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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{SSK}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Pharmacology
|MainCategory=Pharmacology
Line 21: Line 21:
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=Gastrointestinal, Hematology
|SubCategory=Gastrointestinal, Hematology
|Prompt=A 62 year old male patient on immunosuppressive therapy with a past medical history significant for a recent bioprosthetic mitral valve replacement, systolic heart failure, hypertension, and hyperlipidemia, presents to the physician’s office for black-colored stools.  The patient’s medications are metoprolol, ramipril, warfarin, simvastatin, fenofibrate.  He has stopped taking aspirin against medical advice one year ago.  The patient explains that he recently had a bacterial infection and had started antibiotic therapy.   During work-up, INR was measured to be 8 (therapeutic range: 2-3).  Which of the following antibiotics most likely contributed to the patient’s gastrointestinal bleeding symptoms?
|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?
|Explanation=Patients receiving warfarin therapy, such as the case in mechanical valve replacement, must be monitored for possible bleeding at all times using INR.  Introduction of new medications must always take into account the possible interaction with warfarin.  P-450 inhibitors will prevent the elimination of warfarin  in the liver and cause prolonged effects and possible bleeding, On the other hand, P-450 inducers will hasten warfarin elimination and predispose the patient to thrombotic events.
|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.
 
|AnswerA=Levofloxacin
Among the list of antibiotics, ciprofloxacin is an inhibitor of P-450 system.
|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.
Drugs that inhibit P-450 (and cause more warfarin bleeding effect): Macrolides, amiodarone, isoniazid, cimetidine, ritonavir, ciprofloxacin, ketoconazole, sulfonamides, gemfibrozil, quinidine.
|AnswerB=Cephalexin
|AnswerA=Ciprofloxacin
|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.
|AnswerAExp=Ciprofloxacin is an inhibitor of P-450 system, thus causing less warfarin elimination and more systemic effect and possible bleeding.
|AnswerB=Amoxicillin
|AnswerBExp=Amoxicillin is not classically associated with P-450 inhibition.
|AnswerC=Rifampin
|AnswerC=Rifampin
|AnswerCExp=Rifampin is an inducer of the P-450 system.  As a result, warfarin will be eliminated faster; the patient will be predisposed to thrombotic events.
|AnswerCExp=Rifampin is an inducer of the P-450 system.  As a result, warfarin elimination will increase, predisposing the patient to thrombotic events.
|AnswerD=Chloramphenicol
|AnswerD=Imipenem
|AnswerDExp=Chloramphenicol is not classically associated with P-450 inhibition.
|AnswerDExp=Imipenem is renally metabolized and cleared. It does not interfere with the P-450 system and does not interact with warfarin.
|AnswerE=Clindamycin
|AnswerE=Aztreonam
|AnswerEExp=Clindamycin is not classically associated with P-450 inhibition.
|AnswerEExp=Aztreonam does not interfere with the P-450 system and does not interact with warfarin.
|EducationalObjectives=Ciprofloxacin is an inhibitor of P-450 system
|EducationalObjectives=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=First Aid 2014 page 255
|RightAnswer=A
|RightAnswer=A
|WBRKeyword=Ciprofloxacin, Warfarin, Bleeding, Bleed, Drug interaction, P-450, P450, GI bleeding, Black stools, Gastrointestinal
|WBRKeyword=Warfarin, Bleeding, Bleed, Drug interaction, P-450, P450, GI bleeding, Black stools, Gastrointestinal
|Approved=No
|Approved=Yes
}}
}}

Latest revision as of 00:50, 28 October 2020
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::
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