1. Adrenotropic drugs (adrenomimetics, adrenoblockers)
Lecture №2
Adrenotropic drugs (adrenomimetics, adrenoblockers) НА НА

2. which act in adrenergic synapses
Adrenergic drugs -
medical substances
which act in adrenergic synapses

3. postsynaptic membrane
Adrenergic synapse
Phenilalanine
Presynaptic membrane
Thyrosine
Thyrosine
Na+
DOPA
МАО
Dopamine
Ca2+
Desamination
Noradrenaline
КОМТ
Noradrenaline
О-methylation
-, -adrenoreceptors
postsynaptic membrane

4. Adrenergic receptor types
Name
Typical locations
α 1
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.
α 2
Presynaptic adrenergic nerve terminals, platelets, lipocytes, smooth muscle.
Especially – CNS on the brake neurons.
β 1
Postsynaptic effector cells, especially heart; lipocytes.
β 2
Postsynaptic effector cells, especially smooth muscles of the bronchi, myomethrium, vessels of skeletal muscles.
β -specific
Liver (hepatocytes), lyposytes, skeletal muscles

5. Main effects mediated by alpfa and beta-adrenoreceptors
Alpha 1
Alpha 2
Beta1
Beta 2
Beta-specific
Vasoconstric-tion
Increased peripheral resistance
Increase blood pressure
Mydriasis
Increased closure of internal sphincter of the bladder
Sedative effect on CNS, decrease BP
Inhibition of the insulin release
Increase of the all function of the heart (tachycardia increase BP, myocardium contractility, increase oxygen demands of the myocardium
Broncho-dilatation
Relax myometrium
Relax smooth muscles of sleletal muscles
Increase muscle and liver glycogenoly-sis
Increase release of glucagonum
Increase of the methabolic processes in the organism (glycolysis, lypolysis, glycogeno-lysis)

6. 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)

7. 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.

8. 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,- 2-adrenoreceptors

9. 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.

10. 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

11. Contraindications hypertension,
severe atherosclerosis, coronarocardiosclerosis,
cardiogenic and posthemorragic shocks, diabetes mellitus,
thyreotoxicosis

12. 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

13. Dopaminum
Drug of first choice for treatment of shock and collapse of different ethiology, including cardiogenic and hemorrhagic

14. 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

15. 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

17. Dobutaminum Administration 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)

18. 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

19. Fenoterol (berotek, partusisten)
Is stimulant of mostly 2-adreno receptors. Posses broncholytic and tokolytic activity

20. Sympathomimetics

21. 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

22. 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

23. Alfa-adrenoblockers
Prazosinum, (Adversutenum, Pratisolum) – tabl. 0,0005; 0,001; 0,002; 0,005
Doxazosinum (Kardura) – tabl. 0,001; 0,002; 0,004; 0,008

24. Pharmacologic effects of alfa-adrenoblockers
lowering of peripheral vascular resistance
improving of microcirculation and trophics
decrease of blood pressure, postural hypotension
reflex tachycardia

25. 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)

26. 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

27. Beta-adrenoblockers
Note! The name of all β-blockers end in “-olol”, except for labetalol, which has a component of α1-blocking actions.

28. 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

29. 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)

30. Adverse effects of beta-adrenoblockers
Heart failure
Bronchospasm
Allergic reactions (rash, fever, purpura)
Heart arrythmias (bradicardia, atrio ventricular blockade)
CNS disorders (sedation, fatigue, sleep disturbances, depression, sexual disfunctions)
Disturbance of metabolism: hypoglycemic action
Risk of premature interruption of pregnancy

31. 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

33. 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

34. Talinololum (Cordanum)
Administration
disorders of cardiac rhythm (extrasystolies, paroxysmal tachycardia, fibrillation and scintillation of atria)
stenocardia
arterial hypetension

35. cardioselelctive -adrenoblocker of long action
Atenolol (tenormin)
cardioselelctive -adrenoblocker of long action
Administration
ischemic heart disease
essential hypertension
cardiac arrhythmias
acute myocardium infarction

36. Labetalol Contraindications
-, -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

37. Sympatholytics

38. Reserpin Side effects Administration
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 gastro-intestinal tract,
acute attacks of ulcer disease, diarrhea

39. Octadinum nausea, vomiting, swelling of nose mucous membrane,
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

40. Thanks for attention!
Good-bye !