pharmacology adrenergic preparations
TRANSCRIPT
Adrenergic preparations
МАОCОМТ
ά2
ά1β1
β2
Localization of alfa-adrenoceptors
Localization of alfa-adrenoceptors
Localization of beta-adrenoceptorsbeta1
beta 2
Localization of beta2-adrenoceptors
Localization of beta3-adrenoceptors• β3-adrenoceptors
are located in the cells of fatty tissue, in the mast cells and in pancreatic β-cells. Their excitation leads correspondingly to increase of lipolysis, to inhibition of mast cell degranulation and to stimulation of insulin release.
Excitation: • Of α-receptors causes
the increasing of functions (tone of smooth muscles) except intestine and uterus
• Of β- receptors – decreasing of functions (tone of smooth muscles) except heart
Adrenomimetics• Directly acting • – Adrenalini hydrochloridum – α1 α2 β1 β2 β3
• -Noradrenalini hydrotartras – α1 α2 β1
• - Mesatonum - α1
• -Isadrinum - β1 β2
• -Dobutamine - β1
• -Salbutamolum - β2
• Fenoterolum - β2
• Indirect action – • - Ephedrini hydrochloridum α1 α2 β1 β2 β3
The main effects of adrenaline• the increase of automatism (heart rate),• excitability, conduction and
contractility (cardiac output) of myocardium
• the increase of the arterial pressure,• hyperglycemia, • dilation of bronchi, • dilation of pupils • inhibition of mast cell degranulation• increase of oxygen demand and
production of energy.
The main effects of noradrenaline• acts predominantly upon the cardiovascular
system –• increases the arterial pressure (both
systolic and diastolic one) • The rapid increase of arterial pressure
stimulates a reflex reaction from vascular mechanoceptors that leads to the development of sinus bradycardia
• introduced only intravenously because in subcutaneous or intramuscular introduction it causes strong local vasospasm that may be accompanied by development of necrosis.
Ephedrini hydrochloridum• Acts upon the presynaptic membrane and
stimulates noradrenaline release from the sympathetic nerve endings. It also slightly excites the adrenoceptors located on the postsynaptic membrane.
• The same effects as Adrenaline, but it's less active (in 50-100 times), action develops gradually and lasts longer stimulates the CNS, may cause psychomotor excitement, insomnia and euphoria (drug dependence).
• In the repeated introduction of ephedrine within small interval (10-30 mm.) the tachyphylaxis appears
• Ephedra
Indications for use- Adrenaline• anaphylactic shock and some other allergic
reactions, • bronchial asthma, • acute hypotension (collaps), • hypoglycemic coma, • cardiac arrest, • depression of excitability and conduction of
myocardium, • for extension of local anesthetics' action. • Locally- in open angle glaucoma, for the arrest
of capillary hemorrhage• Adrenaline is used only by parenteral way or
locally because its destroyed in oral introduction.
Mesatonum increases BP -indicated in collaps
Indications for use-• Isadrinum - indicated in
bronchial asthma, atrioventricular blockade, bradycardia.
• Salbutamol, fenoterol - bronchial asthma, premature or precipitated labor
• Dobutamine - acute heart failure which accompanies the myocardial infarction.
Alpha-Adrenergic Blockers1. Type of blockade
Tropaphenum – non-competitive; slow onset and long duration. 2-stage blockade.
All the rest: competitive2. Selectivity Nonselective:
Tropaphenum and phentolamine alpha-1 selective: Prazosin, terazosin, others alpha-2 selective: Yohimbine alpha/beta blockers: Labetalol
3. Others: phenothiazines, tricyclic antidepressants
Pharmacological Effects
1. Eye - miosis2. GI tract – Increased
motility3. Urinary bladder –
decreased tone in sphincter
4. Metabolic effects – increased insulin secretion
Imidazoline derivatives - phentolamine
• Many other effects including:• Parasympathomimetic• Increased gastric acid secretion• Cardiac stimulation• Increased secretion from exocrine glands,
such as salivary, sweat, lacrimal, pancreatic
• Coronary artery disease and peptic ulcer relative contraindication to it.
Alpha-1 selective blockersPrazosin
• Less cardiac stimulation since it preserves alpha-2 mediated negative feedback + other mechanisms
• Used in congestive heart failure and in hypertension but tolerance develops with time, maybe due to fluid retention.
• Adverse effects: First dose phenomenon.• Favorable effect on plasma lipids: increase
HDL/LDL ratio
Pharmacological Properties Propranolol
• Cardiovascular Blood pressure, heart rate, cardiac output, peripheral vascular resistance, coronary and organ blood flows
• Pulmonary• Central Nervous System• Metabolic
Antihypertensive Effect of Beta-Blockers Mechanisms
1. Decreased cardiac output2. Inhibition of renin-angiotensin system3. Decreased central sympathetic outflow4. Resetting of baroreceptor 5. Others: prejunctional receptors, prostaglandins, etc.
Beta-Blockers - Adverse Effects
• Cardiac (mechanical; electrical)• Vascular (decreased perfusion)• Pulmonary (bronchocostriction)• Metabolic (diabetes mellitus)• Central Nervous System (depression,
nightmares, etc.)• Withdrawal Syndrome