Adrenergic preparations

МАО

CОМТ

ά2

ά1β1

β2

Localization of alfa-adrenoceptors

Localization of alfa-adrenoceptors

Localization of beta-adrenoceptors

beta1

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: competitive

2. 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 - miosis

2. GI tract – Increased motility

3. 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 output

2. Inhibition of renin-angiotensin system

3. Decreased central sympathetic outflow

4. 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