Antibiotics: Protein synthesis inhibitors

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ehamm
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118958
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Antibiotics: Protein synthesis inhibitors
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2011-11-25 19:55:06
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Antibiotics Protein synthesis inhibitors
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Antibiotics: Protein synthesis inhibitors
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  1. Aminoglycosides: Action/resistance
    • Action: irreversible inhibitors of protein synthesis; bactericidal for gram negative, enter via porin channels, activily transported across cell membrane via O2 dependent mechanism, binds to 30S subunit
    • Resistance: transferase enzymes that inactivate aminoglycosides, changes in porin channels, 30s subunit; enzymes are substrate specific
  2. Aminoglycosides: Pharmacokinetics
    • Absorped poorly from GI tract, require IV admin
    • Do not enter CSF in therapuetic levels
    • Do not enter cells readily
    • Excretion via kidneys, directly proportional to creatine clearance (dosage adjustments in renal failure)
    • Adverse rxn: Nephrotoxicity, ototoxicity (monitor serum levels)
  3. Aminoglycosides: dosing
    • Once daily: Concentration depedent killing; peak concentration/MIC ratio most important predictor of bacterial killing
    • Signigicant Post Antiobiotic Effect
    • Toxicity: Time and concentration dependent; time above threshold especially important
  4. Aminoglycosides: Actions
    • Aerobic gram negative bacteria, staph (in combo), and mycobacteria (combo)
    • Limited to serious infection, including enterobacteriaceae and P. Aeruginosa
  5. Aminoglycosides: Drugs
    • Gentamicin (most commonly used)
    • Tobramycin ( more active against P. Aeruginosa)
    • Streptomycin
  6. Macrolides: Action/resistance
    • Action: bind 50S unit
    • Resistance: reduced permeability, production of esterases, modification of binding site
  7. Macrolides: Drugs
    • Erythromycin: broken down by acid (needs enteric coating), partially excreted by liver
    • Clarithromycin: metabolized in liver
    • Azithromycin: large volume of distribution, low serum level, eliminated slowly
    • Changes in last two improve adsorption, increase half life, increase activity
    • No CSF penetration
  8. Macrolides: Adverse reactions
    • GI adverse effects, elevates serum theophyllin (erythromycin)
    • Elongation of QT interval (erythro, clarithro)
    • Avoid drugs that prolong QT syndrome
  9. Macrolides: Uses
    • Strep, Bordetella, M. Pneumoniae, Legionella, Chlamydia
    • Used predominantly in treatment of respiratory tract infections; mild community acquired pneumonia; pneumococci, M Pneumoniae, C. Pneumonae, and legionella
    • Clarithro, azithro: MAC
    • Clarithro: H Pylori
  10. Lincosamides
    • Clindamycin
    • Binds 50S subunit
    • Oral or IV, metabolized by liver, reduce dose in hepatic failure
    • Higher risk of C Diff
    • Strep, staph, and anaerobic bacteria, protazoa
    • Alternative in beta lactam allergenic people
  11. Tetracyclines
    • Tetracycline, doxycycline, minocyclineBinds 50S subunit
    • Widespread usage created resistance among pneumococcia, GAS, and Staph
    • Decreased absorption when taken orally in conjunction with Ca, Mg, or Al containing products
    • Excreted via kidneys
    • Strong affinity for developing bones/teeth (avoid in kids, pregnant ladies)
    • GI adverse events are commong, photosensitization, and vestibular reactions (monocycline)
    • Chlamydiae, mycoplasmas, spirochetes, acne
  12. Chloramphenicol
    • Used in developing countries
    • High CSF concentrations
    • Gray baby syndrome, irreversible aplastic anemia in 1/30,000
  13. Streptogramins
    • Combo of two different chemical groups, works synergistically
    • Streptogramin B binds 50S subunit
    • excreted via non-renal tissues, long PAE
    • Staph Aureus, Strep P, E. Faecium
    • Gram positive bacteria, VRE
  14. Oxazolidinones
    • Linezolid
    • All gram positive pathogens, including MRSA and VRE
    • Inhibitor of ribosomal protein synthesis, prevent formation of 70S complex
    • 100% oral bioavailability
    • Nonrenal metabolism

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