After reading this article we will learn about the classification of antiadrenergic drugs
These are the drugs which antagonize the pharmacological action of sympathomimetic agents or alter the function of sympathetic nervous system inside the body.
Classification:
On the basis of mechanism of action.
1. α-Adrenoceptor Antagonists:
Phenoxy-benzamine:
(i) Phenoxy-benzamine is a halo-alkyl-amine. It binds covalently to the α receptors (both α1 and α2), producing an irreversible blockade. So, the a-receptor mediated responses are antagonized by the drug.
(ii) It induces postural hypotension. It also increases cardiac output and decreases total peripheral resistance.
(iii) It stimulates CNS, producing nausea, hyperventilation.
(iv) It is used for acute hypertensive episodes due to sympathomimetic, MAO inhibitors, or pheochromocytomas.
Ergot Alkaloids:
(i) Ergotamine and ergotoxine are the two amino acid alkaloids obtained from a fungus Claviceps purpurea.
(ii) They are weak antagonists at α-adrenergic, serotonergic and dopaminergic receptors.
(iii) They also directly stimulate smooth muscle specially in blood vessel and uterus. This effect is due to its partial agonistic action on α receptors.
(iv) They first produce rise in blood pressure (α agonistic action), which is followed by fall in B.P. (α receptor blocking effect).
(v) They initially stimulate CNS (clonic convulsion) followed by depression.
(vi) They contract uterine smooth muscle and cause constriction of pupil.
Prazosin:
(i) Prazosin is a selective blocker of postsynaptic α1 receptors, producing vasodilation of both arteries and veins.
(ii) Prazosin reduces peripheral vascular resistance and lowers arterial blood pressure.
(iii) Unlike nonselective α adrenergic blocker, it does not usually produce reflex tachycardia; because prazosin has no effect on α2 receptors; neurotransmitter feedback inhibition is maintained.
(iv) Fluid retention may occur during long term therapy with prazosin.
Clinical Uses of α Adrenoceptor Antagonists:
(a) Hypertension:
α1 selective antagonists. Prazosin is short acting. Long acting drugs like doxazosin or terazosin is used either alone or in combination with other drugs.
(b) Pheochromocytoma:
Phenoxy-benzamine + β-receptor antagonist
(c) Acute Hypertensive Episodes Due to Sympathomimetic:
Phenoxybenzamine, or phentolamine.
(d) Visceral Ischemia during Circulatory Shock in Animals:
Phenoxy-benzamine- 0.44 to 2.2 mg/kg diluted in 500 ml normal saline or 5% dextrose, slow i.v. inj.
2. β-Adrenoceptor Antagonists:
Propranolol: (Inderal®):
(i) Propranolol is a nonselective β receptor blocker widely used in practice.
(ii) Its main action is on cardiovascular system. It decreases the heart rate and force of contraction, cardiac output and prolongs systole. All effects are due to β1 receptor blockade.
(iii) It reduces blood pressure and reduces blood flow to most tissues except the brain. The mechanism of propranolol’s antihypertensive effect is not yet clear. However, the drug inhibits renin secretion, which may play a-role.
(iv) Propranolol causes bronchoconstriction (β2 blocking effect). Hence it is contraindicated in asthma.
(v) The main toxic symptoms are hypotension and bradycardia. It may also cause oedema due to decrease in renal sodium excretion.
Dose:
Dog → 0.1 mg/kg b.wt., 3 times daily, orally
Cat → 0.5 mg/kg b.wt., 3 times daily, orally.
Timolol is 5-10 times more potent than propranolol. Acebutolol, pindolol, penbutolol and carteolol, all β blockers, also have intrinsic sympathomimetic activity.
Metoprolol: (Betaloc®)
(i) Metoprolol is a selective β1 adrenoceptor blocker.
(ii) It inhibits the ionotropic and chronotropic cardiac responses to isoproterenol.
(iii) It causes fall in blood pressure and is used in the treatment of hypertension.
Dog→(i) Re 5-50 mg, 3 times daily orally or i.m., inj.
Atenolol: (Aten®, Atecard®, Betacard®).
(i) It is a selective β1 adrenegic antagonist.
(ii) It is comparatively long acting than metoprolol.
Dog → 20 – 100 mg, 3 times daily, orally.
Labetalol:
(i) It blocks both α and β receptors and is used in hypertension.
Clinical uses of β-Adrenoceptor Antagonists:
(a) Hypertension, angina pectoris, myocardial infarction and cardiac dysrhythmias.
(b) Glaucoma, hyperthyroidism, anxiety-related muscle tremors, etc.
3. Drugs Inhibiting NE Synthesis:
Methyldopa:
(i) Methyldopa is an effective inhibitor of dopa decarboxylase and thereby decreases the synthesis of catechotamines.
(ii) But the antihypertensive effect of methyldopa is mainly due to its conversion to a false transmitter. It is metabolized by decarboxylation and β-hydroxylation to β-methyl norepinephrine in adrenergic neurons. α- Methyl-norepinephrine displaces norepinephrine from its receptors to cause fall in B.P.
(iii) Methyldopa can be used in hypertension in combination with a diuretic. But it is not used presently due to several adverse effects like sedation, rebound hypertension, oedema, GI disturbances, etc.
4. Drugs Inhibiting NE Storage:
Reserpine:
(i) Reserpine is obtained from Rauwolfia serpentina.
(ii) It depletes catecholamines and serotonin stores in the peripheral and CNS. It interferes with intracellular storage of catecholamines by inhibiting Uptake of NE into vesicles. The transmitter accumulates instead in the cytoplasm, where it is degraded by MAO.
(iii) Reserpine initially may cause rise in B.P. due to inhibition of NE uptake into vesicles. But, later on, it produces fall in B.P. due to depletion of NE storage and release.
(iv) Sedation often results, owing to the depleted stores of catecholamines and serotonin in the brain.
(v) The drug is mainly used in hypertension.
5. Drugs Inhibiting NE Release (Non-Adrenergic Neuron Blocking Drugs):
Guanethidine:
(i) Guanethidine acts presynaptically to inhibit the release of NE from peripheral adrenergic neurons.
(ii) It is taken up by adrenergic nerves (uptake I) and displaces NE from intraneuronal storage granules. This is the reason for initial rise in B.P. produced by guanethidine (large i.v. dose).
(iii) This is followed by a fall in B.P. both in hypertensive and normotensive individuals.
(iv) It causes a slowly developing and long-lasting depletion of NE in sympathetic nerve endings, similar to the effect of reserpine.
(v) It also acts directly on vascular smooth muscles (probably on β2-adrenoceptors) to cause vasodilation.
(vi) It is used in the treatment of hypertension.
(vii) Its antihypertensive effect may be reversed by the indirect acting sympathomimetic drugs, such as amphetamine, ephedrine; because they block uptake I process and displaces guanethidine and NE from storage vesicles.
(viii) Adverse effects → postural hypotension, oedema, etc.
Bretylium:
(i) Bretylium is taken by the adrenergic nerve terminals and blocks the release of NE.
(ii) It also inhibits the re-uptake of NE into nerve terminals.
(iii) Initially, or at high dose, bretylium produces a sympathomimetic effect due to release of catecholamines, before it blocks the action of the nerves.
(iv) It is not used in hypertension, but mainly used as an antiarrhythmic agent.
(v) Adverse effects are tachycardia and strong hypotension.