Pharmacology USMLE Questions: Toxicology Antidotes – Organophosphates, Acetaminophen and Methanol

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Poisonings and their antidotes are reliable points on USMLE Step 1. The exam often asks for the mechanism of the antidote, not just its name. Here are three practice questions. Pick your answer first, then open the explanation.

Question 1: A farmer with pinpoint pupils, drooling and muscle twitching

A 45-year-old farmer is brought to the emergency department 1 hour after spraying his crops. He is sweating and drooling, with tearing, vomiting, diarrhea and wheezing. Pupils are pinpoint, pulse is 48/min, and there are fasciculations in his arms and chest. Atropine is given. Which additional drug can restore the activity of the affected enzyme if given early?

A. Physostigmine
B. Neostigmine
C. Pralidoxime
D. Naloxone
E. Flumazenil

Correct answer: C. Pralidoxime

This is organophosphate poisoning. Organophosphates irreversibly inhibit acetylcholinesterase, causing excess acetylcholine. Muscarinic effects (diarrhea, urination, miosis, bronchorrhea, bradycardia, emesis, lacrimation, salivation) are treated with atropine. Nicotinic effects (fasciculations, weakness, paralysis) are not reversed by atropine. Pralidoxime regenerates acetylcholinesterase if given before the enzyme-inhibitor bond “ages.”

Why the other options are wrong:

  • Physostigmine is a cholinesterase inhibitor; it treats anticholinergic toxicity and would worsen this patient.
  • Neostigmine is also a cholinesterase inhibitor.
  • Naloxone reverses opioids. Opioids cause miosis but not salivation, diarrhea or fasciculations.
  • Flumazenil reverses benzodiazepines.

Question 2: An intentional overdose of a common pain reliever

A 19-year-old woman is brought to the emergency department 6 hours after taking a large number of acetaminophen tablets. She has mild nausea but is otherwise asymptomatic. Her serum acetaminophen level is above the treatment line on the Rumack-Matthew nomogram. The antidote that should be given works mainly by which of the following mechanisms?

A. Inhibiting alcohol dehydrogenase
B. Chelating iron
C. Competitively blocking opioid receptors
D. Alkalinizing the urine
E. Replenishing glutathione

Correct answer: E. Replenishing glutathione

In overdose, acetaminophen overwhelms its normal pathways and more is converted by CYP2E1 to the toxic metabolite NAPQI. Normally, NAPQI is neutralized by glutathione; when glutathione runs out, NAPQI causes centrilobular hepatic necrosis. N-acetylcysteine works mainly by replenishing glutathione. It is most effective when started within 8 hours of ingestion.

Why the other options are wrong:

  • Inhibiting alcohol dehydrogenase is how fomepizole treats methanol and ethylene glycol poisoning.
  • Iron chelation is the action of deferoxamine.
  • Opioid receptor blockade is the action of naloxone.
  • Urine alkalinization with sodium bicarbonate is used for salicylate toxicity.

Question 3: Blurred vision after drinking homemade liquor

A 40-year-old man is brought to the emergency department with headache, vomiting and blurred vision. He says his vision looks like he is “in a snowstorm.” He drank homemade liquor the night before. Laboratory studies show a high anion gap metabolic acidosis and an elevated serum osmolal gap. Which of the following is the most appropriate antidote?

A. N-acetylcysteine
B. Fomepizole
C. Deferoxamine
D. Dimercaprol
E. Pralidoxime

Correct answer: B. Fomepizole

This is methanol poisoning. Methanol is converted by alcohol dehydrogenase to formaldehyde and then formic acid, which causes metabolic acidosis and damage to the optic nerve and retina (blurred, “snowstorm” vision, possibly blindness). Fomepizole inhibits alcohol dehydrogenase and stops formation of the toxic metabolites. Hemodialysis may be needed in severe cases. Fomepizole is also used for ethylene glycol poisoning, which causes kidney injury with calcium oxalate crystals.

Why the other options are wrong:

  • N-acetylcysteine treats acetaminophen overdose.
  • Deferoxamine treats iron poisoning.
  • Dimercaprol treats arsenic, mercury and lead poisoning.
  • Pralidoxime treats organophosphate poisoning.

Key takeaways

  • Organophosphates: atropine for muscarinic effects, pralidoxime to regenerate acetylcholinesterase.
  • Acetaminophen: N-acetylcysteine replenishes glutathione; best within 8 hours.
  • Methanol and ethylene glycol: fomepizole inhibits alcohol dehydrogenase.

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Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.

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