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Antibiotics: Classification and Mechanisms

Apr 28, 2025

Pharmacology of Antibiotics: Lecture Notes

Definition and Classification of Antibiotics

  • Antibiotics: Chemical agents that kill or inhibit the growth of microorganisms.
  • Types of Antibiotics:
    • Broad-spectrum: Act against a wide range of microorganisms.
    • Narrow-spectrum: Act against very few types of microorganisms.
    • Bactericidal: Kill bacteria.
    • Bacteriostatic: Stop bacteria from growing.
  • Selection Criteria:
    • Based on clinical manifestation and patient profile.
    • Guided by culture sensitivity results.

Testing and Measurements

  • Kirby-Bauer Method: Guides selection of effective antibiotic.
  • Dilution Test:
    • Minimum Inhibitory Concentration (MIC): Lowest concentration inhibiting bacterial growth.
    • Minimum Bactericidal Concentration (MBC): Lowest concentration killing 99.9% of bacteria.

Mechanisms of Antibiotics

  • Antibiotics are categorized based on their mechanism of action:
    1. Cell Wall Synthesis Inhibitors
    2. Cell Membrane Integrity Disruptors
    3. Nucleic Acid Synthesis Inhibitors
    4. Protein Synthesis Inhibitors
    5. Metabolic Pathway Inhibitors

Cell Wall Synthesis Inhibitors

  • Importance of Cell Wall: Provides protection and shape, preventing lysis due to osmotic pressure.
  • Types of Bacterial Cell Walls:
    • Gram-Negative: Outer membrane, linked by lipoproteins to thin peptidoglycan.
    • Gram-Positive: Many layers of peptidoglycan, no outer membrane.

Peptidoglycan

  • Structure: Glycan chains of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).
  • Biosynthesis: Catalyzed by transpeptidase enzymes (penicillin-binding proteins).
  • Inhibitors:
    • Beta-lactam antibiotics: Penicillins, cephalosporins, carbapenems, monobactams.

Resistance and Solutions

  • Resistance Mechanisms:
    • Beta-lactamases: Break beta-lactam ring.
    • Beta-lactamase Inhibitors: Avibactam, clavulanic acid, sulbactam, tazobactam.
  • Exceptions: Carbapenems and monobactams don't require beta-lactamase inhibitors.

Side Effects

  • Beta-lactams: Nausea, vomiting, diarrhea, and possible allergic reactions.

Additional Cell Wall Synthesis Inhibitors

  • Fosfomycin: Inhibits MurA enzyme.
  • Cycloserine: Inhibits d-alanine racemase and d-alanine:d-alanine ligase.
  • Vancomycin: Inhibits transpeptidation and transglycosylation.
  • Bacitracin: Inhibits bactoprenol regeneration.

Side Effects

  • Fosfomycin: Nausea, dizziness, headache, diarrhea.
  • Cycloserine: Neurological and psychiatric disturbances.
  • Vancomycin: Redman syndrome, nephrotoxicity, ototoxicity.
  • Bacitracin: Rare skin irritation, nephrotoxicity.

Mycobacterial Cell Wall Synthesis Inhibitors

  • Unique Wall Structure: Inner membrane, peptidoglycan, arabinogalactan, mycolic acid.
  • Antibiotics:
    • Isoniazid: Inhibits mycolic acid synthesis.
    • Ethambutol: Inhibits arabinosyl transferase EmbB.

Side Effects

  • Isoniazid: Hepatotoxicity, peripheral neuropathy.
  • Ethambutol: Optic neuritis.

Cell Membrane Integrity Disruptors

  • Daptomycin: Forms complexes with calcium, causes ion leakage.
  • Polymyxins: Disrupt gram-negative bacteria outer membrane.

Side Effects

  • Daptomycin: Skeletal muscle toxicity.
  • Polymyxins: Nephrotoxicity, neurotoxicity.

These notes cover the key elements of the lecture on the pharmacology of antibiotics, focusing on their classification, mechanisms of action, resistance, and side effects. The detailed breakdown of cell wall synthesis inhibitors and cell membrane integrity disruptors highlights the specific actions and challenges related to antibiotic use.

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