Page 170 - Basic _ Clinical Pharmacology ( PDFDrive )

10 Adrenoceptor Antagonist
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David Robertson, MD, & Italo Biaggioni, MD

C ASE STUD Y

A 38-year-old man has been experiencing palpitations and elicited a sudden and typical episode, with a rise in blood
headaches. He enjoyed good health until 1 year ago when pressure to 210/120 mm Hg, heart rate to 122 bpm, profuse
spells of rapid heartbeat began. These became more severe sweating, and facial pallor. This was accompanied by severe
and were eventually accompanied by throbbing headaches headache. What is the likely cause of his episodes? What
and drenching sweats. Physical examination revealed a caused the blood pressure and heart rate to rise so high
blood pressure of 150/90 mm Hg and heart rate of 88 bpm. during the examination? What treatments might help this
During the physical examination, palpation of the abdomen patient?

Catecholamines play a role in many physiologic and pathophysi- (tumors that secrete catecholamines), and α -selective antagonists
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ologic responses, as described in Chapter 9. Drugs that block their are used in primary hypertension and benign prostatic hyperplasia.
receptors therefore have important effects, some of which are of Beta-receptor antagonist drugs are useful in a much wider variety
great clinical value. These effects vary dramatically according to of clinical conditions and are firmly established in the treatment of
the drug’s selectivity for α and β receptors. The classification of hypertension, ischemic heart disease, arrhythmias, endocrinologic
adrenoceptors into α , α , and β subtypes and the effects of acti- and neurologic disorders, glaucoma, and other conditions.
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vating these receptors are discussed in Chapters 6 and 9. Blockade
of peripheral dopamine receptors is of limited clinical importance
at present. In contrast, blockade of central nervous system (CNS) ■ BASIC PHARMACOLOGY
dopamine receptors is very important; drugs that act on these
receptors are discussed in Chapters 21 and 29. This chapter deals OF THE ALPHA-RECEPTOR
with pharmacologic antagonist drugs whose major effect is to ANTAGONIST DRUGS
occupy α , α , or β receptors outside the CNS and prevent their
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activation by catecholamines and related agonists. Mechanism of Action
For pharmacologic research, α - and α -adrenoceptor antago-
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nist drugs have been very useful in the experimental exploration Alpha-receptor antagonists may be reversible or irreversible in their
of autonomic function. In clinical therapeutics, nonselective interaction with these receptors. Reversible antagonists dissociate
α antagonists are used in the treatment of pheochromocytoma from receptors, and the block can be surmounted with sufficiently
high concentrations of agonists; irreversible drugs do not dis-
sociate and cannot be surmounted. Phentolamine and prazosin
(Figure 10–1) are examples of reversible antagonists. These drugs
and labetalol—drugs used primarily for their antihypertensive
* The authors thank Dr. Randy Blakely for helpful comments, Dr. Brett
English for improving tables, and our students at Vanderbilt for advice effects—as well as several ergot derivatives (see Chapter 16) are
on conceptual clarity. also reversible α-adrenoceptor antagonists or partial agonists.
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