Category:ACE inhibitors

ACE Inhibitors（中文： 血管緊張素轉換酶抑制劑)

ACE inhibitors are antihypertensive drugs that act as vasodilators and reduce peripheral resistance.

They inhibit angiotensin-converting enzyme (ACE), which is involved in the conversion of angiotensin I to angiotensin II. Angiotensin II stimulates the synthesis and secretion of aldosterone and raises blood pressure via a potent direct vasoconstrictor effect.

ACE is identical to bradykininase (kininase II) and ACE inhibitors also reduce the degradation of bradykinin, which is a direct vasodilator and is also involved in the generation of prostaglandins.

The pharmacological actions of ACE inhibitors are thought to be mainly due to the inhibition of the renin-angiotensin-aldosterone system, but since they also effectively reduce blood pressure in patients with low renin concentrations other mechanisms are probably also involved.

ACE inhibitors produce a reduction in both preload and afterload in patients with heart failure. They also reduce left ventricular remodelling, a process that sometimes follows myocardial infarction. Normally, renal blood flow is increased without a change in glomerular filtration rate. ACE inhibitors also reduce proteinuria associated with glomerular kidney disease.

ACE inhibitors are used in the treatment of hypertension and heart failure and are given to improve survival after myocardial infarction and for the prophylaxis of cardiovascular events in patients with certain risk factors. They are also used in the treatment of diabetic nephropathy.

Adverse Effects

The most common adverse effects are due to the vascular effects of ACE inhibitors and include hypotension, dizziness, fatigue, headache, and nausea and other gastrointestinal disturbances.

Pronounced hypotension may occur at the start of therapy with ACE inhibitors, particularly in patients with heart failure and in sodium- or volume-depleted patients (for example, those given previous diuretic therapy). Myocardial infarction and stroke have been reported and may relate to severe falls in blood pressure in patients with ischaemic heart disease or cerebrovascular disease. Other cardiovascular effects that have occurred include tachycardia, palpitations, and chest pain.

Other adverse effects include persistent dry cough and other upper respiratory tract symptoms, and angioedema; these may be related to effects on bradykinin or prostaglandin metabolism. Skin rashes (including erythema multiforme and toxic epidermal necrolysis) may occur; photosensitivity, alopecia, and other hypersensitivity reactions have also been reported.

Most of the adverse effects of ACE inhibitors are reversible on withdrawing therapy. Symptomatic hypotension, including that after overdosage, generally responds to volume expansion with an intravenous infusion of sodium chloride 0.9%.

Precautions

ACE inhibitors are usually contra-indicated in patients with aortic stenosis.They should not generally be used in patients with renovascular disease. The elderly, or patients with peripheral vascular diseases or generalised atherosclerosis, may be at high risk because they may have clinically silent renovascular disease. Renal function should be assessed in all patients before use of ACE inhibitors and should be monitored during therapy. Patients with existing renal disease or taking high doses should be monitored regularly for proteinuria. Regular white blood cell counts may be necessary in patients with collagen vascular disorders, such as SLE and scleroderma, or in patients also given immunosuppressive therapy, especially when they also have impaired renal function. ACE inhibitors should be used with caution in patients with a history of idiopathic or hereditary angioedema.

ACE inhibitors have been associated with fetal toxicity and should not be used during pregnancy.

Interactions

Excessive hypotension may occur when ACE inhibitors are used with diuretics, other antihypertensives, that lower blood pressure.

An additive hyperkalaemic effect is possible in patients receiving ACE inhibitors with potassium-sparing diuretics, potassium supplements (including potassium-containing salt substitutes), or other drugs that can cause hyperkalaemia (such as ciclosporin or indometacin), and serum-potassium concentrations should be monitored. Potassium-sparing diuretics and potassium supplements should generally be stopped before starting ACE inhibitors in patients with heart failure.

The adverse effects of ACE inhibitors on the kidneys may be potentiated by other drugs, such as NSAIDs.