Angiotensin-Converting Enzyme Inhibitors

The class of drugs called angiotensin converting enzyme (ACE) inhibitors, as the class name suggests, reduces the activity of angiotensin converting enzyme. ACE converts angiotensin I produced by the body to angiotensin II in the blood. Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract and narrow the blood vessels. Narrowing of blood vessels increases the pressure within the blood vessels and may lead to high blood pressure (hypertension). By reducing the activity of ACE, ACE inhibitors decrease the formation of angiotensin II which leads to widening (dilation) of blood vessels, and thereby reduces blood pressure. By lowering blood pressure against which the heart must pump, the amount of work that the heart must do is reduced. ACE inhibitors also reduce blood pressure in the kidneys, slowing the progression of kidney disease due to high blood pressure or diabetes. ACE inhibitors are effective for control of blood pressure, congestive heart failure, and prevention of stroke and hypertension, or diabetes-related kidney damage. ACE

inhibitors are especially important because they have been shown to prevent early death resulting from hypertension, heart failure or heart attacks; in studies of patients with hypertension, heart failure, or prior heart attacks, patients who received an ACE inhibitor survived longer than patients who did not receive an ACE inhibitor. ACE inhibitors may be combined with other drugs to achieve optimal blood pressure control. ACE inhibitors are very similar, and all are effective for treating hypertension. Some are eliminated primarily by the kidneys while others are also eliminated in bile and feces. This difference in elimination may be important in choosing among ACE inhibitors in patients with reduced kidney or liver function, who may accumulate drugs that are excreted via the kidneys or liver. Except for captopril and lisinopril, ACE inhibitors are inactive until they are converted to an active form in the body. Common side effects are: dizziness, headache, drowsiness, diarrhea, low blood pressure, weakness, cough, and rash. An abnormal taste (metallic or salty), elevated blood potassium levels, and sexual dysfunction may also occur. A nonproductive and persistent cough may occur in 5%-25% of individuals. It may take up to 2 weeks or longer for coughing to subside after the ACE inhibitor is discontinued. If one ACE inhibitor causes cough, it is likely that the others will also. ACE inhibitors may cause birth defects and, therefore, should not be used during pregnancy.

CAPTOPRIL:

Indications: mild to moderate essential hypertension alone or with thiazide therapy and severe hypertension resistant to other treatment; congestive heart failure with left ventricular dysfunction); following myocardial infarction, see dose; diabetic nephropathy (microalbuminuria greater than 30 mg/day) in insulin-dependent diabetes.

Contraindications: Contraindicated in patients with hypersensitivity to ACE inhibitors (including angioedema). ACE inhibitors should not be used in pregnancy.

Dose and Administration: Hypertension, used alone, initially 12.5 mg twice daily; if used in addition to diuretic, or in elderly, initially 6.25 mg twice daily (first dose at bedtime); usual maintenance dose 25 mg twice daily; max. 50 mg twice daily (rarely 3 times daily in severe hypertension). Heart failure (adjunct), initially 6.25–12.5 mg under close medical supervision, increased gradually at intervals of at least 2 weeks up to max. 150 mg daily in divided doses if tolerated. Prophylaxis after infarction in clinically stable patients with asymptomatic or symptomatic left ventricular dysfunction (radionuclide ventriculography or echocardiography undertaken before initiation), initially 6.25 mg, starting as early as 3 days after infarction, then increased over several weeks to 150 mg daily (if tolerated) in divided doses. Diabetic nephropathy, 75–100 mg daily in divided doses; if further blood pressure reduction required, other antihypertensives may be used in conjunction with captopril; in severe renal impairment, initially 12.5 mg twice daily.

ENALAPRIL:

Indications: Treatment of hypertension alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis.

Contraindications: contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.

Dose and Administration: The recommended initial dose in patients not on diuretics is 5 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 10 to 40 mg per day administered in a single dose or two divided doses. If the diuretic cannot be discontinued an initial dose of 2.5 mg should be used under medical supervision for at least two hours and until blood pressure has stabilized for at least an additional hour. Heart Failure: The recommended dosing range is 2.5 to 20 mg given twice a day.

Enalapril-Hydrochlorothiazide:

Indications: indicated for the treatment of hypertension, this fixed dose combination is not indicated for initial treatment.

Contraindications: see under enalapril.

Dose and Administration: The usual dosage of enalapril is 20 mg per day administered in a single dose; hydrochlorothiazide is effective in doses of 12.5 mg daily.

LISINOPRIL:

Indications: hypertension; symptomatic heart failure; short-term treatment following myocardial infarction in haemodynamically stable patients; renal complications of diabetes mellitus.

Contraindications: see under enalapril.

Dose and Administration: Hypertension, initially 10 mg once daily; if used in addition to diuretic or in cardiac decompensation or in volume depletion, initially 2.5–5 mg once daily; usual maintenance dose 20 mg once daily; max. 80 mg once daily. Heart failure (adjunct), initially 2.5 mg once daily under close medical supervision; increased in steps no greater than 10 mg at intervals of at least 2 weeks up to max. 35 mg once daily if tolerated. Prophylaxis after myocardial infarction, systolic blood pressure over 120 mmHg, 5 mg within 24 hours, followed by further 5 mg 24 hours later, then 10 mg after a further 24 hours, and continuing with 10 mg once daily for 6 weeks (or continued if heart failure); systolic blood pressure 100–120 mmHg, initially 2.5 mg once daily, increased to maintenance dose of 5 mg once daily.

PERINDOPRIL:

Indications: hypertension; symptomatic heart failure; prophylaxis of cardiac events following myocardial infarction or revascularisation in stable coronary artery disease.

Contraindications:  see under enalapril.

Dose and Administration:

Hypertension, initially 5 mg once daily in the morning adjusted according to response; if used in addition to diuretic, in elderly or in renal impairment, initially 2.5 mg once daily; max. 10 mg daily

Heart failure (adjunct), initially 2 mg once daily in the morning under close medical supervision, increased after at least 2 weeks to max. 4 mg once daily if toleratedFollowing myocardial infarction or revascularisation, initially 5 mg once daily in the morning increased after 2 weeks to 10 mg once daily if tolerated; elderly 2 mg once daily for 1 week, then 4 mg once daily for 1 week, thereafter increased to 10 mg once daily if tolerated.

Perindopril-Indapamide:

Indications: treatment of essential hypertension.

Contraindications: previous history of quincke`s oedema, severe renal failure,

pregnancy and lactation.

Dose and Administration: the normal dose one tablet daily.