P Adrenergic Receptor Antagonists

p Adrenergic receptor antagonists are effective in reducing the severity and frequency of attacks of exertional angina and in improving survival in patients after an MI. In contrast, these agents are not useful and may actually exacerbate vasospastic angina. Most p adrenergic receptor antagonists are equally effective in the treatment of exertional angina. Timolol, metoprolol, atenolol, and propra-nolol have been shown to exert cardioprotective effects. The effectiveness of p adrenergic receptor antagonists in the treatment of exertional angina is attributable primarily to a fall in myocardial O2 consumption at rest and during exertion, although there also is some tendency for increased flow toward ischemic regions. The decrease in myocardial O2 consumption is due to a negative chronotropic effect (particularly during exercise), a negative inotropic effect, and a reduction in arterial blood pressure (particularly systolic pressure) during exercise. Not all actions of p adrenergic receptor antagonists are beneficial in all patients. The decreases in heart rate and contractility cause increases in the systolic ejection period and left ventricular end-diastolic volume; these alterations tend to increase O2 consumption. However, the net effect of p adrenergic receptor blockade is usually to decrease myocardial O2 consumption, particularly during exercise. Nevertheless, in patients with limited cardiac reserve who are critically dependent on adrenergic stimulation, p adrenergic receptor blockade can profoundly decrease left ventricular function. Despite this, several p adrenergic receptor antagonists have been shown to reduce mortality in patients with congestive heart failure (see Chapter 33). Numerous p adrenergic receptor antagonists are approved for clinical use in the U.S. (see Chapter 10).

Therapeutic Uses UNSTABLE ANGINA

p Adrenergic receptor antagonists are effective in reducing recurrent episodes of ischemia and the risk of progression to acute MI. Clinical trials have lacked sufficient power to demonstrate beneficial effects of p adrenergic receptor antagonists on mortality. On the other hand, if the underlying pathophysiology is coronary vasospasm, nitrates and Ca2+ channel blockers may be effective, and p adrenergic receptor antagonists should be used with caution. In some patients, there is a combination of severe fixed disease and superimposed vasospasm; if adequate antiplatelet therapy and vasodilation have been provided by other agents and angina continues, the addition of a p adrenergic receptor antagonist may be helpful.

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