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Mean arterial pressure = Cardiac output × Peripheral resistance

The preceding equation is a familiar one from physiology. According to this equation, a decrease in either cardiac output or peripheral resistance will decrease blood pressure. Conversely, if high blood pressure, a sustained increase in blood pressure of 140/90 or higher, is present, something must have increased one of the two variables.

A number of factors will increase cardiac output, including increased heart rate, increased contractility, and increased sodium and water retention. Vasoconstriction will increase peripheral resistance. Decreasing one or more of these factors is the goal of antihypertensive therapy.

As you can probably guess, it is easiest to organize the antihypertensive drugs by their mechanism of action. Some of these drugs are also useful in the treatment of angina or heart failure. Many of these drugs have also been covered in Chapters 11 and 12, so only their use in hypertension will be included here.

  1. Diuretics

  2. Drugs that interfere with the renin-angiotensin system, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)

  3. Drugs that decrease peripheral vascular resistance or cardiac output, including direct vasodilators and drugs that depress the sympathetic nervous system


Diuretics were covered in more detail in Chapter 11. They play an important role in the management of high blood pressure and are often used in combination with other classes of antihypertensive drugs.

The thiazide diuretics are the most commonly used—sometimes in combination with a K+-sparing diuretic to reduce K+ loss. The antihypertensive effect may take 4 to 6 weeks. Hypokalemia is the most common side effect, which may lead to muscle cramps and arrhythmias.


The drugs that interfere in the renin-angiotensin system were covered in detail in Chapter 12.


Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are effective in the treatment of hypertension. They are especially useful in patients with diabetes because they do not affect glucose levels and can slow the progression of renal disease. About 5% of patients will develop a dry cough with ACE inhibitors, but not with ARBs. Both classes of drugs are contraindicated in pregnancy and can take up to 4 weeks to see the full antihypertensive effect.


Spironolactone and eplerenone are antagonists of aldosterone at the mineralocorticoid receptor and can be used to treat hypertension. Remember that aldosterone promotes sodium and water retention and potassium excretion, which leads to an increase in vascular volume and vascular resistance. Blocking the action of the aldosterone receptor will increase urinary excretion of sodium and water. These drugs are ...

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