Adrenergic Receptor Antagonists Excessive sympathetic activity is characteristic of a number of pathological states including: Hypertension Angina pectoris Cardiac arrhythmias Sympatholytics – adrenergic receptor antagonists Block ,  or both Therapeutic effects due to  1 and  1 blockade Adverse effects due to  2 and  2 blockade Therefore  1 and  1 selective antagonists , Section 2, Lecture 5

Non-selective  -blockers Block both  1 and  2 receptors –Ie. phentolamine and phenoxybenzamine Competitive inhibitor Non-competitive inhibitor Chemical sympathectomy Hypertensive Episodes - decreases vascular resistance - lowers BP - smooth muscle relaxation in the bladder Used to treat hypertensive episodes of Pheochromocytoma

Selective  1 -blockers Selectively block  1 receptors – Ie. Alfuzosin, doxazosin, prazosin, terazosin Used in the treatment of chronic hypertension Also used to treat urinary retention in men with benign prostatic hyperplasia

Selective  1 blockers cause less reflex tachycardia than phenoxybenzamine and phentolamine

Adverse effect of  1 blockers Mostly caused by excessive vasodilation Hypotension, dizziness, fainting, reflex tachycardia, palpitation First-dose syncope: effect on BP when they are initially administered

 -adrenergic receptor antagonists Both non-selective and selective  -blockers Non-selective – ie nadolol, pindolol, propranolol, tomilol – Block both  1 receptors in cardiac tissue and  2 in smooth muscle, liver and other tissues Blockade of  1 reduces sympathetic stimulation of heart… Therefore, negative Blockade of  2 may cause broncoconstriction and limit glycogenolysis  Adverse effects!! chronotrope inotrope dromotrope

 1 -antagonist _____  1 -antagonists

Selective  1 -blockers Have greater affinity for  1 than for  2 receptors –Ie Acebutolol, atenolol, esmolol, metoprolol CARDIOSELECTIVE  BLOCKERS Produce fewer adverse effects than non- selective, but their selectivity is not absolute In summary,  -blockers have a number of clinical applications including treatment of: migraines Hypertension angina pectoris cardiac arrhythmia glaucoma

 1- Contract vascular smooth muscle, iris, bladder sphincter muscle  2 -Inhibits NE release  2 - Relaxes bronchial, uterine, and vascular smooth muscle  2 -mediates platelet aggregation;decrease insulin secretion; decreases secretion of aqueous humor  2 -inhibits platelet aggregation; promotes glycogenolysis

Practice Questions Blockade of which receptors is responsible for the therapeutic and adverse effects of adrenergic receptor agonists? Therapeutic:  1,  1 Adverse:  2,  2

Which type of drugs causes chemical sympathectomy? Give an example? Non-Competitive  blocker phenoxybenzamine

What type of adrenergic receptor antagonists can be used in treatment of nocturia in benign prostate hyperplasia? Give an example.  1 blockers Alfuzosin, doxazosin, prazosin, terazosin