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Toxicology Board Review I

Toxicology Board Review I. Ted Melnick, MD November 7, 2007. PEER 7 #16.

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Toxicology Board Review I

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  1. Toxicology Board Review I Ted Melnick, MD November 7, 2007

  2. PEER 7 #16 1. A 15 yo boy is found unresponsive at a party. There is no history of trauma. Vital signs are BP 100/60, HR 40, RR 12, T 36oC. Physical exam is remarkable for absence of gag reflex with some vomit present in his mouth, PERRL and normal-sized, bradycardia, GCS 3. Cardiac monitor reveals narrow-complex sinus brady; FS is normal; there is no response to naloxone. The patient is intubated for airway protection; CT head is normal. Serum EtOH is 20 on arrival. The patient remains comatose for 5 hours but then suddenly awakens, pulls his ETT out, and attempts to leave.

  3. PEER 7 #16 • Which of the following agends induces toxicity that is most consistent with this presentation? • Carisoprodol • Flunitrazepam • GHB • MDMA • Oxycodone, sustained release

  4. PEER 7 #16 • Which of the following agends induces toxicity that is most consistent with this presentation? • Carisoprodol muscle relaxant • Flunitrazepam rohypnol, benzo • GHB • MDMA ecstasy • Oxycodone, sustained release responds to naloxone

  5. GHB • -Hydroxybutyric acid, GABA analog • Anesthetic/cataplexy, Europe • Anabolic, body builders • Euphoria-inducing/sedating, recreational abuse and date rape • Rapid awakening (unlike Rohypnol) • Nystagmus, ataxia, coma, respiratory depression, seizure-like activity, bradycardia, agitation on stimulation, amnesia

  6. PEER 7 #50 2. A 40 yo man passed out while using a gas-powered cement cutter in his garage with the doors closed. His wife called 911; paramedics palced him on oxygen with a NRB mask. On arrival he c/o nausea and mild HA only. A venous blood COHb level of 20% confirms CO poisoning; neuro exam is normal. The hospital’s hyperbaric oxygen chamber is available. What is the rationale for using it to treat this patient?

  7. PEER 7 #50 • To correct the presumed associated metabolic alkalosis more rapidly • To decrease the COHb level more rapidly • To decrease the likelihood of death • To decrease the likelihood of delayed neurologic sequelae • To prevent the development of cardiac dysrhythmias

  8. PEER 7 #50 • To correct the presumed associated metabolic alkalosis more rapidly • To decrease the COHb level more rapidly • To decrease the likelihood of death • To decrease the likelihood of delayed neurologic sequelae • To prevent the development of cardiac dysrhythmias

  9. Carbon Monoxide Poisoning • Most common tox complication in US • Colorless, odorless • Headache, dizziness, nausea, vomiting • CO+Hb bind 200x greater affinity than O2, left shift of O2 dissociation curve • COHb venous as accurate as arterial • Normal 1-2%, Smoker 5-10%, Worrisome 25%

  10. Carbon Monoxide Poisoning • Lipid peroxidation in the brain: suspected mechanism for delayed neuro sequelae • HBO therapy: controversial treatment • No reliable clinical predictor of long term neuro outcome • HBO more rapidly corrects COHb and metabolic acidosis • No evidence that HBO reduces mortality

  11. PEER 7 #86 3. In which of the following situations of known methanol ingestion are both administration of fomepizole (4-methylpyrazole) and performance of hemodialysis most indicated? • pH/Pco2 7.10/10; methanol 0 mg/dL; EtOH 0 mg/dL • pH/Pco2 7.10/10; methanol 10 mg/dL; EtOH 300 mg/dL • pH/Pco2 7.10/10; methanol 30 mg/dL; EtOH 30 mg/dL • pH/Pco2 7.40/40; methanol 50 mg/dL; EtOH 10 mg/dL • pH/Pco2 7.40/40; methanol 200 mg/dL; EtOH 300 mg/dL

