Antimicrobial Drugs

Key Focus Areas

  • Pharmacological properties of drugs

  • Mechanisms of action

  • Side effects

Antimicrobial Drugs

  • Describe properties and actions of main classes:   - Anti-folates   - Cell wall synthesis inhibitors   - Protein synthesis inhibitors   - DNA synthesis inhibitors

Inhibitors of Folate Synthesis

  • Examples: sulfanilamide, trimethoprim

  • Folate vital for DNA synthesis; bacteria synthesize it while humans do not.

  • Selective toxicity due to uptake differences.

  • Notable antibiotic: Prontosil (metabolizes to sulfanilamide).

Key Enzymes in Folate Synthesis

  • Dihydropteroate synthetase: Bacterial enzyme crucial for folic acid synthesis.

  • Dihydrofolate reductase: More sensitive in bacteria than in humans; inhibited by trimethoprim.

Cell Wall Synthesis Inhibitors

  • Beta-lactams: e.g. penicillins, amoxicillin   - Mechanism: Inhibit transpeptidase, leading to cell lysis.   - Side effects: Hypersensitivity, risk of anaphylaxis.   - Resistance issues: Caused by beta-lactamase enzymes; countered with beta-lactamase inhibitors (e.g., clavulanic acid).

  • Glycopeptides: e.g. vancomycin   - Mechanism: Binds to specific cell wall precursors, inhibits synthesis   - Side effects: Autotoxicity, nephrotoxicity.

Protein Synthesis Inhibitors

  • Ribosomal Differences: Bacterial (30s, 50s) vs Mammalian (40s, 60s) allow selective toxicity.

  • Classes of inhibitors:   - Tetracyclines (e.g. doxycycline): reversible binding to the 30s subunit. Side effects include discoloration of teeth.   - Aminoglycosides (e.g. streptomycin): bind irreversibly to the 30s subunit.   - Macrolides (e.g. erythromycin): bind to 50s subunit.   - Chloramphenicol: severe side effects; inhibits mitochondrial protein synthesis.   - Lincosamides (e.g. clindamycin): effect varies with dose.   - Oxazolidinones (e.g. linezolid): interferes with ribosomal assembly.

Inhibitors of DNA Synthesis

  • Fluoroquinolones (e.g. ciprofloxacin): inhibit DNA gyrase, have bactericidal activity.

  • Nitroimidazoles (e.g. metronidazole): binds and inhibits DNA synthesis in anaerobic bacteria.

Antibiotic Resistance Mechanisms

  • Enzymatic inactivation (e.g. beta-lactamases)

  • Altered pathways and binding sites

  • Decreased drug uptake

Summary of Key Antibiotics

  • Linezolid, ciprofloxacin, co-trimoxazole, amoxicillin, penicillin, cefotaxime, clavulanic acid, vancomycin, tetracycline, streptomycin, chloramphenicol, erythromycin, sulfanilamide, metronidazole