Click any card to flip · 16 Step 1 high-yield toxicology concepts0 / 16 seen
LO 2 — APAP Mechanism
At therapeutic doses, ~90% of APAP is cleared as glucuronide/sulfate conjugates. What happens in overdose and what does NAC do?
Answer
In overdose, glucuronidation/sulfation are saturated → shunt to CYP2E1 → toxic metabolite NAPQI depletes hepatic glutathione, binds hepatocyte proteins → centrilobular necrosis. NAC replenishes glutathione and directly conjugates NAPQI. CYP2E1 inducers: chronic alcohol, INH, phenobarb, rifampin.
LO 2 — Rumack-Matthew Nomogram
When is the APAP level drawn, and what is the treatment threshold?
Answer
Level at 4 h post-ingestion (or later if initially later) and plot on Rumack-Matthew nomogram. "Treatment line" = 150 µg/mL at 4 h. Treat above line with NAC. Nomogram doesn't apply to: (1) staggered ingestions, (2) extended-release APAP, (3) unknown ingestion time — in these cases empirically treat.
LO 2 — Salicylate Acid-Base
Describe the classic biphasic acid-base pattern of acute salicylate toxicity.
Answer
Early: respiratory alkalosis (direct stimulation of medullary respiratory center → hyperventilation). Later: anion-gap metabolic acidosis (uncouples oxidative phosphorylation, lactate). Adults → mixed alkalosis + acidosis (normal pH possible); children → pure acidosis. Treat: urine alkalinization with NaHCO₃ (keep urine pH > 7.5); HD for level > 100, AMS, pulm edema.
LO 2 — Toxic Alcohols
Methanol vs ethylene glycol: what metabolites and what organ targets?
What is the formula for the osmolar gap, and which toxins classically raise it?
Answer
Osmolar gap = Measured osm − calculated osm (2·Na + Glu/18 + BUN/2.8 + EtOH/4.6). Normal < 10. Elevated osm-gap → unmeasured solutes: MUD PILES-style mnemonic for alcohols — Methanol, Ethanol, Ethylene glycol, Isopropanol. Classic test: ↑ osm gap + ↑ anion gap + acidosis → methanol/EG. Isopropanol = osm gap + ketosis without acidosis.
LO 2 — Iron Toxicity
What is the mechanism of cellular injury in iron overdose, and what's the antidote?
Answer
Free iron → generates ROS via Fenton reaction → mitochondrial injury, uncouples oxidative phosphorylation → lactic acidosis + hepatic necrosis. Five-phase course: GI (corrosive) → latent → shock/acidosis → hepatic failure → gastric scarring. Iron pills are radiopaque on AXR. Antidote: deferoxamine (chelates free iron → ferrioxamine; urine turns "vin rosé").
LO 2 — Lead Poisoning
How does lead cause microcytic anemia with basophilic stippling, and what are other classic manifestations?
Answer
Lead inhibits δ-ALA dehydratase (ALAD) and ferrochelatase → ↑ δ-ALA, ↑ protoporphyrin IX → sideroblastic anemia + basophilic stippling. Also: cognitive deficits, Burton's lines (gingival), wrist/foot drop, colicky abdominal pain, interstitial nephritis, "lead lines" on long bones. Chelation: succimer (PO, mild-mod) or Ca-EDTA + BAL (severe, encephalopathy).
LO 2 — Carbon Monoxide
Mechanism, classic pulse ox finding, and indications for hyperbaric oxygen.
Answer
CO binds Hb with 200–250× affinity of O₂ → forms COHb → ↓ O₂ delivery + leftward shift of O₂-Hb curve. Pulse ox is normal (reads COHb ~= oxyHb); co-oximetry is required. All patients → 100% O₂. HBO indications: COHb > 25% (or > 15% if pregnant), LOC/syncope, neuro deficits, ECG ischemia, persistent symptoms. Delayed neuropsychiatric syndrome can occur weeks later.
