PH2.1-5 | Autonomic and Peripheral Pharmacology — Glossary

The enzyme that hydrolyses acetylcholine in the synaptic cleft, terminating its action; inhibited reversibly by neostigmine and irreversibly by organophosphate compounds.

The irreversible dealkylation of the phosphorylated AChE-organophosphate complex, which removes one alkyl group and renders the complex non-reactivatable by oximes; time to ageing varies by agent (minutes for soman, hours for agricultural OPCs).

Typically 1:200,000 concentration (5 mcg/mL); causes α1-mediated local vasoconstriction → reduces systemic absorption → prolongs block → increases maximum safe LA dose. Contraindicated in end-arterial tissues (digits, nose, penis, ear pinna).

A G protein-coupled receptor that responds to catecholamines (adrenaline, noradrenaline); subtypes α1, α2, β1, β2, β3 mediate distinct organ responses.

A LA with an amide bond; hepatically metabolised; two 'i's before '-caine' in the name; lower allergy risk than esters. Examples: lignocaine, bupivacaine, ropivacaine, prilocaine, mepivacaine.

The syndrome produced by muscarinic receptor blockade; characterised by dry skin, tachycardia, mydriasis, urinary retention, flushing, hyperthermia, and CNS agitation/delirium ('dry, blind, red, hot, mad, full, fast').

A competitive muscarinic antagonist (parasympatholytic) used in emergency management of symptomatic bradycardia and as the primary antidote in organophosphate poisoning by blocking cholinergic excess.

A GABA-B receptor agonist used to reduce spasticity in multiple sclerosis, spinal cord injury, and cerebral palsy; abrupt withdrawal causes a severe syndrome (hallucinations, hyperthermia, seizures).

An autonomic reflex by which a rise in arterial pressure activates aortic and carotid baroreceptors, increasing vagal tone and decreasing sympathetic output, producing compensatory bradycardia and vasodilation.

LA injection into the IV of an exsanguinated tourniquet-protected limb; lignocaine 0.5% is the only approved LA — bupivacaine is absolutely contraindicated due to risk of refractory cardiac arrest on tourniquet deflation.

A plasma esterase (also called pseudocholinesterase) that hydrolyses succinylcholine and mivacurium; atypical genotypes (dibucaine number) prolong succinylcholine block from 10 minutes to hours.

Toxicity from carbamate pesticides (e.g. carbaryl), which spontaneously and reversibly carbamylate AChE; clinical presentation is identical to OPC poisoning but milder and self-limiting; pralidoxime is generally not required.

The relative preference of a beta-blocker for β1 receptors over β2; agents like atenolol and metoprolol are cardioselective, though selectivity diminishes at high doses.

A class of neurotransmitters and hormones with a catechol ring and amine side-chain; includes adrenaline, noradrenaline, and dopamine, synthesised from tyrosine.

The clinical syndrome produced by excess acetylcholine activity; characterised by DUMBELS (Defaecation, Urination, Miosis, Bradycardia/Bronchospasm/Bronchorrhoea, Emesis, Lacrimation, Salivation) plus nicotinic features (fasciculations, weakness) and CNS effects (seizures).

A skeletal muscle relaxant acting by blocking RyR1 (ryanodine receptor) to inhibit SR Ca²⁺ release; the specific antidote for malignant hyperthermia (2.5 mg/kg IV up to 10 mg/kg); also used in NMS.

The selective blockade of pain and temperature fibres (small, unmyelinated C fibres, Aδ fibres) at lower LA concentrations before loss of touch, proprioception, or motor function — the basis for pain-free labour analgesia without complete motor block.

A selective β1 agonist (primarily inotropic, minimal chronotropic at low doses) used as an IV infusion in acute decompensated heart failure and cardiogenic shock to increase cardiac contractility.

Mnemonic for the muscarinic features of cholinergic toxidrome: Defaecation/Diarrhoea, Urination, Miosis, Bradycardia/Bronchospasm/Bronchorrhoea, Emesis, Lacrimation, Salivation.

