Fungal III Flashcards
What are the two types of azoles?
Imidazole - Clotrimazole, Econazole, Ketoconazole and Miconazole
Triazole - Fluconazole, Itraconazole, Posaconazole and Voriconazole
What is fluconazole not active against?
Moulds
Which fungal drug has the broadest spectrum?
Posaconazole
Does voriconazole has activity against aspergillis?
Yes
What is the difference between imidazole and triazole?
Triazoles have a extra nitrogen in their ring
What is azoles mode of action?
Inhibition of ergosterol biosynthesis - hence selectivity we have cholesterol in our membranes not ergosterol
Inhibit lanosterol 14-alpha-demethylase and inhibit the production of ergosterol - also toxic build up of methyl sterols. inhibition of cell growth or cell death
How are drugs used for serious infections administered?
IV
What are imidazole used for?
Mainly topical and superficial diseases
What are posaconazole used for?
solution, tablet and IV
2nd drug for aspergillus (refractory)
Also has prophylaxiz license
How is fluconazoles administered?
capsules and solutions
What is voriconazole used for?
Tablet and solution, Effective against aspergillus and candidosis. Can be used for prophylaxis
What is less toxic, amphotericin B or fluconazole?
Fluconazole - little difference in effect
What does itrazconazole need to be administered as for prophylaxis of neutropenic patients?
Solution not capsules
What is voriconazole seen as and what is it better than?
Aspergillis and amphotericin B
The more you get in a patient the better with what drug?
Posaconazole
Superior to fluconazole at preventing aspergillius
What metabolises the azoles?
Cytochrome P450
What are the important cytochromes for hydrolysing fungals?
CYP3A4, CYP2C19, CYP2C9
What do azoles help prevent?
The effective metabolism of other drugs - drug level increases and this can work the other way so that azalea level increases
What are the ways in which azole resistance can grow?
Efflux pumps
Target site alteration in C.Albicans, A.fumigatus
Target up-regulation
Bypass pathways
What family of transporters efflux azaleas?
ABC , MDR (Major facilitator family)
What is mutated in C.Albicans?
Lanosterol 14-alpha methylase
Single or multiple mutations
What are the specific mutations in A.fumigatus?
G54, L98, M220
What is upregulated in C.glabrata and C.albicans?
ERG11
What happens in the bypass pathway?
Mutations in ERG3 encoding sterol-5,6-desturase result in loss of function and leads to an accumulation of 14-alpha methylase fecosterol in the final membrane which permits fungal survival
Makes it resistant to amphotericin B
