anti infectives

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anti infectives
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  1. 2 ways pathogens cause disease
    • interfere w normal fcn of host
    • produce toxin
  2. gram stain
    • + blue
    • - pink
  3. bacteriocidal
    • kill bacteria and completely eradicate
    • use in immunocompromised
    • good for hard to reach areas
  4. bacteriostatic
    • suppress growth, but don't kill
    • depend on host immune system to completely eliminate bug
  5. minimum inhibitory concentration
    lowest concentration needed to completely suppress bacterial growth
  6. concentration dependent
    treat with [x] well above MIC- rely on just reaching MIC
  7. time dependent
    need to remain above MIC for a long time, so give over extended period of time, and look at trough levels
  8. beta lactams (drugs, MOA)
    • PCN, Cephalosporins, Carbapenems
    • MOA: weaken bacterial cell wall
    • -bind to PCN binding protein on cell wall
    • -inhibit enzyme(transpeptidase) needed for cell wall synthesis/integrity
  9. Natural PCN
    • MOA: inhibit cell wall synthesis
    • G+
    • DOC for strep, if sensitive
  10. B-Lactamase resistant PCN
    • Nafcillin, oxacillin
    • MOA: inhibit cell wall synthesis
    • G+
    • DOC: staph
  11. AminoPCN
    • Ampicillin, Amoxiliccin
    • MOA: inhibit cell wall synthesis
    • G+, G-, Anaerobe
    • *hypersensitivity rxn, non immunological rash (in pts w/ mono)
  12. Extended Spectrum PCN
    • Piperacillin
    • MOA: inhibit cell wall synthesis
    • G+,G-, anaerobes, pseudomonas
  13. carbapenems
    • B-lactamase resistant
    • ___penem
    • MOA: inhibit cell wall synthesis
    • time dependent
    • very broad spectrum
    • 40% cross rxn w/ PCN
    • G+, G-, Anaerobes, pseudomonas (except ertapenem)
    • *imipinem --> lowers sz threshold
  14. cephalosporins
    • MOA: inhibit cell wall synthesis
    • 1st: mostly G+
    • 2nd: G+, some G-
    • 3rd: mostly G-
    • 4th: G+, G-, pseudomonas
    • Ceftriaxone, Cefotaxime, Cefepime: penetrate CSF
    • 10% PCN cross rxn, less w/ each generation
  15. Aztreoanam (class Monobactam)
    • MOA: inhibits cell wall synthesis
    • G-, pseudomonas
    • limited pcn cross rxn
  16. Vancomycin
    • MOA: inhibits cell wall synthesis
    • G+, MRSA
    • time dependent- adjust dose based on trough levels
    • ADR: red man, nephrotoxic, ototoxic
  17. protein synthesis inhibitors
    aminoglycosides, tertracyclines, macrolides, clindamycin, linezolid, tygacil
  18. Aminoglycocides
    • gent, tobramicin, amikacin
    • MOA: inhibit protein synthesis
    • G-, pseudomonas
    • concentration dependent: use extended interval dosing (big dose once/day)
    • get random level after 10 hrs, see how quickly level is falling
    • post abx effect: residual activity after [] falls below MIC
    • nephrotoxic, ototoxic
  19. Tetracyclines
    • ___cycline (doxy)
    • MOA: inhibit protein synthesis
    • G+, G-, atypical
    • Oral absorption decreased by cations, antacids--> separata by 2 hrs
    • ADR: photosensitivity, tooth development in peds
  20. macrolides
    • Erythromycin, Clarithromycin, Azithromycin
    • MOA: inhibit protein synthesis
    • G+, G-, atypical
    • CYP interactions- least w/ azith
    • don't use with clinda
  21. erythromycin
    • class-macrolide
    • MOA: inhibit protein synthesis
    • G+, G-, atypical
    • --> GI SE
  22. azithromycin
    • class- macrolide
    • MOA: inhibit protein synthesis
    • G+, G-, atypical
    • --> QT prolongation
  23. clindamycin
    • class- lincosamide
    • MOA: inhibit protein synthesis
    • G+, G- anaerobes only
    • can be used for community acquired MRSA, but not nosocomial 
    • ADR: significant GI upset; commonly associated w/ C Diff!