LO 2 — Cyanide
What does cyanide target at the molecular level, and what are the two antidote approaches?
Answer
CN⁻ binds Fe³⁺ in cytochrome c oxidase (complex IV) → halts ETC → cellular asphyxiation, lactic acidosis. Classic: "bitter almond" breath, cherry-red skin, seizures, narrowed arterial-venous O₂ gap. (1) Hydroxocobalamin (binds CN → cyanocobalamin/B12; urine turns red) — preferred, especially in fire smoke-inhalation. (2) Sodium nitrite (induces methemoglobinemia → metHb binds CN) + sodium thiosulfate (sulfur donor for rhodanese).
LO 2 — Methemoglobinemia
Classic causes, pulse-ox pattern, and treatment (including the G6PD caveat).
Answer
Fe²⁺ → Fe³⁺ can't bind O₂. Causes: dapsone, benzocaine, nitrites (poppers), sulfonamides, local anesthetics. Pulse ox reads ~85% regardless of true saturation; blood is "chocolate brown". ABG shows normal PaO₂ with low SaO₂ = "saturation gap." Treat: methylene blue (converts metHb → Hb via NADPH-dependent reductase). Contraindicated in G6PD deficiency (can precipitate hemolysis) — use ascorbic acid or HBO instead.
LO 8 — TCA Toxicity
Name the classic "3 C's" of TCA overdose and the antidote for the cardiotoxicity.
Answer
3 C's: Coma · Convulsions · Cardiotoxicity. Mechanism: Na-channel blockade (wide QRS, R wave in aVR) + anticholinergic (mydriasis, dry skin, retention) + α-blockade (hypotension) + seizure. Treat: IV sodium bicarbonate for QRS > 100 ms — alkalosis + Na⁺ load displaces TCA from Na channel. Avoid flumazenil, physostigmine, class Ia/Ic antiarrhythmics.
LO 8 — Digoxin Toxicity
What ECG/electrolyte findings are classic for digoxin overdose, and why is HD useless?
Answer
ECG: "scooped" ST depression, any arrhythmia; classic = bidirectional VT, atrial tach with AV block. Electrolytes: hyperkalemia in acute OD (Na/K ATPase blockade); chronic → hypokalemia/hypomagnesemia worsen toxicity. Vd ≈ 7 L/kg (almost entirely tissue-bound) → not dialyzable. Treat with digoxin-specific Fab (DigiFab); treat life-threatening hyperkalemia medically but avoid calcium (classic "stone heart" fear — controversial now).
LO 8 — Organophosphate
Why must pralidoxime (2-PAM) be given early, and what does "aging" mean?
Answer
OPs phosphorylate acetylcholinesterase irreversibly. Over hours, a methoxy group is lost — the enzyme-OP complex "ages" to a permanently inhibited state. 2-PAM reactivates AChE only before aging. Give with atropine: atropine treats muscarinic (secretions, bradycardia — titrate to dry lungs); 2-PAM treats nicotinic (weakness, paralysis → respiratory failure is the killer).
LO 10 — β-Blocker vs CCB
How do β-blocker and CCB overdoses differ clinically, and why does insulin help CCB toxicity?
Answer
Both cause bradycardia + hypotension. Distinguishing features: β-blocker often hypoglycemic, normal mental status; CCB often hyperglycemic (pancreatic β-cell Ca²⁺ channel blockade → ↓ insulin) with AMS. HIET (hyperinsulinemic-euglycemic therapy) — high-dose insulin improves myocardial glucose utilization and inotropy. β-blocker antidote: glucagon (cAMP bypass). Refractory: IV lipid emulsion (lipid "sink").
LO 10 — Isoniazid
What three features characterize INH overdose, and what dose of pyridoxine is used?
Answer
3 C's: Coma · Convulsions (refractory) · high-anion-gap metabolic acidosis (Catacidosis). INH + pyridoxine → inactive hydrazone; depletes B6 → ↓ GABA synthesis → seizures. Also inhibits lactate dehydrogenase. Treat: pyridoxine gram-for-gram of INH (or 5 g empiric IV) — corrects BOTH seizures and acidosis. Benzodiazepines alone are inadequate.
