Introduction: Mechanisms of drug-induced toxicity and idiosyncrasy explore how drugs cause harmful effects through predictable dose-dependent pathways and unpredictable immune or genetic reactions. Key concepts include bioactivation to reactive metabolites, oxidative stress, mitochondrial dysfunction, cholestasis, transporter inhibition, hapten formation, the p-i concept, and pharmacogenomics (CYP polymorphisms, HLA alleles). Understanding organ-specific toxicities—hepatotoxicity, nephrotoxicity, cardiotoxicity—and clinical biomarkers (ALT, AST, creatinine, troponin) helps B.Pharm students predict, detect, and manage adverse drug reactions. This topic links molecular mechanisms to clinical outcomes and risk factors such as age, comorbidities, co-medications, and genetics. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What best distinguishes dose-dependent (predictable) toxicity from idiosyncratic toxicity?
- Occurs only in allergic individuals
- Correlates with plasma concentration and dose
- Always immune-mediated
- Has a strong HLA association
Correct Answer: Correlates with plasma concentration and dose
Q2. Bioactivation in drug toxicity refers to which process?
- Conversion of drug to inactive metabolites
- Metabolic activation producing reactive intermediates
- Direct excretion without metabolism
- Binding of drug to plasma proteins only
Correct Answer: Metabolic activation producing reactive intermediates
Q3. Which organ is most commonly affected by drug-induced toxicity due to first-pass metabolism and CYP activity?
- Heart
- Liver
- Bone marrow
- Skin
Correct Answer: Liver
Q4. NAPQI formation from acetaminophen exemplifies which mechanism?
- Immune complex deposition
- Reactive metabolite formation and glutathione depletion
- Ion channel blockade
- Competitive inhibition of renal transporters
Correct Answer: Reactive metabolite formation and glutathione depletion
Q5. Which cellular target is commonly involved in mitochondrial-mediated drug toxicity?
- Ribosomal RNA synthesis
- Electron transport chain complexes
- Plasma membrane phospholipids only
- Extracellular matrix proteins
Correct Answer: Electron transport chain complexes
Q6. The “hapten” hypothesis in immune-mediated drug reactions involves:
- Direct drug activation of T cells without binding
- Drug covalently binding to proteins to form immunogenic complexes
- Drug-induced apoptosis of T cells
- Inhibition of B cell antibody production
Correct Answer: Drug covalently binding to proteins to form immunogenic complexes
Q7. Which HLA allele is famously associated with abacavir hypersensitivity?
- HLA-B*57:01
- HLA-DR4
- HLA-A*02:01
- HLA-B*15:02
Correct Answer: HLA-B*57:01
Q8. The p-i concept refers to:
- Pro-hapten formation followed by immune response
- Pharmacologic interaction of drugs with immune receptors without processing
- Protein-independent drug metabolism
- Predictive in vitro tests for toxicity
Correct Answer: Pharmacologic interaction of drugs with immune receptors without processing
Q9. Inhibition of the bile salt export pump (BSEP) commonly leads to which type of liver injury?
- Steatosis
- Cholestatic liver injury
- Autoimmune hepatitis
- Ischemic hepatopathy
Correct Answer: Cholestatic liver injury
Q10. Which biomarker is most specific for cardiotoxicity from drug-induced myocardial injury?
- ALT
- Troponin
- ALP
- Amylase
Correct Answer: Troponin
Q11. Which genetic factor commonly alters susceptibility to drug-induced toxicity by affecting drug metabolism?
- HLA alleles only
- CYP450 polymorphisms
- Plasma protein levels only
- Membrane lipid composition
Correct Answer: CYP450 polymorphisms
Q12. Which drug is a classic example of causing methemoglobinemia through oxidative metabolites?
- Amoxicillin
- Dapsone
- Ibuprofen
- Warfarin
Correct Answer: Dapsone
Q13. Drug-induced autoimmune-like lupus is most commonly associated with which drugs?
- Hydralazine and procainamide
- Amiodarone and doxorubicin
- Lithium and valproate
- Penicillin and cephalosporins
Correct Answer: Hydralazine and procainamide
Q14. Which mechanism explains chloramphenicol-induced aplastic anemia?
- Direct mitochondrial electron transport stimulation
- Idiosyncratic immune-mediated bone marrow suppression
- Blockade of renal tubular secretion
- Excessive cholestasis
Correct Answer: Idiosyncratic immune-mediated bone marrow suppression
Q15. Which test is used to detect T-cell sensitization to a drug in suspected immune-mediated reactions?
