Q2 LONG ANSWER 10M ★ High-yield

Enumerate the autonomic neurotransmitters and their receptors. Describe the actions of each receptor type and the drugs acting on them.

Physiology · 1st Professional — Pre-Clinical

Site	Transmitter	Receptor
All preganglionic (both divisions)	Acetylcholine	Nicotinic (NN)
Parasympathetic postganglionic	Acetylcholine	Muscarinic
Sympathetic postganglionic	Noradrenaline	Adrenergic (α, β)
Sympathetic to sweat glands	Acetylcholine (exception)	Muscarinic
Adrenal medulla	ACh from preganglionic fibre	Nicotinic → releases adrenaline
Neuromuscular junction (somatic)	Acetylcholine	Nicotinic (NM)

Receptor	G protein	Second messenger	Chief effects
α1	Gq	IP3 / DAG → ↑ Ca2+	Vasoconstriction, mydriasis, sphincter contraction, prostate
α2	Gi	↓ cAMP	Presynaptic inhibition of noradrenaline release; ↓ insulin; platelet aggregation
β1	Gs	↑ cAMP	Heart — ↑ rate, force, conduction; ↑ renin
β2	Gs	↑ cAMP	Bronchodilatation, vasodilatation in muscle, uterine relaxation, glycogenolysis, K+ into cells
β3	Gs	↑ cAMP	Lipolysis; bladder relaxation

Noradrenaline acts mainly on α; adrenaline acts on both α and β
α2 is largely presynaptic and provides negative feedback on transmitter release — the basis of clonidine

Receptor	Type	Site	Effect
NM	Ion channel	Neuromuscular junction	Skeletal muscle contraction
NN	Ion channel	Autonomic ganglia, adrenal medulla	Ganglionic transmission
M1	Gq	CNS, gastric parietal cell	↑ Gastric acid
M2	Gi	Heart	↓ Rate and conduction
M3	Gq	Smooth muscle, glands, eye	Contraction, secretion, miosis

Tyrosine → Tyrosine hydroxylase (rate-limiting) → dopa → Dopamine → noradrenaline (in the vesicle)

Fate — reuptake accounts for 80% (uptake-1 into the nerve terminal); the rest is metabolised by MAO and COMT or diffuses away
Metabolites — VMA and metanephrines, measured in urine to diagnose phaeochromocytoma
Acetylcholine is destroyed within 1 ms by acetylcholinesterase; choline is recaptured

Class	Example	Action / use
α1 agonist	Phenylephrine	Vasoconstrictor, nasal decongestant, mydriatic
α1 blocker	Prazosin, tamsulosin	Hypertension, benign prostatic hyperplasia
α2 agonist	Clonidine	↓ Central sympathetic outflow → antihypertensive
β blocker	Propranolol, atenolol	Angina, hypertension, arrhythmia, thyrotoxicosis
β2 agonist	Salbutamol	Asthma; also tocolytic
Muscarinic blocker	Atropine	Bradycardia, antispasmodic, preanaesthetic, organophosphate poisoning
Anticholinesterase	Neostigmine, pyridostigmine	Myasthenia gravis, reversal of curare

Ganglionic transmission is nicotinic, but is modulated by muscarinic and peptidergic inputs, producing slow EPSPs and IPSPs
Co-transmitters are released with the classical transmitter:

– ATP and neuropeptide Y with noradrenaline

– VIP with acetylcholine — in salivary glands, causing vasodilatation

– Nitric oxide — the NANC (non-adrenergic non-cholinergic) transmitter of gut relaxation and penile erection

Ganglion blockers (hexamethonium, trimethaphan) block both divisions → too many side effects for routine use

β blockers must be used with caution in asthma — blocking β2 causes bronchospasm; cardioselective agents are safer but not entirely safe
Atropine poisoning — "hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter"
Organophosphate poisoning — irreversible cholinesterase inhibition → muscarinic (sludge), nicotinic (fasciculation, paralysis) and CNS features; treated with atropine plus pralidoxime
Adrenaline in anaphylaxis works because it acts on α1 (vasoconstriction), β1 (cardiac) and β2 (bronchodilatation) simultaneously
Local anaesthetic with adrenaline — vasoconstriction prolongs the block and reduces bleeding, but must be avoided in end-arteries such as digits
Cheese reaction — MAO inhibitors plus tyramine-rich food → massive noradrenaline release → hypertensive crisis
Cocaine and tricyclics block uptake-1 → potentiate noradrenaline
Reserpine depletes vesicular stores; guanethidine blocks release — both were early antihypertensives
Selectivity is relative, not absolute — at high dose a cardioselective β1 blocker will also block β2

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