Adrenergic System

Adrenaline as a prototype

Heart

·         β_{1 –} Cardiac stimulant (+ve chronotropic, +ve ionotropic)

·         Act on β₁ receptor in myocardium, pacemaker cells and conducting tissue.

·         Heart rate is increase by increasing slow diastolic depolarization of cells in SAN.

·         It activates latent pacemaker in A-V node and purkinje fibres.

·         In high dose arrhythmia can occur.

·         Cardiac output is enhanced and oxygen consumption is increased, cardiac efficiency is markedly decreased.

·         Reduce refractory period.

Blood vessel

·         Smaller vessel-arterioles – Vasoconstriction (α) and vasodilatation (β) depends on the drugs.

·         Decrease blood flow to skin and mucous membranes and renal beds (α effect 1 and 2).

·         Increased blood flow to the skeletal muscles coronary and liver vessels (β₂ effect) counter balance by a vasoconstriction effect of α receptor.

Blood pressure

·         It depends on concentration of catecholamine present.

·         NA causes rise in systolic, diastolic and mean BP (no β₂ action) – unopposed α action.

·         Isoprenaline causes rise in systolic but fall in diastolic BP (fall BP, β₁ and β₂).

·         Adr causes rise in systolic BP, but fall in diastolic BP means BP gradually rise (slow injection).

·         Decrease peripheral resistance at low concentration. β – Receptors are more sensitive to Adr than α – receptor.

·         Rapid i.v. injection of adrenalin marked rise in systolic and diastolic BP, but BP returns to normal in few minutes.

 Respiration

·         Powerful bronchodilator.

·         Relax bronchial smooth muscle (not NA)

·         Β₂ mediated effect.

·         Physiological antagonist to mediator to bronchoconstriction (e.g. Histamine).

GIT

·         Relaxation of gut muscle (α and β) and constricted sphincter – reduce peristalsis (not clinical importance).

Bladder

·         Relaxed detrusor muscle (β) but constriction of Trigone (smooth triangular region of the internal urinary bladder) – both are anti-voiding effect.

Uterus

·         Adrenaline contracts and relaxes (α and β action) but net effect depends on status of uterus and specific pregnant relaxes but non pregnant – contracts.

Skeletal muscle

·         Facilitation of Ach release in NM junction (α₁).

·         β₂ act directly on muscle fibers.

·         Abbreviate active state and less tension is slow conducting fibers and enhanced muscle spindle firing tremor.

CNS

·         No visible clinical effect in normal doses – as low penetration except restlessness, apprehension and tremor.

·         Activation of α₂ in CNS decrease sympathetic out and reduction in BP and bradycardia (clonidine)

Metabolic effects

·         Increase contraction of glucose and lactic acid.

·         Calorigenesiss (β₂ and β₃)

·         Inhibit insulin secretion (α₂).

·         Decrease uptake of glucose by peripheral tissue.

·         Stimulate Glycogenolysis β effect

·         Increase free fatty acid concentration in blood.

·         Hypokalemia – Initial hypokalemia

Pharmacokinetic

·         All Catecholamines are ineffective orally.

·         Absorbed slowly.

·         Faster from i.m. site

·         Inhalation is locally effective.

·         Not usually given i.v.

·         Rapidly inactivation on liver by MAO and COMT.

Clinical uses

·         Injectable preparation are available in dilutions 1:10000 and 1:00000

·         Dose 0.3-0.5 mg s.c. of 1:10000.

·         Used in

o   Anaphylactic shock

o   Prolonged action of local anaesthetic

o   Cardiac arrest

o   Topically, to stop bleeding

o   Hyperkinetic children (Psychomotor instability, learning disorder, emotional lability, immaturity etc.) – ADHD, minimal brain dysfunction Anorectic (an eating disorder characterized by markedly reduce appetite or total aversion to food.)

Adverse drug reaction

·         Restlessness, throbbing headache, tremor, palpitation.

·         Cerebral hemorrhage, cardiac arrhythmia.

·         Contraindicated in hypertensive, hyperthyroid and angina pectoris.

·         Halothane and β-blockers-not indicated.

Therapeutic classification of adrenergic drugs

1.      Pressor agents

·         NA

·         Ephedrine

·         Dopamine

·         Phenylephrine

·         Methoxamine

·         Mephentamine

2.      Cardiac stimulant

·         Adrenaline

·         Isoprenaline

·         Dobutamine

3.      Bronchodilators

·         Isoprenaline

·         Salbutamol

·         Terbutaline

·         Salmeterol

·         Bambuterol

4.      Nasal decongestants

·         Phenylephrine

·         Xylomethazoline

·         Oxymethazoline

·         Naphazoline

·         Pseudoephedrine

·         Phenyl propanolamine

5.      CNS stimulant

·         Amphetamine

·         Dexamphetamine

·         Methamphetamine

6.      Anorectics

·         Fenfluramine

·         Dexfenfluramine

·         Sibutramine

7.      Uterine relaxant and vasodilator

·         Ritodrine

·         Isoxsuprine

·         Salbutamol

·         Terbutaline