Fungi part B Flashcards
why less antifungal drugs
fungi very similar to human cells
what mycoses are easier to treat?
• easier to treat superficial mycoses than systemic infections
ergosterol
Sterol found in fungal cell membranes;
human cells have cholesterol instead of ergosterol
where is egrosterol concentrated?
at the growing membrane ends
Polyene compounds
action
names and when used?
bind ergosterol in fungal membranes, Drugs cause altered membrane permeability,
leakage of cell constituents, and cell death
Amphotericin B: systemic disease
Nystatin: topical disease
polypenes also bind?
Polyenes also bind cholesterol in mammalian
cells, but less strongly than ergosterol
• this is basis for drug toxicity
• filipin is toxic due to binding of cholesterol
Abbreviated summary of the ergosterol biosynthetic pathway and the sites of action of ITZ
and TBF.
Allylamines action? name? mainyl effective on? formulations?
block ergosterol synthesis by inhibiting squalene epoxidase activity
terbinafine
mainly effective on the dermatophytes
topical or tablet formulations
Azoles
action?
names?
block ergosterol synthesis by inhibiting cytochrome P450-dependent 14a-lanosterol demethylation (c14 demethylase inhibiton)
ketoconazole and itraconazole
ketoconazole
First oral azole (significant number of side effect and drugs interactions)
itraconazole
active against?
improve safety?
Supplants ketoconazole
Active against many fungi and has improved safety profile.
Active against Candida species,Cryptococcus, Aspergillus, endemic (systemic) fungi, and dermatophytes.
Fungal cell wall structure diagram
Echinocandins action? selective? spectrum? why? name? mode of administration/ toxicity?
inhibit synthesis of b-(1,3)-D-glucan, an essential component of fungal cell walls.
More selective than agents that target cell membrane components.
Narrow spectrum: active against Aspergillus and Candida species; these fungi have larger amounts of b-(1,3)-D-glucan
Caspofungin - Intravenous use and minimal toxicity
Pyrimidine inhibition
effective against what spp?
why used with other agents?
interferes with fungal protein and DNA synthesis
Active against Candida species and Cryptococcus neoformans
Always used in combination with another antifungal because resistance develops quickly if used alone
High risk categories for oppurtunistic mycoses
Immunocompromised individuals: blood and marrow transplant solid organ transplant major surgery AIDS neutropenia neoplastic disease (cancer patients) immunosuppressive therapy (e.g. corticosteroids) advanced age premature birth
Burn victims
Long-term IV catheter users
Broad-spectrum antibiotic therapy
Diabetes mellitus
Candidiasis related spp/ important features?
Candida albicans= predominant species colonizing humans responsible for most infections
Candida glabrata= resistant to some antifungals
Candida parapsilosis= common cause of catheter-related infections
several other species of Candida
Candidiasis
local disease vs. systemic invasive disease protections?
what prevents mucosal candidiasis?
Adequate neutrophil function protects against invasive infection, mainly local infections
Local factors and T-cell mediated defense system protects against mucosal candidiasis.
Mucosal candidiasis due to?
Due to decreased T-cell mediated immunity
Other host factors associated with protection against Candida infections:
salivary flow and constituents
blood group & secretor status
epithelial barrier
presence of normal bacterial flora
Most common opportunistic fungal pathogen
candida spp
Oral Candida
infections
acute pseudomem acute erythematous chronic plaque-like chronic erythematous angular chelitis
acute pseudomem candidasis
removable white plaques
acute erhtmatous candidasis
generalized redness/ sore tissue
Plaquelike/nodularcandidiasis
fixed white plaque at the commissures, cannot be removed
Also called chronic hyperplastic candidiasis or candidal leukoplakia
Up to 40% of lesions develop into oral cancer
