There are numerous b blockers, each being an effective antidysrhythmic because it prevents circulating catecholamines from binding to beta receptors. However, specific to each drug is its degree of cardioselectivity, intrinsic sympathomimetic activity, a-adrenergic blockade, and quinidine-like membrane stabilization. The metabolic effects (such as alterations in glycogen metabolism) and pharmacokinetics (relative potency, route of elimination, distribution in fat and brain, and duration of action) of each agent are also unique.
Two types of beta receptors exist in the body. b., receptors are chiefly found in the heart (also kidney and eye), whereas b2 receptors are primarily extracardiac. The cardiovascular response to ^ stimulation includes increased inotropy, increased chronotropy, and increased dromotropy. Therefore b 1 blockade reduces cardiac contractility and myocardial oxygen consumption, decreases heart rate and blood pressure, and slows cardiac conduction velocity.
b2 receptors are primarily in respiratory, uterine, and vascular smooth muscles as well as in the human liver. b 2 stimulation promotes smooth muscle relaxation and glycogenolysis while b2 blockade is associated with bronchoconstriction and alterations in glucose metabolism, namely hypoglycemia.
Metoprolol, atenolol, and esmolol are b rcardioselective drugs. They are better choices for use in patients with a history of asthma, chronic obstructive pulmonary disease (COPD), and diabetes, since the blockade of b2 receptors may result in adverse outcomes. At high doses, some agents lose their cardioselectivity; the exact dose at which this occurs, however, has not been clearly established.
Propranolol is a noncardioselective b-blocker prototype since it inhibits both the b r and b2-receptor response. It reduces the incidence of sudden cardiac death after MI. Labetalol is a noncardioselective b blocker with a radrenergic blocking effects. The b-blocking effects of intravenous labetalol are approximately seven times more potent than the a-blocking effects. Sotalol is a class III antidysrhythmic that has b-antagonistic properties. It is discussed later in the chapter.
Cardioselective b blockers with intrinsic sympathomimetic activity (T§ble..2.5.:2.), such as acebutol, occupy the b receptor and produce low-level stimulation. Despite this stimulation, the receptor is functionally blocked to high sympathetic tone. Theoretically, these drugs would be safer to use in patients with low cardiac output states because of their intrinsic ability to stimulate the heart. This ability may prevent acute drug-induced heart failure, but this has not been proven in clinical trials.
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