A 21-year-old woman comes to the office due to burning on urination and increased urinary frequency for the past 2 days. She has no hematuria, vaginal discharge, or irritation. The patient has no other medical problems. Her temperature is 37 C (98.6 F). Physical examination reveals mild suprapubic tenderness on deep palpation; there is no costovertebral angle tenderness. Urine dipstick is positive for leukocyte esterase and nitrites. The patient is started on trimethoprim, which leads to rapid resolution of her symptoms. Which of the following drugs has the same intracellular target as the drug used to treat this patient?

Question

A 21-year-old woman comes to the office due to burning on urination and increased urinary frequency for the past 2 days.  She has no hematuria, vaginal discharge, or irritation.  The patient has no other medical problems.  Her temperature is 37 C (98.6 F).  Physical examination reveals mild suprapubic tenderness on deep palpation; there is no costovertebral angle tenderness.  Urine dipstick is positive for leukocyte esterase and nitrites.  The patient is started on trimethoprim, which leads to rapid resolution of her symptoms.  Which of the following drugs has the same intracellular target as the drug used to treat this patient?

Quizplus · Accepted Answer

11ec160b_3bf6_20c8_9249_f36cc4a7561e_MD0001_00 Trimethoprim (in bacteria), methotrexate (in human cells), and pyrimethamine (in some protozoa) all prevent the reduction of folic acid to tetrahydrofolate (THF) by inhibiting dihydrofolate reductase (DHFR). Trimethoprim restricts bacterial growth through this process and works particularly well in conjunction with the sulfonamides (eg, sulfamethoxazole), which inhibit an earlier step in the bacterial folic acid pathway (described below). The combination of trimethoprim and sulfamethoxazole produces a "sequential blockade." Methotrexate is a folate antimetabolite that targets rapidly proliferating human cells by halting DNA synthesis through binding DHFR. Methotrexate is cell-cycle specific for the S phase as it prevents synthesis of purine and thymidylic acid (used for pyrimidine synthesis). Pyrimethamine is effective for treatment of malaria and toxoplasmosis because it inhibits parasitic DHFR. (Choice A) Bacitracin prevents mucopeptide transfer into the growing cell wall, thereby inhibiting bacterial cell wall synthesis. (Choice B) Imipenem binds to penicillin binding proteins, thereby inhibiting the final step of peptidoglycan synthesis in bacterial cell walls. Cilastatin can be used in conjunction with imipenem because it prevents renal metabolism of imipenem by competitively inhibiting dehydropeptidase on the renal tubule brush border. (Choice D) Metronidazole binds to DNA within susceptible cells, unraveling the helical structure of DNA and breaking its strands. Protein synthesis is inhibited and the cell dies soon thereafter. (Choice E) As a structural analog of para-aminobenzoic acid (PABA), sulfamethoxazole competes with PABA to inhibit dihydropteroate synthetase, one of the enzymes needed for dihydrofolic acid synthesis. This is an intermediate step in the formation of THF. Educational objective: Trimethoprim, methotrexate, and pyrimethamine inhibit dihydrofolate reductase. Trimethoprim restricts bacterial growth through this process, and works particularly well in conjunction with sulfonamide, which inhibits an earlier step in the bacterial folic acid pathway.

A 21-Year-Old Woman Comes to the Office Due to Burning