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Antimicrobial Drugs Overview

Learning Goals

• Describe the basic mechanism, modes of specific toxicity, and special characteristics of various antimicrobial drugs.

• Distinguish between various types of antimicrobial drugs.

• Understand the “magic bullet” concept and its importance.

• Differentiate between broad and narrow spectrum antibiotics.

• Understand the difference between static and cidal antimicrobial drugs.

• Describe key discoveries in the history of antibiotics.

Antibiotics vs Antimicrobial Drugs

• Antibiotics: Naturally produced agents typically by bacteria or fungi.

• Antimicrobial Drugs: Synthesized chemicals designed to kill or inhibit the growth of microbes.

• Types of antibiotics include:

  • Natural: produced naturally by microorganisms.

  • Synthetic: completely manufactured in a lab.

  • Semi-synthetic: modified natural compounds to enhance effectiveness.

• The term "antibiosis" reflects the antagonistic relationships between organisms.

Penicillin Discovery

• Identified strain: Penicillium chrysogenum from a moldy cantaloupe.

• Goal: mass production of penicillin for medical use.

Antibiotics and Antimicrobial Effectiveness

• Infections: Certain infections can become resistant to antibiotics, example: UTIs resistant to penicillin.

• Testing for Effectiveness: A study tested 7136 molecules in C. elegans to identify 25 with antimicrobial properties (0.35%).

Broad Spectrum vs Narrow Spectrum Antimicrobials

• Broad Spectrum: Effective against a variety of bacteria.

• Narrow Spectrum: Targets specific types of bacteria.

Superinfection

• Definition: Overgrowth of bacteria leading to secondary infections.

• Cause: Disruption of normal microbial community from antibiotic use.

Choosing Antimicrobials

• Consideration when pathogen is unidentified: Pros and cons of using narrow vs broad spectrum antimicrobials.

Pathogen Types

• Bacteria: Prokaryotic cells.

• Fungi, Protozoan, Helminths: Eukaryotic cells.

• Viruses: Reproduce within host cells.

• Ideal antmicrobials should target pathogens without affecting human host cells.

Selective Toxicity and the Magic Bullet Concept

• Origin: Paul Ehrlich's concept of a "magic bullet" implies a drug targeting only pathogens without harm to the host.

• Technical term: Selective toxicity defines this ability.

• Bacteria are easier to target than eukaryotic cells due to structural differences (e.g., cell wall).

Antimicrobial Drug Types

• Antibacterial Drugs (Antibiotics): Target bacteria.

• Antifungal Drugs: Target fungi.

• Antiviral Drugs: Target viruses.

• Antiprotozoan Drugs: Target protozoan parasites.

• Antihelminthic Drugs: Target helminths (worms).

• Static vs. Cidal:

  • Bacteriostatic: Reversibly stops bacterial growth.

  • Bactericidal: Kills bacteria, crucial for severe infections or immunocompromised patients.

Mechanisms of Action of Antimicrobial Drugs

1. Inhibition of Cell Wall Synthesis: e.g., penicillins.

2. Inhibition of Protein Synthesis: e.g., chloramphenicol, tetracyclines.

3. Inhibition of Nucleic Acid Synthesis: e.g., quinolones.

4. Injury to Plasma Membrane: e.g., polymyxin B.

5. Inhibition of Essential Metabolite Synthesis: e.g., sulfanilamide.

Cell Wall Structure in Bacteria

• Key components:

  • Peptidoglycan: Comprised of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM).

• Difference Between G+ and G-: Gram-negative have an outer membrane hindering antibiotic access.

Penicillin Mechanism of Action

• Binds to transpeptidase, disrupting cell wall synthesis by inhibiting cross-linking.

• Primarily affects gram-positive bacteria due to their peptidoglycan structure.

Penicillin Resistance

• Mechanism: Penicillinase (beta-lactamase) breaks the beta-lactam ring.

Semisynthetic Penicillins

• Altered forms of natural penicillins with better efficacy or resistance to beta-lactamase.

• Examples: Methicillin (resistant to beta-lactamase) and Amoxicillin (broader spectrum).

Vancomycin and Other Cell Wall Synthesis Inhibitors

• Vancomycin: Targets peptide chains, used for resistant infections.

• Resistance Issue: Some bacteria modify peptide chains to evade vancomycin.

Ribosome and Protein Synthesis Inhibition

• Mechanisms: Target ribosomes for halting protein synthesis.

• Key antibiotics include:

  • Chloramphenicol: Broad spectrum antibiotic.

  • Doxycycline: Long retention.

  • Streptomycin: Used in tuberculosis treatment.

Antimicrobial Drugs that Target Nucleic Acid Synthesis

• Rifamycins: Target bacterial RNA polymerase to prevent transcription.

• Fluoroquinolones: Inhibit gyrase essential for DNA structure maintenance.

Metabolism Inhibitors

• Sulfonamides & Trimethoprim: Target folic acid synthesis, bacteriostatic when used separately but bactericidal in combination.

Conclusion

• Understanding various types of antimicrobial drugs, their mechanisms, and their implications for treating infections is crucial for effective health care.