatomimetic activity:
Oxprenololum, Pindololum
3) α and β – adrenoblockers - Labetalolum
II. Sympatholytics
Reserpinum
Octadinum
Alfaadrenoblockers
Prazosinum, (Adversutenum,
Pratisolum)
Doxazosinum (Kardura)
Terasosinum
Pharmacologic effects of
alfa-adrenoblockers
lowering of peripheral vascular
resistance
 improving of microcirculation and
trophics
 decrease of blood pressure,
postural hypotension
 reflex tachycardia

Therapeutic uses of
alfa-adrenoblockers

Complex treatment of hypertensive
disease

Disturbances of peripheral
microcirculation

Migraine headache, vertigo

Prostatic hypertrophy (1-antagonists block
-receptors and decrease tone in the smooth
muscle of the bladder neck and prostate and
improves urine flow)
Adverse effects of α-adrenoblockers

ortostatic hypotension, “phenomenon of first
dose”: sudden decreasing of blood pressure
and even development of orthostatic collapse
after first administrations of the drug
Prophylaxis: administration of half-dose before
sleep

tachycardia

vertigo, dizziness,

nasal congestion,

headache,

drowsiness
Betaadrenoblockers
Note! The name of all
β-blockers end in
“-olol”
Pharmacological effects of beta-adrenoblockers
Cardiovascular system - lower blood pressure.
Decrease the heart rate, cardiac output
Heart - decrease all functions of the heart, work and
oxygen consumption of the myocardium
Respiratory tract - contraction of the bronchiolar
smooth muscles (bronchospasm)
Uterus – stimulating of the contractility of pregnant
uterus
Eye - reducing intraocular pressure, due to
decreasing of aqueous humor production.
Metabolic and endocrine effects - decreasing of
glucogenolysis and glucagons secretion. Inhibition
of sympathetic nervous system’ stimulation of
lipolysis
Administration of
beta-adrenoblockers
 Ischemic heart disease
 Long-term prophylaxis after myocardium
infarction and prevention of sudden cardiac
death
 Hyperthyreoidism and anxiety states
(decrease of heart rate)
 Essential hypertension
 Cardiac tachyarrhythmias (extrasystolies,
paroxysmal tachycardia, fibrillation and
scintillation of atria)
 Prophylaxis of migraine headache
 Some causes of glaucoma (timolol)
Side effects of beta-adrenoblockers
 CVS: heart arrythmias (bradicardia, A-V
blockade), heart failure, contraction of coronary
vessels)
 Bronchospasm
 CNS disorders (sedation, fatigue, sleep
disturbances, depression, sexual
disfunctions)
 Disturbance of metabolism: hypoglycemic
action, aterogenic effect
 Disturbances of thyroid glamd functions
 Allergic reactions (rash, fever, purpura)
 Risk of premature interruption of pregnancy
 Rebound syndrome ( of myocardial ischemia)
Anaprilin (Propranololum)
is the prorotype β-adrenergic
antagonist and blocks both β1
and β2 receptors.
Administration
ischemic heart disease
 essential hypertension
 cardiac tachyarrhythmias
 acute myocardium infarction

Cardioselective β -adrenoblockers
Metoprololum (Cоrvitol)
Atenololum (Tenormin)
Talinonololum (Cordanum)
Bisoprololum (
Main peculiarities:
Preferentially block the β1 receptors without
blocking of β2- receptors.
Thus their side effects expect bronchoobstruction,
hypoglycemia and premature labor
Talinololum (Cordanum)
Administration



disorders
of
cardiac
rhythm
(extrasystolies,
paroxysmal
tachycardia,
fibrillation
and
scintillation of atria)
stenocardia
arterial hypetension
Atenolol (tenormin)
cardioselelctive -adrenoblocker of long
action
Administration
 ischemic heart disease
 essential hypertension
 cardiac arrhythmias
 acute myocardium infarction
β-adrenoblockers with intrinsic
sympathomimetic activity
(Oxprenololum, Pindololum)
Peculiarities
Less potent decrease of heart rate
and heart output
Less constrict coronary and
peripheral arteries and bronchi
Less decrease of BP
Moderate cardioprotective action
Don’t не погіршують перебіг
атеросклерозу
Rebound syndrome appears more
seldom
Labetalol
-, -adrenoblocker. The drug blocks 1, 2,
1 and 2-adrenoreceptors
Administration
treatment of patients with essential
hypertension
 hypertensive crisis

Contraindications
Atrio-ventricular blockade,
cardiac insufficiency
Sympatholytics
Reserpin
Is a sum of Rauvolfia (plant) alkaloids. Maximal
hypotensive action develops after 5-7 days of
regular administration of the drug. After the
treatment coarsed effect can still stay for two
weeks.
Administration
treatment of different forms of essential hypertension
(preparations of a second choise)
(combined drugs trirezid, cristepin, adelfan, brinerdin)
Side effects

manifestations of parkinsonism
 fatigue, somnolence, depression,
 bradycardia
 increasing of motor and secretory activity of
tract,
 acute attacks of ulcer disease, diarrhea
gastro-intestinal
Octadinum
Is a sympatholytic with strong hypotensive effect.
During administration of the drug decreasing of
blood pressure develops gradually, after 2-3 days.
After abolition of drug administration the effect still
stays for 2 weeks.
Administration
heavy forms of arterial hypertension
Side effects
general weakness,
 nausea, vomiting,
 swelling of nose mucous membrane,
 diarrhea,
orthostatic collapse

Thanks for attention!
Good-bye !