WBR0156
| Author | PageAuthor::William J Gibson |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pharmacology |
| Sub Category | SubCategory::Musculoskeletal/Rheumatology |
| Prompt | [[Prompt::A 43-year-old woman presents to her primary care physician for increasingly severe joint pain and fatigue over the past three months. She feels significant joint stiffness in the morning, which improves throughout the day. She describes her pain as a persistent, dull pain that “hurts all over”. On physical examination, the physician notes mild joint swelling around the knee and ulnar deviation of the . Laboratory testing reveals a positive ELISA for anti-IgG antibodies. The patient is started on a first-line disease-modifying drug, but three weeks later is found to be critically leukopenic after three weeks. Which of the following medications can be used to specifically reverse the effects of the administered drug?]] |
| Answer A | AnswerA::Infliximab |
| Answer A Explanation | [[AnswerAExp::Incorrect: Infliximab is an antibody directed against TNF-alpha, indicated for use in Rheumatoid arthritis, Crohn’s disease and ankylosing spondylitis. All anti-TNF-alpha agents increase the risk of reactivation TB. While Infliximab can be used to treat Rheumatoid arthritis, it cannot rescue the toxic effects of methotrexate.]] |
| Answer B | AnswerB::Leucovorin |
| Answer B Explanation | [[AnswerBExp::Correct: Leucovorin is equivalent to activated folinic acid. It can be administered to “rescue” the effects of Methotrexate. Methotrexate competitively inhibits folic acid binding to Dihydrofolate reductase, an enzyme responsible for the conversion of dihydrofolic acid to tetrahydrofolic acid. Leucovorin administration bypasses this step in thymidine synthesis and thereby reverses the effect of methotrexate.]] |
| Answer C | AnswerC::Vitamin K |
| Answer C Explanation | AnswerCExp::'''Incorrect:''' Vitamin K is used to reverse the effects of Warfarin. |
| Answer D | AnswerD::Protamine |
| Answer D Explanation | AnswerDExp::'''Incorrect:''' Protamine is used to reverse the effects of heparin. |
| Answer E | AnswerE::Naloxone |
| Answer E Explanation | AnswerEExp::'''Incorrect:''' Naloxone is used to reverse the effects of morphine overdose. |
| Right Answer | RightAnswer::B |
| Explanation | [[Explanation::The patient in this vignette is suffering from rheumatoid arthritis. Rheumatoid arthritis (RA)is more prevalent in females than males. The first-line disease modifying drug for RA is methotrexate. Methotrexate competitively inhibits folic acid binding to Dihydrofolate reductase, an enzyme responsible for the conversion of dihydrofolic acid to tetrahydrofolic acid.
Leucovorin is equivalent to activated folinic acid. It can be administered to “rescue” the effects of Methotrexate. Methotrexate competitively inhibits folic acid binding to Dihydrofolate reductase, an enzyme responsible for the conversion of dihydrofolic acid to tetrahydrofolic acid. Leucovorin administration bypasses this step in thymidine synthesis and thereby reverses the effect of methotrexate. Educational Objective: Leucovorin (folinic acid) can be used to “rescue” methotrexate toxicity.
References: First Aid 2012 Page 399 |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Rheumatoid arthritis, WBRKeyword::RA, WBRKeyword::Methotrexate, WBRKeyword::Chemotherapy, WBRKeyword::Side effect, WBRKeyword::Myelosuppression, WBRKeyword::Leukopenia |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |