ANTIBIOTICS AND ANTIMICROBIAL DRUGS Antibiotics: Antimicrobial substances produced by _____________________________________. Major Genera 1) Penicillium (fungi) 2) Cephalosporium (fungi) 3) Streptomyces (Actinomycetes) 4) Micromonospora (Actinomycetes) 5) Bacillus (Gram + Bacteria) _______________________________________: Inhibit the growth of bacteria. Bactericidal: Kills bacteria. ________________________________-spectrum: Affect only a select group of microbes. Broad-spectrum: Affect large numbers of bacteria (Gm+ and Gm-) Superinfection: Overgrowth by a resistant organism. Modes of Action 1) Inhibition of Cell Wall Synthesis 2) Inhibition of Protein Synthesis 3) Injury to the Plasma Membrane 4) Inhibition of Nucleic Acid Synthesis 5) Inhibition of the Synthesis of Essential Metabolites Inhibitors of Cell Wall Synthesis Penicillin (6 natural Penicillins: G and V most often used) Limitations of Natural Penicillins · Narrow spectrum of activity · Susceptibility to Penicillinases/______________________________ · Pen G destroyed by gastric fluids Advantage: _______________________________________to human tissue. (Except allergic people ~1-5% of adults) Semisynthetic Penicillins Part mold made and part _____________________________________. Side chains are attached to the natural penicillin molecule. Advantages: 1) Broad spectrum 2) More stable in gastric fluid 3) Resistant to Penicillinase 4) Longer shelf life Cephalosporium Cephalosporins: Molecule similar to Penicillin ( b-lactam ring) Broad spectrum of activity. eg. Cephalothin Polypeptide antibiotics Bacillus subtilis: Produces ___________________________________. Topical application against gram-positives. Streptomyces derived: Vancomycin Glycopeptide Important "last line" against antibiotic resistant S. aureus Antimycobacterium antibiotics Isoniazid (INH) Inhibits mycolic acid synthesis. Ethambutol Inhibits incorporation of mycolic acid. Inhibitors of Protein Synthesis _____________________________________________: Broad spectrum activity. May have serious side effects: damage to auditory nerve and kidneys. e.g. Streptomycin, Neomycin, Gentamicin Streptomyces spp.: Streptomycin: Changes shape of 30S portion of _______________________________causes misreading of mRNA. Tetracycline: Interferes with attachment of ____________________________. Chloramphenicol: Binds to 50S portion and inhibits peptide bond formation. Erythromycin: Macrolide (Large molecule) Binds to 50S portion and prevents translocation (movement) of the ribosome along the mRNA. Streptogramins: Gram-positives. Binds 50S subunit, inhibits translation Synercid: Gram-positives. Binds 50S subunit, inhibits translation Oxazolidinones: Linezolid Gram-positives. Binds 50S subunit, prevents formation of 70S ribosome. ____________________________________________________________________________________________________ Injury to the Plasma Membrane Bacillus polymyxa: Produces _________________________________. Used topically. Effective against ___________________________________. ____________________________________________________________________________________________________ Inhibitors of Nucleic Acid Synthesis Rifampin: Inhibits synthesis of ____________________________. Can penetrate tissues and reach therapeutic levels in cerebrospinal fluid. Used to treat tuberculosis. Quinolones and Fluorquinolones: Synthetic drug (Nilidixic acid) Inhibits DNA gyrase needed for DNA replication. Quinolones: Limited use (UTIs). Fluorquinolones: Norfloxacin and Ciprofloxacin: Broad spectrum, penetrate tissues well. May adversely affect the development of cartilage. ____________________________________________________________________________________________________ Competitive Inhibitors of the Synthesis of Essential Metabolites Sulfonamides/Sulfa drugs: Derived from ______________________________________. Structure similar to PABA Prevents synthesis of ______________________________________ (precursors of proteins, DNA and RNA) Mechanisms of Resistance 1) Ability to destroy the antimicrobial 2) Prevent penetration of the antimicrobial 3) Alteration of target structure 4) Active transport (________________________________ pumps) Control of Resistance 1) Administer effective dose and finish the complete dosage. 2) Avoid using outdated, weakened antibiotics 3) Eliminate indiscriminate use. 4) __________________________________________: Two or more antibiotics given simultaneously. Synergistic e.g. Penicillin and Streptomycin. Avoid antagonistic: e.g. Penicillin and Tetracycline. Combine an antibiotic with a b-lactamase inhibitor: _______________________________________ (Amoxicillin combined with Potassium clavulanate). ____________________________________________________________________________________________________ Antiviral Drugs Nucleoside and Nucleotide Analogs Antiviral Drugs Protease inhibitors: Indinavir: HIV Neuraninidase Inhibitors: Zanamivir: Influenza Prevents release/budding of virus Inhibit uncoating: Amantadine: Influenza nterferons: Viral hepatitis ___________________________________________________________________________________ Antiprotozoan Drugs Chloroquine: Inhibits DNA synthesis: Malaria Metronidazole: Interferes with anaerobic metabolism.: Entamoeba, Trichomonas, Giardia Antihelminthic Drugs Niclosamide: Prevents ATP generation: Tapeworms Pyantel pamoate: Neuromuscular block: Intestinal roundworms Mebendazole Inhibits nutrient absorption: Intestinal roundworms Ivermectin: Paralyzes worm: Intestinal roundworms
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