PharmacologyTier 1Medical Sciences concept

Beta-blocker comparative pharmacology (selectivity, ancillary properties, CNS penetration)

Core concept

Drug	Selectivity	Ancillary	Lipophilic	Elimination
Metoprolol	beta-1 selective	-	Lipophilic (CNS)	Hepatic, CYP2D6
Bisoprolol	beta-1 (most selective)	-	Intermediate	Balanced hepatic/renal
Atenolol	beta-1 selective	-	HYDROphilic	Renal - accumulates in CKD
Nebivolol	beta-1 selective	NO-mediated vasodilatation	Lipophilic	Hepatic, CYP2D6
Propranolol	Non-selective	Membrane stabilising	Highly lipophilic	Hepatic, high first-pass
Carvedilol	Non-selective + ALPHA-1 BLOCKADE	Antioxidant, vasodilator	Lipophilic	Hepatic
Labetalol	Non-selective + alpha-1 (~3:1 oral, 7:1 IV)	Partial beta-2 agonist	Moderate	Hepatic
Sotalol	Non-selective	Class III - K channel blockade -> QT prolongation	Hydrophilic	Renal
Pindolol	Non-selective	Intrinsic sympathomimetic activity (ISA)	Lipophilic	Hepatic
Esmolol	beta-1 selective	t-half ~9 min (red cell esterases)	-	Plasma esterases

beta-1: heart (rate, contractility, AV conduction), renin release from JG cells
beta-2: bronchial and vascular smooth muscle relaxation, hepatic glycogenolysis, skeletal muscle K+ uptake, tremor
*Selectivity is relative and is lost at higher doses*

Lipophilicity -> CNS penetration -> nightmares, vivid dreams, fatigue, sleep disturbance (propranolol, metoprolol) but also efficacy in migraine prophylaxis, essential tremor, anxiety-driven somatic symptoms
- Switch to atenolol or bisoprolol if the complaint is nightmares
Alpha-1 blockade (carvedilol, labetalol) -> vasodilatation -> less rise in afterload, and a better metabolic profile (less worsening of insulin resistance and lipids than atenolol/metoprolol)
ISA (pindolol) -> less bradycardia, but no post-MI mortality benefit - avoid in ischaemic heart disease
Sotalol is an antiarrhythmic first and a beta-blocker second: monitor QT, renal function and potassium; risk of torsades
The heart failure evidence base is drug-specific: bisoprolol (CIBIS-II), carvedilol (COPERNICUS), metoprolol succinate (MERIT-HF), nebivolol (SENIORS). Metoprolol tartrate and atenolol are not interchangeable substitutes in HFrEF
Overdose: bradycardia, hypotension, hypoglycaemia, seizures; propranolol is the most dangerous (sodium channel blockade -> broad QRS, seizures)
- Treat with atropine, fluids, high-dose insulin-euglycaemia therapy, glucagon, vasopressors, sodium bicarbonate for QRS widening, and lipid emulsion or ECMO in refractory cases

Asthma - a relative, not absolute, contraindication; cardioselective agents at low dose are usually tolerated where the indication is strong (post-MI, HFrEF). Non-selective agents (propranolol, timolol - including eye drops) are genuinely dangerous
Diabetes - beta-blockade masks the adrenergic warning symptoms of hypoglycaemia (sweating is preserved - it is sympathetic cholinergic) and blunts recovery via glycogenolysis
Peripheral vascular disease and Raynaud's - prefer cardioselective or vasodilating agents
Phaeochromocytoma - never beta-block first: unopposed alpha stimulation -> hypertensive crisis. Alpha-block (phenoxybenzamine or prazosin) first
Cocaine-associated chest pain - the same unopposed-alpha concern; benzodiazepines and nitrates first
Never stop abruptly - upregulated receptors -> rebound tachycardia, hypertension, angina, infarction
Portal hypertension - carvedilol or propranolol reduce variceal bleeding (non-selective beta-2 blockade -> splanchnic vasoconstriction; this is the one indication where non-selectivity is the point)
Thyrotoxicosis - propranolol also inhibits peripheral T4 -> T3 conversion at high dose

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