North American Pharmacist Licensure Examination (NAPLEX) Drug Safety: Interactions, Adverse Effects, and Toxicology Flashcards

24 sample cards from the Drug Safety: Interactions, Adverse Effects, and Toxicology deck

Sampled from the end of the deck, so these are different cards from the ones shown on the syllabus page.

1. What is the toxic dose threshold and toxic metabolite of acetaminophen overdose?

   Hepatotoxicity risk with acute ingestion $\geq 150\ \text{mg/kg}$ or $\geq 7.5\ \text{g}$ in adults. The toxic metabolite is NAPQI (N-acetyl-p-benzoquinone imine), formed via CYP2E1, which depletes glutathione and causes centrilobular hepatic necrosis.

2. What is the antidote for acetaminophen overdose and how does it work?

   N-acetylcysteine (NAC). It replenishes hepatic glutathione and serves as a glutathione substitute to detoxify NAPQI. Most effective within 8-10 hours of ingestion; dosing guided by the Rumack-Matthew nomogram.

3. What tool guides treatment decisions in acute single-ingestion acetaminophen overdose?

   The Rumack-Matthew nomogram, which plots serum acetaminophen concentration against time since ingestion (4-24 h) to determine the need for NAC therapy. Not valid for chronic ingestion or unknown timing.

4. Describe the acid-base and clinical picture of salicylate (aspirin) toxicity.

   Classic mixed disorder: early respiratory alkalosis (direct respiratory center stimulation) followed by a high anion-gap metabolic acidosis. Symptoms include tinnitus, hyperthermia, tachypnea, and altered mental status.

5. How is salicylate toxicity managed, including the role of urinary alkalinization?

   Sodium bicarbonate to alkalinize urine (target urine pH $\approx 7.5$-$8$) traps ionized salicylate, enhancing renal elimination; also correct hypokalemia. Hemodialysis for severe toxicity (levels $> 100\ \text{mg/dL}$ acute, severe acidosis, CNS changes, renal failure).

6. What is the reversal agent for opioid overdose and its mechanism?

   Naloxone, a competitive mu-opioid receptor antagonist. It rapidly reverses respiratory depression; short half-life may require repeat dosing or infusion because many opioids outlast a single dose.

7. What is the reversal agent for benzodiazepine overdose, and what is the key caution?

   Flumazenil, a competitive GABA-A benzodiazepine antagonist. Caution: can precipitate seizures in benzodiazepine-dependent patients or those with co-ingested proconvulsants (e.g., TCAs); use is limited.

8. What is the reversal agent for warfarin, and what adjuncts are used for major bleeding?

   Vitamin K (phytonadione) reverses warfarin by restoring synthesis of factors II, VII, IX, X. For major/life-threatening bleeding, add 4-factor prothrombin complex concentrate (4F-PCC) for rapid reversal; FFP is an alternative.

9. What is the specific reversal agent for dabigatran?

   Idarucizumab, a monoclonal antibody fragment that binds dabigatran and its metabolites with high affinity, providing rapid reversal of its direct thrombin inhibition.

10. What is the reversal agent for factor Xa inhibitors (apixaban, rivaroxaban)?

    Andexanet alfa, a recombinant modified factor Xa decoy that binds and sequesters Xa inhibitors. 4F-PCC is an off-label alternative when andexanet is unavailable.

11. What is the reversal agent for heparin (and partially for LMWH)?

    Protamine sulfate, which binds and neutralizes heparin. It reverses unfractionated heparin completely and low-molecular-weight heparin only partially (~60%).

12. What is the antidote for digoxin toxicity?

    Digoxin immune Fab (DigiFab), which binds digoxin to form an inactive complex cleared renally. Indicated for severe toxicity: life-threatening arrhythmias, $K^{+} > 5\ \text{mEq/L}$ in acute toxicity, or large ingestions.

13. Match the antidote: organophosphate/cholinergic poisoning.

    Atropine (reverses muscarinic effects) plus pralidoxime (2-PAM, reactivates acetylcholinesterase before aging). Treats the cholinergic toxidrome (SLUDGE/DUMBELS symptoms).

14. Match the antidote: methanol or ethylene glycol poisoning.

    Fomepizole (preferred) or ethanol, which inhibit alcohol dehydrogenase to block formation of toxic metabolites (formic acid; oxalic acid). Adjuncts include sodium bicarbonate and hemodialysis.

15. Match the antidote: iron overdose; and cyanide poisoning.

    Iron overdose: deferoxamine (chelator). Cyanide poisoning: hydroxocobalamin (preferred) or the cyanide antidote kit (sodium nitrite + sodium thiosulfate).

16. Match the antidote: beta-blocker and calcium channel blocker overdose.

    Beta-blocker overdose: glucagon (bypasses beta-receptor to raise cAMP). Calcium channel blocker overdose: IV calcium, high-dose insulin euglycemic therapy, and vasopressors; glucagon may also help.

17. Match the antidote: methotrexate toxicity; and isoniazid-induced seizures.

    Methotrexate toxicity: leucovorin (folinic acid) rescue. Isoniazid overdose/seizures: pyridoxine (vitamin $B_6$), which replenishes GABA synthesis cofactor.

18. What is the role of activated charcoal in decontamination, and its key contraindication?

    Activated charcoal adsorbs many ingested toxins in the GI tract; most effective within 1 hour of ingestion. Contraindicated with unprotected airway/altered mental status (aspiration risk) and ineffective for metals (iron, lithium), alcohols, and hydrocarbons.

19. What general supportive measures form the foundation of poisoning management?

    ABCs (airway, breathing, circulation), IV fluids, oxygen, correction of electrolytes/glucose, and continuous monitoring. 'Treat the patient, not the poison' - supportive care is the backbone even when an antidote exists.

20. Which medications are absolutely contraindicated in pregnancy due to teratogenicity?

    Isotretinoin, thalidomide, warfarin (especially 1st trimester), ACE inhibitors/ARBs (2nd-3rd trimester), methotrexate, valproate, and live vaccines. These are well-known human teratogens.

21. What replaced the old FDA pregnancy letter categories (A, B, C, D, X)?

    The Pregnancy and Lactation Labeling Rule (PLLR, 2015) replaced letter categories with narrative subsections: Pregnancy, Lactation, and Females and Males of Reproductive Potential, providing risk summaries and clinical considerations.

22. Why must pediatric drug dosing typically be weight-based, and what calculation is common?

    Children have differing pharmacokinetics (organ immaturity, body composition); doses are individualized by weight or BSA. Common form: $\text{Dose} = \text{mg/kg/day} \times \text{weight (kg)}$, divided into appropriate intervals, not exceeding the adult maximum.

23. Name two drugs with classic pediatric-specific toxicity warnings.

    Aspirin (Reye syndrome in children with viral illness) and tetracyclines (tooth discoloration/enamel hypoplasia, avoided under age 8). Chloramphenicol can cause gray baby syndrome in neonates.

24. What is the Beers Criteria, and give two examples of potentially inappropriate medications in geriatric patients.

    The AGS Beers Criteria list potentially inappropriate medications in adults $\geq 65$ due to elevated risk. Examples: first-generation antihistamines (diphenhydramine - anticholinergic), benzodiazepines (falls/cognitive impairment), and long-term NSAIDs (GI bleed). Geriatric pharmacotherapy favors lower doses ('start low, go slow') given reduced renal clearance.

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