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Autonomic system & adrenoceptors

Fibre lengths, transmitters and receptors at every synapse; then the adrenoceptor subtypes, their G-protein coupling, and which drug hits which.

The two outflows

	Sympathetic	Parasympathetic
Origin	Thoracolumbar — lateral horn of the spinal cord, T1–L2	Craniosacral — cranial nerves III, VII, IX, X and S2–S4
Preganglionic fibre	Short, myelinated, type B	Long, myelinated, type B
Postganglionic fibre	Long, unmyelinated, type C	Short, unmyelinated, type C
Ganglion position	Close to the spinal cord (paravertebral chain)	Close to or within the target organ
Cranial outflow	—	III → eye · VII, IX → glands · X (vagus) → thorax and abdomen to the splenic flexure
Sacral outflow	—	S2–S4 pelvic splanchnic nerves → distal colon and pelvic viscera

The transmitter rules — learn these four lines

ALL preganglionic fibres, sympathetic and parasympathetic alike, release acetylcholine acting on NICOTINIC receptors.
Postganglionic parasympathetic releases ACh acting on MUSCARINIC receptors.
Postganglionic sympathetic releases noradrenaline acting on adrenoceptors — with two exceptions.
The exceptions: sweat glands (sympathetic but cholinergic, muscarinic) and the adrenal medulla, which has no postganglionic neurone at all — it is a modified ganglion, innervated directly by preganglionic fibres, secreting ~80% adrenaline into the blood.

Cholinergic receptors

	Nicotinic	Muscarinic
Type	Ligand-gated ion channel (ionotropic)	G-protein coupled (metabotropic)
Location	All autonomic ganglia · adrenal medulla · neuromuscular junction	Effector organs of the parasympathetic system · sweat glands
Blocked by	Ganglion blockers (hexamethonium); relaxants at the NMJ	Atropine, glycopyrrolate, hyoscine

Adrenoceptors

All are G-protein coupled. All sit on the postsynaptic membrane of the effector organ — except α₂, which is largely presynaptic.

Receptor	G protein	Effects
α₁	G_q	Vasoconstriction → ↑ SVR · bladder and gut sphincter contraction · pupillary dilation (mydriasis) · thick salivary secretion · hepatic glycogenolysis · uterine contraction
α₂	G_i	Presynaptic — inhibits noradrenaline release (negative feedback). Centrally: sedation, analgesia, sympatholysis. Also platelet aggregation and reduced insulin secretion
β₁	G_s	↑ Heart rate (chronotropy) · ↑ contractility (inotropy) · ↑ conduction velocity · renin release from the juxtaglomerular apparatus · lipolysis
β₂	G_s	Smooth muscle relaxation — bronchodilation, vasodilation, uterine relaxation (tocolysis) · glycogenolysis and gluconeogenesis · K⁺ shift into cells · insulin release
β₃	G_s	Lipolysis in brown adipose tissue (thermogenesis, "burn fat") · bladder detrusor relaxation

G-protein coupling — the pathway

G_s (stimulatory): activates adenylyl cyclase → ↑ cAMP → activates protein kinase A. Coupled receptors: β₁, β₂, β₃, histamine H₂, D₁, and TSH.
G_i (inhibitory): inhibits adenylyl cyclase → ↓ cAMP. Coupled receptors: α₂, opioid, dopamine D₂, serotonin, muscarinic M₂.
G_q: activates phospholipase C → IP₃ and DAG → ↑ intracellular Ca²⁺. Coupled receptors: α₁, muscarinic M₁ and M₃, vasopressin V₁, angiotensin II.

Sympathomimetics by receptor

Direct agonists act on the receptor themselves; indirect agents work by releasing stored noradrenaline. The catecholamines are adrenaline, noradrenaline, dopamine, dobutamine and isoprenaline.

Drug	Receptors	Clinical effect
Adrenaline	α and β β predominates at low dose, α at high dose	Low dose: ↑ CO with vasodilation. High dose: marked vasoconstriction. First line in anaphylaxis and cardiac arrest
Noradrenaline	α₁ ≫ β₁	↑ SVR with little chronotropy; reflex bradycardia possible. First-line vasopressor in septic shock
Metaraminol	α₁ (with some indirect action)	↑ SVR; useful bolus vasopressor
Phenylephrine	Pure α₁	↑ SVR, reflex bradycardia. Widely used in obstetrics
Ephedrine	α and β, direct and indirect	↑ HR and BP. Tachyphylaxis with repeated doses as stores deplete
Dopamine	Dopaminergic → β → α with increasing dose	Largely abandoned — no renal protective effect and more arrhythmias
Dobutamine	β₁ > β₂	Inotropy with mild vasodilation
Dopexamine	β₂ and dopaminergic	Vasodilation and splanchnic flow; weak inotrope
Isoprenaline	Non-selective β	Marked chronotropy — used in bradycardia and heart block
Salbutamol	β₂	Bronchodilation; also shifts K⁺ into cells and is tocolytic
Clonidine / dexmedetomidine	α₂ agonist	Sedation and analgesia without respiratory depression; sympatholysis

Note on this table

Your page IMG_0993 lists these drugs but the effects column was cropped off the right edge. The receptor assignments and effects above are the standard ones — re-photograph that page if your version differs and I will reconcile them.

Built from handwritten pages IMG_0991–0993.