Question 1

Q: A 68-year-old man with atrial fibrillation on warfarin (INR 2.5) presents to the emergency department with severe back pain. He was started on ciprofloxacin 3 days ago for a urinary tract infection. Today his INR is 6.2 and he has no signs of bleeding. Which mechanism best explains this drug interaction?

Ciprofloxacin eliminates vitamin K-producing gut bacteria. ***Ciprofloxacin eliminates vitamin K-producing gut bacteria*** - Fluoroquinolones like **ciprofloxacin** disrupt the **gut microbiome**, reducing the population of bacteria responsible for **vitamin K** synthesis. - A decrease in available vitamin K enhances the anticoagulant response of **warfarin**, leading to a significant increase in the **INR**. *Ciprofloxacin inhibits CYP2C9, decreasing warfarin metabolism* - While some fluoroquinolones are inhibitors, **ciprofloxacin** primarily inhibits **CYP1A2** rather than **CYP2C9**, which is the major enzyme for S-warfarin metabolism. - Other antibiotics like **sulfamethoxazole/trimethoprim** or **metronidazole** are the classic causes of interaction via **CYP2C9 inhibition**. *Ciprofloxacin displaces warfarin from plasma protein binding sites* - Displacement from **albumin** can transiently increase the free fraction of a drug, but it is rarely the primary cause of a sustained, high **INR**. - This mechanism is less clinically significant for fluoroquinolones compared to drugs like **sulfonamides** or **salicylates**. *Ciprofloxacin induces hepatic metabolism of warfarin* - **Induction** of hepatic enzymes would increase the metabolism of warfarin, which would **decrease the INR** and lead to subtherapeutic levels. - Common inducers include **rifampin**, **phenytoin**, and **carbamazepine**, which have the opposite effect of what is seen in this patient. *Ciprofloxacin increases renal excretion of warfarin metabolites* - Increasing the **renal clearance** of drug metabolites would typically decrease the drug's activity or have no impact on the active drug concentration. - Warfarin is heavily metabolized by the **liver** before excretion, so altered renal clearance is not a primary mechanism for **elevated INR**.

Question

A 68-year-old man with atrial fibrillation on warfarin (INR 2.5) presents to the emergency department with severe back pain. He was started on ciprofloxacin 3 days ago for a urinary tract infection. Today his INR is 6.2 and he has no signs of bleeding. Which mechanism best explains this drug interaction?

Accepted Answer

Ciprofloxacin eliminates vitamin K-producing gut bacteria

Answer

Ciprofloxacin inhibits CYP2C9, decreasing warfarin metabolism

Answer

Ciprofloxacin displaces warfarin from plasma protein binding sites

Answer

Ciprofloxacin induces hepatic metabolism of warfarin

Answer

Ciprofloxacin increases renal excretion of warfarin metabolites

Drug interactions and adverse effects — MCQs

Drug interactions and adverse effects — MCQs

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