Pharmacology · Short notes

Autonomic Nervous System: Short Notes & Cheat Sheet

Cholinergic and adrenergic transmission, receptor subtypes, and the agonists and antagonists that act on them.

Short notes

Read these before you attempt the topic's MCQs.

The autonomic pathways at a glance

Every preganglionic fibre releases ACh onto nicotinic receptors. The exceptions to learn are sweat glands (sympathetic but cholinergic) and the adrenal medulla (no postganglionic fibre).

Organisation and transmitters

All preganglionic autonomic neurons release acetylcholine (ACh), which acts on nicotinic NN receptors in the ganglia.
Postganglionic parasympathetic neurons release ACh onto muscarinic receptors.
Most postganglionic sympathetic neurons release noradrenaline. The exception is sweat glands: their sympathetic supply is cholinergic and acts on muscarinic receptors.
The adrenal medulla works like a sympathetic ganglion and releases mainly adrenaline (about 80%) straight into the blood.
Renal blood vessels are dilated by dopamine acting on D1 receptors.

Cholinergic transmission and drugs

ACh is made from choline and acetyl-CoA by choline acetyltransferase and destroyed by acetylcholinesterase (AChE). Hemicholinium blocks choline uptake, vesamicol blocks vesicular storage, and botulinum toxin blocks release.
Muscarinic receptors: M1 in the CNS and gastric glands (Gq), M2 in the heart (Gi; slows the heart), and M3 in smooth muscle, glands and the eye (Gq).
Direct agonists: bethanechol for urinary retention (not broken down by AChE, muscarinic-selective); pilocarpine for glaucoma and dry mouth.
Reversible anticholinesterases: neostigmine (quaternary, does not enter the CNS; used for myasthenia and to reverse non-depolarising blockers), pyridostigmine (maintenance in myasthenia), edrophonium (very short; diagnostic test), physostigmine (tertiary, enters the CNS; antidote for atropine poisoning).
For Alzheimer's disease: donepezil, rivastigmine and galantamine.
Irreversible anticholinesterases are the organophosphates (malathion, parathion, nerve agents). Treat poisoning with atropine plus pralidoxime, and give pralidoxime before the enzyme 'ages'.

Anticholinergics and neuromuscular blockers

Atropine (tertiary) is used for bradycardia, as a preanaesthetic, in organophosphate poisoning, and in the eye to dilate the pupil and paralyse focusing (mydriasis with cycloplegia).
Hyoscine (scopolamine) is used for motion sickness. Inhaled ipratropium and tiotropium treat COPD. Tropicamide is a short-acting mydriatic. Oxybutynin and tolterodine treat overactive bladder. Benztropine and trihexyphenidyl treat parkinsonian tremor.
Avoid anticholinergics in angle-closure glaucoma and in benign prostatic hyperplasia (BPH), because they can cause urinary retention.
Succinylcholine is a depolarising blocker. In phase I, neostigmine makes its block worse rather than reversing it. It can cause hyperkalaemia and malignant hyperthermia (treated with dantrolene).
Non-depolarising blockers: d-tubocurarine, pancuronium, vecuronium and rocuronium. Sugammadex reverses rocuronium and vecuronium. Atracurium and cisatracurium undergo Hofmann elimination, so they are safe in liver or kidney failure.

Adrenergic transmission and receptors

Synthesis pathway: tyrosine → DOPA (tyrosine hydroxylase, the rate-limiting step) → dopamine → noradrenaline (dopamine β-hydroxylase, inside the vesicle) → adrenaline (PNMT, in the adrenal medulla).
Noradrenaline's action ends mainly through reuptake (uptake-1), which cocaine and tricyclic antidepressants (TCAs) block. It is broken down by MAO and COMT to VMA.
α1 (Gq): vasoconstriction, mydriasis (radial muscle), contraction of the bladder sphincter.
α2 (Gi): presynaptic inhibition of noradrenaline release; lower insulin secretion.
β1 (Gs): faster heart rate and stronger contraction; renin release. β2 (Gs): bronchodilation, vasodilation in skeletal muscle, uterine relaxation, glycogenolysis, K+ uptake into cells. β3: lipolysis and relaxation of the bladder detrusor (mirabegron).

Adrenergic drugs

Adrenaline is the drug of choice in anaphylaxis (IM, 0.5 mg of 1:1000 for an adult). Noradrenaline is used in septic shock and causes reflex bradycardia. Dobutamine (β1) is used in cardiogenic shock.
Dopamine's effect depends on dose: D1 at low doses, then β1, then α1 at high doses.
Phenylephrine (α1) is a decongestant and dilates the pupil without paralysing focusing. Clonidine and methyldopa are central α2 agonists; methyldopa is safe in pregnancy.
Indirect sympathomimetics: amphetamine and tyramine release noradrenaline (tyramine causes the 'cheese reaction' with MAO inhibitors); ephedrine acts both directly and indirectly.
α-blockers: phenoxybenzamine (irreversible) and phentolamine are used for phaeochromocytoma. Prazosin causes first-dose hypotension. Tamsulosin (α1A-selective) is used for BPH.
β-blockers: propranolol is non-selective; atenolol, metoprolol, bisoprolol and esmolol are β1-selective; labetalol and carvedilol also block α. They can worsen asthma and mask the warning signs of hypoglycaemia, and should never be stopped abruptly.

Cheat sheet

High-yield facts in one place. Cover the right-hand column and test yourself.

Receptors at a glance

Receptor (G-protein)	Key effect
M1 (Gq)	CNS, gastric acid secretion
M2 (Gi)	↓ heart rate, ↓ AV conduction
M3 (Gq)	Bronchoconstriction, secretions, miosis, bladder contraction
NN / NM	Ganglia / skeletal muscle end-plate
α1 (Gq)	Vasoconstriction, mydriasis
α2 (Gi)	↓ NA release (presynaptic), ↓ insulin
β1 (Gs)	↑ heart rate and force, ↑ renin
β2 (Gs)	Bronchodilation, vasodilation, tocolysis, hypokalaemia
β3 (Gs)	Lipolysis, detrusor relaxation

Drugs of choice

Situation	Drug
Anaphylaxis	Adrenaline IM
Organophosphate poisoning	Atropine + pralidoxime
Atropine / anticholinergic poisoning	Physostigmine
Myasthenia gravis (maintenance)	Pyridostigmine
Malignant hyperthermia	Dantrolene
Reversal of rocuronium	Sugammadex
Phaeochromocytoma (pre-op)	Phenoxybenzamine, then β-blocker
Hypertension in pregnancy	Methyldopa, labetalol
Motion sickness	Hyoscine
β-blocker overdose	Glucagon

Memory aids

DUMBBELSS: Muscarinic excess (organophosphate poisoning): Diarrhoea, Urination, Miosis, Bradycardia, Bronchospasm, Emesis, Lacrimation, Salivation, Sweating.
Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter: Atropine toxicity: hyperthermia, dry skin, flushing, blurred vision (mydriasis with cycloplegia), delirium.
β1-selective blockers run from A to M: Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Metoprolol are cardioselective.

Exam traps

Sweat glands are sympathetic but cholinergic (muscarinic). Anticholinergics stop sweating.
After an α-blocker, adrenaline lowers blood pressure (Dale's vasomotor reversal) because its β2 vasodilation is left unopposed.
Neostigmine does not reverse a phase I succinylcholine block; it makes it deeper.
Physostigmine enters the CNS; neostigmine does not.
Phenylephrine dilates the pupil without paralysing focusing; atropine does both.

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