LO 12 — Serotonin vs NMS
How do you distinguish serotonin syndrome from neuroleptic malignant syndrome at the bedside?
Treatment: WBI for radiopaque pills; deferoxamine for serum Fe > 500 µg/dL or systemic toxicity (urine turns "vin rosé").
Six conceptual Step-1 style multiple-choice questions. Select your answer — feedback appears immediately with explanation.
MCQ 1 · LO 2 · APAP
A 19-year-old is brought to the ED 14 hours after ingesting "about 30 extra-strength Tylenol." He feels well and his AST is 32 U/L. Which of the following best explains why he is still at high risk for fulminant hepatic failure?
A.Activated charcoal is now contraindicated
B.NAPQI-induced centrilobular necrosis peaks 72–96 h post-ingestion; early LFTs are nonpredictive
C.He is already past the effective window for any treatment
D.CYP2E1 is upregulated in young adults
E.Glutathione is never depleted in the first 24 h
Answer B. APAP toxicity has a deceptive Phase 1 (0–24 h: nausea only, normal LFTs) before peak hepatotoxicity in Phase 3 (72–96 h). Rumack-Matthew at 4 h (or NAC empirically if > 8 h / unknown time) is mandatory regardless of symptoms. NAC is beneficial even late, especially for fulminant failure.
MCQ 2 · LO 2 · Salicylate
An agitated, hyperventilating 23-year-old has pH 7.48, PaCO₂ 18, HCO₃ 13, anion gap 22, glucose 78. Which of the following best describes the acid-base disturbance?
Answer C. Classic salicylate pattern: respiratory center stimulation (alkalosis) superimposed on uncoupling of oxidative phosphorylation (anion-gap acidosis). pH is slightly alkalemic but both processes coexist. Treat: NaHCO₃ to alkalinize urine (pH > 7.5) for ion trapping; HD if level > 100 mg/dL, AMS, pulmonary edema, renal failure.
MCQ 3 · LO 2 · Toxic Alcohols
A 55-year-old presents with blurred vision and severe metabolic acidosis (pH 7.08, AG 24, osmolar gap 32). Funduscopy shows optic disc hyperemia. The best initial drug therapy is:
A.N-acetylcysteine
B.Fomepizole + folate + hemodialysis
C.Pyridoxine 5 g IV
D.Sodium bicarbonate drip alone
E.Deferoxamine
Answer B. Anion + osmolar gap acidosis with visual changes and optic disc hyperemia = methanol. Fomepizole (preferred over ethanol) blocks alcohol dehydrogenase → prevents formic acid. Add folate (methanol) → accelerates formate clearance. Add HD for severe acidosis, visual symptoms, or methanol > 50 mg/dL. If EG: add pyridoxine + thiamine instead of folate.
MCQ 4 · LO 6 · Decontamination
Which of the following scenarios is the best indication for whole-bowel irrigation rather than activated charcoal?
A.Large benzodiazepine ingestion 45 minutes ago
B.Acetaminophen overdose 30 minutes ago
C.Sustained-release verapamil overdose in a patient who is awake and tolerating fluids
D.Caustic (lye) ingestion
E.Digoxin overdose
Answer C.WBI with polyethylene glycol is ideal for sustained-release / enteric-coated products, metals (iron, lead, lithium), and body packers. Charcoal is preferred for standard pills within 1 h; CCBs are charcoal-bindable but SR formulations escape single-dose charcoal into the distal GI tract. Caustics are an absolute contraindication to both lavage and charcoal.
MCQ 5 · LO 10 · TCA
A 28-year-old is found unresponsive after an amitriptyline overdose. ECG shows QRS 140 ms, R wave in aVR of 4 mm, and hypotension. Which intervention is most appropriate?
