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Adrenoceptor Antagonist Drugs
Catecholamines play a role in many physiologic and pathophysi-ologic responses as described. 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.. Blockade of peripheral dopamine receptors is of minor clinical importance at present. In contrast, blockade of central nervous system dop-amine receptors is very important;
For pharmacologic research, α1- and α2-adrenoceptor antago-nist drugs have been very useful in the experimental exploration of autonomic nervous system function. In clinical therapeutics, non-selective α antagonists are used in the treatment of pheochromo-cytoma (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, arrhyth-mias, endocrinologic and neurologic disorders, glaucoma, and other conditions.
A 46-year-old woman sees her physician because of palpita-tions and headaches. She enjoyed good health until 1 year ago when spells of rapid heartbeat began. These became more severe and were eventually accompanied by throbbing head-aches 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 her episodes? What caused the blood pressure and heart rate to rise so high dur-ing the examination? What treatments might help this patient?
CASE STUDY ANSWER
The patient had a pheochromocytoma. The tumor secretes catecholamines, especially norepinephrine and epinephrine, resulting in increases in blood pressure (via α1 receptors) and heart rate (via β1 receptors). The pheochromocytoma was in the left adrenal gland and was identified by MIBG imaging, which labels tissues that have norepinephrine transporters on their cell surface (see text). In addition, she had elevated plasma and urinary norepinephrine, epinephrine, and their metabolites, normetanephrine and metanephrine. The cate-cholamines made the blood pressure surge and the heart rate increase, producing a typical episode during her examination, perhaps set off in this case by external pressure as the physi-cian palpated the abdomen. Her profuse sweating was typical and partly due to α1 receptors, though the large magnitude of drenching sweats in pheochromocytoma has never been fully explained. Treatment would consist of preoperative control of blood pressure and normalization of blood volume if reduced, followed by surgical resection of the tumor. Control of blood pressure extremes might be necessary during surgery, proba-bly with nitroprusside.
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