Adrenergic Blockers

Adrenergic blockers (sympatholytics) antagonise the actions of catecholamines at α- and β-adrenoceptors. They are among the most heavily examined drug classes in NEET PG because of their crisp receptor selectivity, signature adverse effects, and classic "trap" contraindications (asthma, peripheral vascular disease, pheochromocytoma sequencing).

Classification

Adrenergic blockers are divided by the receptor they antagonise. A firm grasp of selectivity is the single highest-yield concept in this chapter.

Class	Subtype	Prototype drugs	Key feature
α-blockers	Non-selective (α1+α2)	Phenoxybenzamine (irreversible), Phentolamine (reversible)	Reflex tachycardia
	Selective α1	Prazosin, Terazosin, Doxazosin, Tamsulosin, Alfuzosin, Silodosin	Less tachycardia; "first-dose" hypotension
	Selective α2	Yohimbine (rarely tested)	Increases sympathetic outflow
β-blockers	Non-selective (β1+β2)	Propranolol, Nadolol, Timolol, Sotalol, Pindolol	Bronchospasm risk
	Cardioselective (β1)	Atenolol, Metoprolol, Esmolol, Bisoprolol, Nebivolol, Acebutolol, Betaxolol	Safer in mild asthma/COPD
	α+β blockers	Labetalol, Carvedilol	Used in HTN, CHF, pheochromocytoma

High-yield mnemonic for cardioselective (β1) blockers: "A BEAM of Nice Beta-1" → Atenolol, Bisoprolol, Esmolol, Acebutolol, Metoprolol, Nebivolol, Betaxolol. Drugs A–M (alphabetically first half) are largely β1-selective; N–Z (Nadolol, Pindolol, Propranolol, Sotalol, Timolol) tend to be non-selective.

Additional functional sub-divisions

• Partial agonists / Intrinsic Sympathomimetic Activity (ISA): Pindolol, Acebutolol, Celiprolol. They cause less bradycardia and are preferred where resting heart rate is already low; avoided post-MI.
• Membrane-stabilising activity (local anaesthetic): Propranolol, Acebutolol — relevant in overdose (arrhythmias).
• Vasodilatory β-blockers: Nebivolol (releases nitric oxide), Carvedilol & Labetalol (α1 block). High-yield: Nebivolol = most cardioselective + NO-mediated vasodilation.
• Lipid solubility: Propranolol, Metoprolol are lipophilic (cross BBB → nightmares, CNS effects, hepatic metabolism). Atenolol, Nadolol, Sotalol are hydrophilic (renal excretion, fewer CNS effects).

Pharmacology & mechanism

α-receptors mediate vasoconstriction (α1) and presynaptic negative feedback on noradrenaline release (α2). β1 predominates in the heart (↑rate, contractility, AV conduction, renin release), while β2 mediates bronchodilation, vasodilation in skeletal muscle, uterine relaxation, glycogenolysis and tremor.

α1 blockade → arteriolar + venous dilation → ↓peripheral resistance → ↓BP. Reflex baroreceptor activation can cause tachycardia (marked with non-selective agents that also block presynaptic α2, removing the brake on noradrenaline release).

β1 blockade → ↓heart rate, ↓contractility, ↓AV nodal conduction, ↓renin secretion → fall in cardiac output and long-term fall in BP.

β2 blockade → bronchoconstriction (dangerous in asthma), peripheral vasoconstriction (worsens Raynaud/PVD), and masking/prolongation of hypoglycaemia (blocks adrenaline-driven glycogenolysis and warning signs except sweating).

Phenoxybenzamine vs Phentolamine

Feature	Phenoxybenzamine	Phentolamine
Binding	Irreversible (covalent, haloalkylamine)	Reversible, competitive
Selectivity	Non-selective (α1>α2)	Non-selective (α1=α2)
Duration	Long (days — new receptor synthesis needed)	Short (minutes)
Main use	Pre-op pheochromocytoma	Pheochromocytoma crisis, adrenaline extravasation, cocaine-induced HTN, MAOI-tyramine reaction
Effect	"Chemical sympathectomy"	Diagnostic/short procedures

High-yield: Phentolamine is the antidote for dermal necrosis from adrenaline/noradrenaline extravasation (local infiltration). Phenoxybenzamine is the classic agent for preoperative preparation of pheochromocytoma.

