Paper I
Question
Classification of antibiotics based on the mechanism of action
Answer
Antibiotics classified by mechanism of action:
-
Inhibitors of cell wall synthesis:
- Beta-lactams — penicillins, cephalosporins, carbapenems, monobactams — inhibit transpeptidase (penicillin-binding proteins), blocking peptidoglycan cross-linking.
- Glycopeptides — vancomycin, teicoplanin — bind D-Ala-D-Ala terminus of peptidoglycan precursors, blocking their incorporation.
-
Inhibitors of protein synthesis (act on the bacterial 70S ribosome, distinct from the mammalian 80S ribosome, giving selective toxicity):
- 30S subunit inhibitors — aminoglycosides (cause misreading of mRNA), tetracyclines (block aminoacyl-tRNA binding).
- 50S subunit inhibitors — macrolides (block translocation), chloramphenicol (inhibits peptidyl transferase), clindamycin, linezolid (inhibits initiation complex formation).
-
Inhibitors of nucleic acid synthesis:
- Fluoroquinolones — inhibit DNA gyrase and topoisomerase IV, blocking DNA replication.
- Rifampicin — inhibits bacterial DNA-dependent RNA polymerase, blocking transcription.
- Metronidazole — forms toxic free radicals within anaerobic organisms, causing DNA strand breakage.
-
Inhibitors of cell membrane function:
- Polymyxins (colistin) — disrupt the integrity of the bacterial cell membrane, acting like a detergent.
- Daptomycin — inserts into the Gram-positive cell membrane, causing depolarization and disruption of membrane function.
-
Inhibitors of metabolic pathways (antimetabolites):
- Sulfonamides — competitively inhibit dihydropteroate synthase, blocking folate synthesis.
- Trimethoprim — inhibits dihydrofolate reductase, blocking a later step of the same folate synthesis pathway (co-trimoxazole exploits this sequential blockade for synergistic effect).
This classification underlies rational antibiotic selection, since agents acting on different targets can sometimes be combined synergistically (e.g., sulfonamide + trimethoprim), and cross-resistance is generally more likely between agents sharing the same mechanism/target.