- ALT measurement
- Lymphocyte transformation test (LTT)
- Serum creatinine
- Urine dipstick
Correct Answer: Lymphocyte transformation test (LTT)
Q16. Which factor increases risk of acetaminophen hepatotoxicity?
- Chronic alcohol use inducing CYP2E1
- High dietary protein intake
- Low ambient temperature
- Concomitant vitamin C
Correct Answer: Chronic alcohol use inducing CYP2E1
Q17. Which describes an idiosyncratic adverse drug reaction?
- Predictable and dose-related
- Unpredictable, not clearly dose-related, low incidence
- Always reversible on stopping drug
- Occurs in all patients taking high dose
Correct Answer: Unpredictable, not clearly dose-related, low incidence
Q18. Oxidative stress in drug toxicity primarily results from excess:
- Antioxidant enzyme production
- Reactive oxygen species (ROS)
- Glycogen storage
- Lipase activity
Correct Answer: Reactive oxygen species (ROS)
Q19. Which mechanism best explains statin-induced myopathy in susceptible individuals?
- Immune complex deposition in muscle
- Mitochondrial dysfunction and impairment of muscle energy metabolism
- Direct bacterial infection of muscle
- Renal excretion of creatine kinase
Correct Answer: Mitochondrial dysfunction and impairment of muscle energy metabolism
Q20. A drug that forms a reactive intermediate that binds covalently to hepatic proteins is likely to produce which clinical sign?
- Hypoglycemia only
- Hepatocellular injury with raised ALT/AST
- Persistent cough
- Isolated hyperkalemia
Correct Answer: Hepatocellular injury with raised ALT/AST
Q21. Which phenomenon explains increased toxicity when two drugs compete for the same metabolic enzyme?
- Enhanced conjugation
- Drug–drug interaction causing reduced clearance
- Improved renal excretion
- Protein-bound drug displacement only
Correct Answer: Drug–drug interaction causing reduced clearance
Q22. Which biomarker rise suggests early drug-induced kidney injury?
- ALT
- Serum creatinine
- Troponin
- INR
Correct Answer: Serum creatinine
Q23. Idiosyncratic drug reactions with strong HLA associations are best classified as:
- Metabolic toxicities
- Immune-mediated adverse drug reactions
- Purely pharmacologic side effects
- Environmental toxicities
Correct Answer: Immune-mediated adverse drug reactions
Q24. Which is a mechanism of drug-induced cholestasis?
- Inhibition of hepatic bile salt export transporters
- Excess insulin secretion
- Direct activation of cardiac receptors
- Increased renal filtration
Correct Answer: Inhibition of hepatic bile salt export transporters
Q25. Which assay is commonly used preclinically to assess potential for reactive metabolite formation?
- hERG channel assay
- Glutathione trapping and mass spectrometry
- Blood glucose measurement
- Urine culture
Correct Answer: Glutathione trapping and mass spectrometry
Q26. The “danger hypothesis” in drug immunotoxicity emphasizes:
- Only drug structure determines immune response
- Damage signals from injured cells promote immune activation
- Immune responses are independent of tissue injury
- Drug half-life is the sole determinant
Correct Answer: Damage signals from injured cells promote immune activation
Q27. Which class of drugs is well known for causing QT prolongation and torsades de pointes?
- Beta-lactam antibiotics
- Class III antiarrhythmics and some antipsychotics
- ACE inhibitors
- Proton pump inhibitors
Correct Answer: Class III antiarrhythmics and some antipsychotics
Q28. Which preventative strategy can reduce risk of idiosyncratic hypersensitivity for abacavir?
- Co-administration of acetaminophen
- HLA-B*57:01 genetic screening before therapy
- High dose vitamin supplementation
- Avoiding food with drug
Correct Answer: HLA-B*57:01 genetic screening before therapy
Q29. Sulfonamide-induced severe cutaneous adverse reactions often involve which mechanism?
- Direct cholestasis only
- Reactive metabolite formation and immune activation
- Immediate histamine release only
- Renal tubular secretion stimulation
Correct Answer: Reactive metabolite formation and immune activation
Q30. Which clinical feature increases suspicion for immune-mediated drug reaction rather than simple toxicity?
- Rapid, dose-related onset in all patients
- Fever, eosinophilia and rash accompanying organ injury
- Isolated mild nausea
- Progressive dose-dependent hair loss
Correct Answer: Fever, eosinophilia and rash accompanying organ injury
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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