ACE Inhibitors

PHRM 306: Drugs affecting CVS

Introduction
The ACE inhibitors are recommended when the preferred first-line agents (diuretics or blockers) are contraindicated or ineffective. Despite their widespread use, it is not clear if antihypertensive therapy with ACE inhibitors increases the risk of other major diseases.

Classification
Dicarboxylatecontaining ACE inhibitors Enalapril Ramipril Quinapril Perindopril Lisinopril Bezazepril Moexipril Phosphonatecontaining ACE inhibitors Fosinolpril Sulfhydrylcontaining ACE inhibitors Captopril

Actions
The ACE inhibitors lower blood pressure by reducing peripheral vascular resistance without reflexively increasing cardiac output, rate, or contractility. These drugs block the ACE that cleaves angiotensin I to form the potent vasoconstrictor angiotensin II.

Figure Effects of angiotensin-converting enzyme (ACE) inhibitors.

Actions
The converting enzyme is also responsible for the breakdown of bradykinin. ACE inhibitors decrease angiotensin II and increase bradykinin levels. Vasodilation occurs as a result of the combined effects of lower vasoconstriction caused by diminished levels of angiotensin II and the potent vasodilating effect of increased bradykinin.

Actions
By reducing circulating angiotensin II levels, ACE inhibitors also decrease the secretion of aldosterone, resulting in decreased sodium and water retention.

Therapeutic uses
Like -blockers, ACE inhibitors are most effective in hypertensive patients who are white and young. However, when used in combination with a diuretic, the effectiveness of ACE inhibitors is similar in white and black patients with hypertension.

Therapeutic uses
Along with the angiotensin-receptor blockers (ARBs), ACE inhibitors slow the progression of diabetic nephropathy and decrease albuminuria. ACE inhibitors are also effective in the management of patients with chronic heart failure.

Therapeutic uses
ACE inhibitors are a standard in the care of a patient following a myocardial infarction. Therapy is started 24 hours after the end of the infarction.

Adverse effects
Common side effects include dry cough, rash, fever, altered taste, hypotension (in hypovolemic states), and hyperkalemia.

Adverse effects
The dry cough, which occurs in about 10 percent of patients, is thought to be due to increased levels of bradykinin in the pulmonary tree. (mainly women) Angioedema (rash) is a rare but potentially life-threatening reaction and may also be due to increased levels of bradykinin.

Adverse effects
Hyperkalemia: Potassium levels must be monitored, and potassium supplements (or a high potassium diets) or potassium-sparing diuretics are contraindicated. Because of the risk of angioedema and firstdose syncope, ACE inhibitors may be first administered in the physician's office with close observation.

Adverse effects
Reversible renal failure can occur in patients with severe bilateral renal artery stenosis. ACE inhibitors are fetotoxic and should not be used by women who are pregnant.