1. Antimicrobial Agents

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1. Antimicrobial Agents
2011-07-26 01:58:41
PH162A midterm2

public health microbiology midterm 2 lecture 1
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  1. chemotherapy
    • treatment of a disease with chemical agents
    • for infectious diseases, therapy with antimicrobial agents
  2. curative treatment
    can cure the disease because it directly affects the causative microorganism
  3. palliative treatment
    only relieves symptoms, does not cure
  4. chemoprophylaxis
    use of antimicrobial agents to prevent infectious diseases
  5. Paul Ehrlich
    • first stated the idea of selective toxicity
    • coined the term chemotherapy and popularized the idea of a magic bullet = compounds that kill the microorganism without harming the host
    • developed salvarsan, first safe and effective treatment of syphilis
  6. selective toxicity
    • ideal chemotherapeutic agent =
    • kills the microorganism
    • little or no harm to host
    • benefit must be weighed against adverse effects - good drug has CI >>1.0
    • Chemotherapeutic Index = (maximum tolerable dose/ kg body weight) / (minimum effective dose/ kg body weight)
  7. antibiotic
    • any substance produced by a microorganism that inhibits the growth of other organisms
    • coined by Selman Waksman
  8. semi-synthetic antibiotic
    an antibiotic that has had its chemical structure altered in the lab
  9. synthetic antibiotic
    wholly synthesized in the lab
  10. spectrum
    • narrow spectrum = acts on one or few species
    • - pencillin, sulfonamides

    • broad spectrum = acts on many species and groups
    • - tetracyclines
  11. -cidal drugs
    kill the organism directly
  12. -static drugs
    • inhibition of growth without killing
    • suppress growth long enough to allow clearance by immune system
  13. routes of administration
    • oral
    • topical
    • suppository
    • intramuscular
    • intravenous
  14. side effects
    • toxicity
    • allergy
    • destruction of endogenous bacteria
  15. specific mechanisms of action
    • anti-metabolites (competitive analogues)
    • bind and block mechanism
    • injure a cell component
    • miscellaneous mechanisms of action
  16. anti-metabolites (competitive analogues)
    • have similar chemical structure to an essential compound
    • substitute for actual compound
    • mess up normal function
  17. sulfa drugs (sulfonamides)
    • mechanism of action - competes with para-aminobenzoic acid in the synthesis of folic acid in bacteria
    • selective toxicity - humans obtain folic acid from diet, do not synthesize
  18. acyclovir
    • mechanism of action - guanine analogue, substitutes during DNA replication, causes early termination
    • selective toxicity - much greater affinity for viral polymerases than human
  19. bind and block mechanism
    • inhibitors of cell wall synthesis, protein synthesis
    • block and bind polymerase
  20. beta-lactams (penicillin family)
    • mechanism of action - interfere with the formation of the peptidoglycan crosslinks in the bacterial cell wall
    • selective toxicity - human cells do not have cell walls
  21. tetracycline family
    macrolides (erythromycin, azithromycin)
    bind to ribosomes and inhibit at the translational stage of protein synthesis
  22. tetracycline family
    • mechanism of action - bind 30S ribosomal subunit in bacteria
    • selective toxicity - human cells do not have 30S subunit
  23. azidothymidine (AZT)
    • bind and block polymerase
    • mechanism of action - inhibits viral reverse transcriptase
    • selective toxicity - 100X greater affinity for viral reverse transcriptase than for human polymerases
  24. polymixins
    • antibacterial agents
    • detergent-like action increases cell permeability and causes leakage of essential metabolites
  25. amphotericin
    • antifungal agents
    • increases membrane permeability by forming holes, causing leakage
  26. imidizoles
    • antifungal agent
    • thickens cell membrane so that essential nutrients cannot enter
  27. griseofulvin
    • inhibits mitosis of fungal cells by disrupting the mitotic spindle
    • narrow spectrum, only certain species of fungi
  28. piperazine, ivermectin
    • paralyze worm, can't stay connected to host intestine
    • binds calcium ion channel in nerve and muscle
    • selective toxicity - these channels are different in humans
  29. chloroquine
    prevents biocrystalization that inactivates heme so parasites die from accumulation of heme
  30. probiotics
    living bacteria prevent colonization by pathogenic bacteria
  31. bacteriophages
    won't harm host, only infect bacteria
  32. mechanisms of resistance
    • mutation: occur at certain frequency in any type of microorganism
    • transduction: bacteriophages can carry gene for antibiotic resistance to another cell
    • conjugation between bacteria: resistance genes located on plasmids
    • transformation: genetic resistance selected for by the presence of the antibiotic
  33. types of resistance
    • alteration of receptors (target) - can no longer bind
    • alteration in membrane permeability
    • alteration of metabolic pathways
    • production of a new enzyme which inactivates the antimicrobial
    • antimicrobial efflux pumps
  34. practices that encourage resistance
    • over-the-counter sale of antibiotics without prescription
    • overprescribing without proper diagnosis
    • prescribing without checking resistance patterns in community and/or testing for resistance
    • unnecessary prophylaxis for surgery
    • use of antibiotics in animal feed
    • using same antimicrobials on all patients instead of switching
    • not reserving certain drugs as a last resort
    • patients not completing full course