Chapter 10 Micro

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melprouty80
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Chapter 10 Micro
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2011-03-17 08:30:33
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Chapter 10 Microbiology
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  1. Chemotherapeutic agents
    drugs to treat a disease
  2. Antimicrobial drugs
    interfere with the growth of microbes within a host
  3. Antibiotic
    substance produced by a microbe that inhibits another microbe
  4. Selective toxicity
    a drug that kills harmful microbes without damaging the host
  5. A look back
    • began in 1909 with Paul Ehrlich
    • arsenic compound for treatment of syphilis
    • salvarsan
    • 1929- Fleming discovered penicillin, produced by Penicillium mold
    • cointed ter antibiotic
    • 1932- Gerhard Domagk discovered sulfanilamide
    • first to use agent to treat wide array of bacterial infections
    • prontosil: red dye
  6. Antibiotics
    naturally produced antimicrobial agent
  7. Semi-synthetics
    chemically altered antibiotics that are more effective than naturally occurring one
  8. Synthetics
    completely synthesized in a lab
  9. Narrowspectrum
    an agent that works against a single gram negative, gram positive, or a few organisms
  10. Broadspectrum
    an agent that is effective against a wide variety of gram positive and gram negative organisms
  11. Bacteriacidal
    an agent that kills the organisms
  12. Bacteriostatic
    an agent that temporarily inhibits the growth of the organism long enough for the bodys defense mechanism to take over
  13. Penicillin
    selectively toxic, bacteriocidal

