Drug Interactions and Contraindications Flashcards

St John's Wort (Hypericum perforatum) is contraindicated with numerous prescription medications because it:

Answer: Induces CYP3A4 and P-glycoprotein, reducing plasma levels of many drugs

St John's Wort is a potent inducer of CYP3A4, CYP2C9, and P-glycoprotein, significantly reducing plasma concentrations of drugs such as cyclosporin, oral contraceptives, antiretrovirals, and warfarin.

Grapefruit juice increases the bioavailability of certain drugs primarily by:

Answer: Inhibiting intestinal CYP3A4 and OATP1B1, reducing first-pass metabolism and hepatic uptake

Furanocoumarins in grapefruit juice irreversibly inhibit intestinal CYP3A4 and inhibit OATP transporters, reducing first-pass metabolism and increasing bioavailability of susceptible drugs such as simvastatin, felodipine, and cyclosporin.

A patient on metronidazole consumes alcohol and develops flushing, tachycardia, nausea and vomiting. This reaction is best described as:

Answer: Disulfiram-like reaction due to aldehyde dehydrogenase inhibition

Metronidazole inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation when alcohol is ingested, producing the characteristic disulfiram-like reaction.

Aspirin is contraindicated in children under 16 years with viral illnesses because of the risk of:

Answer: Reye's syndrome, a rare but potentially fatal encephalopathy and hepatopathy

Aspirin use in children during viral infections (influenza, varicella) is associated with Reye's syndrome, characterised by acute liver failure and encephalopathy, though the exact mechanism is not fully elucidated.

ACE inhibitors are classified as Category D in pregnancy and should be avoided particularly from the second trimester because they:

Answer: Reduce fetal renal perfusion, causing oligohydramnios, renal tubular dysplasia and fetal death

ACE inhibitors block angiotensin II, which is critical for fetal renal development from the second trimester onward; use leads to oligohydramnios, fetal renal failure, limb contractures, pulmonary hypoplasia and death.

Co-administration of trimethoprim with methotrexate poses a significant risk of:

Answer: Severe bone marrow suppression due to additive antifolate effects

Both methotrexate and trimethoprim inhibit dihydrofolate reductase (DHFR); their combined use produces additive antifolate toxicity, causing severe myelosuppression, megaloblastic anaemia and mucositis.

Enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) reduce the effectiveness of combined oral contraceptives because they:

Answer: Induce hepatic CYP3A4 and CYP2C9, increasing first-pass metabolism of contraceptive steroids

Enzyme-inducing antiepileptics upregulate CYP3A4 and CYP2C9, significantly increasing hepatic metabolism of ethinylestradiol and progestogens, reducing contraceptive plasma levels and risking contraceptive failure.