A.Flumazenil to reverse presumed benzodiazepine co-ingestion
B.Physostigmine to reverse anticholinergic features
C.IV sodium bicarbonate bolus
D.IV amiodarone for QRS prolongation
E.Hemodialysis
Answer C. TCA cardiotoxicity = Na-channel blockade → wide QRS, R wave in aVR. IV sodium bicarbonate (1–2 mEq/kg) alkalinizes and provides Na⁺ load to overcome blockade. Targets: QRS < 100, pH 7.50–7.55. Avoid flumazenil (seizures), physostigmine (asystole), class Ia/Ic antiarrhythmics. HD ineffective (highly protein bound, large Vd).
MCQ 6 · LO 10 · CO
A pregnant woman at 22 weeks is found confused in her home after a furnace malfunction. SpO₂ on room air is 99%, but COHb on co-oximetry is 18%. Which of the following is the strongest indication for hyperbaric oxygen in this patient?
A.COHb > 10% alone
B.Pregnancy combined with any neuro symptoms or COHb > 15%
C.Normal SpO₂ on room air
D.Cherry-red skin color
E.Serum lactate < 2
Answer B. Fetal Hb binds CO even more avidly than maternal Hb and is eliminated more slowly. HBO indications: COHb > 25% (or > 15% if pregnant), LOC/syncope, neurologic deficits, ECG ischemia, persistent symptoms despite normobaric O₂. SpO₂ is always falsely normal in CO poisoning — don't be reassured.
Five Step 1–style clinical vignettes. Read the full stem, select your answer, and review the explanation.
Vignette 1 · Organophosphate
A 42-year-old farm worker is brought in after spraying his orchard. He has copious oral secretions, bronchospasm, diarrhea, pinpoint pupils, fasciculations in his tongue and thighs, and rising respiratory distress. HR 42, BP 88/54. The most critical first pharmacologic step is:
A.Naloxone 2 mg IV
B.Atropine 2 mg IV, doubled every few minutes until secretions dry
C.IV hydroxocobalamin
D.Activated charcoal via NG tube
E.Pralidoxime as a single agent
Answer B. Classic cholinergic toxidrome (SLUDGE/DUMBELS). Atropine is dosed titrating to dry bronchial secretions (not to HR) — airway patency is the priority. Add 2-PAM to treat the nicotinic paralysis and reverse AChE inhibition before aging. Respiratory failure is the killer.
Vignette 2 · Iron Overdose
A 3-year-old ingested an unknown amount of her mother's prenatal iron tablets 4 hours ago. She has had hematemesis and bloody diarrhea, pH 7.25, anion gap 20, AST 110, serum iron 680 µg/dL. Abdominal radiograph shows multiple radiopaque pills in the stomach. Most appropriate next step?
A.Administer activated charcoal 1 g/kg
B.Whole-bowel irrigation with PEG and IV deferoxamine
C.Induce emesis with ipecac
D.Initiate hemodialysis
E.Succimer PO
Answer B. Iron is not adsorbed by charcoal (metal) — WBI is the decontamination of choice for radiopaque pills in the stomach. Serum Fe > 500 µg/dL or systemic toxicity → IV deferoxamine. Ipecac is obsolete. HD is ineffective for iron. Succimer is a lead chelator.
Vignette 3 · Methemoglobinemia
A 35-year-old man presents with cyanosis and dyspnea after oral/pharyngeal topical anesthesia with benzocaine spray. SpO₂ reads 84% on 100% NRB; blood is chocolate brown. PaO₂ on ABG is 420 mm Hg. He has no known medical history. The best treatment is:
A.IV methylene blue 1–2 mg/kg
B.IV hydroxocobalamin
C.IV sodium thiosulfate
D.IV N-acetylcysteine
E.Fresh frozen plasma
Answer A. Classic methemoglobinemia (benzocaine, dapsone, nitrites). Pulse ox pegged ~85%; "saturation gap" (normal PaO₂, low SaO₂). Methylene blue provides an electron acceptor for NADPH-MetHb reductase. Contraindicated in G6PD deficiency (hemolysis) — use ascorbic acid or HBO instead. Hydroxocobalamin = cyanide.
