Pharmacology, Toxicology and Addiction MedicineTier 1Disease (DEADMAN)

Toxidromes - cholinergic

Description

Muscarinic (SLUDGE): Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis + Bradycardia, Bronchorrhoea/bronchospasm, Miosis
Nicotinic: fasciculations, weakness, tachycardia (can mask bradycardia), HTN, paralysis
Causes: organophosphate/carbamate pesticides, nerve agents, some mushrooms (Inocybe, Clitocybe), physostigmine/donepezil overdose

Epidemiology

Agricultural/occupational exposure (pesticides) - most common context
Deliberate self-poisoning with organophosphates - major cause of poisoning death in agricultural regions globally

Aetiopathogenesis

Acetylcholinesterase inhibition -> ACh accumulation at muscarinic + nicotinic synapses and centrally
- Organophosphates: irreversible phosphorylation, can undergo "ageing" (permanent inactivation) - time-critical to treat
- Carbamates: reversible inhibition, shorter clinical course

Diagnosis

Clinical toxidrome - miosis + secretions + bradycardia + fasciculations
RBC cholinesterase - confirms exposure, does not guide acute management
ECG - bradycardia, QT prolongation

Management

Decontamination first

Remove clothing, wash skin - protect staff from secondary contamination

Antidotes

Atropine - titrate to drying of secretions, not heart rate or pupil size - large, repeated doses often needed, no ceiling dose
Pralidoxime - reactivates acetylcholinesterase before ageing occurs; most effective given early; organophosphate only (carbamate inhibition is already reversible)
Benzodiazepines for seizures

Airway

Intubation may be needed for bronchorrhoea/paralysis
Avoid succinylcholine - metabolised by (the now-inhibited) cholinesterase -> prolonged paralysis

Associations

Intermediate syndrome - proximal muscle weakness/resp failure 24-96h after apparent recovery, before delayed neuropathy
Organophosphate-induced delayed neuropathy (OPIDN) - weeks later, axonal, often irreversible

Natural history & complications

Mortality mainly from resp failure (bronchorrhoea + paralysis)
Acetylcholinesterase recovery: weeks for organophosphates (needs resynthesis unless treated early with pralidoxime) vs hours-days for carbamates

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