Anti-fungals Flashcards
Amp B - Class
Polyene
Amp B - MOA
Ergosterol -> pores -> electrolytes leak -> cell membrane
Amp B - Spectra
Cryptococcus
Candidiasis
Histoplasmosis
Asperigillus
Amp B - Formulation
Formulation: Na deoxycholate (conventional) Aritifical lipids (liposomes)
Amp B - Liposomes
Reduced renal toxicity
Increased CSF penetration
Costly
Amp B - PK
Poor CSF penetration
Renal dysfx - dose adjustment
Amp B - SE
Fevers, chills, thrombophlebitis - slow infusion
Nephrotoxicity - CI in renal impairment
Ototoxicity
HypoTN - may require K supplement
5-FC - Class
Fluorinated pyrimidine analogue
5-FC - MOA
Cytosine permease -> Cytosine deaminase -> 5-FU ->
1) FUTP -> Uridylic acid -> Protein synthesis
2) FdUMP -> Thymidylate synthase -> DNA synthesis
5-FC - Fungistatic/cidal?
Fungistatic
5-FC - Clinical
ONLY Combi w AmpB for Candidiasis & Cryptococcus ( cannot be used alone)
5-FC - PK
Good oral
Penetrate CSF
Renal dysfx - dose adj
5-FC - SE
GI
BM suppression
Hepatotoxicity
Echinocandins - MOA
Inhibit B-1,3-glucan synthase complex -> Cell wall
Echinocandins - PK
Poor oral
No CSF
Renal dysfx - No dose adj needed
Liver dysfx - Dose adj
Echinocandins - Clinical
1st line - Invasive candidiasis
2nd line - Invasive aspergilliosis
Triazoles - MOA
Inhibit C-14 a-demethylase -> Block conversion from Lanosterol to Ergosterol -> Cell membrane
Name the 3 Triazoles
Fluconazole
Itraconazole
Voriconazole
Fluconazole (Triazole) - Spectra
Candidiasis Cryptococcous Histoplasmosis Blastomycosis Vulvovaginal candidiasis - single oral dose Fungal meningitis
Fluconazole (Triazole) - PK
Good oral
Good CSF
Renal dysfx - dose adj
Excreted unchanged in urine = Good for UTI
Itraconazole (Triazole) - PK
Good oral
Poor CSF
Low pH better for absorption (Take w/ food & coke)
Voriconazole (Triazole) - PK
Good oral
Good CSF
Itraconazole (Triazole) - Spectra
Broader than Fluconazole Blastomycosis Asperigillosis Onychomycosis Oral candidiasis (oral solution)
Voriconazole (Triazole) - Spectra
Broad spec
1st line - Invasive asperigillosis
Candida
Triazoles - SE/CI
N/V Hepatotoxicity QT prolongation Cardiotoxicity (Itraconazole) Neurotoxicity - Visual disturbance (Voriconazole) CI: Pregnancy
Triazoles - DDI
Inhibit CYP3A4
- Warfarin
- Cyclosporine
- Oral hypoglycemic agents
Clotrimazole (Imidazoles) - Spectra
Dermatophytes
Oropharyngeal candidiasis
Vulvovaginal candidiasis (Cream)
Name the 2 Imidazoles
Clotrimazole
Miconazole
Imidazoles - Formulation in vulvovaginal candidiasis
Clotrimazole - cream
Miconazole - Pessary
Miconazole (Imidazoles) - Spectra
Tinea Vulvovaginal candidiasis (Pessary)
Nystatin - Class
Polyene
Nystatin - MOA
Similar to AmpB
Nystatin - Spectra
Oropharyngeal candidiasis (mouthwash) Vulvovaginal candidiasis (intravaginal) Cutaneous candidiasis (Topical) GI fungal infections
Imidazoles - SE
Skin irritation
Edema
Nystatin - SE
Skin irritation
Terbinafine - MOA
Inhibit squalene epoxidase -> Block conversion of squalene to lanosterol -> Cell membrane
Terbinafine - Spectra
Trichophyton
Onychomycosis
Tinea captitis (Oral)
Oral formulations of what 2 antifungals for Tinea captitis?
Itraconazole
Terbinafine
Terbinafine - PK
Poor oral
Extensive metabolism by CYP
Excreted mainly in urine
Hence avoid in hepatic & renal dysfx
Terbinafine - SE/CI
GI
Hepatic failure
Exacerbate SLE
Avoid in breastfeeding
Terbinafine - Pregnancy?
Vaginal > Oral
Terbinafine - DDI
with Azoles = Increase serum [Terbinafine]
Incr halflife of SSRI/MAOIs
