Pharmacology: Anti fungal drugs flashcards

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Pharmacology for medical students, nursing students, pharmacology students, and university students!

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Pharmacology: Anti fungal drugs flashcards

  1. 1. Drug Classes  Polyenes: Amphotericin B & Nystatin  Flucytosine  Azoles  Echinocandins  Griseofulvin  Terbinafine  Tolnaftate
  2. 2. Polyenes  Amphotericin B & Nystatin  MoA: binds ergosterol on fungal cell membrane  creates pores  fungicidal/fungistatic  Amphotericin B is insoluble in water so complexed with bile salt or lipids; it is for general use (affects many spp) in SYSTEMIC infections  Nystatin has poor absorption from mucous membranes; use for Candida spp  good for obese and diabetic pts
  3. 3. Polyene Toxicity  Amphotericin B  TI is narrow  Acute: HA, arthralgia, nausea/vomiting, fever, hypotension, Th rombophlebitis, delirium, seizures  Chronic: Malaise, weight loss, NEPHROTOXICITY, anemia
  4. 4. Flucytosine (5 – FC)  Distributes in all body tissues  Almost entirely excreted by kidneys  Converted to 5 – FU (fluorouracil – chemotherapeutic agent)  Fungal resistance develops fast during flucytosine monotherapy  use in combination with other antifungals
  5. 5. Flucytosine MoA  5-FC is taken up into fungal cells  converted to 5-FU  5-FU is phosphorylated to produce 5fluorouridine monophosphate (5 – FUMP) – this metabolite can be used in 2 pathways  First pathway: 5-FUMP is converted to 5-FdUMP  acts as an irreversible inhibitor of Thymidylate Synthetase (aids in making molecules for new DNA) – thus, inhibits fungal DNA synthesis  Second pathway: 5-FUMP converted to 5-FUDP  inhibits RNA synthesis  Ultimate effect: Fungicidal/Fungistatic
  6. 6. Flucytosine Toxicity  Adverse effects due to 5 – FU  Reversible MYELOSUPPRESSION (13%)  LIVER DYSFUNCTION (10%)
  7. 7. Azoles  Ketoconazole, Itraconazole  Structure contains 5 membered azole ring  MoA: Inhibition of fungal ergosterol synthesis  inhibits Lanosterol 14 – α – Demethylase  fungicidal/fungistatic  Cross resistance is common  Ketoconazole can inhibit human sterol synthesis & Cyp P450 enzymes  Seborrheic Dermatitis – ketoconazole shampoo
  8. 8. Azole Toxicity  Gynecomastia (ketoconazole)  Liver toxicity  Hypokalemia, hypertension  Itraconazole
  9. 9. Echinocandins  Newest class of antifungals; large cyclic  Caspofungin, Micafungin, Anidulafungin  MoA: noncomp inhibitors of Beta-D-Glucan Synthase (makes components of fungal cell wall)  disrupts integrity of fungal cell wall (not cell membrane!)  Fungicidal  Targets: Aspergillus & Candida  Resistance develops via FSK1 mutations  No major toxicities
  10. 10. Griseofulvin       Absorption ~ 50%  improved by fatty foods Ineffective topically Induces liver enzymes Distributes only in keratinized tissues MoA: inhibits fungal mitosis  Fungistatic Use: Dermatophytes – tx is continued until tissue is replaced with normal healthy tissue  Hair: 1 month; Skin/Finger nails: 6 – 9 months; Toe nails: 12 months  Toxicity: induces CYP enzymes, Photosensitivity  Itraconazole is more effective for toe nail infections (Onychomycosis)
  11. 11. Terbinafine  Distribution almost only in keratinized tissue and fat  MoA: inhibits fungal enzyme Squalene Epoxidase (inhibits ergosterol biosynthesis)  accumulation of squalene is toxic to fungi  fungicidal  Effective for onychomycosis  Contraindicated in use with CYP inducers/inhibitors
  12. 12. Summary
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