Pharm- antibiotics II

  1. indications for tetracyclines
    broad antibacterial spectrum, good for organisms not susceptable to cell-wall synthesis inhibitors

    rickettsia, chlamydia, mycoplasma, borrelia (lyme dz), anthrax, etc
  2. how tetracyclines work
    bind to 30s ribosomal subunit, preventing protein synthesis at ANY phase of the elongation process

    selective toxicity b/c they can't penetrate into mammalian cells
  3. tetracycline side effects
    GI irritation (decreased if milk taken at same time, but milk decreases the action of tetracylines)

    tooth discoloration in children under 8

    hepatic toxicity in pregnant women
  4. mechanism of action of chloramphenicol
    inhibits protein synthesis by binding reversibly to 50s subunit

    peptide bond can't be established

    will not bind to the 80s subunit of mammaliam cells, but will bind to ribosomes derived from mammalian cell mitochondria

    • the use of chloramphenicol should be limited to when there are no other drugs available, and the benefits of the drug far outweigh the risk of potential toxicities
    • - salmonella, rickettsia, bacterial meningitis
  5. chloramphenicol toxicity
    • 1. Gray Syndrome (in neonates)
    • 2. Leukopenia (can inhibit protein synthesis by ribosomes in mitochondria of mammalian cells, including stem cells in the marrow
    • 3. Aplastic anemia
  6. macrolide abx
    erythromycin, clarithromycin, azithromycin, telithromycin, etc

    can be used as a substitute for penicillin in pen-sensitive patients
  7. macrolide mechanism of action
    erythromycin inhibits translocation step in elongation
  8. clindamycin especially good against...
    anaerobes, esp. B. fragilis
  9. common clindamycin side effect
    • ulcerative colitis
    • - pseudo-membranous colitis, fairly common
    • - due to Clostridium difficile
    • - giving with vancomycin prevents this, but the high cost of vanco is prohibitive
  10. all inhibitors of bacterial protein synthesis are bacteriostatic, except for the aminoglycosides, which are bacteriocidal
    very true
  11. major side effects of bacterial protein synthesis inhibitors
    • 1. aminoglycosides (vestibulocochlear impairment)
    • 2. clindamycin (antibiotic-associated colitis)
    • 3. chloramphenicol (aplastic anemia)
  12. fluroquinolones are all derivatives of ...
    niladixic acid
  13. fluroquinolones are all...
  14. fluoroquinolones are contraindicated in...
    pts younger than 18yrs (due to risk of cartilage deterioration)

    pregnant and nursing women

    may cause tendonitis in adult patients
  15. mupirocin
    inhibits bacterial protein synthesis

    used to treat topical (nasal) MRSA infections
  16. synercid
    a streptogramin

    inhibits bacterial protein synthesis by binding to the ribosomal RNA of the 50s subunit (does not bind to eukaryotic rRNA)
  17. linezolid
    for life-threatening vancomycin resistant MRSA infections
  18. daptomycin
    irreversibly binds to bacterial cell membrane

    rapidly depolarizes cell membrane

    destroys ion concentration gradient

    leads to cell death
  19. metronidazole (Flagyl) uses
    active against MO that carry out the phosphoroclastic reaction

    blockage leads to toxic intermediates that interact with DNA, and are bacteriocidal

    selective toxicity since mammalian cells do not carry out the phosphoroclastic reaction
  20. metronidazole precautions
    "disulfiram" reaction with alcohol

    potentiation of warfarin effects via interference with warfarin metabolism

    stop nursing during and for 2 days after use
  21. polymyxins mechanism of action
    destroys selective permeability of cytoplasmic membrane


    have a very low therapeutic index
  22. isoniazid used to tx...
  23. rifampin
    binds to b subunit of bacterial RNA polymerase, but not in eukaryotic cells

    kills resting and intracellular tubercle bacilli

    never used alone due to rapid, single step development of resistance
  24. pyrazinamide
    used to tx TB

    inhibits mycolic acid synthesis
  25. ethambutol
    inhibits mycolic acid synthesis, but via different mechanism than isoniazid

    used as first line drug if TB strains are known to be resistant to isoniazid
  26. treating TB
    always use at least 2 drugs with first line drugs

