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Lecture №2
Adrenotropic drugs
(adrenomimetics,
adrenoblockers)
НА
НА
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
α1
α2
β1
β2
Typical locations
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.
Especially – CNS on the brake neurons.
Postsynaptic effector cells, especially heart; lipocytes.
Postsynaptic effector cells, especially smooth muscles
of the bronchi, myomethrium, vessels of skeletal
muscles.
β -specific Liver (hepatocytes), lyposytes, skeletal muscles
Main effects mediated by alpfa and beta-adrenoreceptors
Alpha 1
Alpha 2
Beta1
Vasoconstriction
Increased
peripheral
resistance
Increase
blood
pressure
Mydriasis
Increased
closure of
internal
sphincter of
Sedative
effect on
CNS,
decrease
BP
Inhibition
of the
insulin
release
Increase of the
the bladder
all function of
the heart
(tachycardia
increase BP,
myocardium
contractility,
increase
oxygen
demands of
the
myocardium
Beta 2
Bronchodilatation
Relax
myometrium
Relax smooth
muscles of
sleletal
muscles
Increase
muscle and
liver
glycogenolysis
Increase
release of
glucagonum
Betaspecific
Increase of
the
methabolic
processes
in the
organism
(glycolysis,
lypolysis,
glycogenolysis)
Classification of adrenotropic drugs
І. Adrenomimetics
1. --adrenomimetics (Adrenalini hydrochloridum)
2. -adrenomimetics (Noradrenalini hydrotartras
Mesatonum, Naphtizinum)
3. -adrenomimetics (Salbutamol, Phenoterol,
Dobutaminum)
ІІ. Sympathomimetics (Ephedrini hydrochloridum)
ІІІ. Adrenoblockers
1. -adrenoblockers (Prasosinum, Doxasosinum)
2. -adrenoblockers (Anaprilinum, Atenololum,
Talinololum, Metoprololum)
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
 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
Naphtisin
Xylometazolin
are a2-adrenomimetics of direct action
Usage
for rhinitis in a form of nose 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 a-, b-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
2) β – adrenoblockers
Systemic (non-selective) - Anaprilinum
(Propranololum)
Cardioselective - Metoprololum, Atenololum
3) α and β – adrenoblockers - Labetalolum
II. Sympatholytics
Reserpinum
Octadinum
Alfaadrenoblockers
Prazosinum, (Adversutenum,
Pratisolum) – tabl. 0,0005;
0,001; 0,002; 0,005
Doxazosinum (Kardura) – tabl.
0,001; 0,002; 0,004; 0,008
Pharmacologic effects of alfaadrenoblockers




lowering of peripheral vascular
resistance
improving of microcirculation and
trophics
decrease of blood pressure, postural
hypotension
reflex tachycardia
Therapeutic uses of alfaadrenoblockers


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”, except for labetalol, which has
a component of α1-blocking actions.
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)
Adverse effects of beta-adrenoblockers
Heart failure
Bronchospasm
Allergic reactions (rash, fever, purpura)
Heart arrythmias (bradicardia, atrioventricular blockade)
CNS disorders (sedation, fatigue, sleep
disturbances, depression, sexual
disfunctions)
Disturbance of metabolism: hypoglycemic
action
Risk of premature interruption of
pregnancy
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) - tab. 0,05; 0,1;
amp. 1% - 5 ml
Atenololum (Tenormin) - tab. 0,05; 0,1
Talinonololum (Cordanum)- dr.0,05; tab. 0,1.
Main speculiarities:
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
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
intestinal tract,
 acute attacks of ulcer disease, diarrhea
gastro-
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 !