Antihypertensive Drugs

The initial antihypertensive effect of diuretics is to decrease intravascular volume and cardiac output. With continued use, cardiac output returns to baseline levels. The long term antihypertensive action of diuretics is a decrease in arteriolar tone related to changes in intracellular calcium.

Thiazide and thiazide like diuretics are commonly used to treat hypertension. Use of the lowest possible dose minimizes side effects. Hypokalemia is the most important side effect. Loop blocking diuretics, such as furosemide, should be reserved for use in patients with renal insufficiency or congestive heart failure. Potassium sparing diuretics, usually used in combination with a thiazide, may be useful if a patient is prone to hypokalemia or in congestive heart failure.

The antihypertensive mechanism of action of beta adrenergic blocking agents includes a decrease in both cardiac output and renin release. Beta blockers without intrinsic sympathetic activity are associated with reduced morbidity and mortality. Beta blockers are especially useful in hypertensive patients with concomitant coronary artery disease and/or congestive heart failure. These drugs should not be used in patients with bronchospasm or advanced degrees of heart block.

ACE inhibitors block the formation of angiotensin II, promoting vasodilation and decreased aldosterone. They are very effective in patients with left ventricular dysfunction, diabetes and patients with proteinuria. They also decrease the progression toward end stage renal disease. These drugs are very well tolerated, although some patients develop a dry cough that requires discontinuation of the drug, or change to an angiotensin receptor blocker, or ARB. Angiodema is a rare but potentially lethal adverse effect.

Calcium channel blockers can also be used to reduce blood pressure. There are two main types, dihydropyridines and non-dihydropyridines. Their primary mechanism of action is to decrease arterial smooth muscle tone. Important side effects of dihydropyridines include peripheral edema and gingival hyperplasia. An important side effect of the non-dihydropyrides is constipation.

Angiotensin receptor blocers, or ARBs, block angiotensin II receptors promoting vasodilation and decreased aldosterone. The are very effective in patients with left ventricular dysfunction, diabetes and patients with proteinuria. They also decrease the progression towards end stage renal disease. These drugs are very well tolerated.

Direct renin inhibitors block the ability of renin to cleave angiotensin I from angiotensinogen, therefore reducing angiotensin II levels. They also act at a tissue level and are very long acting, combine well with diuretics and are very well tolerated.

Additional antihypertensive drugs that may be used in patients whose hypertension is refractory to initial drug therapy include direct acting vasodilators, such as hydralazine and minoxidil, alpha1 blockers and central alpha2 agonists. These drugs have not been shown to decrease morbidity and mortality as has been demonstrated with beta blockers and diuretics.