Which drugs utilize the theory of antimetabolites?

• A. Penicillin and amoxicillin
• B. Sulfa and Trimethoprim, PAS (p-aminosalicylic acid), and 6-mercaptopurine
• C. Acyclovir and ganciclovir
• D. Ciprofloxacin and levofloxacin

Answer: (B)

Antimetabolites work by mimicking essential cellular metabolites and blocking key biosynthetic pathways needed for growth, especially nucleotide synthesis. In bacteria, many antimetabolites target folate metabolism, which is crucial for producing nucleotides.

Sulfonamides resemble PABA and competitively inhibit dihydropteroate synthase, preventing the first step of folate production. Trimethoprim acts later in the same pathway by inhibiting dihydrofolate reductase, further blocking the formation of tetrahydrofolate and, consequently, purines and thymidylate. PAS also disrupts folate metabolism in microbes, contributing to its antimetabolite effect. 6-mercaptopurine is a purine analog that interferes with purine nucleotide synthesis and function, integrating into nucleic acids or inhibiting enzymes in the pathway.

Other drugs listed do not act through substrate-like antagonism of metabolic pathways. Penicillins and amoxicillin inhibit bacterial cell wall synthesis. Acyclovir and ganciclovir are antiviral nucleoside analogs that terminate DNA synthesis after activation, not by blocking a metabolic pathway. Ciprofloxacin and levofloxacin inhibit DNA gyrase/topoisomerase to prevent DNA replication, not nucleotide synthesis via folate or purine pathways.