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50 Cards in this Set
- Front
- Back
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What is the mechanism of Amphotericin B?
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Formation of a pore in the fungal membrane by binding to ergosterol
FUNGICIDAL |
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What is the mechanism of resistance to Amphotericin B?
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Rare
When it does happen, it's due to the alteration in membrane ergosterol |
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What is the absorption of Amphotericin B?
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None in the GI tract
Administered via IV |
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What is the distribution of Amphotericin B?
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Widely distributed
Sequestered into cell membranes (think logically here: sterols in human membranes. Side effects, long distribution) Poor CSF penetrance |
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What is the metabolism and half life of Amphotericin B?
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Terminal half life of 15 days
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What is the excretion of Amphotericin B?
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2-5% excreted unchanged in the urine after IV dose.
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What are the adverse effects of Amphotericin B?
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Fever within an hour
NEPHROTOXICITY Anemia |
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What formulation of Amphotericin B decreases nephrotoxicity?
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Lipid formulation
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What is the mechanism of nephrotoxicity with Amphotericin B?
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Binding to the sterols inside kidney cell membranes, increasing perameability
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What are the clinical uses of Amphotericin B?
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Broad spectrum antifungal
IV administration for severe fungal infections |
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What other antifungal drug is Amphotericin B commonly administered with?
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Flucytosine
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What other antifungal drug is Flucytosine commonly administered with?
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Amphotericin B
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What enzyme is necessary for the activation of 5-Flucytosine? Where is it found?
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Cytosine deaminase
Inside fungi |
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What is the active form of 5-Flucytosine? What kind of drug is this normally?
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5-Fluorouracil
A chemotherapeutic |
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What is the mechanism of action of 5-Flucytosine?
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Inhibition of DNA synthesis through blocking of thymadylate synthase
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In what situations does resistance to 5-Flucytosine develop?
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When the drug is used alone.
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What are the mechanisms of resistance to 5-Flucytosine?
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Decreased uptake of the drug through alterations of membrane transporters
Decreased activation of the drug by cytosine deaminase |
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What is the bioavailability of 5-Flucytosine?
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Very available orally
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What is the distribution of 5-Flucytosine?
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Widely distributed
PENETRATES THE CSF WELL! |
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What are antifungal drugs that can penetrate the CSF?
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5-Flucytosine
Fluconizole |
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What is the metabolism and half life of 5-Flucytosine?
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Needs to be metabolized to 5-florouracil by cytosine deaminase for activity
T1/2 = 3-6 hr. |
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What is the excretion of 5-Flucytosine?
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80% excreted unchanged in urine
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What are the adverse effects of 5-Flucytosine?
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Bone marrow toxicity
Elevation of hepatic enzymes GI irritation All of these are more prevalent in AIDS patients |
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What is the mechanism of bone marrow toxicity by 5-Flucytosine?
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Conversion of 5-Flucytosine to 5-Fluorouracil by GI flora
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What is the typical clinical use of 5-Flucytosine + Amphotericin B?
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Severe Cryptococcus infections
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What is the mechanism of action by Azole antifungals.
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Inhibition of lanosterol 14-alpha-demethylase
Can't convert lanosterol to ergosterol FungiSTATIC |
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Are the Azoles highly selective for fungal enzymes?
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No...not too terribly selective.
IC50 is only 10X greater in humans. |
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What are the mechanisms of resistance to the Azole antifungals?
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Decreased accumulation of azole due to increased efflux by ATP binding cassette proteins
Decreased affinity of lanosterol-14alpha-demethylase for the azole Overepxression of lanosterol-14alpha-demhtylase |
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What are the four Azole antifungals?
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Fluconazole
Itraconazole Voriconazole Posaconazole |
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What is the Azole antifungal that penetrates the CSF?
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Fluconazole
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What is the Azole antifungal that is metabolized in a short period of time?
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Voriconazole
6 hrs. |
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What are the two Azole antifungals that are excreted in the bile?
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Itraconazole
Posaconazole |
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What is the Azole antifungal that is excreted renally and penetrates the CSF?
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Fluconazole
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What is the absorption of Azole antifungals?
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Orally bioavailable
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What are the adverse effects of Azole antifungals?
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GI disturbances
Hepatotoxicity Teratogenic to fetuses: DON'T USE IN PREGNANCY! |
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What is the Azole antifungal that causes visual disturbances?
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Voriconazole
See funny colored lights |
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What liver enzyme does the Azole antifungals effect? What is the effect?
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CYP3A4, a hepatic P450 enzyme. Inhibition
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What enzyme metabolizes the Azole antifungals?
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CYP3A4
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What is an example of a drug that can decrease the plasma levels of Azole antifungals? How?
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Rifampin
The induction of P450s. |
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What are the clinical uses of Azole antifungals?
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Broad spectrum activity
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What is a unique uses of Fluconazole?
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Coccidioidal meningitis
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What is safer for patients, Voriconazole or Amphotericin B?
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Voriconazole.
Less fever, less nephrotoxicity. |
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What is an example of a echinocandin?
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Caspofungin
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Caspofungin is a member of what antifungal drug class?
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Echinocandins
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What is the mechanism of action of the echinocandins?
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Inhibition of the synthesis of Beta-1,3-D-glucan
Fungicidal |
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What is the absorption of Caspofungin?
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Not orally absorbed
IV administration |
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What is the distribution of Caspofungin?
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Well distributed
DOESN'T PENETRATE THE CSF! |
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What is the metabolism and half life of Caspofungin?
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Extensive metabolism
Long terminal half life: 40-50 hr. |
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What are the adverse effects of Caspofungin?
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Flushing
Fever Infusion-related phlebitis Headache Elevation of liver enzymes |
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What are the clinical uses of Caspofungin?
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Candida infections, especially candida galbrata, which is resistant to the azole antifungals.
Invasive aspergillosis |
