Antifungals 2
Terms
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- amphotericin B is related to what antibiotics
- macrolide
- one of the 200 polyene macrolide antibiotics
- amphotericin B
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MOA for amphotericine B?
cidal or static? -
Binds ergosterol and creates pores.
Fungicidal - uses for amphotericin B
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systemic mycosis
CNS mycosis
Topical for candidiasis - Amphotericin B's more toxic cousin
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Nystatin
For topical use only - Administration of amphotericin
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emulsified in fat and given IV over 2-4 hours.
Given intrathecally for CNS infection
Not absorbed in GI - Metabolism and excretion of Ampho B
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No metabolism
Slowly excreted renally with T-1/2 of 15 days - SE of ampho B
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fever, hypotension, tachypnea (give with cortisol or antipyretics)
80% dose-dependent nephrotoxicity
reversible anemia - Drug interaction for Ampho B
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Aminoglycosides and Cyclosporin for nephrotoxicity
induces hypokalemia increasing digitalis toxicity
Increase muscular blockade with nicotinic anticholinergics - This drug increases muscular blockade with nictonic anticholinergics
- Amphotericin B
- MOA Flucytosine
- Fungi deaminate it to 5-Flurouracil (mammalian cells don't) and it incorporates into RNA and inhibits thymidate synthetase
- Resistance to Flucytosine
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Develops Rapidly
Decreased uptake, decreased conversion - Uses for flucytosine
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Chromoblastomycosis
With Ampho B for crypto and system candidiasis - ADME Flucytosine
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Well absorbed GI
Penetrates CSF
No metabolism
Excreted renal 3-5 hours - Side effects of flucytosine
- Dose dependent bone marrow supression
- Only used alone for tx of Chromoblastomycosis
- Flucytosine
- Which azoles has adverse effects with Terfenadine
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Ketoconazole and Itraconazole
Erythromycin too
Fluconazol is ok - Ketoconazole use
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Broad spect antifungal
Blastomycosis, esophageal candidiasis
Bacteriastatic, so not for gravely ill or immunocompromised patients - ADME Ketoconazole
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Adsorbed orally in low acid (antacids and H2 reduce adsorption)
Good distribution, but not to CSF
Excreted in feces - Side effect of ketoconazole
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GI
Inhibitis P450
Inhibits steroid and testosterone synthesis (ammenorrhea, gynocomastia) - Drug interaction with Ketoconazole
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Rifampin and Pheytoin increase clearance.
Antacids and H2 lower adsorption
Increases effects of anticoagulants
Increases Cyclopsorine and Pheytoin toxicity
Causes arrythmia with Terfenadine - Drug of choice for oral or esophogeal candidiasis
- Fluconazole
- Uses for Fluconazole
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Oral or Esophageal candidiasis
Crytopcoccosis
Not for aspergillosis - ADME of fluconazole
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More soluble than keto - oral or IV
Distributes to CSF
No metabolism (no P450 effects)
Renal - Side effects of Fluconazole
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Increase Cyclosporine and Pheytoin toxicity
Steve-Johson syndrome, hepatic necrosis
Increase oral anticoagulation - Itraconazole vs ketoconazole
- Same except itraconazole has increased effects on sporotrichosis and aspergillosis
- ADME for itraconazole
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same as ketoconazole
Take with meal
metabolize in liver but excreted in urine (not feces) - Side effect of itraconazole
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GI
Arrythmia with Terfenadine
Long QT with high doses
Decreased steroid and testosterone synthesis (P450) - Drug interaction with itraconazole
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Isonizaide, Rifampin and Pheytoin decrease its levels
Increases levels of Cyclopsorine, Warfarin, Sulfonyureas, Pheytoin Digoxin - Voriconazole
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Fluconazole with aspergillosis coverage
Metabolized by P450 (fluconazole isn't) - Side Effect of Voriconazole
- Visual disturbances, CNS effects, rare fulminent hepatitis
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This antifungal causes visual disturbances
What unique use does it have? -
Voriconazole
Treats aspergillosis - Caspofungin and Micafungin
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Cell wall inhibitors (glycan)
For oral esophageal candidiasis, aspergillosis and prophylaxis against systemic candidiasis in immune compromised - Nystatin
- Cousin of ampho B for topical use only (candidiasis)
- Tx for topical dermatophytes
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Imidiazole/Triazoles
Like miconazole - Griseofulvin MOA
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binds microtubules and inhibits mitosis
Accumulates in keratinocytes which eventually replace infected cells - Use of griseofulvin
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For dermatophytes resistant to topical antifungals
Needs 1-12 months - ADME for Griseofulvin
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Poorly soluble
Excreted in Urine
Does not accumulate in tissue - Side effects and drug interaction of Griseofulvin
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Headaches, GI, reported porphyria
Barbituates decrease absorption
Decreases the effect of oral contraceptives and anticoagulants - Reported cases of hepatotoxicity and intermittend porphyria with this drug
- Griseofulvin
- Itraconazole is the expensive form of what?
- Ketoconazole
- Which azoles penetrate the BBB
- Only fluconazole
- Oral availability differences for azoles
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Keto needs acid
Fluconazole well absorbed
Itraconazole needs to given with a meal