How do beta blockers work?

Beta blockers were introduced in the early 1960s for hypertensive patients to protect against cardiovascular morbidity and mortality and were shown to be beneficial for other heart conditions.^1-3 Beta blockers are beta-adrenergic blocking agents that competitively inhibit the binding of catecholamines at beta-adrenergic receptors.⁴ Beta blockers centrally inhibit sympathetic outflow, slow heart rate, decrease cardiac contractility, and inhibit renin release thus reducing renin-angiotensin-aldosterone system activity.⁵ Through these actions, beta blockers exhibit antihypertensive, antiarrhythmic, and anti-ischemic effects.

There are many kinds of beta blockers, with different pharmacodynamics and pharmacokinetic properties⁶ and can be classified according to various actions.^6,7

Table 1. Beta Blocker Characteristics⁸

Beta-1 Receptor Selectivity

Three adrenergic receptors (beta-1, beta-2, alpha) are variably affected by different beta blockers.⁷ Most beta blockers either specifically target beta-1-adrenergic receptors (selective) or block both beta-1- and beta-2-adrenergic receptors (non-selective).⁸ More recent beta blockers also block alpha-1-adrenergic receptors. Beta blockers such as atenolol and metoprolol only block beta-1-adrenergic receptors⁸ while beta blockers such as carvedilol block both beta-1 and beta-2 adrenergic receptors, along with exhibiting alpha-1 adrenergic activities.⁹ Beta blockers prevent norepinephrine from binding to these receptors.

Vasodilatory Activity

Mechanisms by which beta blockers lower blood pressure differ drastically between nonvasodilating and vasodilating beta blockers. Nonvasodilating beta blockers lower blood pressure by reducing cardiac output while not affecting peripheral vascular resistance.⁸ More recent vasodilating beta blockers, such as carvedilol and labetalol, mediate peripheral vasodilation by additionally blocking alpha-1-adrenergic receptors, and in the case of carvedilol and nebivolol,^8,10 also by increasing the release of endothelium-derived nitric oxide. Vasodilating beta blockers lower blood pressure by decreasing peripheral vascular resistance while maintaining cardiac output.⁸ They also have antioxidant, anti-inflammatory, or anti-proliferative activities. 

^References

1. Frishman WH. A historical perspective on the development of β-adrenergic blockers. Am J Hypertens. 2007;9(s4):19-27.
2. Black JW, Stephenson JS. Pharmacology of a new adrenergic beta-receptor-blocking compound (Nethalide). Lancet. 1962;2(7251):311-314.
3. Black JW, Crowther AF, Shanks RG, Smith LH, Dornhorst AC. A new adrenergic betareceptor antagonist. Lancet. 1964;1(7342):1080-1081.
4. Koch-Weser J, Frishman WH. beta-Adrenoceptor antagonists: new drugs and new indications. N Engl J Med. 1981;305(9):500-506.
5. Egan BM, Basile J, Chilton RJ, Cohen JD. Cardioprotection: the role of beta-blocker therapy. J Clin Hypertens. 2005;7(7):409-416.
6. Larochelle P, Tobe SW, Lacourciere Y. beta-Blockers in hypertension: studies and meta-analyses over the years. Can J Cardiol. 2014;30(5 Suppl):S16-22.
7. Helfand M, Peterson K, Christensen V, Dana T, Thakurta S. Drug Class Reviews: Drug Class Review: Beta Adrenergic Blockers: Final Report Update 4. Portland (OR): Oregon Health & Science University, Portland, Oregon.; 2009. In.
8. Kountz DS. Are tolerability concerns a class effect of beta-blockers in treating patients with hypertension? Postgrad Med. 2009;121(1):14-24.
9. Frishman WH, Henderson LS, Lukas MA. Controlled-release carvedilol in the management of systemic hypertension and myocardial dysfunction. Vasc Health Risk Manag. 2008;4(6):1387-1400.
10. Pedersen ME, Cockcroft JR. The vasodilatory beta-blockers. Curr Hypertens Rep. 2007;9(4):269-277.