WBR0519

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Gastrointestinal, SubCategory::Hematology
Prompt	[[Prompt::A 62-year-old man with a past medical history significant for bioprosthetic mitral valve replacement presents to the physician’s office for tar-colored stools. The patient is maintained on metoprolol, ramipril, warfarin, and simvastatin. Upon further questioning, the patient explains that he recently recovered from a bacterial pneumonia and is currently continuing his antibiotics regimen. On physical examination, you notice several bruises on the forearms and shins. Work-up reveals an INR of 8 (therapeutic range: 2-3). Which of the following antibiotics is most likely responsible for this patient’s symptoms?]]
Answer A	AnswerA::Levofloxacin
Answer A Explanation	AnswerAExp::Levofloxacin is an inhibitor of the P-450 system, decreasing warfarin elimination and prolonging its half-life. This increases the effect of warfarin and predisposes patients to a higher risk of bleeding.
Answer B	AnswerB::Cephalexin
Answer B Explanation	AnswerBExp::Cephalexin is excreted unchanged in the urine and is not metabolized by the liver. It does not interfere with the P-450 system and does not interact with warfarin.
Answer C	AnswerC::Rifampin
Answer C Explanation	AnswerCExp::Rifampin is an inducer of the P-450 system. As a result, warfarin elimination will increase, predisposing the patient to thrombotic events.
Answer D	AnswerD::Imipenem
Answer D Explanation	AnswerDExp::Imipenem is renally metabolized and cleared. It does not interfere with the P-450 system and does not interact with warfarin.
Answer E	AnswerE::Aztreonam
Answer E Explanation	AnswerEExp::Aztreonam does not interfere with the P-450 system and does not interact with warfarin.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Patients receiving warfarin therapy, such as the case in mechanical valve replacement, must be monitored and dose adjusted to maintain their anticoagulation within a certain therapeutic range. The prothrombin time (PT) or its more standardized counterpart, the international normalized ratio (INR), are used as measures of the extrinsic pathway inhibited by warfarin administration. Patients with bioprosthetic valve replacement require anticoagulation with an INR maintained at 2.0 - 3.0. Those with mechanical valve replacements require a slightly higher range of 2.5 - 3.5. The introduction of new medications must always take into account possible interactions with warfarin. P-450 inhibitors will prevent the elimination of warfarin in the liver and cause prolonged effects and possibly bleeding. On the other hand, P-450 inducers will increase warfarin metabolism and elimination and predispose the patient to thrombotic events. Among the list of antibiotics, ciprofloxacin is an inhibitor of P-450 system. Drugs that inhibit P-450 (and cause more warfarin bleeding effect): Macrolides, amiodarone, isoniazid, cimetidine, ritonavir, ciprofloxacin, ketoconazole, sulfonamides, gemfibrozil, quinidine. Newer oral anticoagulant have been approved in the past decade that do not require monitoring and that have very limited drug interactions. Educational Objective: Levofloxacin is an inhibitor of the P-450 system, decreasing warfarin elimination and prolonging its half-life, predisposing patients to a higher risk of bleeding. References: ]]
Approved	Approved::Yes
Keyword	WBRKeyword::Warfarin, WBRKeyword::Bleeding, WBRKeyword::Bleed, WBRKeyword::Drug interaction, WBRKeyword::P-450, WBRKeyword::P450, WBRKeyword::GI bleeding, WBRKeyword::Black stools, WBRKeyword::Gastrointestinal
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::