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Class identifiersUseHypertensionATC codeC09Biological targetangiotensin-converting enzymeClinical dataAHFS/Drugs.comDrug ClassesConsumer ReportsBest Buy DrugsWebMDMedicineNet  RxListExternal linksMeSHD000806

An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is apharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure.

This group of drugs cause relaxation of blood vessels, as well as a decreasedblood volume, which leads to lowerblood pressure and decreased oxygen demand from the heart. They inhibit theangiotensin-converting enzyme, an important component of the renin-angiotensin-aldosterone system.

Frequently prescribed ACE inhibitors include perindopril, captopril, enalapril,lisinopril, and ramipril.

Medical use

Mechanism of action

Adverse effects

Common adverse drug reactionsinclude: hypotension, cough,hyperkalemia, headache, dizziness,fatigue, nausea, and renal impairment.[12][13] ACE inhibitors might increase inflammation-related pain, perhaps mediated by the buildup ofbradykinin that accompanies ACE inhibition.[14]

The main adverse effects of ACE inhibition can be understood from their pharmacological action. The other reported adverse effects are hepatotoxicity and effect on the fetus.[13]

Renal impairment is a significant potential adverse effect of all ACE inhibitors, that directly follows from their mechanism of action. Patients starting on an ACE inhibitor usually have a modest reduction in glomerular filtration rate (GFR) that stabilizes after several days. However, the decrease may be significant in conditions of decreased renal perfusion, such as renal artery stenosis, heart failure, polycystic kidney disease, or volume depletion. In these patients, maintenance of GFR depends on angiotensin-II-dependent efferent vasomotor tone. Therefore, renal function should be closely monitored over the first few days after initiation of treatment with ACE inhibitor in patients with decreased renal perfusion.[13] A moderate reduction in renal function, no greater than 30% rise in serum creatinine, that is stabilized after a week of treatment, is deemed acceptable as part of the therapeutic effect, providing the residual renal function is sufficient. This is especially a problem if the patient is concomitantly taking anNSAID and a diuretic. When the three drugs are taken together, the risk of developing renal failure is significantly increased.[15]

Hyperkalemia is another possible complication of treatment with an ACE inhibitor due to its effect on aldosterone. Suppression of angiotensin II leads to a decrease in aldosterone levels. Since aldosterone is responsible for increasing the excretion of potassium, ACE inhibitors can cause retention of potassium. Some people, however, can continue to lose potassium while on an ACE inhibitor.[16]Hyperkalemia may decrease the velocity of impulse conduction in the nerves and muscles, including cardiac tissues. This leads to cardiac dysfunction and neuromuscular consequences, such as muscle weakness, paresthesia, nausea, diarrhea, and others. Close monitoring of potassium levels is required in patients receiving treatment with ACE inhibitors who are at risk of hyperkalemia.[13]

Another possible adverse effect specific for ACE inhibitors, but not for other RAAS blockers, is an increase inbradykinin level.[13] Elevated bradykinin level due to ACE inhibition can be a cause of dry cough, angioedema and/or rash, hypotension, and inflammation-related pain.

A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors, although the role of bradykinin in producing these symptoms has been disputed.[17]Patients who experience this cough are often switched to angiotensin II receptor antagonists.

Some patients develop angioedema due to increased bradykinin levels. A genetic predisposition may exist toward this adverse effect in patients who degrade bradykinin more slowly than average.[18]

Rash and taste disturbances, infrequent with most ACE inhibitors, are more prevalent in captopril, and this is attributed to its sulfhydryl moiety. This has led to decreased use of captopril in clinical setting, although it is still used in scintigraphy of the kidney.

A severe rare allergic reaction can affect the bowel wall and secondarily cause abdominal pain.[citation needed]

In pregnant women, ACE inhibitors taken during all the trimesters have been reported to cause congenital malformations, stillbirths, and neonatal deaths. Commonly reported fetal abnormalities include hypotension,renal dysplasia, anuria/oliguria,oligohydramnios, intrauterine growth retardation, pulmonary hypoplasia,patent ductus arteriosus, and incomplete ossification of the skull.[13][19] Overall, about half of newborns exposed to ACE inhibitors are adversely affected.[20]