Q5 LONG ANSWER 10M ★ High-yield

Classify adrenergic blocking drugs. Describe the pharmacological actions, uses and adverse effects of beta-blockers.

Pharmacology · 2nd Professional — Para-Clinical

Classification of Adrenergic Blockers

Group	Drugs	Features
Alpha — non-selective, irreversible	Phenoxybenzamine	Covalent, non-competitive; blockade lasts days
Alpha — non-selective, reversible	Phentolamine	Competitive and short-acting
Alpha1-selective	Prazosin, terazosin, doxazosin, tamsulosin	Less reflex tachycardia, because presynaptic alpha2 autoreceptors are left intact to restrain noradrenaline release
Alpha2-selective	Yohimbine	Little clinical use
Ergot alkaloids	Ergotamine, ergotoxine	Partial agonist and blocking actions
Beta — non-selective	Propranolol, timolol, nadolol, sotalol	Block beta1 and beta2
Beta1-selective ("cardioselective")	Atenolol, metoprolol, bisoprolol, esmolol	Safer, though not safe, in asthma and diabetes; selectivity is lost at higher doses
With additional vasodilator action	Carvedilol and labetalol (also alpha1 block); nebivolol (releases nitric oxide)	Carvedilol is used in cardiac failure; labetalol in pregnancy and hypertensive emergency
With intrinsic sympathomimetic activity	Pindolol, acebutolol	Partial agonists; less bradycardia; avoided after myocardial infarction

Beta-blockers — Actions and Uses

Indication	Basis
Hypertension	Reduced cardiac output, reduced renin release, and a central effect; no longer first-line except in specific settings
Angina	Reduced heart rate, contractility and wall stress lower myocardial oxygen demand; the slower rate also lengthens diastole and improves coronary perfusion
After myocardial infarction	Proven reduction in mortality and reinfarction
Chronic cardiac failure	Carvedilol, bisoprolol, metoprolol succinate improve survival by opposing chronic sympathetic overactivity — started at a low dose and increased slowly, since abrupt full blockade worsens failure
Arrhythmia	Class II antiarrhythmic; rate control in atrial fibrillation
Thyrotoxicosis	Rapid symptomatic relief of tremor, palpitation and anxiety; propranolol also inhibits peripheral T4 to T3 conversion
Glaucoma	Timolol drops reduce aqueous humour formation
Others	Migraine prophylaxis, essential tremor, performance anxiety, portal hypertension (propranolol reduces variceal bleeding), phaeochromocytoma after alpha blockade

CLINICAL PEARL

Beta-blockers are given in cardiac failure — the very condition they were once thought to cause. Acutely they reduce contractility and can decompensate a patient. But chronic sympathetic overactivity is itself what damages the failing heart, so blocking it improves survival over months. The resolution is entirely in the dosing: start very low, increase very slowly, and never in acute decompensation.

Adverse Effects and Contraindications

Bronchospasm — beta2 blockade; asthma is a contraindication, and even cardioselective agents are used only with care
Bradycardia and heart block; contraindicated in second and third degree block
Worsening of acute cardiac failure and of peripheral vascular disease (cold extremities, claudication)
Masking of hypoglycaemia in diabetics — tremor and palpitation are suppressed, though sweating is preserved because it is cholinergic; recovery from hypoglycaemia is also delayed
Metabolic — raised triglycerides and reduced HDL; impaired glucose tolerance
CNS — fatigue, nightmares, depression and reduced exercise tolerance, chiefly with lipid-soluble agents such as propranolol
Abrupt withdrawal causes rebound angina, arrhythmia, hypertension and infarction, from receptor up-regulation; the dose must always be tapered
Impotence, a frequent unstated reason for non-adherence

Alpha-blockers — Uses and Problems

Phaeochromocytoma — phenoxybenzamine before surgery, with a beta-blocker added only afterwards; phentolamine for intra-operative crises
Benign prostatic hyperplasia — tamsulosin, alfuzosin relax prostatic and bladder neck smooth muscle, giving rapid symptomatic relief
Hypertension — prazosin and doxazosin; now used chiefly as add-on therapy
First-dose phenomenon — marked postural hypotension and syncope after the first dose of prazosin; the first dose is small and given at bedtime
Other effects — reflex tachycardia (much less with alpha1-selective agents), nasal stuffiness, failure of ejaculation, and intra-operative floppy iris syndrome with tamsulosin, which the ophthalmic surgeon must be told about before cataract surgery

Comparison of Alpha and Beta Blockade

Feature	Alpha-blockers	Beta-blockers
Blood pressure	Falls by vasodilatation	Falls by reduced cardiac output and renin
Heart rate	Reflex tachycardia	Bradycardia
Postural hypotension	Marked	Uncommon
Effect on lipids	Favourable — HDL rises	Unfavourable
Bronchi	No effect	Bronchospasm
Chief uses	Phaeochromocytoma; prostatic hypertrophy	Angina, post-infarction, failure, arrhythmia, thyrotoxicosis

Applied Aspects

Never stop a beta-blocker abruptly — taper over one to two weeks; sudden withdrawal has precipitated fatal infarction
Alpha before beta in phaeochromocytoma, without exception
Give the first dose of prazosin at bedtime and warn the patient about standing up
Beta-blocker overdose is treated with atropine, fluids, and glucagon, which raises cardiac cAMP by a route that bypasses the blocked beta receptor
Ask about asthma before prescribing any beta-blocker, including timolol eye drops — topical ocular beta-blockers are absorbed systemically and have caused fatal bronchospasm
Tell the ophthalmologist if a patient takes tamsulosin, because floppy iris syndrome complicates cataract surgery and forewarning changes the technique
Beta-blockers are no longer first-line for uncomplicated hypertension in most guidelines, but remain first-line after infarction, in angina, in arrhythmia and in cardiac failure
Esmolol has a half-life of minutes, which makes it useful where the effect may need to be withdrawn quickly — in perioperative and intensive care
Labetalol is the beta-blocker of choice in pregnancy, and atenolol is avoided because of fetal growth restriction
Timolol eye drops are absorbed systemically and have caused fatal bronchospasm and bradycardia; punctal occlusion after instillation reduces this

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