Clinical uses (the exam favourites)

Hypertension

• β-blockers are no longer first-line for uncomplicated HTN (poor stroke prevention vs ACEi/ARB/CCB/thiazide) but remain first-line when HTN coexists with angina, post-MI, heart failure, or tachyarrhythmia.
• α1-blockers (prazosin/doxazosin) are add-on, especially with BPH + HTN. The ALLHAT trial showed doxazosin had more heart failure than chlorthalidone — hence not first-line.

Pheochromocytoma (very high-yield sequencing)

Always α-block first, then β-block.

1. Start phenoxybenzamine (α) 10–14 days pre-op →
2. Add a β-blocker only after adequate α-blockade (to control reflex tachycardia) →
3. Adequate salt/volume loading →
4. Intra-op crisis: phentolamine or sodium nitroprusside; esmolol for tachyarrhythmia.

High-yield (classic trap): Giving a β-blocker FIRST in pheochromocytoma causes unopposed α-vasoconstriction → hypertensive crisis. β2-mediated vasodilation is lost while α1 vasoconstriction is intact. The same principle applies to cocaine-induced chest pain — avoid pure β-blockers.

Benign prostatic hyperplasia (BPH)

• α1-blockers relax prostatic and bladder-neck smooth muscle (α1A subtype).
• Tamsulosin & Silodosin = α1A-selective → uroselective, less postural hypotension, but cause retrograde ejaculation and Intra-operative Floppy Iris Syndrome (IFIS) during cataract surgery.

Glaucoma

• Timolol (non-selective β-blocker, topical) reduces aqueous humour production → lowers intraocular pressure. Betaxolol is the β1-selective topical option, preferred in patients with airway disease. Note: timolol is a treatment, not a contraindication, in glaucoma.

Migraine prophylaxis

• Propranolol is first-line prophylaxis (also timolol, metoprolol). Not for acute attacks.

Other notable uses

• Thyrotoxicosis / thyroid storm: Propranolol (also blocks peripheral T4→T3 conversion).
• Essential tremor & performance/stage anxiety: Propranolol.
• Portal hypertension / variceal bleed prophylaxis: Non-selective β-blockers (propranolol, nadolol, carvedilol) — β2 block causes splanchnic vasoconstriction.
• Heart failure (HFrEF): Only carvedilol, bisoprolol, metoprolol succinate (sustained-release), nebivolol are proven to ↓mortality. Mnemonic: "Comfortable Beds Make Naps."
• Hypertrophic obstructive cardiomyopathy (HOCM): β-blockers reduce outflow obstruction.
• Sotalol is a class II + III antiarrhythmic (β-block + K⁺ channel block → QT prolongation).
• Esmolol: ultra-short acting (t½ ≈ 9 min, esterase metabolism) — perioperative tachycardia/HTN, aortic dissection.
• Labetalol: drug of choice in hypertensive emergency of pregnancy / pre-eclampsia and in acute aortic dissection (with esmolol).

Adverse effects

β-blockers

• Bronchospasm (β2) — relative contraindication in asthma; cardioselective agents safer but not fully safe.
• Bradycardia, AV block, hypotension, worsening of acute decompensated heart failure.
• Masking of hypoglycaemia and blunted recovery → caution in brittle/insulin-dependent diabetics (sweating is preserved as a warning sign because it is cholinergic).
• Cold extremities, worsening PVD/Raynaud (β2 block → unopposed α vasoconstriction).
• Dyslipidaemia: ↑triglycerides, ↓HDL (less with carvedilol/nebivolol due to vasodilation).
• CNS: fatigue, nightmares, depression, decreased libido (lipophilic agents — propranolol).
• Abrupt withdrawal → rebound hypertension/angina/MI (β-receptor upregulation). Taper over 1–2 weeks.

α1-blockers

• First-dose orthostatic hypotension & syncope (give prazosin at bedtime, low starting dose).
• Reflex tachycardia, nasal congestion, fluid retention.
• IFIS and retrograde ejaculation with tamsulosin.

High-yield: "First-dose effect" = prazosin. Always start low and at night. Non-selective α-blockers (phentolamine, phenoxybenzamine) cause prominent reflex tachycardia because they also block presynaptic α2.

