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A&D 2010: Antifungals
Gah
96
Medical
Professional
01/31/2007

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Term
Treatment for superficial mycoses
Definition
* Polyenes, azoles in creams
* Also griseofulvin, allylamines
Term
Treatment for systemic mycoses
Definition
* Polyenes azoles
* In combination with 5-flucytosine
Term
What type of local therapy can be used for vulvovaginal candidiasis?
Definition
Pessary
Term
Oral therapy is used for what type of mycoses
Definition
Skin and nail infections for up to one year
Term
Systemic mycoses are treated via what route?
Definition
Oral or IV
Term
Major chemical feature of polyenes
Definition
They are amphipathic and therefore capable of inserting into membranes
Term
What do polyenes primarily bind to?
Definition
Sterols with poor specificity, mainly ergosterol
Term
Polyene used for systemic fungal infections
Definition
Amphotericin B (IV)
Term
Why are the polyenes toxic?
Definition
Cross-reaction with cholesterol in host cell
Term
How are the polyenes administered
Definition
Chiefly IV because of poor absorption; can be given p.o. to treat GI infections
Term
Polyene used for topical treatment of superficial dermatophytoses, including oral and intestinal Candida infections
Definition
Nystatin
Term
Adverse reactions of systemic polyene administration
Definition
* Fever
* Nephrotoxicity
* Hypokalemia (cardiotoxicity)
Term
Less toxic form of polyenes
Definition
Lipid formulations of amphotericin B
Term
How polyenes disrupt fungal membranes
Definition
Multiple polyenes bind, form pore and cause lysis
Term
Primary antifungals used
Definition
Polyenes
Term
T/F: Most antifungal therapy uses amphipathic drugs
Definition
True (polyenes are amphipathic)
Term
Are most antifungals fungocidal or -static?
Definition
Fungocidal
Term
Mechanism of action of azoles
Definition
Inhibit synthesis of ergosterol
Term
Clinical uses of ketoconazole
Definition
* Systemic and mucocutaneous infections
* Prevention of Candida infection in immunocompromised
Term
Is ketoconazole good against cryptococcal meningitis?
Definition
No because it doesn't get into CNS well
Term
Adverse reactions of ketoconazole
Definition
* GI distress
* Hepatotoxicity
* Steroid synthesis inhibition
Term
Why fluconazole is less toxic to humans
Definition
Less active against mammalian cytochrome P450
Term
Relative antifungal spectra of ketoconazole, fluconazole, and itraconazole
Definition
Itraconazole > fluconazole > ketoconazole
Term
Itraconazole toxicity
Definition
* Many CYP interactions
* Hepatotoxicity
Term
Topically tend to be imidazole or triazoles?
Definition
Imidazole
Term
Biggest concern of azole administration
Definition
Resistance, which is why 3rd generation of azoles were created
Term
Broadest class of azoles
Definition
Itraconazoles
Term
Drugs that inhibit squalene epoxidase
Definition
Allylamines (eg, terbinafine)
Term
Consequences of squalene epoxidase inhibition
Definition
* Buildup of intracellular squaline (fungotoxic)
* Decreased ergosterol synthesis
Term
Adverse reactions to terbinafine
Definition
* GI distress
* Taste disturbances
* Hepatotoxicity
Term
Therapeutic niche for terbinafine
Definition
* Tinea cruris
* Tinea corporis
Term
General class of antifungals associated with cell wall synthesis inhibition
Definition
Echinocandins
Term
Antifungal that inhibits beta-(1,3)-glucan synthase
Definition
Caspofungin
Term
Fungal targets of caspofungin
Definition
* Candida
* Aspergillus
Term
Adverse reactions of caspofungin
Definition
* Nausea
* Vomiting
* Fever
* Phlebitis
Term
Inhibitor of beta-(1,3)-glucan synthase
Definition
Caspofungin
Term
Mechanism of action of flucytosine and fluorouracil
Definition
Inhibition of DNA and RNA synthesis
Term
Caspofungin inhibits a beta-(1,3)-glucan synthase that is active during what stage of fungal growth?
Definition
During formation of bud (thus very effective against yeast cells while not great against filamentous except for Aspergillus)
Term
Why caspofungin might be less effective against hyphal organisms than budding organisms
Definition
* Hyphae generally more stable
* Don't form cell wall septa
Term
Are flucytosine and fluorouracil effective if administered alone?
Definition
No, because of side effects
Term
Fluorouracil is an inhibitor of what stages of metabolism?
Definition
RNA and DNA synthesis
Term
Active form of 5-flucytosine
Definition
5-Flurouracil
Term
Antifungals that interacts with polymerized microtubules and keratin
Definition
Griseofulvin
Term
Mechanism of mitosis inhibition of griseofulvin
Definition
Disrupt mitotic spindle by binding polymerized microtubules
Term
Side effects of griseoflvin
Definition
* Transient headache
* Mental confusion, fatigue, visual impairment
* GI distress
Term
Niche uses of griseofulvin
Definition
Superficial dermatophytes
* Trichophyton
* Epidermophyton
* Microsporum
Term
How fungi cause disease
Definition
* Allergy
* Toxins
* Destroy tissue (mycosis)
Term
Morphology of most pathogenic fungi
Definition
Yeast or molds
Term
How do fungi get their nutrients?
