Beta blockers are competitive antagonists of beta-adrenergic receptors. There are two receptor classes. Beta-1 receptors, located in the heart, lead to increases in heart rate, contractility, and antrioventricular conduction when stimulated. Blockade of beta-1 receptors attenuates these increases, particularly during exercise or stress, but also during rest if resting adrenergic tone is increased. Several beta blockers produce low-level receptor stimulation, offsetting the effects of receptors blockade in the resting state while maintaining antagonism during exercise or stress”this is referred to as intrinsic sympathomimetic activity (ISA).
Beta-2 receptors are more widespread than beta-1 receptors. Activation of these receptors results in such diverse actions as bronchodilation, peripheral vasodilation, and lipolysis. Many adverse effects of beta blockers, such as bronchospasm, are due to beta-2 receptor blockade. Agents that are beta-1 specific, or cardioselective, have been developed to minimize these adverse effects. This preferential blockade is not complete however, and some beta-2 receptor antagonism can be observed at standard pharmacologic doses.
What are the cardiovascular indications for beta-blocker therapy other than hypertension and angina pectoris?
What are the signs and symptoms of beta-blocker toxicity? How is this best treated?
Beta-blocker toxicity, although rare, should be considered in any patient experiencing the sudden onset of bradycardia and hypotension. Generalized seizures can also occur, especially with use of agents that are both lipophilic and have membrane-stabilizing effects. Other reported symptoms include peripheral cyanosis and coma. A history of hypertension, coronary artery disease, or chronic beta-blocker therapy should heighten the suspicion for this diagnosis.
Glucagon is the most effective agent for treating the hemodynamic disturbances due to beta-blockers; epinephrine should be considered second-line therapy, and atropine and isoproterenol are frequently ineffective. Glucagon exerts both positive inotropic and chronotropic effects on the heart. The inotropic effects are not affected by beta blockade, but the increase in heart rate with glucagon may be blunted by beta blockade, and temporary transvenous pacing may be necessary. The initial dose of glucagon is 3 mg or 0.05 mg/kg given intravenously over 30 seconds followed by a continuous infusion at 5 mg/hr or 0.07 mg/kg/hr. The infusion is tapered slowly as the patient improves.
How is beta-blocker therapy used following myocardial infarction?
Beta blockers decrease the risk of death in approximately 20% of patients following myocardial infarction. This benefit is due almost entirely to a reduction in cardiovascular deaths, both sudden and nonsudden, and is independent of the timing of drug administration. Administration of beta-blocker therapy within hours after infarction provides the additional benefits of limiting infarct size and reducing the risks of nonfatal reinfarction and recurrent ischemia.
The advantages of long-term therapy may be diminished in low-risk subgroups, but data are lacking on which patients can forgo therapy. For example, a 45-year-old man presenting with his first myocardial infarction who has been treated successfully with thrombolytics, has a normal ejection fraction, inferior location, and single-vessel coronary disease is at low risk and may not benefit from long-term beta-blockade. Characteristics of postinfarction survivors likely to receive maximum benefit from long-term administration include:
Impaired LV function
Persistent ischemia (angina, abnormal postinfarction stress test, significant coronary disease supplying viable myocardium)
Complex ventricular ectopy
Coexisting illness treatable with beta blockade (hypertension, supraventricular tachycardia, anxiety, etc.)
A 19-year-old woman is referred for recurrent fainting spells. A head-up tilt test elicits hypotension and bradycardia, and her symptoms are reproducible. Why might beta-blocker therapy be appropriate?
Neurocardiogenic syncope (common faint) is often a cause of temporary loss of consciousness in young people. Syncope follows profound vasodilatation, bradycardia, or a combination of these responses. It seems paradoxical that beta blockers would be effective in treating this disorder. It is postulated that in response to a diminished venous return to the heart, such as from prolonged standing, adrenergic tone is enhanced. This results in vigorous myocardial contraction, which stimulates intramyocardial mechanoreceptors (C fibers). Activation of these fibers may override the normal baroreceptor-mediated reflex and produce bradycardia and vasodilatation, which leads to hypotension and syncope. The negative inotropic effects of beta blockers may diminish C-fiber activation, allowing normal reflex physiology to prevail. A follow-up tilt test on therapy in this patient should be attempted to reproduce her symptoms and ensure the effectiveness of therapy.
What are the mechanisms of action of beta blockers? Photo Gallery
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