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Section IIICardiovascular drugsACE inhibitors and angiotensin II receptor antagonists are used widely in the treat-
ment of hypertension.β-Blockers (cf. Chapter 13 )reduce sympathetically mediated
release of renin, which contributes to their antihypertensive effects.Angiotensin-converting enzyme (ACE) inhibitors
ACE inhibitors are used in all grades of heart failure and in patients with myocardial
infarction with left ventricular dysfunction where it improves the prognosis. They
are used in hypertension especially insulin-dependent diabetics with nephropathy.
However hypertension is relatively resistant to ACE inhibition in the black poulation
where concurrent diuretic thereapy may be required. While most drugs should be
continued throughout the peri-opereative period, ACE inhibitors and angiotensin II
receptor antagonists should be omitted due to the increased frequency of peri-
operative hypotension.
From a kinetic point of view ACE inhibitors may be divided into three groups:
Group 1. Captopril – an active drug that is metabolized to active metabolites.
Group 2. Enalopril, ramipril – prodrugs, which only become active following
hepatic metabolism to the diacid moiety.
Group 3. Lisinopril – an active drug that is not metabolized and is excreted
unchanged in the urine.
Inother respects the effects of ACE inhibitors are similar and are discussed under
captopril.Captopril
Presentation
Captopril is available as 12.5–50 mg tablets that may also be combined with
hydrochlorothiazide. The initial dose is 12.5 mg although 6.25 mg may be prudent
for those with heart failure.Mechanism of action
Captopril is a competitive ACE inhibitor and therefore prevents the formation of
angiotensin II and its effects. Afterload is reduced to a greater degree than preload.Effects
Cardiovascular – captopril reduces the systemic vascular resistance significantly,
resulting in a fall in blood pressure. The fall in afterload may increase the cardiac
output particularly in those with heart failure. Heart rate is usually unaffected but
may increase. Baroreceptor reflexes are also unaffected. Transient hypotension
may occur at the start of treatment, which should therefore be initiated in the
hospital for patients with anything more than mild heart failure.
Renal – the normal function of angiotensin II to maintain efferent arteriolar pres-
sure (by vasoconstriction) at the glomerulus in the presence of poor renal perfusion