  12. PEER 7 #86 3. In which of the following situations of known methanol ingestion are both administration of fomepizole (4-methylpyrazole) and performance of hemodialysis most indicated? • pH/Pco2 7.10/10; methanol 0 mg/dL; EtOH 0 mg/dL • pH/Pco2 7.10/10; methanol 10 mg/dL; EtOH 300 mg/dL • pH/Pco2 7.10/10; methanol 30 mg/dL; EtOH 30 mg/dL • pH/Pco2 7.40/40; methanol 50 mg/dL; EtOH 10 mg/dL • pH/Pco2 7.40/40; methanol 200 mg/dL; EtOH 300 mg/dL

  13. Methanol (solvent in paints, wiper fluid, antifreeze)alcohol dehydrogenase (AD)Formaldehydealcohol dehydrogenaseFormic aciddelayed: acidosisabd pain CNS depression snowstorm vision

  14. Osmolal gap if >10: 2 Na + Gluc/18 + BUN/2.8 + ETOH/3.7 Methanol Ethylene glycol Diuretics (osmotic diuretics like mannitol) Isopropyl alcohol Ethanol

  15. Methanol • EtOH gtt: (goal level 100 mg/dL) competes for metabolism by AD, delaying metabolism of methanol • Fomepizole: inhibits AD, given q12, expensive, less toxic than EtOH • Hemodialysis: mandatory if severe acidosis, ocular toxicity

  16. PEER 7 #107 4. A 65 yo man with a severly depressed level of consciousness is brought to the ED by his grandson, who admits that his grandfather has been making moonshine. Labs reveal glucose of 80, EtOH of 40, and hgb of 8. Wrist drop is found on exam. Which of the following statements regarding the cause of his AMS is correct?

  17. PEER 7 #107 • Adults are generally thought to be at higher risk of CNS toxicity than children • Has a known physiological role at low levels • Is associated with a motor neuropathy more commonly than a sensory one • Most important route of exposure in occupational setting is typically ingestion • Withdrawal from the agent can be life threatening

  18. PEER 7 #107 • Adults are generally thought to be at higher risk of CNS toxicity than children children • Has a known physiological role at low levels no physiological role • Is associated with a motor neuropathy more commonly than a sensory one • Most important route of exposure in occupational setting is typically ingestion inhalation • Withdrawal from the agent can be life threatening EtOH

  19. Lead Toxicity • Moonshine produced with lead-containing radiators causing lead encephalopathy • Rare cause of severe lead toxicity • More typical: Occupational inhalation • Interrupts heme synthesis resulting in anemia • Motor > sensory neuropathy • Children more susceptible due to young BBB • Chelate: DMSA or BAL then EDTA

  20. PEER 7 #121 5. Which of the following statements regarding warfarin is correct? • Cimetidine antagonizes the effect of warfarin • Clarithromycin antagonizes the effect of warfarin • Concerns about the risks of increased thrombogenesis soon after initiation of warfarin therapy are largely theoretical • Warfarin-induced skin necrosis is the most common complication of warfarin treatment • Warfarin-induced skin necrosis typically occurs soon after warfarin therapy is started

  21. Wikipedia Fun Fact • The early 1920s saw the outbreak of a previously unrecognized disease of cattle in the northern United States and Canada. Cattle would die of uncontrollable bleeding from very minor injuries, or sometimes drop dead of internal hemorrhage with no external signs of injury.

  22. PEER 7 #121 5. Which of the following statements regarding warfarin is correct? • Cimetidine antagonizes the effect of warfarin inhibits • Clarithromycin antagonizes the effect of warfarin inhibits • Concerns about the risks of increased thrombogenesis soon after initiation of warfarin therapy are largely theoretical no • Warfarin-induced skin necrosis is the most common complication of warfarin treatment • Warfarin-induced skin necrosis typically occurs soon after warfarin therapy is started

  23. Fun Fact • In 1921, Frank Schofield, a Canadian veterinarian, determined that the cattle were ingesting moldy silage made from sweet clover that functioned as a potent anticoagulant. The identity of the anticoagulant substance in moldy sweet clover remained a mystery until 1940 when Karl Paul Link and his student Harold Campbell, chemists working at the University of Wisconsin, determined that it was the coumarin derivative 4-hydroxycoumarin.