    • -PO dose less than IV dose b/c of ADR
    • don't use w/ macrolides
  24. linezolid
    • MOA: inhibit protein synthesis
    • G+, MRSA
    • ADR: thrombocytopenia, GI, HA
    • weak MAOI, watch for serotonergic effects w/ other seroteonin agents
  25. tygacil
    • class- glycylcycline
    • MOA: inhibit protein synthesis
    • G+, MRSA, G-
    • ADR: n/v (premedicate), hypotension
    • only for complicated skin, intra-abd infections
  26. DNA replication inhibitors
    fluoroquinolones, Flagyl
  27. fluoroquinolones
    • ____floxacin(cipro, levaquin,avelox)
    • MOA: inhibit DNA replication
    • action: G+ (minimal in cipro), G-, atypical
    • ADR: QT pronlongation, tendonitis, CYP, CNS disturbances, phototoxic
    • poor oral absorption w/ antacids, cations- separate by 2 hr
  28. ciprofloxacin
    • class- fluoroquinolone
    • MOA: inhibit DNA replication
    • minimal G+, G-, pseudomonas, atypical
  29. levofloxacin
    • class- fluoroquinolone
    • MOA: inhibit DNA replication
    • G+, G-, pseudomonas at high doses, atypical
  30. moxifloxacin
    • class- fluoroquinolone
    • MOA: inhibit DNA replication
    • G+, G-, atypical, anaerobe
  31. flagyl
    • class- fluoroquinolone
    • MOA: inhibit DNA replication
    • anaerobes
    • good tissue penetration: CNS, Bone, abscess
    • DOC for C diff, protozoans
    • ADR: disulfiram rxn w/ EtOH, increased [coumadin]
  32. Sulfonamide
    • Bactrim (trimethoprim and sulfamethoxazole are both sulfonamides that block 2 different
    • enzymes, always used together)
    • MOA:folic acid metabolism inhibitor
    • G+, G-, community acquired MRSA, PCP
    • **Sulfa
    • ADR: rash, bone marrow suppression, thrombocytopenia
    • **avoid w/ G6PD deficiency 
  33. Cell membrane agents
    Daptomycin, Colistin
  34. Daptomycin
    • MOA: inhibit cell membrane synthesis
    • G+: resistant infections only (MRSA, VRSA)
    • also when MIC for vanc is really high
    • concentration dependent- don't need to check levels
    • inactivated by surfactant: can't use in lungs
    • ADR: muscle pain, elevated CPK -monitor q wk
    • -d/c if CPK> 10x, or>5x w/ s/s (xnormal limit)
  35. colistin
    • MOA: inhibit cell membrane synthesis
    • G-
    • good for multi drug resistant
    • very nephrotoxic!
