Angiotensinconverting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors come in two basic forms: an active drug form, best represented by captoril, and a prodrug form, represented by enalapril. Recently, enalaprilat, the active form of enalapril, became available for intravenous use. However, there are many ACE inhibitors available today, and all work to inhibit the conversion of the prohormone, angiotensin I, to the potent endogenous vasoconstrictor, angiotensin II. Besides being a vasoconstrictor, angiotensin II stimulates aldosterone release to increase sodium and water retention. Aside from these two effects, ACE inhibitors have other mechanisms of action to decrease total peripheral resistance without increasing heart rate or cardiac output. For example, by inhibiting ACE (also known as bradykininase), the degradation of the vasodilator peptide, bradykinin, is prevented.

Adverse effects of ACE inhibitors include hypotension, angioedema, rash, anaphylactoid reactions, cough, drug fever, proteinuria, glomerulopathy, neutropenia, and agranulocytosis. With overdoses of ACE inhibitors, the most important concern is hypotension, which can be profound. The preferred therapy to reverse the hypotension is the administration of normal saline, and, if necessary, vasopressors, such as intermediate or high-dose dopamine, can be added. Although ACE inhibitors are dialyzable, peritoneal dialysis and hemodialysis are not recommended at this time. Naloxone has been reported to be useful in reversing the hypotension induced by captopril, although its mechanism is unclear.

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