PEBC Drug Interactions and Adverse Drug Reactions — Questions and Answers
Question 1: A patient on warfarin begins taking clarithromycin for a respiratory infection. Which mechanism best explains the increased bleeding risk?
- Clarithromycin displaces warfarin from plasma protein binding sites
- Clarithromycin inhibits CYP3A4 and CYP2C9, reducing warfarin metabolism and increasing its plasma levels (Correct answer)
- Clarithromycin enhances renal excretion of warfarin metabolites
- Clarithromycin directly inhibits vitamin K-dependent clotting factors
Correct answer: Clarithromycin inhibits CYP3A4 and CYP2C9, reducing warfarin metabolism and increasing its plasma levels
Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits CYP2C9, which metabolizes warfarin. Inhibition of these enzymes reduces warfarin clearance, elevating INR and increasing hemorrhage risk. INR should be monitored closely.
Question 2: Which combination represents a potentially life-threatening pharmacodynamic drug interaction requiring strict avoidance?
- Metformin and lisinopril
- Serotonergic antidepressant (SSRI) and tramadol (Correct answer)
- Atorvastatin and amlodipine
- Metoprolol and amlodipine
Correct answer: Serotonergic antidepressant (SSRI) and tramadol
Combining an SSRI with tramadol (which also inhibits serotonin reuptake and is a weak serotonin agonist) can precipitate serotonin syndrome — a potentially fatal drug reaction characterized by hyperthermia, neuromuscular abnormalities, and autonomic instability.
Question 3: A patient taking a monoamine oxidase inhibitor (MAOI) for depression consumes a meal rich in tyramine (e.g., aged cheese, cured meats). What adverse reaction is most likely?
- Severe hypoglycaemia due to impaired glucose metabolism
- Hypertensive crisis due to uninhibited tyramine-induced norepinephrine release (Correct answer)
- Serotonin syndrome due to tyramine's direct serotonergic activity
- QT prolongation due to tyramine interference with cardiac ion channels
Correct answer: Hypertensive crisis due to uninhibited tyramine-induced norepinephrine release
MAOIs inhibit monoamine oxidase in the gut and liver that normally degrades tyramine. When tyramine is absorbed intact, it triggers massive norepinephrine release from sympathetic nerve terminals, causing potentially fatal hypertensive crisis — the classic MAO-tyramine food interaction.
Question 4: Which of the following is a Type A (augmented) adverse drug reaction?
- Anaphylaxis to penicillin in a sensitized patient
- Drug-induced agranulocytosis from carbamazepine
- Bradycardia and hypotension from an excessive dose of metoprolol (Correct answer)
- Stevens-Johnson syndrome from allopurinol
Correct answer: Bradycardia and hypotension from an excessive dose of metoprolol
Type A adverse drug reactions are dose-dependent, predictable extensions of the drug's known pharmacological effect. Bradycardia from beta-blocker overdose is a predictable, dose-related ADR. Types B (bizarre) reactions like anaphylaxis and SJS are idiosyncratic and not related to normal pharmacology.
Question 5: A patient is started on simvastatin 80 mg and also takes gemfibrozil for hypertriglyceridemia. Which serious drug interaction risk should prompt the pharmacist to intervene?
- Increased risk of hyperglycaemia due to combined metabolic effects
- Increased risk of myopathy and rhabdomyolysis due to elevated simvastatin plasma concentrations (Correct answer)
- Decreased efficacy of simvastatin due to gemfibrozil-induced CYP3A4 induction
- Increased risk of hepatotoxicity from combined liver enzyme elevation
Correct answer: Increased risk of myopathy and rhabdomyolysis due to elevated simvastatin plasma concentrations
Gemfibrozil inhibits OATP1B1 and CYP2C8, significantly increasing simvastatin plasma concentrations and dramatically raising the risk of myopathy and rhabdomyolysis. This combination is generally contraindicated; if a fibrate is needed, fenofibrate is preferred over gemfibrozil with statins.
Question 6: The Naranjo Adverse Drug Reaction Probability Scale is used in pharmacy practice for which primary purpose?
- Calculating a patient's risk of future drug allergies based on genetic markers
- Assessing the probability that an observed adverse event is causally related to a specific drug (Correct answer)
- Ranking the severity of drug interactions in clinical databases
- Determining the appropriate dose reduction for renally impaired patients
Correct answer: Assessing the probability that an observed adverse event is causally related to a specific drug
The Naranjo Scale is a standardized questionnaire (10 items) used to estimate the likelihood that an adverse clinical event is caused by a specific drug. It scores responses to generate a probability category: definite, probable, possible, or doubtful — essential for pharmacovigilance and ADR reporting.
PEBC Drug Interactions and Adverse Drug Reactions
A patient on warfarin begins taking clarithromycin for a respiratory infection.
Which mechanism best explains the increased bleeding risk?