  36. MRSA
    • vanc
    • linezolid
    • tigecycline (tygacil)
    • daptomycin
  37. community acquired MRSA
    • clindamycin
    • bactrim
  38. pseudomonas
    • Extended spectrum PCN (zosyn)
    • Carbapenem (imi/mero, NOT erta)
    • 4th gen cephalosporin (cefepime)
    • Aztreonam
    • Aminoglycosides (genta, tobra, amikacin)
    • cipro
    • levofloxacin (in high doses)
    • colistin
  39. anaerobes
    • AminoPCN 
    • -amox/clav (augmentin)
    • -amp/sulb (unasyn)
    • Extended Spectrum PCN (zosyn)
    • Carbapenem
    • Clindamycin
    • Tygasil
    • flagyl
  40. atypical
    • tetracycline (doxy, minocycline)
    • macrolides (erythro, clarithro, azithro)
    • Fluoroquinolones: cipro, levo, moxi
  41. Amphotericin B
    • class- Polyene
    • MOA: target cell membrane ergosterol --> leaking cell contents
    • broadest spectrum antifungal, but very toxic
    • ADR: nephrotoxic (Mg/K wasting, low GFR, high SCr); infusion related chills/fever/rigors
    • newer version less toxic
  42. nystatin
    • class- Polyene
    • MOA: target cell membrane ergosterol --> leaking cell contentsbroadest spectrum antifungal, but very toxic
    • ADR: nephrotoxic (Mg/K wasting, low GFR, high SCr); infusion related chills/fever/rigors
    • so toxic, cant use systemic, only topical
  43. fluconazole
    • MOA: target ergosterol synthesis
    • good against candida
    • good oral absorption
    • 25 hr 1/2 life
    • dose dependent CYP inhibitor: watch coumadin/dilantin
  44. imidazoles
    • MOA:target ergosterol synthesis
    • clotrimazole, miconazole
    • OTC/topical
  45. voriconazole
    • VFEND
    • MOA: target ergosterol synthesis
    • broad spectrum,
    • very bioavailable (IV/PO), but poor urinary penetration
    • DOC: aspergillosis
    • ADR: visual disturbances
    • CYP: substrate AND inhibitor
    • avoid IV in renal probs
  46. flucytosine
    • MOA: converted to 5FU which inhibits fungal DNA synthesis (pyrimidine)
    • limited spectrum, used with ampho B
    • ADR: marrow suppression
  47. echinocandins
    • ___fungin
    • MOA: inhibit cell wall synthesis- no interaction w/ human cells
    • broad spectrum, only for systemic infections- but poor urinary penetration
  48. lamasil
    • MOA: inhibit enzyme for ergosterol synthesis (allylamine)
    • oral and topical
    • AE: hepatotoxic w/ systemic use
  49. covers everything when used together
    azithromycin, vancomycin, zosyn
  50. agent that only covers anerobes
    flagyl (used for c.diff)
  51. top choice for UTI
    • cipro
    • macrobid - only gets into urine
  52. top choice for community acquired pneumonia
    - Avelox or Levequin (gram +, gram -, and atypicals)
  53. top choice for GI
    • carbapenems and zosyn
    • (both cover G+/G-, and anaerobe)
  54. top choice for hospital acquired pneumonia
    vancomycin and zosyn
  55. DNA viruses
    • rely on host polymerases for replication
    • HBV
    • Herpes
  56. RNA viruses
    • DONT rely on host polymerase
    • HAV, HCV
    • flu
    • HIV
  57. viral life cycle
    • absorption: stick to cell w/ specific receptors
    • penetration: fusion w/ plasma membrane or endocytosis (some can cross directly)
    • uncoating
    • viral genome replication
    • maturation
    • release--> lysis or budding (uses host cell membrane) carry to infect more cells
  58. inactivated flu vaccine
    • IM
    • for everyone >6 mos
    • may have flu like s/s
    • C/I egg allergy b/c grown in eggs
  59. live flu vaccine
    • nasal
    • for ages 2-49
    • not in peds, elderly, immunocompromised 
    • may have flu like s/s
    • C/I egg allergy b/c grown in eggs
  60. tamiflu
    • PO flu treatment- good absorption
    • MOA: inhibit neuramidase- the enzyme necessary for replication
    • use: w/in 2 days of symptom onset
    • ADR: GI
