Pharm Test 3: Antifungal Drugs

  1. Polyenes
    Amphtericin B, Nyastatin
  2. Binds sterole moiety (primarily ergosterol)
    Forms pores/ channels that increase membrane permeability
    Causes leakage of intracellular molecules
    Polyenes (Amp B, Nyastatin)
  3. Mechanism of Resistance to Polyenes (Amp B)
    Species with notable resistance?
    • Bacteria replaces ergosterol w/ precursor sterols
    • Candida lusitaniae
    • Aspergillus nidulans
  4. Which drug is dosed only topically to treat Candida (folds of obese patients with fungal infxns)
  5. Amp B is used to treat
    Candida, Aspergillus, Coccidoides, Rhisopus, Cryptococcus, Blastomyces, Histoplasma
  6. Amp B:  Fungistatic of Fungicidal?
  7. Clinical roles of Amp B?
    Meningitis, mucormycosis, neutropenic fever
  8. Toxicity of AmpB (3)
    • Infusion-related rxns (Worst with ABCD)
    • Azotemia   (Treat w/ K+, Mg2+)
    • Anemia (Decreased productionof erythropoietin)
  9. Name 4 azoles
    • Itraconazole
    • Fluconazole
    • Voriconazole
    • Posaconazole
  10. What drugs work by inhibiting 14-a-sterole demethylase?
  11. Azoles work by inhibiting (2 things)
    14-a-sterol demethylase, impairs biosynthesis of ergosterol
  12. Resistance to the Azoles is by accumulation of mutations in

    (Protects heme in enzyme pocket from binding)
  13. Azoles:  Fungistatic or Fungicidal?
  14. What is the spectrum of action of azoles?
    Candida, Blastomyces, Histoplasma, Coccidiodes
  15. What drug interacts with the CYP450 pathway? (not other drug friendly)
  16. Which azole must have the stomach acidity to be absorbed?
    • Itraconazole
    • (If they're on an H2 antagonist or PPI, they shouldn't take itraconazole)
  17. Itraconazole  is PO only.  What forms?  Are these interchangeable?
    Capsule and liquid, the dosing levels are different so very hard to interchange
  18. Adverse effect of Itraconazole?
    CHF (also contraindicated in pregnancy)
  19. Tx of Cryptococcus meningitis or transplant prophylaxis?
  20. What does Fluconazole treat?
    Cryptococcus meningitis, transplant prophylaxis, candidiasis
  21. Why is SBECD required with Voriconazole?
    It is necessary for absorption of the drug
  22. Who can't receive Voriconazole?  Why?
    Pts. w/ decreased renal function because SBECD (which is required for Voriconazole absorption) causes nephrotoxicity
  23. SBECD is necessary for absorption of?
  24. Why is Posaconazole not really clinically useful?
    Very difficult to reach therapeutic levels, the drug is cleared too rapidly.
  25. Which azole causes visual side effects/ hallucinations?
  26. N/V/D, Hepatotoxicity, abdominal paint, QT prolongation are adverse effects of what class of drugs?
  27. Echinocandins (3)
    • Caspofungin
    • Micafungin
    • Anidulafungin
  28. Echnocandins inhibit cell wall synthesis by inhbiting
    • 1,3-B-D-glucan synthase
    • (Reduces structural integrity, fungal cell wall--> osmotic instability, death)
  29. Which class of drugs inhibits cell wall synthesis by inhibiting 1,3-B-D-glucan synthase?
  30. Mechanism of resistance to Echnocandins is a mutation in
    Fks1p (subunit of glucan synthase)
  31. Echnocandins:  Fungistatic or Fungicidal?
  32. Echnocandins:
    1) Oral bioavailability?
    2) Protein bound?
    3)  Cleared by?
    • 1)  Not orally bioavailable
    • 2)  Highly protein bound
    • 3)  Hepatic clearance
  33. Treat deeply invasive candidiasis
  34. Don't give pts. w:
    Renal impairment-
    Hepatic impairment-
    • Renal impairment- Voriconazole
    • Hepatic impairment- Caspfungin
  35. Treat deeply invasive candidiasis, esophageal candidiasis, prophylaxis HSCT
  36. Treat candidemia, esophageal candidiasis
  37. Which class of drugs acts on RNA and is the only antifunga that can have synergy w/ other antifungals?
Card Set
Pharm Test 3: Antifungal Drugs
Antifungal Drugs