antifungals Flashcards
Polyenes: amphotericin (IV) and nystatin (suspension powder) MOA
bind to ergosterol in the cell membrane leading to pore formation and efflux of K leading to cell death
which is has the broader spectrum: mphotericin (IV) and nystatin MOA
amphotericin B
the 2 majot toxicities for Amph-B
- infusion-related- cytokine release
2. nephrotoxicity- approx. 30% of pt. will have this
Nystatin is used for
mucocutaneous candidiasis only topical infections
inhibits squalene epoxidase activity early in ergosterol synthesis pathway; deficiency of ergosterol in fungal cell membrane leading to fungal cell death
terbinafine (allylamines)
terbinafine (allylamines) spectrum of activity
dermatophyte (skin and nail) infections
terbinafine (allylamines) side effects
change in tastes perception and decreased appetite
Azoles MOA
inhibit ergosterol synthesis in cell membrane
inhibition of cytochrome P450-dependent 14α-lanosterol demethylase activity
***all are metabolized via hepatic cytochrome P450 system and thus are associated with drug interactions
interactions differ with each agent
zoles: Toxicities (2 major)
- hepatitis
2. QTc prolongation
Fluconazole is not active against
Aspergillus spp
First line therapy for Invasive Pulmonary Aspergillosis
voriconazole
voriconazole polymorphisms in CYP2C19 can lead to_________ metabolism
________ CYP43A4 – anticipate drug interactions
voriconazole polymorphisms in CYP2C19 can lead to slow or rapid metabolism
Inhibits CYP43A4 – anticipate drug interactions
voriconazole adverse effects
vision changes
Clinical uses: mucosal candidiasis, systemic candidiasis, Cryptococcosis
**Penetrates most body tissues including CNS, eye, and urine
fluconazole
Commonly used for prophylaxis of invasive fungal infection in stem cell transplant patients and patients with prolonged neutropenia
posaconazole
Mechanism of action
Disrupt fungal cell wall
inhibit Beta-(1,3)-D-glucan synthase
Beta-(1,3)-D-glucan is a fungal cell wall polysaccharide essential for Candida and Aspergillus species
Echinocandins
Echinocandins fungicidal against
candida spp
Echinocandins side effect
minimal!!!!! it is a selective fungal cell wall target
Flucytosine
MOA
Interrupts fungal DNA and protein synthesis by inhibiting pyrimidine inhibitors
Flucytosine resistance and tox
Resistance rapidly develops with monotherapy
and bone marrow suppression
Echinocandins (Caspofungin
) have minimal toxicity because
mammalian cells do not have cell walls