LA injection into the epidural space (between ligamentum flavum and dura mater), producing nerve root blockade; a catheter can be placed for continuous infusion; used for labour analgesia and major surgery.

A LA with an ester bond between the aromatic ring and amine chain; hydrolysed by plasma pseudocholinesterase; metabolised to PABA → higher allergy risk. Examples: procaine, cocaine, chloroprocaine, benzocaine.

An exaggerated blood pressure fall after the first dose of a selective α1-blocker (e.g. prazosin), due to sudden reduction in vascular tone without compensatory reflex; mitigated by starting with a low bedtime dose.

A quaternary muscarinic antagonist used perioperatively to counteract the muscarinic effects of neostigmine; preferred over atropine in elderly patients because it does not cross the BBB and thus avoids confusion/agitation.

Heart failure with reduced ejection fraction (LVEF <40%); characterised by impaired LV contractility. Carvedilol, bisoprolol, and metoprolol succinate have proven mortality benefit in this condition.

Spontaneous chemical degradation of atracurium and cisatracurium at physiological temperature and pH, independent of hepatic or renal function; makes these drugs safe in organ failure.

Bupivacaine 0.5% in 8% dextrose solution (specific gravity > CSF); used for spinal/intrathecal anaesthesia; 'sinks' to the dependent part of the subarachnoid space, allowing position-controlled block distribution.

A quaternary muscarinic antagonist administered by inhalation for COPD and asthma; blocks M3 receptors in bronchial smooth muscle without systemic or CNS effects due to its inability to cross the BBB or GI mucosa significantly.

The prototype amide LA with intermediate duration and fastest onset among amides (pKa 7.9); also a Class 1b antiarrhythmic (IV for ventricular arrhythmias); maximum doses 3 mg/kg plain, 7 mg/kg with adrenaline.

20% lipid emulsion given IV (1.5 mL/kg bolus then infusion) to treat LA systemic toxicity, particularly bupivacaine-induced cardiac arrest; the lipid phase extracts the lipophilic LA from cardiac tissue (lipid sink hypothesis).

A drug that reversibly blocks voltage-gated Na⁺ channels in nerve axons, interrupting action potential propagation and producing sensory and/or motor block in the distribution of the affected nerve.

A life-threatening pharmacogenomic crisis (RYR1 mutation) triggered by volatile anaesthetics or succinylcholine; characterised by uncontrolled SR Ca²⁺ release → hyperthermia, rigidity, metabolic acidosis; treated with dantrolene IV.

Conversion of haemoglobin iron from Fe²⁺ to Fe³⁺ by oxidising agents, reducing oxygen-carrying capacity; caused by prilocaine (metabolite o-toluidine) and benzocaine in excess; treated with methylene blue 1–2 mg/kg IV.

A G protein-coupled receptor activated by ACh (and muscarine) at postganglionic parasympathetic synapses; subtypes M1–M5 mediate diverse organ effects; blocked by atropine.

A reversible, quaternary AChE inhibitor that does not cross the BBB; used to reverse non-depolarising neuromuscular blockade post-anaesthesia and to treat myasthenia gravis; given with atropine or glycopyrrolate to prevent muscarinic excess.

A drug that interrupts transmission at the neuromuscular junction, producing skeletal muscle paralysis; classified as depolarising (succinylcholine) or non-depolarising (rocuronium, atracurium, vecuronium).

A ligand-gated ion channel activated by ACh (and nicotine) at the neuromuscular junction (N_M) and autonomic ganglia (N_N); mediates skeletal muscle contraction and ganglionic transmission respectively.

An endogenous catecholamine and first-line IV vasopressor for septic shock; acts on α1 (vasoconstriction) and β1 (cardiac inotropy) with negligible β2 activity.

A class of irreversible acetylcholinesterase inhibitors used as pesticides and chemical warfare agents; cause cholinergic excess (DUMBELS toxidrome) by covalent phosphorylation of AChE serine residue.

