1. Antimicrobial Drugs

2. Antimicrobial Drugs: Antibiotic: Substance produced by a microorganism that in small amounts inhibits the growth of another microbe. Antibiotic producing microbes include: uGram-Positive Rods: u Bacillus subtilis: Bacitracin u Bacillus polymyxa: Polymyxin uFungi u Penicillium notatum: Penicillin u Cephalosporium spp.: Cephalothin uActinomycetes: u Streptomyces venezuelae: Chloramphenicol u Streptomyces griseus: Streptomycin u Streptomyces nodosus: Amphotericin B u Micromonospora purpurea: Gentamycin

3. Antibacterials: Relatively easy to develop and find with low toxicity because prokaryotic cells are very different from host cells. Antihelminthic, antiprotozoan, and antifungal drugs: More difficult to develop because eukaryotic cells resemble human cells. Antivirals: Most difficult to develop because virus reproduces using host cell enzymes and machinery. u Spectrum of Antimicrobial Activity uBroad Spectrum: Effective against many different types of bacteria (e.g.: both gram positive and negative). Examples: Tetracycline u Narrow Spectrum Antibiotics: Effective against a subset of bacteria (either gram positive and negative). u Examples: Penicillin, Isoniazid (Mycobacteria only}

4. Antimicrobial Mechanisms of Action u Inhibition of Cell Wall Synthesis: Interfere with peptidoglycan synthesis. u Result in cell lysis. u Low toxicity. u E.g.: Penicillin and vancomycin. u Inhibition of Protein Synthesis: Interfere with prokaryotic (70S) ribosomes, also found in mitochondria. u Most have broad spectrum of activity u Tetracycline, chloramphenicol, erythromycin, and streptomycin.

5. Antimicrobial Mechanisms of Action u Injury to the Plasma Membrane: Cause changes in membrane permeability. u Result in loss of metabolites and/or cell lysis. u Many polypeptide antibiotics. u E.g.: Polymyxin B (antibacterial) or miconazole (antifungal). u Inhibition of Nucleic Acid (DNA/RNA) Synthesis: Interfere with DNA replication and transcription. u May be toxic to human cells. u E.g.: Rifampin and quinolones..

6. Antimicrobial Mechanisms of Action u Inhibition of Synthesis of Essential Metabolites: Involve competitive inhibition of key enzymes. u Closely resemble substrate of enzyme. u E.g.: Sulfa drugs inhibit the synthesis of folic acid.

7. Safety Concerns with the Use of Antimicrobials: u Toxicity uKidney damage uLiver damage u Interactions with other medications uMay neutralize effectiveness of contraceptive pills uHypersensitivity reactions uAnaphylactic reactions to penicillin uFetal damage/risk to pregnant women u Tetracycline causes discoloration of teeth in children and may cause liver damage in pregnant women uFluoroquinolones may cause cartilage damage. uAntibiotic Resistance