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Cholinergic Toxicity
Introduction
Cholinergic toxicity is the least frequently encountered of the classic toxidromes in clinical toxicology. Patients typically present with altered level of consciousness, weakness, bradycardia and are ‘wet’ (lacrimation, salivation, bronchorrhoea and sweating).
Mechanism of Toxic Effects
Cholinergic toxicity occurs when there is excess acetylcholine activity in the body. This can occur from decreased breakdown of acetylcholine due to the presence of acetylcholinesterase inhibitors or direct stimulation by acetylcholine receptor agonists.
Cholinergic agents
Acetylcholinesterase Inhibitors (effect both muscarinic and nicotinic system) include:
Organophosphate and carbamate pesticides
Nerve agents
Donepezil
Physostigmine, rivastigmine, neostigmine, pyridostigmine Acetylcholine receptor agonists include:
Nicotine receptor agonists * Nicotine – nicotine containing products, nicotine in plants
Varenicline
Neonicotinoid insecticides
Muscarine receptor agonists * Mushroom species including CKGE_TMP_i Amanita muscaria CKGE_TMP_i , CKGE_TMP_i Clitocybe CKGE_TMP_i and CKGE_TMP_i Inocybe sp CKGE_TMP_i .
Clinical Presentation
CNS effects: Coma, seizures, agitation/delirium Autonomic effects: salivation, lacrimation, sweating, flushing, miosis Neuromuscular effects: Fasciculations, weakness/paralysis Cardiovascular effects: Bradycardia or tachycardia (common early), hyper/hypotension Respiratory effects: Bronchoconstriction, bronchorrhea Gastrointestinal effects: vomiting, diarrhoea
Management
The main priorities in management are treatment of muscarinic effects and airway management. For advice regarding specific agents, see the relevant monograph. Antidote- Atropine: Treat muscarinic effects, particularly bradycardia and pulmonary secretions, early, with atropinisation. Atropine dosage can vary widely based on the causative agent and degree of toxicity. Toxicity secondary to organophosphates or carbamates may require cumulative doses of up to 100mg. Give: atropine 0.6mg (child 0.02 mg/kg up to 0.6mg) intravenously, repeat every 3-5 minutes, doubling the dose on each occasion until end-points achieved. End-points: clear chest without wheeze, HR >80bpm, systolic BP >80. It is common to require an ongoing infusion of 10-20% of the total dose of atropine required to achieve atropinisation of the patient per hour. During titration observe for signs of over atropinisation (confusion, pyrexia, loss of bowel sounds). Intravenous benzodiazepines should be used to manage agitation and seizures. The exact role of pralidoxime is controversial and is discussed in more detail in the organophosphate monograph.