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ACE inhibitors

1. Mechanism. ACE inhibitors inhibit the production of angiotensin II from angiotensin I

(see Fig. 4.2) by blocking the activity of ACE1; they do not inhibit ACE2. Blocking ACE1
also diminishes the breakdown of the potent vasodilator bradykinin.
a. These agents counteract elevated peripheral vascular resistance and sodium and
water retention resulting from angiotensin II and aldosterone.

b. ACE inhibitors are becoming increasingly important in the treatment of CHF and
have been shown to prevent or slow the progression of heart failure in patients with
ventricular dysfunction.
c. ACE inhibitors increase cardiac output and induce systemic arteriolar dilation
(reduce afterload).
d. ACE inhibitors cause venodilation and induce natriuresis, thereby reducing
e. These drugs are especially useful for long-term therapy.
2. Therapeutic uses. ACE inhibitors are very useful in the treatment of CHF, reducing

of recurrent post-myocardial infarction (MI), reducing the progression of
renal disease in
nephropathy, and treating hypertension. These agents have the advantage of

producing minimal electrolyte disturbances and fewer adverse effects than many other
agents used to treat hypertension.
3. Selected drugs (see Table 4.1 for a complete listing)
a. Enalapril is a prodrug that is deesterified in the liver to produce enalaprilat, which
inhibits ACE.
(1) Therapeutic uses. Enalapril is a first-line drug in the treatment of CHF and is used
to treat mild-to-severe hypertension. Diuretics enhance its activity.
(2) Adverse effects and contraindications. Blood dyscrasias and aplastic anemia
rare but serious adverse effects of enalapril. Renal function may be impaired.
b. Captopril, the first ACE inhibitor and the only sulfur-containing ACE inhibitor, is
absorbed from the gastrointestinal (GI) tract and is metabolized to disulfide conjugates.
Drug absorption is decreased 30% by food. It does not enter the central
nervous system (CNS). Captopril produces adverse effects that include rash, taste
disturbance, pruritus, weight loss, and anorexia.
c. Lisinopril is an ACE inhibitor that permits once-a-day dosing. The bioavailability of
lisinopril is not affected by food.
4. Adverse effects common to all ACE inhibitors include a dry cough and, rarely,
especially of the face (both due to increased bradykinin levels), hypotension, and