PHARMACOLOGY OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS AS A GUIDE TO THEIR USE IN CONGESTIVE HEART-FAILURE

The pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitors are difficult to assess for several reasons. First, these compounds exert their influence by inhibiting an intermediary enzyme of a cascade of enzymatic events, whose ratelimiting enzyme (renin) is not directly affected by ACE inhibition. Second, renin and angiotensin I accumulate during ACE inhibition and a change in the dose of an ACE inhibitor could produce sudden shifts of angiotensin I to angiotensin II. Third, components of the circulating renin system require the interaction of several organ systems and effector sites. Fourth, the kinetics of ACE inhibitors can be influenced by the organ systems responsible for drug absorption, metabolism and excretion, and the functional status of these systems can be affected by the heart failure process. Fifth, at least some portion of the cardiovascular effects of ACE inhibitors is influenced by the contributions of other systems whose physiologic effects may be of importance in some patients with congestive heart failure. Sixth, the potential impact of tissue-bound ACE is not yet fully understood. Finally, for appropriate drug dosing, the effects of aging on the heart failure process, the extent of renin system activity, and the disposition of ACE inhibitors need to be considered. Because of their complex pharmacokinetics, treatment with ACE inhibitors has been guided by their pharmacodynamic and clinical characteristics. © 1990.