    • active against influenza a/b, swine flu
  61. Zanamivir/relenza
    • inhaled flu treatment: mostly in oropharynx
    • MOA: inhibit neuramidase- the enzyme necessary for replication
    • use: w/in 2 days of symptom onset
    • ADR: bronchospasm
    • active against infuenza a/b
  62. Ribavarin (RSV)
    • Use: severe RSV pna in infants/peds; inhaled
    • not recommended for routine use b/c of risk to healthcare workers administering the aerosol + not consistently effective
    • *don't use w/ vents
    • preg cat X
  63. Synagis
    • use: RSV prevention in high risk Peds
    • MOA: monoclonal antibody, prevents replication
    • avail: IM
    • very expensive, monthly dosing q month december-march
  64. herpes
    • infect epithelial mucose then travel up peripheral nerve to neuron where remains inactive
    • symptomatic: cells transcribe lytic genes
    • latent: transcribe "latency associated transcript" (LAT)
  65. Acyclovir
    • use: HSV, Zoster, herpes encephalitis 
    • Prodrug activated by viral phosphorelation w/ thymidine kinase- won't have any effect if cells don't have virus
    • MOA: inhibits DNA synthesis (nucleoside analog)
    • avail: IV, PO, topical
    • ADR: phlebitis, nephrotoxic, neurotoxic
    • -need adequate hydration to prevent renal crystals; also give slow infusion
    • poor oral availability --> need high doses
    • good distribution --> CSF
  66. thymidine kinase
    enzyme responsible for viral phosphorylation --> activate acyclovir
  67. valacyclovir
    • use: HSV, shingles
    • prodrug of acyclovir, with better PO absorption
    • ADR: neutropenia, nephrotoxicity, HA, GI
    • caution: TTP/HUS in immunocompromised
  68. famicyclovir
    • use: shingles, genital HSV
    • MOA: inhibits DNA synthesis
    • avail: PO
    • PK/PD: rapid and thorough absorption, hepatic metabolism
    • ADR: GI, HA, dysmenorrhea
  69. mouth creams for HSV
    • denavir, abreva
    • MOA: inhibit viral entry
    • OTC
  70. trifluridine
    opthalmic HSV treatment
  71. ganciclovir
    • Use: CMV retinitis, pneumoniis, colitis, viremia, and prophylaxis
    • Avial: Iv, PO, occular implant, eye gel
    • pk/pd: poor oral bioavailability
    • ADR: thrombocytopenia, sterility (may be irreversible at high doses)
    • terratogenic: avoid pregnancy for 90 days
    • more broad spectrum than acyclovir --> more effective, but more marrow suppression
    • monitor CBC weekly: stop if plt<25000 or ANC <500
  72. valgancyclovir
    • prodrug of gancyclovir w/ better bioavailability
    • avail: PO
    • ADR: thrombocytopenia, sterility (may be irreversible at high doses)
    • terratogenic: avoid pregnancy for 90 daysmore broad spectrum than acyclovir --> more effective, but more marrow suppression
    • monitor CBC weekly: stop if plt<25000 or ANC <500
  73. cidofovir
    • Use: CMV retinitis after failed 1st line tx
    • MOA: inhibits viral DNA polymerase
    • avail: IV 
    • pk/pd:long 1/2 life
    • ADR: nephrotoxic, neutropenia
    • CI: pts on other nephrotoxics
    • must give with probenacid to prolong exposure, prevent elimination
  74. foscavir
    • Use: resistant HSV/VSV/CMV
    • MOA: inhibit dna/rna polymerase
    • avail: IV
    • ADR: nephrotoxic, chelates cations --> lyte/mineral imbalances- need to replace
    • dose limiting toxicity: need aggressive pre hydration; usually in 2nd wk
  75. which hep can be chronic?
    B, C, D
  76. intron A
    • (interferon alpha)
    • Use: chronic HCV, HBV
    • MOA: blocks viral entry, protein synthesis, viral assembly, and release
    • avail: subQ, IV
    • dose: 3x/week
    • ADR: neutropenia
    • contraindicated in pregnancy, men w/ pregnant partners
  77. pegasys
    • (interferon alpha)
    • Use: chronic HCV, HBV
    • MOA: blocks viral entry, protein synthesis, viral assembly, and release
    • avail: subQ, IV
