Antimicrobial Drugs Chemotherapy: The use of drugs to treat a disease

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Presentation transcript:

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

Microbial Sources of Antibiotics

Antibiotic Spectrum of Activity

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

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}

Mechanisms of Antimicrobial Action 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

The Action of Antimicrobial Drugs Bactericidal Kill microbes directly Bacteriostatic Prevent microbes from growing

The Action of Antimicrobial Drugs

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

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.

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

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.

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

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

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

Competitive Inhibitors Sulfonamides (sulfa drugs) Inhibit folic acid synthesis Broad spectrum

Competitive Inhibitors

Sulfonamides’ Side Effects Rash Nausea Drug fever Vomiting Jaundice Blood complications Kidney damage

Criteria for the evaluation of quality of antimicrobial drug use

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.