Antimicrobial Drugs Summary

Controlling Microbial Growth in the Body: Antimicrobial Drugs

History of Antimicrobial Agents

  • Drugs/Chemotherapeutic Agents: Affect physiology, act against diseases, treat infections.

  • Key Figures:

    • Paul Ehrlich: "Magic bullets" (Arsenic compounds).

    • Alexander Fleming: Discovered penicillin from Penicillium.

    • Gerhard Domagk: Discovered sulfanilamide.

    • Selman Waksman: Antibiotics from natural sources.

  • Types of Antimicrobial Agents:

    • Semisynthetics: Chemically altered for effectiveness.

    • Synthetics: Completely lab-synthesized.

Mechanisms of Antimicrobial Action

  • Selective Toxicity: Key for effective chemotherapy.

  • Types of Agents:

    • Antibacterial drugs: Largest diversity.

    • Fewer drugs for eukaryotic infections.

    • Limited antiviral drugs.

  • Mechanisms:

    1. Inhibition of Cell Wall Synthesis:

    • Prevents cross-linkage of NAM (N-acetyl muramic acid) subunits.

    • Beta-lactams: Bind to enzymes to inhibit wall synthesis.

    1. Inhibition of Protein Synthesis:

    • Targets prokaryotic ribosomes (70S) vs. eukaryotic (80S).

    1. Disruption of Cytoplasmic Membranes:

    • E.g., Amphotericin B affects fungal membranes.

    1. Inhibition of Metabolic Pathways:

    • Interferes with unique pathogen metabolic processes.

    1. Inhibition of Nucleic Acid Synthesis:

    • Affects DNA replication and RNA transcription.

    1. Prevention of Virus Attachment:

    • New area of drug development.

Clinical Considerations in Prescribing Antimicrobial Drugs

  • Ideal Antimicrobial Agent:

    • Readily available, inexpensive, stable, effective, non-toxic.

  • Spectrum of Action:

    • Narrow-Spectrum: Fewer organisms.

    • Broad-Spectrum: Many organisms; risk of superinfections.

  • Effectiveness Testing:

    • Diffusion susceptibility test.

    • Minimum inhibitory/bactericidal concentration tests.

  • Routes of Administration:

    • Topical, oral, intramuscular, intravenous.

  • Safety and Side Effects:

    • Toxicity; potential adverse reactions; allergies; disruption of normal microbiota.

Resistance to Antimicrobial Drugs

  • Development Mechanisms:

    • Mutations; acquisition of R plasmids.

  • Resistance Mechanisms:

    1. Enzymatic destruction of drugs.

    2. Prevention of drug entry.

    3. Altered drug targets.

    4. Altered metabolic pathways.

    5. Efflux pumps expel drugs.

  • Multiple Resistance: Acquiring resistance to multiple drugs; especially common in healthcare settings.

  • Retarding Resistance:

    • Maintain high drug concentrations; use combinations of antimicrobial agents; develop new drug variations.