Definition
Feed on dead or decaying tissue (hence saprophytic)
Term
Three locations of fungal infections
Definition
* Superficial
* Subcutaneous
* Systemic
Term
Fungal species associated with lung and meningeal infections
Definition
Cryptococcus neoformans
Term
Fungal species associated with oral and GI tract infections
Definition
Candida albicans
Term
Fungal species associated with subcutaneous infection of the arms and hands
Definition
Sporothrix schenckii
Term
Fungal species that causes Athlete's foot (superficial infection of skin and between toes)
Definition
* Epidermophyton
* Trichophyton
Term
Fungal genome ploidy
Definition
Can be haploid or diploid
Term
Fungal cell wall components
Definition
* Chitin
* Glycoproteins (mannans, glucans)
Term
Monomeric subunit of chitin
Definition
N-acetylglucosamine
Term
Are fungi autotrophs or heterotrophs?
Definition
Heterotrophs, specifically saprophytes (live on dead organic matter)
Term
How do fungi obtain nutrients?
Definition
Secrete degradative enzymes (proteases, lipases, glucanases, etc.) into immediate invironment
Term
Natural fungal habtat
Definition
Moist environment (soil, water) containing decaying organic matter
Term
Morphological transition required for virulence in C. albicans
Definition
Budded-to-hyphal transtion
Term
Fungal morphology associated with filamentous growth of cells with well defined borders
Definition
Pseudohyphal growth
Term
Fungal morphology associated with filamentous growth of cells whose borders are not easily discerned
Definition
Hyphae
Term
Do both fungi and bacteria have sterols in their cell membranes?
Definition
No, only fungi (and other eukaryotes) have sterols. (Mycoplasma is the one bacterial species that violates this rule; it does have sterols in its cell membrane.)
Term
Do fungi have generally have endo- and exotoxins?
Definition
No
Term
Saccharomyces cerevisiae and Neurospora crassa exist vegetatively in a haploid or diploid state?
Definition
Both
Term
Are ascospores similar to bacterial endospores?
Definition
No; ascospores are sexual spores intended for fungal reproduction, while endospores are intracellular spores that provide protection.
Term
Another name for meiosis in fungi
Definition
Sporulation
Term
How does Saccharomyces cerevisiae generate zygotes?
Definition
Haploid ascospores of the a and alpha variety join together
Term
Primary method by which filamentous fungi reproduce and spread within the environment
Definition
Ascospores
Term
Structure responsible for fungal color as seen on food
Definition
Conidia
Term
How are conidia and ascospores developed?
Definition
* Conidia: asexually (mitosis of a haploid cell)
* Ascospores: sexually (meiosis of a diploid cell)
Term
What type of spore is often used to identify fungal species?
Definition
Conidia
Term
Species of what two fungal genera cannot be discerned under the microscope?
Definition
* Aspergillus
* Candida
Term
Non-culture methods using antigens are useful for differentiating between species of what two fungal genera?
Definition
* Cryptococcus
* Histoplasma
Term
Dye used to stain conidia
Definition
Lactophenol cotton blue
Term
How is a 10% KOH solution useful for identifying fungal infections?
Definition
Solution dissolves mammalian tissue to isolate fungal cells
Term
Stains used histologically to stain fungi pink or black
Definition
* Pink: Periodic acid Schiff (PAS)
* Gomori's methenamine silver (GMS)
Term
Spherules visible on microscopy is suggestive of a fungal infection by what organism?
Definition
Coccidioides
Term
Typical immune response to fungi
Definition
Cell-mediated (humoral response isn't useful)
Term
Why Candida albicans is so frequently seen in nosocomial infections
Definition
It's a commensal organism
Term
Between 1980 and 1990, the frequency of what type of fungal infection increased the most?
Definition
Bloodstream infections (400%)
Term
Fungi capable of avoiding clearance in the lungs
Definition
* Aspergillus
* Cryptococcus
* Histoplasma
Term
C. albicans must grow in what form in order to penetrate epithelium?
Definition
Hyphae
Term
Does auxotrophy make an organism more, or less virulent?
Definition
Less virulent
Term
Fungal goals achieved by fungus-mediated host tissue necrosis
Definition
* Overcomes tissue barriers
* Provides nutrients for fungus
Term
Deletion of what protease genes can cause attenuated virulence in C. albicans?
Definition
SAP1-3 genes
Term
Two mechanisms by which C. albicans can cross epithelial barriers?
Definition
* Induced phagocytosis (like Salmonella)
* Hyphal penetration
Term
What fungal organisms require a budded-hyphal transition for virulence?
Definition
* Candida
* Histoplasma
Term
What fungal species can grow as yeast or hyphae?
Definition
* Blastomyces
* Candida
* Histoplasma
Term
Once C. albicans reaches the blood, what form does it assume?
Definition
Budded form (following a hyphal-to-budded transition)
Term
Define spherules
Definition
Multinucleate cells containing hundreds of Coccidioides endospores
Term
During what phase of growth do Coccidioides form spherules?
Definition
Saprophytic phase (a form of hyphal growth)
Term
Fungi that secrete phospholipases targeting the host cell membrane
Definition
* Aspergillus
* Candida
* Cryptococcus
Term
Unique characteristics of Candida and Histoplasma required for virulence
Definition
Budded-to-hyphal transition
Term
Fungi that can degrade cell membranes with phospholipases
Definition
* Aspergillus
* Candida
* Cryptococcus
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