Vignette 4 · Digoxin Toxicity
A 78-year-old with CKD on digoxin for AFib presents with yellow-green halos in her vision, nausea, and fatigue. ECG shows scooped ST depression, atrial tachycardia with 2:1 AV block. K⁺ 6.2, Mg 1.3, serum digoxin 4.2 ng/mL. Which intervention is most appropriate?
A.IV calcium gluconate for hyperkalemia
B.Digoxin-specific Fab fragments + Mg repletion
C.Emergent hemodialysis
D.IV amiodarone
E.Activated charcoal 50 g PO
Answer B. Digoxin toxicity: yellow halos, any rhythm, hyperkalemia (Na/K ATPase blockade). DigiFab is the antidote; repletes Mg as well. HD ineffective (Vd ~7 L/kg). Historically calcium was avoided in hyperK for fear of "stone heart," but DigiFab is the definitive therapy. MDAC is adjunctive for acute ingestion.
Vignette 5 · Sympathomimetic vs Anticholinergic
A 24-year-old is agitated and hyperthermic (40.1°C), HR 138, BP 180/100, pupils 7 mm. His skin is diaphoretic and bowel sounds are hyperactive. Which toxidrome and agent is most likely?
A.Anticholinergic — diphenhydramine
B.Sympathomimetic — cocaine or methamphetamine
C.Serotonin syndrome — SSRI + tramadol
D.Cholinergic — organophosphate
E.Opioid withdrawal
Answer B. Both anticholinergic and sympathomimetic cause mydriasis, tachycardia, HTN, agitation, and hyperthermia. Discriminator: anticholinergic = dry skin, absent bowel sounds, urinary retention; sympathomimetic = diaphoresis, hyperactive bowel sounds, normal bladder. Serotonin syndrome would feature clonus/hyper-reflexia (lower > upper).
Step-1 classic trap statements. Click True or False for each — explanation appears with the correct answer.
Trap 1 · LO 2 · APAP
Normal LFTs at 12 hours after an acute APAP ingestion safely rule out hepatotoxicity and allow for immediate discharge.
FALSE. Phase 1 (0–24 h) of APAP toxicity has normal LFTs. Hepatotoxicity peaks in Phase 3 (72–96 h). Always obtain a 4-hour post-ingestion APAP level and plot on the Rumack-Matthew nomogram; treat above the 150 µg/mL line with NAC.
Trap 2 · LO 2 · Salicylate
A salicylate-poisoned adult with pH of 7.42 can be safely monitored without further intervention.
FALSE. Adult salicylate toxicity produces a mixed respiratory alkalosis + anion-gap acidosis; pH may be normal despite severe illness. Use salicylate level, clinical findings, and anion gap — not pH — to guide therapy. Indications for HD: level > 100 (acute) / > 60 (chronic), AMS, pulmonary edema, renal failure, refractory acidosis.
Trap 3 · LO 2 · CO
A normal SpO₂ of 98% excludes significant carbon-monoxide poisoning.
FALSE. Standard pulse oximetry cannot distinguish COHb from oxyHb — SpO₂ is always normal in CO poisoning. Diagnosis requires co-oximetry. Treat with 100% O₂; HBO for severe/pregnant/neuro cases.
Trap 4 · LO 10 · Digoxin
A patient with acute digoxin overdose and K⁺ of 7.0 mEq/L should receive IV calcium gluconate as the first intervention.
FALSE. Classic teaching avoids calcium in digoxin toxicity (theoretical "stone heart"). The definitive treatment is digoxin-specific Fab fragments, which also reverses the hyperkalemia by restoring Na/K ATPase. Recent evidence shows calcium may be safe, but Fab is always the answer on the test.
Trap 5 · LO 10 · Benzos + TCA
Flumazenil is appropriate for any patient with unexplained AMS from a presumed benzodiazepine overdose.
