By MRCSA in MRCS Part A — 04 Jul 2026

23 ADRENERGIC RECEPTORS

# 24 ADRENERGIC RECEPTORS

👩‍⚕️ Adrenergic pharmacology is one of the highest-yield MRCS Part A topics. Every question collapses to the same logic: identify the receptor, its location, predict the effect.

What are adrenergic receptors?

G-protein coupled receptors activated by noradrenaline, adrenaline and dopamine. Five clinically relevant subtypes, each defined by its second messenger:

➡ α1 ➡ Gq ➡ ↑ IP3 / DAG ➡ ↑ intracellular Ca²⁺ ➡ smooth muscle contraction

➡ α2 ➡ Gi ➡ ↓ cAMP ➡ presynaptic inhibition of noradrenaline release

➡ β1, β2, β3 ➡ Gs ➡ ↑ cAMP ➡ tissue-specific effects

All three β receptors share the same signalling pathway but produce opposite-looking effects (cardiac stimulation vs smooth muscle relaxation). The differentiator is location, not signalling.

Master table — learn this first

Receptor	G-protein	Second messenger	Main locations	Key effects	Prototype drugs
α1	Gq	↑ IP3/DAG, ↑ Ca²⁺	Vascular smooth muscle, GI/bladder sphincters, iris radial muscle	Vasoconstriction (↑ SVR, ↑ BP), mydriasis, sphincter contraction (urinary retention), ejaculation	Phenylephrine, noradrenaline, metaraminol
α2	Gi	↓ cAMP	Presynaptic sympathetic terminals, CNS (locus coeruleus), pancreatic β-cells, platelets	↓ Noradrenaline release (negative feedback), sedation, ↓ insulin release, platelet aggregation	Clonidine, dexmedetomidine
β1	Gs	↑ cAMP	SA node, AV node, ventricular myocytes, juxtaglomerular apparatus	↑ HR (chronotropy), ↑ contractility (inotropy), ↑ conduction (dromotropy), ↑ renin release	Dobutamine, adrenaline, noradrenaline
β2	Gs	↑ cAMP	Bronchial smooth muscle, skeletal-muscle arterioles, uterus, liver, pancreas	Bronchodilation, vasodilation (↓ SVR), uterine relaxation (tocolysis), glycogenolysis, ↑ insulin release	Salbutamol, salmeterol, terbutaline
β3	Gs	↑ cAMP	Adipose tissue, detrusor muscle	Lipolysis, detrusor relaxation (used in overactive bladder)	Mirabegron

👩‍⚕️ Memory hook: "1 heart, 2 lungs" — β1 is for the single organ (heart), β2 is for the paired organs (lungs) and other smooth muscle that needs to relax.

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Catecholamine receptor profiles

Drug	Receptor affinity	Net effect
Noradrenaline	α1 ≫ β1 > β2 (negligible)	Vasoconstriction, modest inotropy, reflex bradycardia possible
Adrenaline	Low dose: β1 + β2 dominant; high dose: α1 dominant	Low: ↑ HR, ↑ CO, bronchodilation, mild diastolic drop. High: vasoconstriction, ↑ BP
Dopamine	Low (D1) → renal vasodilation; mid (β1) → ↑ CO; high (α1) → vasoconstriction	Dose-dependent
Isoprenaline	β1 = β2 (no α)	↑ HR, ↑ CO, vasodilation

👩‍⚕️ Classic SBA trap — adrenaline's biphasic BP response. The diastolic dip at low dose is mediated by β2 vasodilation in skeletal muscle; high-dose α1 then wins and BP climbs.

Selected drugs by receptor target

➡ Phenylephrine ➡ pure α1 ➡ nasal decongestant, intra-op hypotension; reflex bradycardia

➡ Clonidine ➡ central α2 agonist ➡ antihypertensive, analgesic adjunct

➡ Dobutamine ➡ β1 ≫ β2 ➡ inotrope when BP preserved, CO low

➡ Salbutamol ➡ β2 selective ➡ asthma, hyperkalaemia, tocolysis

➡ Mirabegron ➡ β3 agonist ➡ overactive bladder

➡ Phentolamine ➡ non-selective α blocker (reversible) ➡ hypertensive crisis

➡ Phenoxybenzamine ➡ irreversible non-selective α blocker ➡ phaeochromocytoma pre-op

➡ Bisoprolol, atenolol, metoprolol ➡ β1-selective (cardioselective); propranolol = non-selective

High-yield clinical correlations

Phaeochromocytoma — α before β

A catecholamine-secreting tumour, usually of the adrenal medulla. Tumour handling at surgery releases a surge of catecholamines, risking hypertensive crisis.

