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Chapter 6   antimicrobial drugs
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Chapter 6 antimicrobial drugs

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  • 1. Antimicrobial Drugs Chemotherapy: The use of drugs to treat a disease Antimicrobial drugs: Interfere with the growth of microbes within a host Antibiotic: A substance produced by a microbe that, in small amounts, inhibits another microbe Selective toxicity: A drug that kills harmful microbes without damaging the host
  • 2. Microbial Sources of Antibiotics
  • 3. Antibiotic Spectrum of Activity
  • 4. Antimicrobial Drugs:Antibiotic: Substance produced by a microorganism that in small amounts inhibits the growth of another microbe.Antibiotic producing microbes include: Gram-Positive Rods:  Bacillus subtilis: Bacitracin  Bacillus polymyxa: Polymyxin Fungi  Penicillium notatum: Penicillin  Cephalosporium spp.: Cephalothin Actinomycetes:  Streptomyces venezuelae: Chloramphenicol  Streptomyces griseus: Streptomycin  Streptomyces nodosus: Amphotericin B  Micromonospora purpurea: Gentamycin
  • 5. • Antibacterials: Relatively easy to develop and find with low toxicity because procaryotic cells are very different from host cells.• Antihelminthic, antiprotozoan, and antifungal drugs: More difficult to develop because eucaryotic cells resemble human cells.• Antivirals: Most difficult to develop because virus reproduces using host cell enzymes and machinery. Spectrum of Antimicrobial Activity Broad Spectrum: Effective against many different types of bacteria (e.g.: both gram positive and negative). Examples: Tetracyclin  Narrow Spectrum Antibiotics: Effective against a subset of bacteria (either gram positive and negative). Examples: Penicillin, Isoniazid (Mycobacteria only}
  • 6. Mechanisms of AntimicrobialAction Bacteria have their own enzymes for  Cell wall formation  Protein synthesis  DNA replication  RNA synthesis  Synthesis of essential metabolites Viruses use host enzymes inside host cells Fungi and protozoa have own eukaryotic enzymes The more similar the pathogen and host enzymes, the more side effects the antimicrobials will have
  • 7. The Action of Antimicrobial Drugs Bactericidal  Kill microbes directly Bacteriostatic  Prevent microbes from growing
  • 8. The Action of Antimicrobial Drugs
  • 9. Antimicrobial Mechanisms of Action  Inhibition of Cell Wall Synthesis: Interfere with peptidoglycan synthesis.  Result in cell lysis.  Low toxicity.  E.g.: Penicillin and vancomycin. Other antibiotics in the penicillin family (B-lactams): Ampicillin, Methicillin, and Oxacillin
  • 10. Antimicrobial Mechanisms of Action Inhibition of Protein Synthesis: Interfere with procaryotic (70S) ribosomes, also found in mitochondria.  Most have broad spectrum of activity  Tetracyclin, chloramphenicol, erythromycin, and streptomycin.
  • 11. Antimicrobial Mechanisms of Action  Injury to the Plasma Membrane: Cause changes in membrane permeability.  Result in loss of metabolites and/or cell lysis.  Many polypeptide antibiotics.  E.g.: Polymyxin B (antibacterial) or miconazole (antifungal).  Inhibition of Nucleic Acid (DNA/RNA) Synthesis: Interfere with DNA replication and transcription.  May be toxic to human cells.  E.g.: Rifampin and quinolones
  • 12. Antimicrobial Mechanisms of Action  Inhibition of Synthesis of Essential Metabolites: Involve competitive inhibition of key enzymes.  Closely resemble substrate of enzyme.  E.g.: Sulfa drugs inhibit the synthesis of folic acid which is necessary for DNA and RNA synthesis.
  • 13. Inhibitors of Cell Wall Synthesis Antibiotics effective against Mycobacteria: interfere with mycolic acid synthesis or incorporation. This process inhibits the synthesis of mycolic acid which required for themycobactericidalbacterial cell wall. Isoniazid is to rapidly- dividing mycobacteria but is bacteriostatic if the mycobacterium is slow-growing
  • 14. Isoniazid may cause side effects: diarrhea vision problems eye pain numbness or tingling in the hands and feet skin rash fever swollen glands sore throat unusual bleeding or bruising stomach pains or tenderness
  • 15. Sulfonamides AKA “sulfa drugs” Effective against a broad range of microorganisms Block specific step in biosynthetic pathway of folic acid Interfere with PABA and folic acid formation, thereby destroying bacteria
  • 16. Competitive Inhibitors Sulfonamides (sulfa drugs)  Inhibit folic acid synthesis  Broad spectrum
  • 17. Competitive Inhibitors
  • 18. Sulfonamides’ Side Effects Rash Nausea Drug fever Vomiting Jaundice Blood complications Kidney damage
  • 19. Criteria for the evaluation ofquality of antimicrobial drug use
  • 20. Safety Concerns with the Use of Antimicrobials:  Toxicity  Kidney damage  Liver damage  Bone marrow (Chloramphenicol and aplastic anemia)  Interactions with other medications  May neutralize effectiveness of contraceptive pills  Hypersensitivity reactions  Anaphylactic reactions to penicillin  Triple antibiotic ointment (rashes & neomycin B)  Fetal damage/risk to pregnant women  Tetracyclin causes discoloration of teeth in children and may cause liver damage in pregnant women  Fluoroquinolones may cause cartilage damage.  Dysbiosis: Host’s normal beneficial flora killed off, causing various symptoms such as diarrhea, digestive problems (constipation, gas), yeast infections, etc. Probiotics and antifungals can help.  Antibiotic Resistance: Multiple antibiotic resistant is becoming a huge problem. MRSA= Methicillin Resistant Staphylococcus aureus.