The metabolite of ester local anaesthetics (procaine, chloroprocaine); responsible for the higher incidence of allergic reactions to ester LAs; cross-reactivity between esters is expected; no PABA from amide metabolism.

A UK RCT (Perkins et al., NEJM 2018) enrolling adults with out-of-hospital cardiac arrest; adrenaline improved 30-day survival (ROSC higher) but not survival with favourable neurological outcome vs placebo.

The initial flaccid paralysis produced by succinylcholine through persistent end-plate depolarisation; fasciculations precede the block; reversed spontaneously by BChE hydrolysis; NOT reversed by neostigmine.

An irreversible, non-selective alpha-adrenoceptor blocker that forms a covalent bond with the receptor; used pre-operatively in phaeochromocytoma to establish sustained alpha-blockade.

A reversible, tertiary amine AChE inhibitor that crosses the BBB; used as the specific antidote for anticholinergic toxidrome (reverses both peripheral and central muscarinic blockade).

The pH at which 50% of a weak acid/base is ionised and 50% is unionised; for LAs, determines the fraction available in the unionised (membrane-penetrating) form at physiological pH — lower pKa = faster onset.

An acetylcholinesterase reactivator (oxime) given alongside atropine in organophosphate poisoning; must be administered before 'ageing' of the phosphorylated enzyme to be effective.

An oxime antidote for organophosphate poisoning; reactivates phosphorylated AChE by cleaving the phosphate bond — effective only before irreversible 'ageing' of the enzyme-phosphate complex.

The prototype ester local anaesthetic; short duration; hydrolysed to PABA; historically important but largely superseded by amides; metabolite PABA mediates the higher allergy rate of ester LAs.

An anaesthetic technique for patients at aspiration risk (full stomach, emergency surgery) combining rapid IV induction agent + fast-onset NMBD (succinylcholine or high-dose rocuronium) to secure the airway quickly.

A surge in blood pressure following abrupt withdrawal of a beta-blocker, caused by receptor upregulation during chronic blockade that renders the system supersensitive to endogenous catecholamines.

A steroidal non-depolarising NMBD with fast onset at RSI dose (1.2 mg/kg); reversed by neostigmine or sugammadex; preferred when succinylcholine is contraindicated for RSI.

The Ca²⁺ release channel in the sarcoplasmic reticulum of skeletal muscle; triggered by T-tubule depolarisation (dihydropyridine receptor coupling); mutations in RYR1 cause malignant hyperthermia susceptibility.

Velocity-dependent increase in tonic stretch reflex resulting from upper motor neuron lesion, causing increased muscle tone, clonus, and exaggerated deep tendon reflexes; treated with centrally acting spasmolytics, not NMBDs.

The only depolarising NMBD in clinical use; causes initial fasciculations followed by Phase 1 flaccid block; hydrolysed by butyrylcholinesterase; contraindicated in hyperkalaemic states and MH susceptibility.

A modified gamma-cyclodextrin that encapsulates rocuronium or vecuronium in a 1:1 complex, rapidly reversing neuromuscular blockade at any depth; dose-dependent: 2/4/16 mg/kg for routine/deep/emergency reversal.

A drug that mimics or enhances the effects of sympathetic nervous system activation, either by direct receptor agonism or by promoting catecholamine release.

Rapid diminution of drug response with repeated administration, seen with indirect-acting sympathomimetics (e.g. ephedrine) due to depletion of the neuronal noradrenaline store.

A central α2 agonist acting at spinal cord interneurons to reduce excitatory amino acid release; used for spasticity management; adverse effects include sedation, hepatotoxicity, and hypotension.

A pattern of four electrical nerve stimuli at 2 Hz used to monitor neuromuscular blockade depth; the count of twitches (0–4) and the fade ratio guide NMBD reversal; TOF ratio ≥0.9 indicates adequate recovery.

The phenomenon by which LAs block Na⁺ channels more effectively in frequently firing neurons; high-frequency pain fibres (C, Aδ) are blocked preferentially over low-frequency motor fibres at the same LA concentration.