Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used in the treatment of hypertension, chronic kidney disease, and heart failure. In addition to efficacy, these agents have the additional advantage of being particularly well tolerated since they produce few idiosyncratic side effects and do not have the adverse effects on lipid and glucose metabolism seen with higher doses of diuretics or beta blockers [1,2]. (See "Antihypertensive drugs and lipids".)
The specific side effects that are observed with ACE inhibitors and ARBs will be reviewed here. The use of these drugs in disorders such as hypertension, heart failure, and proteinuric chronic kidney disease are discussed elsewhere.
Although high-dose captopril therapy was initially associated with a variety of presumed sulfhydryl group-related complications such as rash, neutropenia, taste abnormalities, and even the nephrotic syndrome, these problems have become uncommon since the maximum dose was reduced to 100 to 150 mg/day and particularly with the use of other ACE inhibitors.
The side effects that do occur are primarily related directly or indirectly to reduced angiotensin II formation. These include hypotension, acute renal failure, hyperkalemia, and problems during pregnancy . There are other complications—cough, angioedema, and anaphylactoid reactions—that are thought to be related to increased kinins since ACE is also a kininase (see below). This is an important distinction clinically because the side effects related to reduced angiotensin II, but not those related to kinins, are also seen with the ARBs. (See "Renin-angiotensin system inhibition in the treatment of hypertension".)
Hypotension — Weakness, dizziness, or syncope may result from an excessive reduction in blood pressure. In the ONTARGET trial, hypotensive symptoms sufficient to discontinue the drug occurred in 1.7 percent of the 8576 patients who received ramipril . First dose hypotension, which can be marked in hypovolemic patients with high baseline renin levels, can be minimized by not beginning therapy if the patient is volume depleted and by discontinuing prior diuretic therapy for three to five days. Hypotension can also occur after the initiation of therapy in patients with congestive heart failure . The risk can be minimized by beginning with a very low dose, such as 2.5 mg BID of enalapril. (See "Treatment of hypertension in patients with heart failure".)