Adrenergic Receptor Antagonists

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

59-291, 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!!

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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 absoluteIn 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