5.46 Part B Flashcards
Antifungal Drugs
• fewer effective agents because of similarity
of
• easier to treat — mycoses than — infections
fungal cells and human cells
superficial, systemic
ergosterol
Sterol found in fungal cell membranes;
human cells have cholesterol instead of
ergostero
Antifungal treatments
Polyene compounds -
bind ergosterol in fungal membranes
Polyene compounds
examples (2)
Amphotericin B systemic disease
Nystatin topical disease
Polyene compounds - Drugs cause (3)
altered membrane
permeability,
leakage of cell constituents, and cell death
Polyenes also bind — in mammalian
cells, but less strongly than ergosterol
cholesterol
Polyenes also bind cholesterol in mammalian
cells, but less strongly than ergosterol
• this is basis for —
• — is toxic due to binding of cholesterol
drug toxicity
filipin
terbinafine (TFB) to
itraconazole (ITZ)
Allylamines-
block ergosterol synthesis by inhibiting
squalene epoxidase activity
Allylamines ex
terbinafine
Allylamines
mainly effective on the —
(2) formulations
dermatophytes
topical or tablet
Azoles
block ergosterol synthesis by inhibiting cytochrome
P450-dependent 14a-lanosterol demethylation
Azoles
First oral azole (significant number of
(2)).
side effect and drugs interactions
Supplants ketoconazole
Active against many fungi and has improved
safety profile. Active against Candida species,
Cryptococcus, Aspergillus, endemic (systemic)
fungi, and dermatophytes.
Echinocandins
inhibit synthesis of b-(1,3)-D-glucan, an
essential component of fungal cell walls.
More selective than agents that target cell
membrane components.
Echinocandins
Narrow spectrum:
active against Aspergillus and Candida species;
these fungi have larger amounts of b-(1,3)-D-glucan
Caspofungin (2)
- Intravenous use
- minimal toxicity
Pyrimidine inhibition -
interferes with fungal protein and
DNA synthesis
Pyrimidine inhibition Active against (2)
Candida species and Cryptococcus neoformans
Pyrimidine inhibition
Always used in combination with another antifungal because
resistance
develops quickly if used alone
High risk categories (5)
Immunocompromised individuals: Burn victims Long-term IV catheter users Broad-spectrum antibiotic therapy Diabetes mellitus
Immunocompromised individuals:
9
blood and marrow transplant solid organ transplant major surgery AIDS neutropenia neoplastic disease (cancer patients) immunosuppressive therapy (e.g. corticosteroids) advanced age premature birth
Candida albicans
predominant species colonizing humans
responsible for most infections
Candida glabrata
resistant to some antifungals
Candida parapsilosis
common cause of catheter-related infections
Candidiasis
local disease vs. systemic invasive disease
Adequate neutrophil function protects against invasive infection.
Local factors and T-cell mediated defense system protects against
mucosal candidiasis
Mucosal candidiasis on palate
of a patient with AIDS
Due to
decreased T-cell
mediated immunity (however,
no invasion of tissue here)
Other host factors associated with
protection against Candida infections:
(4)
salivary flow and constituents
blood group & secretor status
epithelial barrier
presence of normal bacterial flora