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DRUGS THAT INTERFERE WITH THE RENIN-ANGIOTENSIN SYSTEM

The renin-angiotensin system plays a central role in the regulation of fluid balance in the body. Before moving on to the drugs that interfere in this system, take a few moments to review the physiology (Figure 12–1). Note that this system utilizes the kidney, liver, lungs, and adrenal glands. In addition, review the roles for renin, angiotensinogen, angiotensin I, and angiotensin II. Who does what and where?

FIGURE 12–1

The renin-angiotensin-aldosterone system.

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS

Angiotensin-converting enzyme (ACE, also known as peptidyldipeptide hydrolase or peptidyl dipeptidase) converts angiotensin I to angiotensin II, which is a potent vasoconstrictor and stimulator of aldosterone secretion. The aldosterone then promotes sodium and water retention and potassium excretion. This leads to an increase in vascular volume and an increase in peripheral vascular resistance.

Angiotensin-converting enzyme (ACE) inhibitors block the synthesis of angiotensin II.

Blocking the synthesis of angiotensin II leads to a decrease in levels of this circulating vasoconstrictor, which results in a decrease in blood pressure (i.e., afterload). ACE inhibitors also reduce aldosterone secretion, which results in a net water loss (also decreasing afterload).

The currently available ACE inhibitors (“-prils”) are listed in the following table. Feel free to add to this list as needed.

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ACE Inhibitors

captopril

benazepril

ENALAPRIL

fosinopril

LISINOPRIL

moexipril

quinapril

ramipril

trandolapril

ACE inhibitors have several uses, most prominently in the treatment of patients with hypertension (see Chapter 13) and heart failure (see Chapter 14). In hypertensive patients, ACE inhibitors reduce blood pressure while causing little or no change in cardiac output. The antihypertensive effects of the ACE inhibitors are additive with the effects of many other drugs.

These drugs are particularly useful in hypertension that is a result of increased renin levels. Because they do not affect glucose levels, ACE inhibitors are also used in the treatment of hypertension in patients with diabetes. ACE inhibitors have been shown to preserve renal function in patients with nephropathy. The major side effects of these drugs are headache, dizziness, abdominal pain, confusion, renal failure, and impotence. ACE inhibitors can also cause a dry cough thought to be due to bradykinin.

ANGIOTENSIN II RECEPTOR BLOCKERS

These drugs are competitive antagonists of the AT1 angiotensin receptor.

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Angiotensin II Receptor Blockers (ARBs)

candesartan

eprosartan

LOSARTAN

irbesartan

olmesartan

telmisartan

VALSARTAN

Notice that, so far, the names of the drugs in the preceding box all end in “-sartan.” However, this is no guarantee that new ones under development will retain the “-sartan” ending.

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