Clinical Pharmacology Corner: Beta-Adrenergic Receptors Antagonists

Commentary by Helen Kourlas, PharmD

Beta-adrenergic receptor antagonists, commonly known as beta-blockers (B-blockers) have been used for decades to treat hypertension, ischemic heart disease and some arrhythmias – and more recently to treat congestive heart failure. (1,2) Typically, B receptors are located in the heart (B1) and in peripheral vessels (B2) and the binding of catecholamines (epinephrine, norepinephrine and dopamine) to B1 receptors produce positive chronotropic and inotropic effects, while the binding of the B2 receptors produce a vasodilatory response in the peripheral circulation. The most profound therapeutic actions seen with the use of B-blockers are on the cardiovascular system; additionally B-blockers have effects on cardiac rhythm and automaticity.(2 )Slowed atrioventricular (AV) conduction with an increased PR interval is a related result of adrenoceptor blockade in the AV node. In the vascular system, B-receptor blockade opposes B2-mediated vasodilation. This may acutely lead to a rise in peripheral vascular resistance from unopposed α-receptor-mediated effects as the sympathetic nervous system responds to a lowered blood pressure due to the fall in cardiac output. (3)Although the acute administration of these agents can cause a rise in peripheral vascular resistance, chronic use leads to a decrease in peripheral vascular resistance in patients with hypertension. How this phenomenon eventually occurs is still unknown. Nonselective and B1-blocking agents have also been shown to antagonize the release of renin caused by the sympathetic nervous system with chronic administration of these agents. (3)

Typically, these agents can be distinguished by several unique characteristics. These include variable affinity for B1 and B2 receptors and inhibition of α receptors, variable lipid solubility, their capacity to induce vasodilation and lower peripheral vascular resistance, and their pharmacokinetic properties. (1,2)The chart below provides a detailed description of available FDA approved agents and their unique characteristics.

Adverse reactions due to B-blocker treatment include both cardiac and non-cardiac events. The cardiac adverse reactions include exacerbating heart failure or precipitating heart failure in those with preexisting myocardial dysfunction, as well as other complications from negative chronotropic effects. (3) Non-cardiac events include increased airway resistance, possible exacerbation of peripheral artery disease, hyperkalemia, depression, fatigue and sexual dysfunction. (3)

Among other concerns to keep in mind with the use of B-blockers is that non-selective agents should not be used in patients with asthma or chronic obstructive pulmonary disease because it may lead to increased airway resistance. This is a result of the existence of bronchodilating B2 receptors in the lung tissue. Additionally, the chronic use of B-blockers has been linked to increased plasma concentrations of very-low-density lipoproteins (VLDL) and decreased concentrations of HDL cholesterol. (3)Both of these changes are potentially unfavorable in terms of risk of cardiovascular disease, therefore the risks and benefits should be weighed.

See Beta Blocker Table

References:

1. Hoffman BB. Adrenoceptor Antagonist Drugs. Basic & Clinical Pharmacology. 10th Edition 2007. http://onlinestatref.com/. Accessed July 23, 2007

2. Westfall TC, Westfall DP. Adrenergic Agonists and Antagonists. Section II Goodman & Gilman’s The Pharmacological Basis of Therapeutics. Eleventh Edition. 2006

3. Podrid PJ. Major Side Effects of Beta-Blockers. Uptodate Online. https://www.clinicalcorrelations.org/wp-admin/www.uptodateonline.com. Accessed July 23, 2007 .

Share: Twitter | Facebook | Email