Mechanism of Anti-Fungals Flashcards
What are the two main classes of fungi?
Yeasts - Replicate via budding.
Filamentous - Replicate by filamentous extension
Name some examples of yeast fungi an example of their disease
Candida spp - Thrush, fungaemia (in immunocompromised)
Cryptococcus neoformans - Meningitis, pneumonia.
Pityriasis versicolor - chronic skin infections
Name some examples of filamentous fungi an example of their disease
Aspergillus spp - Pulmonary or ocular infection.
Mucor - farmers lung
Dermatophytes eg, epidermophyton - chronic infections of the skin and nails
Name the main classes of anti-fungal drugs
- Tri-azole,
- Polyenes,
- Flucytosine,
- Echinocandins,
- Terbinafine,
- Griseofulvin
Name some examples of tri-azoles and their features
Fluconazole - well absorbed after oral administration, good penetration (can treat meningitis) and excreted in urine.
Itraconazole -require acidic environment in stomach can cause liver damage.
Posaconazole - Treatment of invasive infections that haven’t responded to other treatment.
Voriconazole - used in life-threatening infections
Describe the mechanism of fluconazole
It inhibits 14 alpha-demethylase which inhibits ergosterol biosynthesis which is essential for formation of cell membrane
Describe the mechanism of resistance for fluconazole
Efflux pumps which forces drug out of cell
Name examples of polyenes and their features
- Amphotericin, not orally absorbed so is given via IV infusion to treat systemic infections. Toxic side effects are common but liposomal version is much less toxic
- Nystatin, not absorbed when taken orally but used as for oral infections
Describe the mechanism of actions of polyenes
Imbeds itself into the cell membrane forming a pore that allows for leakage of electrolytes which causes the cell to die. This is also the reason it causes toxicity
Describe clinical features of flucytosine
It is used to treat serious infection adjunct to other anti-fungals eg, amphotericin. However it has significant toxicity and can cause bone marrow suppression which needs monitored
Describe the mechanism of action of flucytosine
It forms a false nucleotide and therefore disrupts nucleic acid and protein synthesis. Therefore preventing cell division Amphotericin increases cell permeability which allows more flucytosine into the cell.
Name examples of echinocandins and what they can be used against.
Anidulafungin, caspofungin and micafungin. They are fungicidal against candida spp, but only fungistatic against aspergillus spp. They are not effective against infections of CNS
Describe the mechanism of echinocandins
They inhibit 1,3 beta glucan in the cell wall polysaccharide. The polysaccharide coating protects the cell from osmotic stress so when this is disrupted the cell bursts.
What can terbinafine be used against?
It can be used topically to treat darmatophyte infections.
What is the mechanism of terbinafine?
It inhibits squalene epoxidase which prevents formation of ergosterol and leads to accumulation of toxic products