FALSE. Flumazenil can precipitate withdrawal seizures in chronic benzo users and unmask TCA seizures in co-ingestion. Reserve for isolated iatrogenic benzo overdose in non-chronic users. For undifferentiated poisoning, support airway and breathing.
Trap 6 · LO 2 · Methanol
Folate is the correct adjunct for ethylene glycol poisoning, while thiamine and pyridoxine are given in methanol poisoning.
FALSE — reversed.Methanol gets folate (accelerates formate → CO₂ + H₂O via 10-formyl-THF). Ethylene glycol gets thiamine + pyridoxine (shunt glyoxylate to nontoxic α-hydroxy-β-ketoadipate and glycine, not oxalate). Mnemonic: methanol - folate; glycol - thiamine/B6.
Trap 7 · LO 10 · Methylene Blue
Methylene blue is the treatment of choice for methemoglobinemia in all patients regardless of G6PD status.
FALSE. Methylene blue's reductive action requires NADPH — patients with G6PD deficiency cannot regenerate NADPH and may develop hemolysis or paradoxical worsening. Alternatives: ascorbic acid, exchange transfusion, HBO.
Trap 8 · LO 12 · SS vs NMS
Lead-pipe rigidity and hyporeflexia favor serotonin syndrome over neuroleptic malignant syndrome.
High-yield Step 1 pearls to drill the night before. Each card highlights a single exam trigger.
BuzzwordVin Rosé Urine
Iron overdose treated with deferoxamine. Urine turns pink-red as ferrioxamine is excreted. Classic test-picture pairing with radiopaque pills on AXR and a pediatric ingestion history.
BuzzwordSnowstorm Vision / Blind After Moonshine
Methanol poisoning. Formic acid → retinal toxicity, optic disc hyperemia, permanent blindness if untreated. Pair with ↑ anion gap + ↑ osmolar gap. Treat: fomepizole + folate + HD.
Normal PaO₂ with low SpO₂ reading (pulse ox stuck near 85%) + chocolate-brown blood = methemoglobinemia. Causes: benzocaine, dapsone, nitrites, primaquine. Treat: methylene blue (check G6PD first).
BuzzwordBitter Almond Breath + Narrow A-V O₂ Gap
Cyanide poisoning — usually after fire smoke inhalation. Cellular asphyxiation with lactic acidosis. Treat: hydroxocobalamin (preferred) or Na-nitrite + Na-thiosulfate. Smoke-inhalation pitfall: co-existing CO poisoning needs 100% O₂.
Testing NoteR wave in aVR
R wave > 3 mm in aVR with QRS > 100 ms = TCA cardiotoxicity. Predictive of seizures & arrhythmia. Give IV NaHCO₃; avoid flumazenil, physostigmine, Ia/Ic antiarrhythmics.
Integrating toxicology into clinical scenarios. Use these to connect isolated facts into full patient stories.
Acute Presentation
Bilious vomiting + AMS + AG acidosis in a young adult
Think toxic alcohols, salicylate, APAP, INH. Order the universal tox quartet (APAP, salicylate, ECG, glucose) plus anion gap, osmolar gap, lactate, VBG. "Unknown poisoning" answers nearly always include empiric NAC (if APAP possible), NaHCO₃ (for TCA/salicylate/wide QRS), and aggressive airway support.
Occupational Emergency
Farm worker with copious secretions + bradycardia
Classic organophosphate exposure. Bystander and provider PPE matter — skin absorption is a route. Atropine to dry secretions (not titrated to HR), 2-PAM within hours (before aging). Expect respiratory failure; have airway ready. Confirm with decreased RBC (or plasma) cholinesterase.
Pediatric Ingestion
Toddler with radiopaque pills + hematemesis
Classic iron pathway. Charcoal useless (metal). WBI until pills clear; IV deferoxamine for serum Fe > 500 or systemic toxicity; intensive support in Phase 3 shock. Monitor for delayed pyloric strictures in Phase 5.