U01.05.020 Anticholinesterase poisoning

Anticholinesterases poisoning is most commonly caused by organophosphates (e.g., parathion), which irreversibly inhibit Acetylcholinesterase (AChE), the enzyme responsible for breaking down acetylcholine (ACh). Organophosphates are widely used as insecticides, and poisoning is frequently observed in farmers due to their occupational exposure.

Muscarinic Effects (DUMBBELSS)

Organophosphate poisoning causes an accumulation of acetylcholine at muscarinic receptors, leading to a range of symptoms summarized by the acronym DUMBBELSS:

Diarrhea
Urination
Miosis (pupil constriction)
Bronchospasm
Bradycardia
Emesis
Lacrimation (tearing)
Sweating
Salivation

Nicotinic Effects

The increased acetylcholine also affects nicotinic receptors, leading to neuromuscular blockade, which can resemble the effects of succinylcholine. This manifests as muscle weakness and paralysis.

Central Nervous System (CNS) Effects

CNS symptoms of anticholinesterase poisoning may include:

Respiratory depression
Lethargy
Seizures
Coma

Treatment and Reversal

Atropine: A competitive inhibitor of acetylcholine at muscarinic receptors. It can cross the blood-brain barrier (BBB) and alleviate both muscarinic and CNS symptoms.
Pralidoxime: A reactivator of acetylcholinesterase that works by dephosphorylating the inhibited enzyme. It is effective in reversing nicotinic effects but must be administered early, as it does not readily cross the BBB.

Summary Table: Treatment Approach

Symptom	Treatment	Notes
Muscarinic effects	Atropine	Competitively inhibits acetylcholine, works on both peripheral and CNS symptoms.
Nicotinic effects	Pralidoxime	Must be given early for effectiveness, does not cross BBB.
CNS effects	Atropine (for CNS symptoms) + Pralidoxime (if given early)	Atropine crosses BBB to address respiratory depression and lethargy.

Points to Remember

Organophosphates irreversibly inhibit AChE, leading to the accumulation of acetylcholine at both muscarinic and nicotinic receptors.
Muscarinic symptoms are remembered using DUMBBELSS.
Nicotinic symptoms include neuromuscular blockade.
Atropine is the first-line treatment, especially for muscarinic and CNS symptoms.
Pralidoxime is used for nicotinic effects but must be given early and does not cross the BBB.

Key Takeaways for USMLE Step 1:

Recognize the classic symptoms of organophosphate poisoning and understand the treatment options.
Be able to differentiate between muscarinic and nicotinic effects of acetylcholine buildup.
Understand the mechanisms of action of atropine and Pralidoxime in reversing the symptoms of poisoning.

USMLE Step 1 Review Series

Curriculum