WBR0633

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pharmacology
Sub Category	SubCategory::Infectious Disease
Prompt	[[Prompt::A 59 year old woman on chronic prednisone therapy for giant cell arteritis is referred to an infectious disease specialist for 3 weeks of fatigue, sore throat, and generalized lymphadenopathy with recent onset blindness in her left eye. The patient is diagnosed with a protozoal illness and the physician decides to initiate therapy. He explains to the patient that the drug he intends to use works by a similar mechanism to a chemotherapeutic agent that causes bone marrow suppression. He reassures the patient that much like the chemotherapeutic agent, if this medication were to affect her, addition of folinic acid to her treatment would correct the bone marrow effects. Which of the following drugs is the physician prescribing to this patient?]]
Answer A	AnswerA::Sodium Stibogluconate
Answer A Explanation	AnswerAExp::Sodium stibogluconate is the treatment of choice for leishmaniasis. It is not associated with myelosuppression. Common side effects are phlebotoxicity and pancreatitis.
Answer B	AnswerB::Suramin/Melarsoprol
Answer B Explanation	[[AnswerBExp::Suramin and melarsoprol are used in the treatment of Trypanosoma brucei the causative agent of African sleeping disease. The combination does not cause myelosuppression. Common side effects include arsenic toxicity since melarsoprol is an organic compound of arsenic.]]
Answer C	AnswerC::Nifurtimox
Answer C Explanation	[[AnswerCExp::Nifurtimox is the treatment of choice for Trypanosoma cruzi the causative agent of Chagas disease. It is not associated with myelosuppresion. A common side effect is anorexia seen in approximately 10% of patients and sometimes leading to discontinuation of therapy.]]
Answer D	AnswerD::Pyrimethamine
Answer D Explanation	AnswerDExp::Pyrimethamine is the treatment of choice combined with sulfadiazine for toxoplasmosis. It causes myelosuppression that can be avoided by administering leucovorin or folinic acid.
Answer E	AnswerE::Methotrexate
Answer E Explanation	AnswerEExp::Methotrexate is a chemotherapeutic agent that inhibits DHFR and causes myelosuppresion salvageable through leucovorin administration. However, methotrexate is not used in the treatment of protozoal infection.
Right Answer	RightAnswer::D
Explanation	[[Explanation::This patient has the classical presentation of acute systemic toxoplasmosis complicated by ocular toxoplasmosis especially in the context of her chronic prednisone therapy. Pyrimethamine is an antiprotozoal agent that acts by a mechanism similar to methotrexate and trimethoprim by inhibiting the enzyme dihydrofolate reductase (DHFR) leading to the inhibition of thymidine synthesis and DNA secondarily. The commmon side effect of this class of medications is the interaction with human DHFR especially in rapidly dividing cells (e.g: bone marrow stem cells) causing pancytopenia, and liver dysfunction. "Leucovorin (folinic acid) rescue" is the term used for the treatment used in patients showing signs of marrow suppression. Leucovorin, an active metabolite of folic acid, is very effective in restoring the synthesis of thymidine by bypassing the required DHFR enzyme. Educational Objective: Pyrimethamine is an antiprotozoal agent that acts by inbibiting dihydrofolate reductase. It can lead to myelosuppresion reversible with Leucovorin or folinic acid. References: Karsenty J, Gorin NC, Valensi P, Mornet M, Najman A, Duhamel G. [Pancytopenia following pyrimethamine treatment of toxoplasmosis]. Nouv Presse Med. 1980;9(36):2658-60. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Pyrimethamine, WBRKeyword::Methotrexate, WBRKeyword::Anti-protozoals, WBRKeyword::Dihydrofolate reductase, WBRKeyword::Leucovorin, WBRKeyword::Folinic Acid
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