Contraindications (NEET PG traps)

Drug class	Contraindicated / avoid in
Non-selective β-blockers	Bronchial asthma, COPD, peripheral vascular disease/Raynaud, 2nd/3rd degree AV block, severe bradycardia, decompensated CHF, Prinzmetal (variant) angina
All β-blockers	Pheochromocytoma before α-blockade; cocaine toxicity; concurrent verapamil/diltiazem (risk of severe bradycardia/asystole)
α-blockers	Caution in elderly (falls), CHF (doxazosin), syncope

High-yield: In Prinzmetal/variant angina (coronary vasospasm), non-selective β-blockers worsen spasm via unopposed α — use CCBs/nitrates instead.

High-yield: β-blocker + non-dihydropyridine CCB (verapamil/diltiazem) = dangerous additive negative chronotropy/dromotropy → heart block.

β-blocker overdose: management

Presentation: bradycardia, hypotension, hypoglycaemia, seizures, bronchospasm; QRS/QT changes with membrane-stabilising agents (propranolol, sotalol).

Stepwise: IV fluids → atropine → IV glucagon (specific antidote, bypasses β-receptor by ↑cAMP) → high-dose insulin-euglycaemia therapy → vasopressors → consider intralipid for lipophilic agents → pacing if refractory.

High-yield: Glucagon is the antidote of choice in β-blocker overdose; it increases intracellular cAMP independent of the β-receptor.

Key differentials / "look-alike" comparisons

Confusable pair	Distinguishing point
Tamsulosin vs Prazosin	Tamsulosin = α1A-selective, uroselective, IFIS; Prazosin = non-selective α1, first-dose effect
Carvedilol vs Labetalol	Both α+β; Carvedilol favoured in HFrEF; Labetalol in pregnancy HTN/dissection
Atenolol vs Propranolol	Atenolol = β1-selective, hydrophilic (renal, fewer CNS); Propranolol = non-selective, lipophilic
Esmolol vs Sotalol	Esmolol = ultra-short β1; Sotalol = β + K⁺ block (class III, ↑QT)
Nebivolol vs Metoprolol	Nebivolol = most β1-selective + NO vasodilation

Recently asked / exam angle

• "Drug given first in preoperative pheochromocytoma" → Phenoxybenzamine (α-blocker), never β first.
• "Antidote for adrenaline extravasation" → Phentolamine.
• "Most cardioselective β-blocker / β-blocker that releases NO" → Nebivolol.
• "β-blocker contraindicated in asthma" → any non-selective (propranolol/timolol); cardioselective relatively safer.
• "α1-blocker causing Intra-operative Floppy Iris Syndrome" → Tamsulosin.
• "Antidote of β-blocker poisoning" → Glucagon.
• "β-blockers proven to reduce mortality in HFrEF" → carvedilol, bisoprolol, metoprolol succinate, nebivolol.
• "Drug for migraine prophylaxis" → Propranolol.
• "Topical β-blocker for glaucoma" → Timolol (Betaxolol if airway disease).
• "β-blocker that also blocks T4→T3 conversion in thyroid storm" → Propranolol.
• Reasoning-type: "Why does β-blocker worsen Prinzmetal angina?" → unopposed α coronary vasospasm.

Rapid revision

• α first, then β in pheochromocytoma — reverse causes hypertensive crisis.
• Phenoxybenzamine = irreversible, long-acting; Phentolamine = reversible, short; antidote for catecholamine extravasation.
• Prazosin = first-dose orthostatic hypotension; give at bedtime.
• Tamsulosin/Silodosin = α1A-selective → BPH, but cause IFIS and retrograde ejaculation.
• Cardioselective (β1): Atenolol, Bisoprolol, Esmolol, Metoprolol, Nebivolol, Betaxolol, Acebutolol.
• Nebivolol = most β1-selective, vasodilates via nitric oxide.
• HFrEF β-blockers: carvedilol, bisoprolol, metoprolol succinate, nebivolol.
• Glucagon = antidote for β-blocker overdose.
• Non-selective β-blockers are contraindicated in asthma, PVD, Prinzmetal angina, AV block.
• Propranolol = migraine prophylaxis, essential tremor, thyrotoxicosis, portal HTN.
• Labetalol = HTN in pregnancy; Esmolol = ultra-short, aortic dissection.
• Never stop a β-blocker abruptly → rebound HTN/angina/MI; taper over 1–2 weeks.
• Sotalol = class II + III antiarrhythmic, prolongs QT.
• β-blockers mask hypoglycaemia (sweating preserved) — caution in insulin-dependent diabetics.
• Timolol topical lowers IOP in glaucoma by reducing aqueous production.