    MOA: Competitively combine with transpeptidase(penicillan binding agent). Inhibits crosslinking of PTG. Cell wall synthesis is arrested and the bacteria dies
  14. Methicillin (semisythetic) penicillin
    • penicillin
    • amoxicillin
    • ampicillin
  15. Cephalosporin
    • kflex
    • ceclor
    • cefzil
    • vantin
  16. Monobactam
    azactam
  17. Resistance to beta-lactam antibiotics: What four ways do bacteria defend themselves from the PCN family?
    • 1. alter porins
    • 2. Gm+ and Gm- possess beta-lactamase enzymes that cleave beta-lactam ring (penicillinase)
    • 3. alter structure of transpeptidase so antibiotics cant bind (methicillin-resistan staphylococcus aureus (MRSA))
    • 4. Gm+ and Gm- may develop the ability to actively pump out beta-lactams before it binds to the transpeptidase
  18. Beta-lactamase inhibitor enzymes
    • they are given in combination with penicillins to create a beta-lactamase resistant combination
    • Clavulanic acid
    • amoxicillin and clavulanic acid: augmentin
    • Sulbactam
    • ampicillin and sulbactam: unasyn
    • Tazobactam
    • piperacillin and tazobactam: zosyn
  19. Inhibitors of cell wall synthesis
    • Bacitracin
    • Vancomycin
    • Isoniazid
  20. Why is Isoniazid used in treating the genus Mycobacterium?
    • members of the genus mycobacterium have an atypical cell wall that contain mycolic acid
    • acid fast stain used to see it
    • cause leprosy and tuberculosis
    • Isoniazid (INH) inhibits the enzyme, fatty acid synthaseandis the drug of choice, generally used in combination with rifampin and ethambutol
  21. Antifungal drugs inhibition of cell wall synthesis
    • target synthesis of beta-glucans and result in an incomplete cell wall
    • echinocandins
    • binds to 1,3 b-glucan synthase
    • used to treat candida and pneumocystis
    • caspofungin (cancidas)
  22. Polymyxin B
    • made from a specific form of bacillus
    • caues disruption of the plasma membrane by attaching to the phospholipids causing holes in PM
    • effective against gram negative bacteria
    • pseudomonas
    • toxic to human kidneys
    • topical
    • combined with bacitracin and neomycin in over the counter preparation
  23. Antifungal disruption of plasma membranes
    • Amphotericin B
    • attaches to ergosterol and dirupts membrane and causes lysis
    • Azoles
    • inhibits lanosterol a-demethylase
    • enzyme converts lanosterol to ergosterol
    • dirupts plasma membrane
    • miconazole/clotrimazole
    • triazoles (fluconazole and itraconazole)
  24. Inhibitors of protein synthesis
    • Chloramphenicol
    • Aminoglycosides
    • Tetracyclines
    • Macrolides
    • Antisense nucleic acids
  25. Chloramphenicol
    • Broad spectrum
    • binds 50S subunit, inhibits peptide bond formation
    • serious toxicity
    • suppression of bone marrow
  26. Aminoglycosides
    • streptomycin, neomycin, gentamicin, tobramycin
    • broad spectrum
    • bind to 30S and cause misreading of mRNA
    • toxicity can cause hearing impairment and/or kidney damage
  27. Tetracyclines
    • broad spectrum
    • effective against Gram + and Gram-, rickettsias, and chlamydia
    • interferes with tRNA attachment
    • forms complexes with calcium and can strain developing teeth and affect strength of developing bones
  28. Macrolides
    • gram positives
    • binds 50S, prevents translation
    • erythromycin
    • azithromycin
    • clarithromycin
  29. Antisense nucleic acids
    • fomiversen
    • cytomegalovirus and eye infections
    • prevents formation of 70S initiation complex
    • oxazolidinones (zyvox)
    • vancomycin and methicillin-resistant staphylococcus aureus
  30. Inhibition of metabolic pathways by competitive inhibition
    • Sulfonamides (sulfa drugs)
    • structural similar to PABA
    • inhibit folic acid synthesis
    • broad spectrum
  31. Inhibition of nucleic acid synthesis
    • compounds can interefere with function of nucleic acids (nucleoside analogs)
    • nucleoside analogs can distort shapes of nucleic acid molecules and prevent further replication, transcription, or translation
    • most often used agains viruses; viral DNA polymerases moer likely to incorporate and viral nucleic acid synthesis more rapid than that in host cells
    • also effective agains rapidly dividing cancer cells
  32. Inhibitors of nucleic acid synthesis rifampin
    • Rifampin
    • binds to bacterial RNA polymerase
    • antituberculosis
    • Quinolones and Fluroquinolones
    • Inhibits DNA gyrase(uncoils DNA)
    • Broader spectrum synthetic versions: ciproflaxin(anthrax) limited use in children
  33. Antifungal drugs-inhibition of microtubules(mitosis)
    • Griseofulvin
    • produced by a species of penicillium
    • used for superficial mycoses of hair and nail (tinea capitis or ringworm)
    • binds slectively to keratin
    • blocks microtubles and inhibits mitosis
    • Tolnaftate
    • mechanism of action: not known
    • used for athletes foot
  34. Anti-viral medicatons
    • no peptidoglycan wall
    • no ribosomes
    • no plasma membrane
    • current anti-viral medications attack steps in viral replication
    • only attack actively replicating viruses
    • most are fake viral nucleotides, derail viral replicaton
  35. Antiviral drugs enzyme inhibitors
    • Protease inhibitors
    • Indinavir:
    • prevents HIV protease to trim viral proteins down to working size
    • prevents capsid formation
    • Inhibit attachment
    • Zanamivir
    • influenza
    • Inhibit uncoating
    • Amantadine
    • influenza
    • Interferons prevent spread of viruses to new cells
    • viral hepatitis
    • Reverse transcriptase inhibitors: RNA to DNA
    • HIV
  36. Disk-diffusion test
    • also known as the kirby-bauer test
    • petri plate is "seeded" with test organism
    • filter paper disks are impregnated with chemotherapeutic agents are place of surface
  37. E test
    • more advanced diffusion test
    • can measure minimal inhibitory concentration (MIC)
  38. Broth dilution test
    • used to determine MIC
    • plus minimal bactericidal concentration
    • wells that show no growth (higher concentration than MIC) are cultured in drug free broth
    • no growth= bacteriocidal
    • growth= basteriostatic
  39. Routes of administration
    • topical: application of dug if infection is external
    • oral: simplest; lower drug concentrations; no reliance on health care provider; patients do not always follow prescribing information
    • intramuscular: requires needle; contration never as high as IV administration
    • intravenous: requires needle or catheter; drug contration diminishes as liver and kidneys remove drug from circulation: must know how antimicrobial agent will be distributed to infected tissues
  40. Toxicity
    • exact cause of many adverse reactions poorly understood
    • drgs may be toxic to kidneys, liver or nerves
    • considerations needed when prescribing drugs to pregnant women
  41. Allergies
    • although allergic reactions are rare, they may be life threatening
    • anaphylactic shock
    • disruption of normal flora
  42. Mechanisms of antibiotic resistance
    • a variety of mutations can lead to antibiotic reistance such as:
    • enzymatic destruction of drug
    • prevention of penetration of dug
    • alteration of dugs target site
    • alter their metabolic activity
    • rapid enjection of the drug
    • mycobacterium tuberculosis produces MfpA protein, which binds to DNA gyrase preventing the binding of fluoroquinolone drugs
    • resistance genese are often on plasmids or transposons that can be transferred between bacteria
  43. How does antibiotic misuse cause antibiotic resistance?
    • misuse of antibiotics selects for resistance mutants
    • misuse includes:
    • using outdated, weakened antibiotics
    • using antibiotics for the common cold and other inappropriate conditions
    • use of antibiotics in animal feed
    • failure to complete the prescribed regimen
    • using someone elses leftover prescription
  44. How to fight against(retard) resistance?
    • patient should finish entire course of antimicrobial
    • limit use of antimicrobials to necessary cases
    • use synergistic antimicrobials
    • develop new variations of existing drugs: second-generation drugs and third-generation drugs
    • search for new antibiotics, semi-synthetics, and synthetics
    • bacteriocins
    • design drugs complementary to the shape of microbial proteins to inhibit them
  45. Bacitracin
    • inhibits lipid carrier, bactoprenol
    • prevents transport of NAM subunits through cell wall
    • effective as a topical treatment against gram positives
    • Staphylococci
    • Streptococci
  46. Vancomycin
    • glycopeptide derived from streptomyces
    • prevents insertion of NAMs and NAGs into PTG wall
    • important "last line" against antibiotic resistant S. aureus
  47. Zone of inhibition
    No growth in the immediate area around the disc - the larger the zone the more sensitive the microbe is to the drug
  48. Minimal inhibitory concentration (MIC)
    lowest antibiotic concentration that prevents visible bacterial growth

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