PSA Drug Interactions 5

Question 1

A patient on simvastatin drinks large amounts of grapefruit juice daily and develops muscle pain. What is the mechanism?

Accepted Answer

Furanocoumarins in grapefruit irreversibly inhibit intestinal CYP3A4 and reduce P-glycoprotein efflux, markedly increasing simvastatin bioavailability

Answer

Furanocoumarins (e.g., bergamottin) in grapefruit irreversibly inhibit gut-wall CYP3A4, substantially increasing the oral bioavailability of CYP3A4-metabolized statins and raising myopathy risk.

Question 2

A chronic heavy alcohol user takes regular doses of acetaminophen (paracetamol) for pain. What interaction increases hepatotoxicity risk?

Accepted Answer

Alcohol induces CYP2E1, increasing production of the hepatotoxic NAPQI metabolite beyond glutathione's neutralizing capacity

Answer

Chronic alcohol use induces CYP2E1, accelerating conversion of acetaminophen to NAPQI; this toxic metabolite depletes glutathione stores and causes hepatocellular necrosis even at therapeutic doses.

Question 3

A patient on warfarin substantially increases their intake of green leafy vegetables (kale, spinach). The INR unexpectedly falls. What is the mechanism?

Accepted Answer

Pharmacodynamic antagonism: increased dietary vitamin K provides more substrate for vitamin K epoxide reductase, restoring clotting factor synthesis

Answer

Warfarin blocks vitamin K epoxide reductase; increased dietary vitamin K overcomes this blockade by providing more substrate, driving clotting factor gamma-carboxylation and reducing the INR.

Question 4

Valproate is added to a patient's existing lamotrigine regimen for epilepsy. The lamotrigine dose must be halved because:

Accepted Answer

Valproate inhibits UGT1A4-mediated glucuronidation of lamotrigine, approximately doubling its half-life and plasma levels

Answer

Valproate is a potent inhibitor of UGT1A4, the enzyme responsible for lamotrigine's primary glucuronidation pathway, reducing lamotrigine clearance by approximately 50% and requiring dose adjustment.

Question 5

A renally impaired patient on digoxin starts verapamil for rate control. The digoxin level rises to a toxic concentration. What is the primary mechanism?

Accepted Answer

Verapamil inhibits P-glycoprotein-mediated renal and biliary excretion of digoxin, reducing its elimination

Answer

Verapamil inhibits P-glycoprotein in the renal tubule and biliary epithelium, the primary secretory pathways for digoxin; renal impairment compounds this by independently reducing filtration-based elimination.

(PSA) Prescribing Safety Assessment Practice Test

(PSA) Prescribing Safety Assessment Practice Test

PSA Drug Interactions 5