Antifungals Flashcards
Which groups of antifungals have an action that inhibits membrane synthesis?
Azoles
Echinocandins (Caspofungin)
Which groups of antifungals have an action that inhibits membrane function?
Polyenes
Allylamines
Which groups of antifungals have an action that inhibit nucleic acid synthesis and mitosis?
Others - Flucytosine, Griseofulvin
What is the mechianism of action of Azoles?
Inhibit 14-alpha-demethylase (cytochrome p-450 enzyme) which is responsible for producing ergosterol
=> ergosterol deplete => inhibit membrane formation
Th. fungi is killed by:
- inhibition of growth (inhibition of membrane formation)
- increased permeability of membrane
- accumulation of toxic sterol intermediates in cell
Describe the interactions of Azoles with other drugs
Many drug interactions due to varying effects on human p450 enzymes
What are the two classes of Azoles?
Imidazoles
Triazoles
When are imidazoles used?
Only in topical treatment because of its toxicity
- treatment of candida
- treatment of tinea
Give examples of Imidazoles
Ketoconazole
Miconazole
Clotrimazole (an active ingredient in Canesten)
Give examples of Triazoles
Fluconazole
itraconazole
Voriconazole
What can Fluconazole be used against?
Candida, Cryptococcus, Dermatophytes
- Candida krusei often resistant
Fluconazole can be administered in which ways?
Topical
Oral - well absorbed from GIT
Rarely IV
Why does fluconazole give good systemic availability?
Penetrates CSF
Excreted unchanged by kidney
What can Voriconazole be used against?
Life-threatening Candida
Aspergillus infection
Voriconazole can be administered in which ways?
Oral
IV - avoid in renal impairment
What can Itraconazole be used against?
Candida
Aspergillus
Cryptococcus
Itraconazole can be administered in which ways?
Oral - varying availability
IV
Name two side effects specific to Itraconazole
Negative ionotrope => decreased muscle contractions
Liver damage and drug interactions
Name a side effect specific to Voriconazole
Visual impairment
What is the mechanism of Echinocandins, specifically Caspofungin?
Glucan synthase inhibitors
Caspofungin = weakens cell wall via inhibiting beta-glucan synthase
What can Caspofungin be used against?
Aspergillus
Candida
In which ways can Caspofungin be administered?
IV only
- must start with loading dose
- caution in hepatic impairment
What is the mode of action of Allylamines?
Inhibits ergosterol synthesis by inhibiting the enzyme squalene epoxidase
- Th. inhibits membrane synthesis
Give examples of Allylamines
Naftifine
Terbinafine
What is Terbinafine used for?
Superficial dermaphyte infections
- administerd topical or oral
What is the mode of action of Polyenes?
Increase membrane permeability by binding to Ergosterol
- Th. pore foormation and leakage of cations
Give examples of Polyenes
Amphotericin
Nystatin
What is Amphotericin active against?
Systemic Aspergillus
Candida
Cryptococcus
How can amphotericin be administered?
IV or intrathecally only
- negligible GI absorption
- high bound protein in blood
Why may amphotericin cause hypokalaemia?
Due to renal toxicity effects
What is nystatin used against?
Superficial candidiasis
- topical only
- nappy rash, thrush
What is the mode of action of Flucytosine?
Inhibits DNA synthesis by inhibiting enzymes needed to produce thymidlyic acid (req. for DNA synthesis)
Why must Flucytosine only be used in combination with Amphotericin?
Since resistance regularly occurs
What is the mode of action of Griseofulvin?
Inhibits fungal mitosis
- used for dermatophyte infections
What treatment would be used to treat vulvovaginal candidiasis?
Clotrimazole
alternative: Fluconazole
What treatment would be used to treat fungal nail infection?
Terbinafine
What treatment would be used to treat oral candidiasis?
Nystatin oral susension
Fluconazole = 2nd line
What treatment would be used to treat tinea pedis (athletes foot)?
Clotrimazole 1% cream
What treatment would be used to treat candidaemia (non-CNS)?
Fluconazole - oral
AmBisome = 2nd line
What treatment would be used to treat aspergillosis (non-CNS)?
Voriconazole IV
AmBisome = 2nd line