Rule: α blockade first (phenoxybenzamine, started 7–14 days pre-op), then β blockade. Reverse the order and β blockade removes β2 vasodilation while leaving α1 vasoconstriction unopposed — the "unopposed α" crisis with worsening hypertension. β blockers are added later to control reflex tachycardia.

> Pearl: "α before β" is one of the most reliably examined facts in surgical pharmacology.

Hypertensive crisis — phentolamine

Acute catecholamine-driven hypertension (intra-op phaeochromocytoma, MAOI–tyramine reaction, cocaine toxicity) is treated with phentolamine IV — a short-acting non-selective α blocker.

Anaphylaxis and shock

Adrenaline is first-line in anaphylaxis because it covers every receptor you need: α1 reverses vasodilation, β1 supports CO, β2 relieves bronchospasm and stabilises mast cells.

In septic shock (low SVR) → noradrenaline restores vascular tone via α1. In cardiogenic shock with preserved BP → dobutamine augments inotropy via β1 without raising afterload.

β2 in surgical practice

➡ Drives K⁺ intracellularly (hyperkalaemia, with insulin–dextrose)

➡ Uterine relaxation (tocolysis — terbutaline)

➡ Fine tremor and tachycardia at higher doses (β1 cross-reactivity)

Holliday–Segar for paediatric maintenance fluids

➡ First 10 kg ➡ 100 mL/kg/day

➡ Next 10 kg ➡ 50 mL/kg/day

➡ Each kg > 20 ➡ 20 mL/kg/day

Common exam traps

➡ β1 vs β2 — same second messenger, opposite-looking effects. Location decides.

➡ α2 is inhibitory — presynaptic, reduces sympathetic outflow. Clonidine lowers BP.

➡ Dobutamine lowers BP via β2 vasodilation, not via lack of α activity.

➡ Phenylephrine causes reflex bradycardia — pure α1 ↑ BP → baroreceptor ↓ HR.

➡ "α before β" in phaeochromocytoma — never reverse the order.

[Image: MCQs banner]

Test yourself

Which intracellular second messenger system is activated by α1 adrenergic receptors?

((Gq → phospholipase C → IP3/DAG → ↑ Ca²⁺::☑️ Correct — smooth muscle contraction follows the rise in cytosolic calcium.))
((Gs → adenylyl cyclase → ↑ cAMP::This is the β-receptor pathway, not α1.))
((Gi → ↓ cAMP::This is α2, which inhibits noradrenaline release presynaptically.))
((Direct ligand-gated ion channel::Adrenergic receptors are GPCRs, not ionotropic.))
((Tyrosine kinase receptor::Used by insulin and growth factors, not catecholamines.))

👩‍⚕️ Gq for α1, Gi for α2, Gs for all β — a three-line fact that unlocks dozens of SBAs.

Which receptor mediates bronchodilation?

((α1::Vascular smooth muscle vasoconstriction, not bronchial.))
((α2::Presynaptic inhibition of noradrenaline release; not on bronchi.))
((β1::Cardiac chronotropy and inotropy; minimal pulmonary effect.))
((β2::☑️ Correct — Gs/cAMP relaxes bronchial smooth muscle; target of salbutamol.))
((β3::Adipose and detrusor, not airway.))

A patient with a suspected phaeochromocytoma is being prepared for adrenalectomy. Which is the most appropriate first step in pre-operative pharmacological management?

((Atenolol::β blockade first leaves α1 unopposed — risks hypertensive crisis.))
((Phenoxybenzamine::☑️ Correct — irreversible α blockade started 7–14 days pre-op; β blocker added later for reflex tachycardia.))
((Propranolol::Non-selective β blocker — same "unopposed α" danger if used first.))
((Amlodipine::Calcium channel blocker is adjunctive only; not the primary step.))
((Labetalol::Mixed α/β but the β effect dominates — α blockade is insufficient if used as monotherapy first-line.))

👩‍⚕️ "α before β" — one of the most reliably examined facts in surgical pharmacology.

Which adrenergic receptor is responsible for the chronotropic effect of adrenaline on the heart?

((β₂::Bronchial and vascular smooth muscle relaxation, not cardiac rate.))
((α₁::Vascular vasoconstriction; no direct cardiac rate effect.))
((α₂::Presynaptic inhibitory autoreceptor — reduces noradrenaline release.))
((β₁::☑️ Correct — SA node β1 drives chronotropy; also raises contractility.))
((β₃::Adipose lipolysis and bladder relaxation, not cardiac.))

👩‍⚕️ "β1 = 1 heart" — you have one heart, β1 is the cardiac receptor.

Which is the first-line vasopressor in septic shock?

