====== 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 //Amanita muscaria//, //Clitocybe// and //Inocybe sp//. ---- ===== 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. ---- ===== =====