    • dose: 1x/week (lasts longer than intron A, but has worse SE)
    • ADR: neutropenia
    • contraindicated in pregnancy, men w/ pregnant partners
  78. Ribavarin (HCV)
    • use: chronic HCV- in combo w/ interferon alpha
    • MOA: unknown/nucleotide analog
    • avail: po
    • ADR: hemolytic anemia, neutropenia
    • pregnancy category X
  79. Bocepravir (victrelis)
    • HCV1 protease inhibitor
    • quicker, but have to use w/ interferon/ribavarin
    • PK: inhibit CYP
    • ADR: neutropenia, anemia, GI, alopecia, arthralgia
  80. telepravir (incivek)
    • HCV1 protease inhibitor
    • quicker, but have to use w/ interferon/ribavarin
    • PK: inhibit CYP
    • ADR: anemia, rash
  81. Adefovir
    • use: HBV, HIV
    • MOA: NRTI
    • avail: PO
    • ADR: nephrotoxic, lactic acidosis
    • avoid in HIV b/c can --> NRTI resistant HIV b/c of low doses used to tx HBV
  82. tenofovir
    • use: HBV
    • MOA: NRTI
    • avail: PO
    • ADR: lactic acidosis
  83. lamivudine
    • use: HBV, HIV (different dosing)
    • MOA: NRTI
    • avail: PO
    • ADR: pancreatitis, lactic acidosis
    • best tolerated NRTI
  84. entecavir (Baraclude)
    • use: chronic HBV
    • MOA: inhibits DNA polymerase and viral replication
    • avail: PO
    • no risk of HIV resistance
  85. retrovirus
    RNA --> dna --> incorporated into host cell
  86. AIDS
    CDR <200
  87. seroconversion
    development of HIV antibodies --> tests +
  88. HAART
    • 2 NRTS + NNRTI/PI/II
    • for pts with OI, pregnancy, CDR 350-500, age>50
  89. HIV replication cycle
    • binding and fusion: via CCR5 receptor (later shifts to CXCR4)
    • reverse transcription: RNA converted into  DNA
    • Integration: Viral dna intergrates into host dna
    • transcription: production of viral proteins
    • viral rna/proteins move to cell surface --> budding: new, immature virus break free 
    • maturation: protease cuts protein chain --> working virus
  90. NRTI
    • backbone of HIV tx
    • MOA: nucleoside/tide analogs incorporated into viral dna
    • ADR: can be taken up by mitochindra --> can't reproduce --> lactic acidosis
  91. zidovudine (retrovir)
    • NRTI
    • Use: HIV in pregnancy- starting 14 wks, and infant for 6 wks
    • only NRTI avail IV
    • ADR: bone marrow suppression
  92. Didanosine (videx)
    • NRTI (not used as much)
    • ADR: pancreatitis, peripheral neuropathy
    • give on empty stomach b/c absorption decreased by food
  93. Stavudine (Zerit)
    • NRTI (not used as much)
    • ADR: peripheral neuropathy
  94. abacavir (Ziagen)
    • NRTI 
    • have to test for hypersensitivity w/ HLAB*5701. r/t genetic variation, can be fatal. usually presents in 1st 6 wks of tx
  95. Tenofovir disproxil fumarate (viread)
    • NRTI
    • (not the same tenofovir as for hep)
  96. Emtricitabine (emtriva)
    • NRTI
    • ADR: hyperpigmentation of palms and soles
  97. NNRTI
    • MOA: binds to and inhibits reverse transcriptase (same effect as nrti, but different action)
    • PK: metabolized by and induce CYP
    • ADR: severe rash
    • very prone to resistance, one you fail one (viral load not decreasing) fail whole class
  98. Efavirenz (sustiva)
    • MOA: NNRTI-binds to and inhibits reverse transcriptase
    • 1st line tx
    • PK: metabolized by and induce CYP
    • ADR: CNS symptoms- give at night
    • terratogenic
  99. Etravirine
    • MOA: NNRTI-binds to and inhibits reverse transcriptase
    • PK: metabolized by and induce CYP
    • generally well tolerated
    • only use in HIV1 resistant to other ARVs
  100. nevirapine (Viramune)
    • MOA: NNRTI-binds to and inhibits reverse transcriptase
    • PK: metabolized by and induce CYP
    • ADR: hepatitis
    • not active against HIV2
  101. Delavirdine (rescriptor)
    • MOA: NNRTI-binds to and inhibits reverse transcriptase
    • PK: metabolized by CYP.