    2 months isoniazid (or ethambutol) + rifampin + pyrazinamide followed by 4 months isoniazid (or ethambutol) + rifampin


    9 months isoniazid + rifampin
  27. mycobacterium avium complex (MAC)
    disseminated MAC happens in up to 40% of aids patients, often limited to lungs

    if only one drug is used, resistance develops quickly
  28. rifambutin
    rifampin derivative, more effective against MAC than rifampin
  29. clarithromycin and azithromycin
    excellent against many strains of MAC
  30. clofamizine
    initially a leprosy drug, found to be effective against MAC
  31. amphotericin B
    anti fungal

    binds to ergosterol in fungal membranes, leads to cell leaking

    selective toxicity since mammalian cells have cholesterol instead of ergosterol

    must be given IV b/c not absorbed orally
  32. griseofulvin
    inhibits fungal mitosis by binding to microtubules of the mitotic spindle

    deposited in keratin after oral dose (good to treat fungal infection of hair, nails, skin)

  33. ketoconazole
    inhibits fungal ergosterol synthesis by inhibition of sterol 14-a-demethylase

    broad spectrum antifungal

    its derivatives FLUCONAZOLE AND ITRACONAZOLE are better against cryptococcus neoformans (opportunistic in AIDS patients
  34. terbinafine (Lamisil)
    inhibits squalene epoxidase

    esp good for fungal infections of nails
  35. tolnaftate (Tinactin)
    Tx of most cutaneous fungal infections

    inhibits fungal ergosterol synthesis
  36. smallpox
    eradicated, used to be a major problem

    Group 1 in Baltimore classification
  37. poliomyelitis
    leads to paralysis, used to be a major problem
  38. hepatitis
    virus that has been associated with many forms of cancer

    Hep B is Group 7 in Baltimore classification

    Hep C is Group 4 in Baltimore classification
  39. classification of influenza A viruses
    based on hemagglutinin subtype (H1 to H16) and neuraminidase (N1 to N9)

    H1N1, etc
  40. zanamivir and oseltamivir (Tamiflu)
    inhibitors of influenza viral neuraminidase

    this enzyme needed for progeny release from infected cells
  41. ribavirin mechanism of action
    reduces number of guanine nucleotides that can be formed

    inhibits viral RNA capping
  42. ribavirin uses
    aerosol to Tx viral pheumonia and bronchiolitis caused by respiratory syncytial virus (RSV) in kids

    has been used in IV to Tx Lassa virus and Hanta virus
  43. acyclovir
    used to Tx herpes simplex virus

    selective toxicity due to the fact that the mammalian thymidine kinase will not phosphorylate the drug

    Tx genital herpes, herpes zoster, etc
  44. ganciclovir
    used to Tx cytomegalovirus infections

    inhibits viral DNA polymerase

  45. interferon uses
    used to Tx hepatitis infections

    recombinant alpha interferons used clinically

    interfere with viral life cycle at several stages, most importantly is inhibition of viral mRNA translation

    can treat Hep B, Hep C, and HPV
  46. zidovudine
    inhibits viral reverse transcriptase and also causes chain termination

    viral resistance can happen rapidly

    DOC in AIDS treatment

    may prevent the passage of AIDS virus from pregnant mother to fetus
  47. nonnucleoside reverse transcriptase inhibitors
    bind to a site distant from the active site in the p66 subunit of HIV-1 reverse transcriptase

    induces conformational change, thus reducing activity
  48. HAART = highly aggressive antiretroviral therapy
    can often suppress viral load to undetectable levels, but a latent viral reservoir remains that is not susceptable to HAART which can develop resistance to therapy

    relies on combination therapy

    need life-long treatment in most cases
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Pharm- antibiotics II