  24. Fun Fact • Over the next few years, numerous similar chemicals were found to have the same anticoagulant properties. Link continued working on developing more potent coumarin-based anticoagulants for use as rodent poisons, resulting in warfarin in 1948. (The name warfarin stems from the acronym WARF, for Wisconsin Alumni Research Foundation + the ending -arin indicating its link with coumarin.) Warfarin was first registered for use as a rodenticide in the US in 1952.

  25. Warfarin • Blocks activation of vitamin K • Vitamin-K dependent factors: pro-clotting II, VII, IX, X; and anti-coagulant protein C and S • Thormbogenic early due to short half-life of protein C and S • Skin necrosis early due to thrombosis of small cutaneous vessels: treat with heparin and vitamin K

  26. PEER 7 #136 6. A 47 yo man with bipolar disorder presents with confusion, tremulousness, and hyperreflexia. Regarding the agent that the patient is most likely poisoned from, which of the following is correct? • Activated charcoal is effective at decreasing the serum half-life • Chronic toxicity is usually the result of renal failure or intravascular volume depletion • CNS symptoms correlate well with serum levels • Diabetes mellitus is a complication of long-term therapy • It is associated with neuroleptic malignant syndrome

  27. PEER 7 #136 6. A 47 yo man with bipolar disorder presents with confusion, tremulousness, and hyperreflexia. Regarding the agent that the patient is most likely poisoned from, which of the following is correct? • Activated charcoal is effective at decreasing the serum half-life kayexalate, HD • Chronic toxicity is usually the result of renal failure or intravascular volume depletion • CNS symptoms correlate well with serum levels no, delayed CNS uptake/elimination • Diabetes mellitus is a complication of long-term therapy insipidus • It is associated with neuroleptic malignant syndrome serotonin syndrome

  28. Lithium • Tremor, confusion, slurred speech, seizure, coma, increase QT arrhythmias, GI complaints • Tremor: Fine=side effect, coarse=toxicity • Narrow therapeutic window • Excreted renally on Na transporter • If Na low, more Li & Na reabsorbed • Therefore, ARF/decreased volume can easily cause chronic toxicity

  29. PEER 7 #153 7. With regard to salicylate poisoning, which of the following is correct? • A negative plain radiograph excludes the presence of enteric-coated or sustained-release aspirin in the GI tract • Ensuring hypoventilation after intubation is critical in management • Reversible sensorineuronal hearing loss correlates with serum salicylate levels • The Done nomogram is essential in guiding therapy • Urinary pH is a determinant of mortality

  30. PEER 7 #153 7. With regard to salicylate poisoning, which of the following is correct? • A negative plain radiograph excludes the presence of enteric-coated or sustained-release aspirin in the GI tract no • Ensuring hypoventilation after intubation is critical in management hyperventilation • Reversible sensorineuronal hearing loss correlates with serum salicylate levels • The Done nomogram is essential in guiding therapy serial levels and clinical picture • Urinary pH is a determinant of mortality no

  31. Salicylates • ASA, Pepto-Bismol, oil of wintergreen • Activated charcoal • Enteric-coated may be seen on Xray • Reversible sensorineuronal hearing loss correlates with levels • Mild: N/V, GI complaints • Moderate: vomiting, hyperventilation, sweating, tinnitus • Severe: fever, neuro dysfunction, renal failure, pulmonary edema, ARDS

  32. Salicylates • Anion-gap acidosis and primary respiratory alkalosis (can have volume contraction metabolic alkalosis as well) • If intubated, maintain hyperventilation or patient will become acidemic which is associated with mortality • Sodium bicarb to alkalinize urine and enhance elimination • HD if clinical deterioration despite supportive care, renal failure, severe acid-base disturbance, AMS, ARDS

