Mechanism of action of anti-fungals Flashcards
What are the main yeasts that infect humans?
replicate by budding
- Candida spp.
- Cryptococcus neoformans
- Pityriasis versicolor
- Systemic yeasts e.g Histoplamsa capsulatum
What are the main filamentous fungi? (replicate via filamentus extensions)
- Aspergillus spp
- Dermatophytes
What are the 3 types of illness caused by aspergillosis?
- Inflammatory response (e.g hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis)
- Aspergilloma (normally form in individuals who have had some other lung
disease) - Invasive aspergillosis
How are aspergillomas usually treated?
Through surgical excision
Name 4 tri-azole drugs?
- Fluconazole
- Itraconazole
- Posaconazole
- Voriconazole
What tri-azole drug is achieves very good penetration into the CCF?
Fluconazole
What are the cautions of fluconazole?
- Hepatic impairment
- Suseptibility to QT interval prolongation
- Renal impairment
- Hepatic impairment
- Pregnancy
What pathway do tri-azole drugs target?
IMPORTANT
- Ergosterol biosynthetic pathway
- Mainly stops Lanosterol being converted into ergosterol
- Mainly inhibits 14 alpha-demethylase
- Stops the biosynthesis of the steroid component of the cell wall
Name a way in which resistance to fluconazole can develop?
Efflux pumps which pump the fluconazole out of the cell
What are the 2 main polyenes?
- Amphotericin and nystatin (can be used topically or by IV infusion NOT orally)
What can amphotericin be used to treat?
- Severe systemic fungal infections (IV)
What can standard amphotericin cause intravenously?
- Severe kidney problems (can lose a lot of electrolytes)
- Usually given in a liposomal form (can decrease the toxic effects)
How does amphotericin work?
Amphotericin embeds itself in the cell membrane causing a leakage (binds to ergosterol)
What is flucytosine used against?
Predominantly systemic yeast and fungal infections. Adjunct to amphotericin in cryptococcal or severe systemic candidiasis
Describe the mechanism of action of flucytosine when used with amphotericin
- Amphotericin B increases cell permeability (5-FC can pass through this)
- Flucytosine (5-FC) forms a false nucleotide (pyrimidine)
- Disrupts nucleic acid and protein synthesis
- Binds to thymidylate synthase and stops DNA syntheis and DNA division from occuring