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48 Cards in this Set
- Front
- Back
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What are the two classes of azole drugs? |
Imidazoles (miconazole)
Triazoles (fluconazole) |
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In general, (imidazoles or triazoles?) are more slowly metabolized and have a smaller effect on human sterol metabolism |
Triazoles |
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Mechanism of action of the azole drugs |
Inhibition of lanosterol demethylase (ERGII) |
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Why do the azole drugs cause side effects? |
1) Human lanosterol demethylase is similar to the fungal form of the protein and can be inhibited by azole drugs
2) Lanosterol demthylase is a CYP enzyme, and azole drugs can inhibit human CYPs |
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Why shouldn't azole antifungals be administered with cyclophosphamide? |
Cyclophosphamide is a prodrug that is activated by CYPs, so co-administration with azole antifungals can reduce its serum levels |
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Resistance to azole antifungals usually involves... |
Mutations in lanosterol demethylase |
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What is the prototypical triazole? |
Fluconazole |
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Fluconazole is the drug of choice for... |
Candidosis
Cryptococcal or coccidioidal meningitis |
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How is fluconazole administered? |
Orally
I.V. |
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Can fluconazole cross the blood-brain barrier? |
Yes |
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Side effects of fluconazole |
Nausea
Vomiting
Rash
Significant drug interactions (warfarin, cyclosporine, phenytoin, lovastatin, oral hypoglycemics, and protease inhibitors) |
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What is the prototypical imidazole? |
Miconazole |
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What are the two prototypical polyenes? |
Amphotericin B
Nystatin |
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What is the mechanism of action of the polyenes? |
They bind to ergosterol and disrupt the cell membrane, causing leakage of electrolytes and small molecules |
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Amphotericin B is effective against a (broad or narrow?) spectrum of fungi |
Broad |
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Is resistance to amphotericin B common? |
No |
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Side effects of amphotericin B |
Fever, chills, and allergic reactions following I.V. injection
Renal dysfunction (dose-limiting) |
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Nystatin is used only for... |
Topical treatment
Oral candidosis |
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Side effects of nystatin |
Minimal when used topically
Highly toxic after parenteral administration |
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Which fungi are sensitive to azoles and polyenes? |
Candida albicans
Histoplasma capsulatum
Blastomyces dermatitidis
Cryptococcus neoformans |
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Which fungi are insensitive to azoles and polyenes? |
Candida glaburata
Microsporum canis/audouini |
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How are Candida glaburata infections treated? |
Topical flucytosine and boric acid |
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What is the mechanism of action of flucytosine? |
Selectively enters fungal cells via a cytosine-specific permease enyzme, where it is converted to the active metabolites 5-FU and 5-FdUMP which inhibits thymidylate synthase |
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Why aren't mammalian cells affected by flucytosine? |
They do not convert flucytosine to fluorouracil |
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Resistance to flucytosine arises through... |
Decreased uptake of the drug or decreased cytosine deaminase activity |
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How is flucytosine administered? |
Orally |
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Does flucytosine cross the blood-brain barrier? |
Yes |
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Flucytosine is always administered with ____ to slow development of resistance |
Amphotericin B |
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Side effects of flucytosine |
Bone marrow depression (leucopenia and thrombocytopenia)
Nausea, vomiting, and diarrhea due to the release of 5-FU by the gastrointestinal flora |
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How are Microsporum canis/audouini infections of hair and nails treated? |
Griseofulvin |
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What is the mechanism of action of griseofulvin? |
Binds to polymerized microtubules, disrupting the mitotic spindle and blocking replication in mitosis |
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Why doesn't griseofulvin affect mammalian cells? |
It is very specific to fungi |
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What other drug has a mechanism that is similar to griseofulvin's? |
Paclitaxel |
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How is griseofulvin administered? |
Orally |
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Where does griseofulvin accumulate in the body? |
In skin at sites of newly synthesized keratin-containing tissues |
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Side effects of griseofulvin |
CYP inducer (drug interactions) |
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What is the mechanism of action of terbinafine? |
Inhibition of squalene epoxidase (an enzyme in the synthesis of ergosterol) |
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How is terbinafine administered? |
Topically
Orally |
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Where does terbinafine accumulate when administered orally? |
In skin and especially at nail beds |
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Terbinafine is used to treat.... |
Fungal infection of nails
Tinea infections |
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What is the mechanism of action of caspofungin? |
Non-competitive inhibition of fungal cell wall synthesis |
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Caspofungin is active against... |
Candida and Aspergillus species |
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Caspofungin is not active against... |
Histoplasma species |
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Caspofungin is approved for treatment of... |
Invasive aspergillosis and esophageal candidosis where amphotericin B or fluconazole have failed |
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Is there cross-resistance against amphotericin B/fluconazole and caspofungin? |
No |
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How is caspofungin administered? |
I.V. |
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For which type of diseases would caspofungin be useful? Why? |
Systemic infections, because it is administered I.V. |
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Side effects of caspofungin? |
Phlebitis and histamine-like reactions at the injection site |
