antifungals

• fungal targets

  cell membrane. cell wall, nucleic acid synthesis
• antifungals that disrupt the cell membrane

  polyenes
• mode of action of polyenes

  destabilise the cell membranes by acting on ergosterol, cause leakage of cell constituents
• examples of polyenes

  nystatin and amphotericin
• amphotericin B spectrum


  broad

  candida spp, asperfillus fumigatus, mucorales, cryptococcus, histoplasma
• amphotericin B toxicity


  renal and rigors
• therapeutic uses of amphotericin B?

  systemic mycoses

  major interaction with aminoglycoside
• nystatin spectrum?


  broad
• nystatin toxicity?


  not as toxic as amphotericin, topical, oral, creams, ointments
• nystatin therapeutic use?

  mild oropharyangeal candidiasis, cutaneous and superficial fungal infections
• inhibition of ergosterol biosynthesis in the cell membrane?

  azoles
• ergosterol disruption in the cell membrane?

  polyenes
• mode of action of azoles?

  disrupts ergosterol synthesis by inhibiting a critical enzyme, ergosterol depletion causes leakage and death
• azoles have fungistatic activity
• azoles spectrum

  narrow

  candida albicans

  cryptococcus

  no activity against moulds
• terbinafine for treatment of tinea oral or topical
• terbinafine inhibits squalene epoxidase
• inhibition of beta-1,3-glucan synthesis in the cell wall?

  echinocandins
• route of administration for echinocandins?

  IV only
• echinocandins is not metabolised by cytochrome P450 so it has fewer drug-drug interactions in comparison to azoles
• co-trimoxazole for pneumocystis