Beta Blockers (Lab)

Beta blockers (beta-adrenergic receptor antagonists) are among the most widely prescribed cardiovascular drugs. Understanding them requires a foundation in the autonomic nervous system (ANS) and adrenergic receptor pharmacology.

Adrenaline (epinephrine) and noradrenaline (norepinephrine) are catecholamines that bind to alpha- and beta-adrenergic receptors, which are all G protein-coupled receptors (GPCRs). Alpha-1 receptors (Gq-coupled) are found predominantly in skin and GIT vasculature, causing vasoconstriction via phospholipase C activation and increased intracellular Ca2+; in the myocardium they have a minor positive inotropic role that becomes more relevant in heart failure. Alpha-2 receptors (Gi-coupled) are primarily presynaptic in the CNS, reducing noradrenaline release and decreasing sympathetic outflow; a vascular subset (alpha-2B) can also cause vasoconstriction.

Beta-1 receptors (Gs-coupled) are the predominant adrenergic receptors in the heart. Stimulation via adenylate cyclase and cAMP increases: inotropy (contractile force), chronotropy (heart rate), dromotropy (AV conduction velocity), and lusitropy (ventricular relaxation rate). Beta-1 receptors are also found in the kidney, where they stimulate renin secretion from juxtaglomerular cells. Beta-2 receptors (Gs-coupled) cause bronchodilation in the lungs and vasodilation in skeletal muscle and liver blood vessels; in the myocardium they play a secondary role that becomes important in heart failure. Beta-3 receptors are found in adipose tissue, GIT, and have emerging cardiac roles.

Acetylcholine acts on nicotinic (ionotropic) and muscarinic (GPCR) receptors. M2 muscarinic receptors on atrial cardiomyocytes oppose sympathetic activity by slowing SA node pacemaker activity and AV node conduction.

Beta blockers competitively antagonise catecholamines at beta-adrenergic receptors. They are largely without intrinsic agonist activity at rest, but some agents (e.g. metoprolol) act as inverse agonists, reducing baseline adenylate cyclase activity. Selectivity varies: propranolol blocks both beta-1 and beta-2 non-selectively; atenolol and metoprolol are cardioselective (beta-1 preferring), though high doses produce beta-2 blockade; carvedilol blocks beta-1, beta-2, and alpha-1 receptors.

Clinical indications include cardiac dysrhythmias (tachycardia, atrial fibrillation), angina (reduced myocardial O2 demand by lowering heart rate and force), post-myocardial infarction (short-term), and hypertension (particularly with high sympathetic tone). Lipid-soluble agents such as propranolol cross the blood-brain barrier and are used for anxiety, PTSD, and migraine prophylaxis.

Noradrenaline administered intravenously to an intact organism produces bradycardia (paradoxically) because it binds alpha-1 and alpha-2 receptors in vascular smooth muscle, causing vasoconstriction, raising total peripheral resistance and mean arterial blood pressure, which triggers the baroreceptor reflex to reduce heart rate.