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41 Cards in this Set
- Front
- Back
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What is the most common type of mucocutaneous oral fungal infection
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candidiasis
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Antifungal MOA:
polyene antibiotics griseofulvin antimetabolites |
-bind ergosterol which compromises fungal cell membrane
-assc w/microtubules -pyrimidine analog to inhibit fungal DNA/RNA synthesis |
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antifungal MOA:
azoles allylamines glucan synthesis inhibitors |
-block ergosterol synthesis by binding to fungal P450
-block ergosterol synth at diff step -inhibit glucan synthesis (cell wall component) |
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Which antifungal has the broadest spectrum
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-amphotericin B
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Which antifungal is the drug of choice in life-threatening fungal infections
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amphotericin B
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Amphotericin B
-cidal/static -MOA |
-cidal, but can be static only
-binds ergosterol to form membrane pores (alters permeability, leaks ions, cell dies) |
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amphotericin B selective toxicity
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-mammalian cells don't have ergosterol (cholesterol)
-binds cholesterol much less, but still does (toxicity) |
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How does resistance develop to amphotericin B
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-when binding of drug to ergosterol is impaired
1) decreased ergosterole (tx w/azoles) 2) ergosterol affinity for ampB decreased |
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amphotericin B
-absorption -delivery |
-poorly from GI, so only used topically for superficial infections or parenterally for systemic
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amphotericin B
-metabolism -disribution |
-extensive, kidney excretion
-distrubtion based on formula |
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adverse effects of amphotericin b:
topical oral IV |
-local irritation
-local/mild GI irritation -fever, chills, muscle spasms, headache, hypotension, allergic rxn, reversible nephrotoxicity, anemia (from reduced epo) |
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What is the most importan of the amphotericin B toxicity
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-nephrotoxicity - almost always seen w/IV administration
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Three drugs that interact w/amphotericin B
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digitalis - heart failure due to hypokalemia
azoles - cause fungi to be resistant to amp-B nephrotoxic agents - aminoglycosides, cyclosporines enhance the renal toxicity |
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What are the three key differences b/t nystatin and amphotericin
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-narrower spectrum of activity
-too toxic to be used parenterally -not metabolized |
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What is nystatin used to tx
side effects |
-candidal infections of oral cavity
-bitter and unpleasant taste |
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Griseofulvin
-static/cidal -used to tx what -MOA -drug effects |
-static
-dematophytosis (hair, skin, nails) -interacts with polymerized microtubules to block mitosis -induces CYP isoforms - other drugs affected (warfarin, oral contraceptives) |
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flucytosine
-used to tx what -static/cidal |
-systemic fungal infections
-static |
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flucytosine
MOA |
-cytosine deaminase in fungus converts it to 5-fdUMP which compete to block fungal DNA synthesis, also incorporated to make defective RNA
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flucytosine
-selective toxicity |
-human cells can't convert to 5-FU
-uptake in human cells is poor |
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flucytosine
-how is it usually prescribed |
-in combon with amphotericin B to work synergistically
-poor therapeutic index alone |
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Flucytosine
-basis for resistance -oral/CNS/excretion |
-mutations in cytosine permease or cytosine deaminase
-good oral bioavailability, good CNS penetration, renal excretion |
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flucytosine adverse effects
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-GI intolerance, depresses bone marrow b/c bacteria in gut can convert it to 5-FU which is an anti-cancer drug
-results in anemia, leukopenia, thrombocytopenia |
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name the three members of the imidazole class and what makes them in this class
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-ketoconazole
-miconazole -clotrimazole -azole ring contains 2 N atoms |
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name the two members of the triazoles and what makes them in this class
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-fluconazole
-itrconazole -azole ring contains 3 N atoms |
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Azoles in general
-static/cidal -MOA -selective toxicity |
-static
-inhibit ergosterol synthesis and accumulate lanosterol -affect fungal CYPs greater than mammalian CYPs |
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Which type of antifungal is much less specific so it has greater incidence of unwanted drug interactions
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imidazoles - also can cause hepatitis
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How does ketoconazole differ from the other imidazoles
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-greater propensity to inhibit mammalian CYPs
-inhibits adrenal and gonad hormone synthesis -interferes w/metabolism of other drugs |
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What is the only imidazole used systemically
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ketoconazole
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What major side effect is the reason ketoconazole is limited in use systemically
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-symptomatic hepatitis
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T/F - miconazole is available systemically
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-false, too toxic, only topical
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What is clotrimazole ideal for treating
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-candidiasis as an alternative to nystatin (more effective and tastes better)
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Three reasons itraconazole is better than ketoconazole
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-broader spectrum
-faster onset -less impact on mammalian CYPs |
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What is itraconazole used to tx
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-aspergillus
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Which azole has good CNS penetration and is used to treat fungal meningitis
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fluconazole
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T/F - some organisms have intrinsic resistance to fluconazole
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-true
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Three uses for fluconazole
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-first line agent for invasive infections by candida
-refractory mucocutaneou candidiases -prophylaxis in IC pts |
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Voriconazole is more potent than what two antifungals
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-itraconazole or fluconazole
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T/F - voriconazole is useful against aspergillus
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-true
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allylamines:
-structure -MOA -spectrum |
-terbinafine
-inhibits ergosterol by blockign squalene epoxidase -effective against dermatophytes |
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Allylamines are good for dermatophyte infections why
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-good absorption from GI tract, lipophilic and accumulate in skin, nails and fatty tissues
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Glucan synthesis inhibitors
MOA Spectrum |
-inhibits glucan synthesis = weakens cell wall
-primary aspergillus and candida, IV administration |
