Details Title: A&D 2010: Antifungals Description: Gah Total Flash Cards: 96 Created: 01/31/2007 06:05:17		New Users: To study from this flashcard set, or to create your own your own study flash cards, REGISTER HERE. Existing Users: CLICK HERE. Additional Medical Flashcards
Cards in this set: 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