Term
Amphotericin B
Natamycin
Nystatin |
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Definition
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Term
Naftifine
Terbinafine
Butenafine
Tolnaftate |
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Definition
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Term
Caspofungin
Anidulafungin
Micafungin |
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Definition
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Term
Fluconazole
Itraconazole
Ketoconazole
Posaconazole
Terconazole
Voriconazole |
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Definition
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Term
cell wall
mitotic spindles
DNA synthesis
Cellular metabolism |
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Definition
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Term
fungi: eukaryotes, cell wall & cell membrane, ergosterol
mammals: eukaryotes, cell membrane, cholesterol
bacteria: prokaryotes, cell wall & cell membrane, peptidoglycan |
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Definition
| biochemical differences between mammalian, fungal, and bacterial cells |
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Term
[image]
ergosterol vs cholesterol
fungal cell walls consist of ergosterol and mammal cell membranes consist of cholesterol
the B ring of ergosterol has an extra double bond that makes the ring system more planer, also the alkyl double bond makes the molecule more rigid
cholesterol in membranes makes it more fluid
ergosterol in the wall makes it more rigid (more tightly packed) |
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Definition
| *chemical differences between ergosterol and cholesterol* |
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Term
macrocyclic lactones with hydrophilic and lipophilic regions
bind ergosterol
higher affinity for ergosterol than cholesterol = selective toxicity
polyenes become part of the fungi cell membrane creating a pore
disruption of the membrane interferes with fungi cell respiration (loss of K+) and glycolysis
FUNGICIDAL |
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Definition
| *MOA of polyenes: Amphotericin B, Nystatin, Natamycin* |
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Term
[image]
Amphotericin B
[image]
Nystatin
missing double bond makes nystatin so toxic it can only be used topically |
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Definition
| *chemical structure differences between Amphotericin B and Nystatin (polyenes that bind ergosterol)* |
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Term
resistance during treatment is uncommon; polyene-resistant yeast infections develop in high risk cancer patients
tolerance varies
CSF levels low - too large to cross the BBB
Slow IV administration
metabolism unknown
elimination of most of the drug unknown |
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Definition
| resistance and ADME of polyenes (Amphotericin B, Nystatin, and Natamycin) |
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Term
ergosterol biosynthesis inhibitors
inhibit 14-alpha-demethylase
[image]
binds with the apoprotein which determines selectivity for the fungal demethylase vs CYP450 enzymes (in the box)
[image] |
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Definition
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Term
[image]
azoles - subcategory imidazoles
[image]
azoles - subcategory triazoles, 3 nitrogens in the ring = improved activity |
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Definition
| *Azole structural chemistry* |
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Term
potent inhibitor of CYP3A4
absorption: pH dependent
[image]
ketoconazole is a dibasic molecules, the ionized form is soluble. for the drug to be ionized, the pH of the stomach should be less than 2.9 |
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Definition
| *metabolism and absorption of ketoconazole* |
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Term
inhibitor of CYP2C9
*Doubles the AUC of warfarin*
*Decreases the metabolism of phenytoin* |
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Definition
| *drug interactions of fluconazole* |
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Term
ketoconazole
fluconazole
itraconazole
voriconazole |
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Definition
| *azoles that are metabolized by CYP3A4* |
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Term
inhibitors of ergosterol biosynthesis
inhibits squalene epoxide
[image] |
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Definition
| MOA of allylamines (naftifine, terbinafine, butenafine, tolnaftate) |
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Term
inhibitor of ergosterol biosynthesis
inhibits isomerase and reductase
[image]
not currently marketed in the US
used for dermatophytic infections
others used in agriculture |
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Definition
| MOA of morpholines (amorolfine) |
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Term
inhibits glucan synthesis by inhibiting beta-1,3-glucan synthase
glucan synthase is imporant polymer in fungal cell wall |
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Definition
| *MOA of echinocandins (caspofungin, anidulafungin, micafungin)* |
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Term
inhibits thymidylate synthase
selective toxicity: flucytosine is a prodrug that can only be converted to the active form through a fungal enzyme
inhibition of thymidylate synthase leads to an inhibition in DNA synthesis or an inhibition of protein synthesis (by incorporation into fungal RNA) |
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Definition
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Term
Incorporates into keratin cells
inhibits cell division by mitotic spindle inerference
interferes with DNA replication |
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Definition
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Term
doesn't have the same ring system so won't cause an allergic reaction
in penicillin allergies, the beta lactam ring opens and binds to a hapten that causes the allergic response. Griseofulvin doesn't have think ring system. |
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Definition
can patients who are allergic to penicillin take griseofulvin (derived from Penicillium)?
[image] |
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Term
nonspecific metabolic disruption
interferes with DNA biosynthesis and cell respiration |
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Definition
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Term
nonspecific interaction with fungal cell wall
FUNGISTATIC |
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Definition
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