    • Only NNRTI that doesn't induce CYP
    • absorption better in acidic environment, avoid acid suppressants
  102. Ripiverine (Edurant)
    • MOA: NNRTI-binds to and inhibits reverse transcriptase
    • PK: metabolized by and induce CYP
    • ADR: qt prolongation
    • take w/ food to enhance absorption
  103. Protease Inhibitors
    • MOA: inhibits cleaving of viral proteins- last step in maturation
    • OK: inhibit CYP
    • ADR: metabolic syndrome (DM 2 mos after starting tx), increased bleeding risk
  104. Ritonavir (norvir)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • *booster to help decrease exposure to S-T-D
  105. S-T-D
    • Saquinivir
    • Tipranavir
    • Darunavir 
    • need to be used w/ ritonavir b/c metabolized extensively by liver
  106. Lopinavir/Ritonavir (Kaletra)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • oral solution contains EtOH caution disulfram rxn w/ flagyl
  107. Indinavir
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • ADR: nephrolithiasis, hyperbilirubinemia
    • (stones don't impair kidney fxn, resolve w/ hydration)
  108. Saquinavir (Invirase)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • needs to be used w/ ritonavir
  109. Nelfinavir (Viracept)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • ADR: dose limiting diarrhea
  110. Amprenavir (Agenerase)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • ADR: GI
    • avoid in sulfa allergies
    • C/I: pregnancy, <4yr, renal/heaptic probs, flagyl/disulfiram
  111. Atazanavir (Reyataz)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • requires acidic environment for absorption
    • ADR: jaundice, PR prolonged (2nd AV block)
    • less hyperlipidemia
  112. Tipranavir (Aptivus)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • ADR: severe hepatitis, intracranial hemorrhage
    • *Sulfa allergy
    • needs to be used w/ ritonavir
    • can adapt to changes in protease: used when Resistant to other PIs
  113. Darunavir (Prezista)
    • MOA: PI- inhibits cleaving of viral proteins- last step in maturation
    • used when resistant to other PIs
    • Sulfa allergy
    • needs to be used w/ ritonavir
  114. Raltegravir (Isentress)
    • MOA: integrase inhibitor
    • use: treatment experienced pts w/ multi resistant virus
  115. Elvitegravir
    combo only for treatment-naive pts
  116. Enfuvirtide (fuzeon)
    • MOA: fusion inhibitor- blocks receptor
    • use: treatment experienced pts w/ multi resistant virus w/ CCR5 
    • CYP metabolism
  117. Truvada
    Emtricitabine + tenofovir
  118. Atripla
    truvada (Emtricitabine + tenofovir)+ efavirenz (sustiva- nnrti)
  119. HIV post exposure prophylaxis
    • occupational: 2 NRTI (+ PI)
    • non occupation: 2 NRTI+ sustiva or kaletra
  120. kaletra
    lopinavir + ritonavir
  121. PEDs HIV
    2 NRTI + kaletra or sustiva or viramune
  122. Tuberculosis
    • can be latent for a long time- activate when immunocompromised
    • mostly in lungs, but can disseminate
  123. TB treatment
    • RIPE
    • rifampin and Isoniazid X 6 mos
    • Pyrazinamide and Ethambutol only for 1st 2
    • (4 drugs for 2 months, then 2 drugs for 4 months)
  124. multi drug resistant TB
    resistant to INH and Rifampin
  125. Isoniazid (INH)
    • use: active/latent TB
    • MOA: uknown
    • ADR: dose related peripheral neuropathy (supplement w/ pyroxidine)
    • hepatotoxic (monitor LFT monthly)- risk inc w/ age
  126. Rifampin
    • Use: Active/latent TB
    • MOA: inhibit bacterial RNA polymerase
    • ADR: hepatotoxic (more s/s than INH), red-orange body fluids
  127. Rifabutin
    • use: MAC (mycobacterium avium complex) prophylaxis/tx, TB
    • MOA: inhibit bacterial RNA polymerase
    • ADR: GI, body fluid discoloration
  128. Pyrazinamide
    • use: active TB
    • MOA: unknown
    • ADR: hepatotoxic, hyperuircemia (r/t renal excretion of uric acid- not gout)
  129. Ethambutol
    • Use: active TB, disseminated MAC, 
    • MOA: supresses incorporation of mycolic acid into cell wall
    • ADR: optic neuritis (resolves)

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