PHARMACOLOGY OF ANTIHYPERTENSIVE AGENTS
All antihypertensive agents act at one or more of the four anatomic control sites and produce their effects by interfering with normal mechanisms of blood pressure regulation. A useful classification of these agents categorizes them according to the principal regulatory site or mechanism on which they act. Because of their common mechanisms of action, drugs within each category tend to produce a similar spectrum of toxicities. The categories include the following:
1. DIURETICS, which lower blood pressure by depleting the body of sodium and reducing blood volume and perhaps by other mechanisms.
2. SYMPATHOPLEGIC AGENTS These lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac function, and increasing venous pooling in capacitance vessels with an overall effects reduce cardiac output. 3.
3. DIRECT VASODILATORS These reduce pressure by relaxing vascular smooth muscle, thus dilating resistance vessels and—to varying degrees—increasing capacitance as well.
4. AGENTS THAT BLOCK PRODUCTION OR ACTION OF ANGIOTENSIN These thereby reduce peripheral vascular resistance and (potentially)
blood volume. The fact that these drug groups act by different mechanisms
permits the combination of drugs from two or more groups with increased efficacy and, in some cases, decreased toxicity.
5. DRUGS THAT ALTER SODIUM & WATER BALANCE
Dietary sodium restriction has been known for many years to decrease
blood pressure in hypertensive patients. With the advent of diuretics,
sodium restriction was thought to be less important. However, there
is now general agreement that dietary control of blood pressure is a
relatively nontoxic therapeutic measure and may even be preventive.
Even modest dietary sodium restriction lowers blood pressure (though
to varying extents) in many hypertensive persons.
6. CENTRALLY ACTING-SYMPATHOPLEGIC DRUGS
Centrally acting sympathoplegic drugs were once widely used in the treatment of hypertension. With the exception of clonidine, these drugs are rarely used today.
Mechanisms & Sites of Action
These agents reduce sympathetic outflow from vasomotor centers in the brainstem but allow these centers to retain or even increase their sensitivity to baroreceptor control.
METHYLDOPA
Methyldopa was widely used in the past but is now used primarily for hypertension during pregnancy. It lowers blood pressure chiefly by reducing peripheral vascular resistance, with a variable reduction in heart rate and cardiac output. Most cardiovascular reflexes remain intact after administration of methyldopa, and blood pressure reduction is not markedly
dependent on posture.
