The clinical use of angiotensin-converting enzyme inhibitors
Section snippets
Physiology of the RAAS
The RAAS has two components—circulating and tissue. Whereas the former component participates acutely in maintaining adequate systemic hemoperfusion, the latter component is chronically operative at the local tissue level. Despite these differences, both components share pathways for synthesis and degradation.1 Upon initial RAAS activation, renin synthesized from both renal and extra-renal tissues is released in response to stimuli such as glomerular hypoperfusion, sympathetic stimulation, and
ACE inhibitor pharmacology
From an understanding of the physiology of the RAAS, the pharmacodynamic response of ACE antagonism may be predicted: a short-term dose-dependent decrease in AG-II levels, preload and afterload reduction, lowering of both the systolic and diastolic pressure with little or no change in the cardiac output, reduction of proteinuric nephropathy, and inhibition of bradykinin degradation. More exclusive effects of certain ACE inhibitors such as ramipril and quinapril, perhaps mediated through AT1
Clinical applications of ACE inhibitors
The following is a discussion of disease entities in which ACE inhibitors have been proven to be efficacious. These include hypertension, symptomatic or asymptomatic left ventricular systolic dysfunction, post-myocardial infarction, renal failure, and diabetic nephropathy.
Side effects and contraindications
The use of ACE inhibitors in clinically indicated conditions at recommended doses has been established as safe and effective. As with all drugs, recognition and management of drug side effects and toxicity is critical. Provided in Table 5 is a review of the major ACE inhibitor side effects listed by organ system.
ACE inhibitors are generally safe and well-tolerated in patients with advanced compensated heart failure with poor left ventricular systolic function. It is important to ensure that
ACE inhibitors and ARBs
The major use of ARBs in addition to or in substitution of ACE inhibitors may be appreciated through an understanding of the ACE escape concept, which is a decrease in the efficacy of ACE inhibitors secondary to an increase in circulating AG-II levels from chronic ACE inhibition. To overcome this excess AG-II concentration, ARBs, which competitively block AG-II receptor binding, may be used. And although AG-II receptor upregulation may occur, experimental data suggest that there is insufficient
Conclusions
The RAAS is an important neurohormonal pathway that can be targeted by ACE inhibition in the successful management of cardiovascular diseases. Thus, whenever possible, ACE inhibitors should be used in the treatment of patients with acute MI, asymptomatic or symptomatic left ventricular dysfunction, diabetic nephropathy, renal failure, and hypertension. Furthermore, this therapy should generally be implemented taking into consideration a patient’s hemodynamic profile, race, renal function,
Selected clinical pearls
- 1.
Captopril requires tid dosing, enalapril bid, all the others qd, based on their pharmacokinetic profiles, making captopril useful when an initial challenge is needed and making enalapril a less reasonable choice than when it was first introduced.
- 2.
Trandolapril, quinapril, benazapril, and ramapril (in that order) have greater lipophilicity (and thereby presumed tissue ACE inhibition) than the other ACE inhibitors. Inhibition of tissue ACE likely has clinical relevance regarding the following:
- a
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2014, Pharmacology and TherapeuticsCitation Excerpt :ACE inhibition hence elicits dose-dependent reduction in Ang II levels, with concomitant inhibition of bradykinin degradation and lowering of systolic and diastolic pressure (Dunn et al., 1984; Erdos et al., 1999; Wong et al., 2004). The pharmacokinetic profiles of different ACE-Is are distinguished by their biochemical structure and bioavailability, plasma half-life, elimination profile and their distribution and affinity for tissue-bound ACE (Brown & Vaughan, 1998; Wong et al., 2004). As reviewed by Wong et al., ACE-Is can be divided into 3 subgroups, based on the molecular structure of their active moieties; sulfydryl-containing, dicarboxyl-containing and phosphorus-containing (Wong et al., 2004).