Learning Objective

By the end of this section, students should be able to recognize the clinical features of anticholinesterase (organophosphate) poisoning, differentiate muscarinic, nicotinic, and CNS effects, and describe the mechanisms of antidotes such as atropine and pralidoxime—high-yield for USMLE Step 1.

Anticholinesterase (Organophosphate) Poisoning

Etiology:

• Often due to organophosphates (e.g., fenthion, parathion, malathion) that irreversibly inhibit acetylcholinesterase (AChE).
• Commonly seen in farmers using these compounds as insecticides.

1. Muscarinic Effects

• Diarrhea
• Urination
• Miosis
• Bronchospasm
• Bradycardia
• Emesis
• Lacrimation
• Sweating
• Salivation

Mnemonic: DUMBBELSS

Treatment:

• Atropine (competitive muscarinic antagonist)
  • Crosses BBB → relieves CNS symptoms

2. Nicotinic Effects

• Neuromuscular blockade (similar to the succinylcholine mechanism)

Treatment: Pralidoxime (2-PAM)

• • Regenerates AChE via dephosphorylation if given early
  • Must be coadministered with atropine to prevent transient worsening of symptoms
  • Does not readily cross the BBB

3. CNS Effects

• Respiratory depression
• Lethargy
• Seizures
• Coma

High-Yield Step 1 Pearls

• Muscarinic = DUMBBELSS
• Nicotinic = muscle weakness/paralysis
• CNS = seizures, coma, respiratory depression
• Atropine = muscarinic symptoms (crosses BBB)
• Pralidoxime = nicotinic symptoms, regenerates AChE (early administration critical)