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Chemotherapy > Fungal III > Flashcards

Fungal III Flashcards

1
Q

What are the two types of azoles?

A

Imidazole - Clotrimazole, Econazole, Ketoconazole and Miconazole
Triazole - Fluconazole, Itraconazole, Posaconazole and Voriconazole

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2
Q

What is fluconazole not active against?

A

Moulds

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3
Q

Which fungal drug has the broadest spectrum?

A

Posaconazole

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4
Q

Does voriconazole has activity against aspergillis?

A

Yes

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5
Q

What is the difference between imidazole and triazole?

A

Triazoles have a extra nitrogen in their ring

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6
Q

What is azoles mode of action?

A

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

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7
Q

How are drugs used for serious infections administered?

A

IV

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8
Q

What are imidazole used for?

A

Mainly topical and superficial diseases

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9
Q

What are posaconazole used for?

A

solution, tablet and IV
2nd drug for aspergillus (refractory)
Also has prophylaxiz license

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10
Q

How is fluconazoles administered?

A

capsules and solutions

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11
Q

What is voriconazole used for?

A

Tablet and solution, Effective against aspergillus and candidosis. Can be used for prophylaxis

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12
Q

What is less toxic, amphotericin B or fluconazole?

A

Fluconazole - little difference in effect

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13
Q

What does itrazconazole need to be administered as for prophylaxis of neutropenic patients?

A

Solution not capsules

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14
Q

What is voriconazole seen as and what is it better than?

A

Aspergillis and amphotericin B

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15
Q

The more you get in a patient the better with what drug?

A

Posaconazole

Superior to fluconazole at preventing aspergillius

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16
Q

What metabolises the azoles?

A

Cytochrome P450

17
Q

What are the important cytochromes for hydrolysing fungals?

A

CYP3A4, CYP2C19, CYP2C9

18
Q

What do azoles help prevent?

A

The effective metabolism of other drugs - drug level increases and this can work the other way so that azalea level increases

19
Q

What are the ways in which azole resistance can grow?

A

Efflux pumps
Target site alteration in C.Albicans, A.fumigatus
Target up-regulation
Bypass pathways

20
Q

What family of transporters efflux azaleas?

A

ABC , MDR (Major facilitator family)

21
Q

What is mutated in C.Albicans?

A

Lanosterol 14-alpha methylase

Single or multiple mutations

22
Q

What are the specific mutations in A.fumigatus?

A

G54, L98, M220

23
Q

What is upregulated in C.glabrata and C.albicans?

A

ERG11

24
Q

What happens in the bypass pathway?

A

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

Chemotherapy (18 decks)

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