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Chapter: Clinical Pharmacology: Cardiovascular drugs

ACE inhibitors

ACE inhibitors are typically used when beta-adrenergic blockersor diuretics are ineffective. Commonly prescribed ACE inhibitors include: · benazepril · captopril · enalapril · enalaprilat · fosinopril · lisinopril · moexipril · quinapril · ramipril · trandolapril.

ACE inhibitors

ACE inhibitors are typically used when beta-adrenergic blockersor diuretics are ineffective. Commonly prescribed ACE inhibitors include:

 

·                 benazepril

 

·                 captopril

 

·                 enalapril

 

·                 enalaprilat

 

·                 fosinopril

 

·                 lisinopril

 

·                 moexipril

 

·                 quinapril

 

·                 ramipril

 

·                 trandolapril.

Pharmacokinetics

 

ACE inhibitors are absorbed from the GI tract, distributed to most body tissues, metabolized somewhat in the liver, and excreted by the kidneys. Ramipril is also excreted in stool. Enalaprilat is the only ACE inhibitor that’s administered I.V.

Pharmacodynamics

 

ACE inhibitors reduce blood pressure by interrupting the renin-angiotensin-aldosterone system. Normally, the kidneys maintain blood pressure by releasing the hormone renin. Renin acts on the plasma protein angiotensinogen to form angiotensin I. Angio-tensin I is then converted to angiotensin II. Angiotensin II, a po-tent vasoconstrictor, increases peripheral resistance and pro-motes the excretion of aldosterone. Aldosterone, in turn, pro-motes the retention of sodium and water, increasing the volume of blood the heart needs to pump.

Conversion diversion

 

ACE inhibitors prevent the conversion of angiotensin I to an-giotensin II. As angiotensin II is reduced, arterioles dilate, reduc-ing peripheral vascular resistance.

Less water, less work

By reducing aldosterone secretion, ACE inhibitors promote the excretion of sodium and water, which reduces the amount of blood the heart needs to pump, thereby lowering blood pressure.

Pharmacotherapeutics

 

ACE inhibitors may be used alone or with another drug, such as a thiazide diuretic, to treat hypertension. Certain ACE inhibitors— such as captopril, enalapril, fosinopril, lisinopril, quinapril, ramipril, and trandolapril—may also be used to treat patients with heart failure or following MI. Such situations include:

 

·                 left ventricular systolic failure (unless contraindicated or intol-erant)

 

·                 left ventricular systolic dysfunction without symptoms of heart failure

 

·                 reducing mortality following acute MI (especially in patients with prior myocardial injury)

 

·         preventing or delaying the development of left ventricular dila-tion and overt heart failure in patients with left ventricular dys-function (recent or remote)

 

·                 possible production of complementary effects (combined with beta-blockade)

 

·                 history of or present fluid retention (combined with diuretics).

 

Ramipril is also indicated to prevent major cardiovascular events in patients with a history of vascular disease or diabetes. It’s also used to reduce overall cardiovascular risk, including death, nonfatal MI, nonfatal stroke, and complications of diabetes. Captopril is also indicated for the long-term treatment of diabetic neuropathy.

Drug interactions

 

ACE inhibitors can cause several different types of interactions with other cardiovascular drugs. All ACE inhibitors enhance the hypotensive effects of diuretics and other antihypertensives such as beta-adrenergic blockers. They can also increase serum lithium levels, possibly resulting in lithium toxicity.

 

When ACE inhibitors are used with potassium-sparing diuret-ics, potassium supplements, or potassium-containing salt substi-tutes, hyperkalemia may occur.

 

Individual items

 

ACE inhibitors interact with many other medications, prescription as well as over-the-counter (OTC). For example, patients taking ACE inhibitors should avoid taking all NSAIDs. Besides decreas-ing the antihypertensive effect of ACE inhibitors, NSAIDs may al-ter renal function. Also, antacids may impair the absorption of fos-inopril, and quinapril may reduce the absorption of tetracycline.

 

A patient taking ACE inhibitors shouldn’t take prescriptions or OTC medications or herbal products without first consulting his physician. (See Adverse reactions to ACE inhibitors.)

 

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