  33. PEER 7 #177 8. A 33 yo woman presents 7 hours after ingesting “about 30” Extra-Strength Tylenol tablets. She is asymptomatic. Acetaminophen level testing is ordered, but results will not be available for 2 hours. Which of the following treatment strategies is most appropriate? • Administer activated charcoal • Administer the intial dose of N-AC • Cancel the test, and request psychiatry consultation • Perform gastric lavage, and administer activated charcoal • Take no action pending test results

  34. PEER 7 #177 8. A 33 yo woman presents 7 hours after ingesting “about 30” Extra-Strength Tylenol tablets. She is asymptomatic. Acetaminophen level testing is ordered, but results will not be available for 2 hours. Which of the following treatment strategies is most appropriate? • Administer activated charcoal too late • Administer the intial dose of N-AC • Cancel the test, and request psychiatry consultation ha, ha • Perform gastric lavage, and administer activated charcoal too late • Take no action pending test results lethal dose, NAC 100% effective if <8 hrs

  35. Acetaminophen • GI decontamination has little effect >2 hours post-ingestion • Activated charcoal decreases absorption • Stage I: <24 hrs, asymptomatic, N/V, anorexia, drowsiness • Stage II: 1-2 days, increase in liver enzymes and size, RUQ pain, renal failure • Stage III: 3-4 days, liver failure-preventable if NAC given within 8 hours, death • Stage IV: 5 days, recovery

  36. PEER 7 #192 9. A 30 yo man presents after accidentally spilling household rust remover on his leg. He had no pain initially but has since developed persistent pain. Signs of skin damage are minimal. If the patient is suffering systemic toxicity, which of the following lab abnormalities is expected? • Alkalemia • Hypercalcemia • Hyperkalemia • Hypermagnesemia • Hyponatremia

  37. PEER 7 #192 9. A 30 yo man presents after accidentally spilling household rust remover on his leg. He had no pain initially but has since developed persistent pain. Signs of skin damage are minimal. If the patient is suffering systemic toxicity, which of the following lab abnormalities is expected? • Alkalemia acidosis • Hypercalcemia hypocalcemia • Hyperkalemia • Hypermagnesemia hypomagnesemia • Hyponatremia no effect on Na

  38. Hydroflouric Acid • Rust removers, etching/frosting glass, semiconductors, tanning, cleaning stone/brick • Pain out of proportion to exam: deeply penetrates tissue, local injury may not be obvious/delayed • Systemic toxicity can cause electrolyte abnormalities and dysrhythmias, faster onset • Copious irrigation, calcium gluconate (topical, SC, intradermal, IV, intraarterial)

  39. PEER 7 #204 10. Which of the following metabolic complications is most likely to occur in the setting of both therapeutic use and overdose of valproic acid? • Elevated ammonia • Elevated calcium • Elevated carnitine • Low sodium • Metabolic alkalosis

  40. PEER 7 #204 10. Which of the following metabolic complications is most likely to occur in the setting of both therapeutic use and overdose of valproic acid? • Elevated ammonia • Elevated calcium hypocalcemia • Elevated carnitine low carnitine • Low sodium hypernatremia • Metabolic alkalosis acidosis

  41. Valproic Acid • Blocks ammonia entrance into urea cycle • Elevated ammonia can be seen at therapeutic levels • Cause mental status changes • Valproate can cause hepatitis, but typically elevated ammonia without hepatotoxicity

  42. PEER 7 #217 11. A 28 yo man presents complaining of withdrawal symptoms. He is yawning and sneezing; physical examination reveals mydriasis and piloerection. Which of the following statements regarding this withdrawal syndrome is correct? • Altered level of consciousness is typical • Buprenorphine administration is contraindicated • Clonidine is an effective treatment • Convulsions occasionally occur • Inpateint therapy is required

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