Review Question - QID 100598

Angiotensin Converting Enzyme (ACE) inhibitors, such as lisinopril, have a well-known side effect of dry, non-productive, persistent cough.

ACE-inhibitors block the conversion of angiotensin I to angiotensin II. An inhibition of the latter molecule has downstream effects that ultimately cause dilation of blood vessels leading to a decrease in blood pressure. ACE-inhibitors are often used in combination with other drugs to treat heart disease. A common side-effect of this drug is cough, which is thought to be caused by increasing levels of bradykinin, substance P, and/or prostaglandins, as ACE is involved in the degradation of bradykinin and substance P. For patient's in whom ACE-inhibitors result in intolerable cough, angiotensin-receptor blocking (ARB) agents (i.e. losartan, valsartan, etc) can be employed.

According to the American Family Physician handout on ACE-inhibitors, they are a safe medication with few side effects that were initially developed to treat hypertension. They are currently used in the management of high blood pressure, myocardial infarction, heart failure, kidney disease, and atherosclerosis. A dry cough is a frequent side effect seen in approximately 1 out of every 10 people taking an ACE-inhibitor. First or second-dose dizziness can also be seen with ACE-inhibitor use.

Parish et al. discuss the adverse effects of ACE-inhibitors. The most common adverse effects are cough and skin rash. Hyperkalemia is frequently seen in conjunction with ACE-inhibitor use. The resultant hyperkalemia stems from the fact that ACE-inhibitors decrease plasma aldosterone concentrations as a downstream effect. The hyperkalemia rarely becomes a serious problem as long as dietary potassium intake is properly regulated. The dry cough associated with ACE-inhibitor use seems to be fairly well tolerated and controlled with NSAID supplementation.

Illustration A depicts an overview of the renin-angiotensin-aldosterone (RAA) pathway. Illustration B depicts where ACE inhibitors function along the RAA pathway.

Incorrect Answers:
Answer 1: Aspirin, an antiplatelet agent, does not have the side effect of cough.
Answer 3: Hydrochlorothiazide is an antihypertensive diuretic agent that does not result in cough.
Answer 4: Beta-blockers such as metoprolol do not have cough as a major side effect, although some non-selective and B2-blocking agents, such as propanolol, can result in airway constriction that can affect breathing.
Answer 5: Calcium-channel blockers, such as nifedipine, are not known to cause dry cough.