((Adrenaline::Second-line — its β1 activity causes excess tachycardia and lactate rise.))
((Noradrenaline::☑️ Correct — α1-dominant restores SVR with modest β1 to maintain CO.))
((Dopamine::Higher arrhythmia rate than noradrenaline; no longer first-line.))
((Dobutamine::β1 inotrope with β2 vasodilation — would worsen low SVR.))
((Vasopressin::V1 agonist used as second-line adjunct, not monotherapy.))

👩‍⚕️ Septic shock = pathological vasodilation → you need α1 to restore vascular tone.

In cardiogenic shock with preserved systolic blood pressure, which drug improves contractility while having minimal effect on vascular tone?

((Adrenaline::Mixed α/β — potent vasoconstriction and tachycardia unsuitable for isolated inotropy.))
((Noradrenaline::α1-dominant — raises SVR, not contractility.))
((Dobutamine::☑️ Correct — β1 inotrope with mild β2 vasodilation; ideal when BP preserved but CO low.))
((Dopamine::Dose-dependent receptor activity makes haemodynamic profile less predictable.))
((Phenylephrine::Pure α1 — raises afterload without inotropy, would worsen CO.))

Which receptor activity of dobutamine is responsible for its blood-pressure-lowering effect?

((β1::Raises HR and contractility — would tend to raise BP, not lower it.))
((β2::☑️ Correct — vascular smooth muscle relaxation reduces SVR and BP.))
((α1::Would cause vasoconstriction and raise BP.))
((α2::Presynaptic central effect; negligible at dobutamine doses.))
((Muscarinic M2::Dobutamine is a sympathomimetic — no muscarinic activity.))

A 24-year-old man develops anaphylaxis after a peanut exposure. Which combination of receptor effects makes adrenaline first-line treatment?

((α1 only::Reverses vasodilation but does not relieve bronchospasm.))
((β2 only::Bronchodilates but does not reverse hypotension or angio-oedema.))
((α1 + β1 + β2::☑️ Correct — vasoconstriction, inotropy and bronchodilation simultaneously.))
((α2 + β1::Would reduce sympathetic outflow centrally — the opposite of what is needed.))
((β1 + β3::Cardiac and adipose effects only — no airway or vascular benefit.))

A patient with intra-operative hypertensive crisis during phaeochromocytoma resection requires acute BP control. Which is the most appropriate drug?

((Labetalol::Mixed α/β but β activity predominates — risk of unopposed α effect.))
((Esmolol::β1-selective — leaves α1 vasoconstriction untreated.))
((Phentolamine::☑️ Correct — short-acting non-selective α blocker rapidly antagonises α1 vasoconstriction.))
((Adenosine::Used for SVT, not catecholamine-driven hypertension.))
((Glyceryl trinitrate::Useful adjunct but does not target the underlying α1 stimulation.))

Which receptor mediates the increase in renin release from the juxtaglomerular apparatus?

((α1::Mediates afferent arteriolar vasoconstriction, not renin release.))
((α2::Presynaptic inhibitory; not the JGA stimulus.))
((β1::☑️ Correct — sympathetic β1 stimulation of the JGA drives renin secretion.))
((β2::Vascular and bronchial smooth muscle relaxation, not renin.))
((β3::Adipose and bladder effects only.))

👩‍⚕️ β1 blockers (e.g. bisoprolol) lower BP partly by reducing renin release — links cardiac pharmacology to RAAS.

Revision summary

➡ α1 ➡ Gq ➡ vasoconstriction, mydriasis, sphincter contraction ➡ phenylephrine, noradrenaline

➡ α2 ➡ Gi ➡ presynaptic ↓ NA release, ↓ insulin, sedation ➡ clonidine

➡ β1 ➡ Gs ➡ ↑ HR, ↑ contractility, ↑ renin ➡ dobutamine

➡ β2 ➡ Gs ➡ bronchodilation, vasodilation, uterine relaxation, glycogenolysis ➡ salbutamol

➡ β3 ➡ Gs ➡ lipolysis, detrusor relaxation ➡ mirabegron

➡ Noradrenaline = α1 ≫ β1 ➡ septic shock first-line

➡ Adrenaline = all receptors; high dose α1 dominant ➡ anaphylaxis first-line

➡ Dobutamine = β1 ≫ β2 ➡ cardiogenic shock with preserved BP

➡ Phenylephrine = pure α1 ➡ reflex bradycardia

➡ Phaeochromocytoma ➡ α blockade (phenoxybenzamine) BEFORE β blockade ➡ never reverse the order

➡ Hypertensive crisis (catecholamine excess) ➡ phentolamine IV

➡ β2 extra uses ➡ hyperkalaemia (K⁺ shift), tocolysis