P-Blockers competitively antagonize the responses to catecholamines that are mediated by p-receptors (see Chapter 11).These drugs have a number of clinical uses, including treatment of cardiac arrhythmias (see Chapter 10) and angina pectoris (see Chapter 17), for which their therapeutic benefit is directly related to the blockade of p-receptors in the myocardium.
P-Blockers are also used in the treatment of hypertension, although this seems to be somewhat paradoxical in that blockade of vascular smooth muscle p-receptors might be expected to unmask or leave unopposed re sponses to catecholamines that occur through vascular a-receptors. Unopposed a-mediated responses would be expected to increase, rather than decrease, blood pressure. Nevertheless, (3-blockers have proved to be quite effective antihypertensive agents, and they have an important place in the treatment of primary hypertension.
The mechanism by which (-blockers produce a sustained reduction in blood pressure in patients with primary hypertension is not completely understood, but it may include such actions as reduction in renin release, antagonism of central nervous system (CNS) ( -receptors, or antagonism of presynaptic facilitatory ( -receptors on sympathetic nerves.
Decreases in heart rate and cardiac output are the most obvious results of administration of ( -blockers. Initially, blood pressure is not much affected, since peripheral vascular resistance will be reflexly elevated as a result of the drug-induced decrease in cardiac output. The reduction of blood pressure that occurs in chronic treatment correlates best with changes in peripheral vascular resistance rather than with a drug-induced variation in heart rate or cardiac output.
The reduction in plasma volume produced by ( -blockers contrasts with the increased volume seen with other types of antihypertensives. Tolerance to the anti-hypertensive actions of ( -blockers therefore is less of a problem than with the vasodilating drugs. An additional difference from the vasodilators is that plasma renin activity is reduced, rather than increased, by propranolol (Inderal). Orthostatic hypotension does not occur with (-blockers.
The (-blockers are quite popular antihypertensive drugs. They are well tolerated, and serious side effects are seldom observed. When used alone over several weeks, (-blockers produce a significant reduction in blood pressure in approximately 30% of patients with mild to moderate hypertension. Thus, (-blockers can be employed as a first step in the management of high blood pressure. However, they are often used in conjunction with a diuretic when therapy with a single agent is not satisfactory. The combination of a (-blocker, thiazide diuretic, and vasodilator provides significant control of moderate to severe hypertension in approximately 80% of patients.
From a hemodynamic viewpoint, there are several obvious advantages to using a (-blocker in combination with a vasodilator. Reflex-mediated cardiac stimulation is a common feature of vasodilator treatment and can severely limit its antihypertensive effectiveness. A (-blocker will reduce the cardiac stimulation and thus preserve the effectiveness of the vasodilator. Conversely, the vasodilator will prevent the increase in peripheral vascular resistance that occurs on initiation of treatment with a (-blocker. Furthermore, vasodilator treatment initiates reflexes that lead to an increase in plasma renin activity. Thus, (-blockers, such as propranolol, that reduce plasma renin activity are of obvious value.
Although the (-blockers are well-tolerated drugs and patient compliance is good, there may be problems with their administration, particularly in patients with decompensated hearts and cardiac conductance disturbances. These potential problems and the adverse effect of (-blockers are described in detail in Chapter 11.
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