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

Catecholamines play a role in many physiologic and pathophysiologic responses, as described in Chapter 9. * Drugs that block their receptors, therefore, have important effects, some of which are of great clinical value. These effects vary dramatically according to the drug’s selectivity for α and β receptors. The classification of α and β adrenoceptors subtypes and the effects of activating these receptors are discussed in Chapters 6 and 9. Blockade of peripheral dopamine receptors is of limited clinical importance at present. In contrast, modulation of central nervous system (CNS) dopamine receptors is very important, as discussed in Chapters 21, 28, and 29. This chapter deals with pharmacologic antagonist drugs whose major effect is to occupy α or β receptors and prevent their activation by catecholamines and related agonists.

Nonselective α antagonists are used in the treatment of pheochromocytoma (tumors that secrete catecholamines), and α1-selective antagonists are used in primary hypertension and benign prostatic hyperplasia. Beta-receptor antagonist drugs are useful in a much wider variety of clinical conditions and are firmly established in the treatment of hypertension, ischemic heart disease, arrhythmias, endocrinologic and neurologic disorders, glaucoma, and other conditions.

*The author thanks David Robertson, MD, for his contributions to previous versions of this chapter.


Mechanism of Action

Alpha-receptor antagonists may be reversible or irreversible in their interaction with these receptors. Reversible antagonists dissociate from receptors, and the block can be overcome with sufficiently high concentrations of agonists; irreversible drugs do not dissociate and cannot be surmounted. Phentolamine and prazosin (Figure 10–1) are examples of reversible antagonists. Phenoxybenzamine forms a reactive ethyleneimonium intermediate (see Figure 10–1) that covalently binds to α receptors, resulting in irreversible blockade. Figure 10–2 illustrates the effects of a reversible drug in comparison with those of an irreversible agent.


Structure of several α-receptor–blocking drugs.


Dose-response curves to norepinephrine in the presence of two ...

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