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17 Cards in this Set
- Front
- Back
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Polyenes:
Target Examples |
Target: cell membrane: bind ergosterol
Ex: Ampho B Nystatin |
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Amphotericin B:
Drug Category Method of Administration Mechanism of Action Why doesn't it affect human cells? Pharmcokinetics (V/D) Toxicity Resistance |
Category: Polyene
IV ONLY! Poor PO absorption Mech: Disrupt osmotic integrity of fungal membrane via pore formation (binds membrane sterol, ergosterol) Affinity for ergosterol is 500 times greater than for cholesterol (found in human cells)! Large V/D so penetrates tissue well (stays in body for a few months) Most toxic antimicrobial in clinical use; NEPHROTOXICITY (dec'd glomerular filtration, loss of urinary [ ] ability) Resistance: Rare but may be due to dec'd ergosterol levels in cell wall of fungi Resistance ma occur in Candida and Aspergillus |
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What kind of drug is used in empiric therapy?
Example of empiric anti-fungal? |
Empiric Tx = initiation of treatment prior to determination of a firm diagnosis.
Drug would need to be broad-spectrum Ex: Ampho B |
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What advantages do the lipid formulations of amphotericin B offer?
Under what circumstances would a lipid formulation be prescribed? How do the pharmacokinetics of liposomal amphotericin B differ from its traditional formulation? |
Reduced toxicity
Only use if traditional ampho B fails or is unacceptably toxic (remember: need to adjust doses for diff formulations) Lipo Amp B has a LOWER V/D (higher Cmax), and larger THERAPEUTIC INDEX (can give higher doses of Amp B) |
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Flucytosine:
Drug Category Method of Administration Mechanism of Action Pharmacokinetics (V/D) Toxicity Resistance |
Flucytosine = 5-FC
PO antifungal 100% absorbed, renally excreted, short half life, excellent CSF penetration Toxicity: GI, hepato; BM SUPPRESSION Resistance develops rapidly, must use in combination with ampho B (typically used in tx of cryptococcal meningitis) Resistance gen in candida and cryptococcal infections |
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Imidazoles and Triazoles:
Target Examples Method of Administration Pharmacokinetics (V/D) Resistance |
Target: cell membrane: inhibit ergosterol synthesis by inhibiting fungal CYP450 sterol demethylase
Imidazoles Ex: Clotrimazole Miconazole Ketoconazole Triazoles Ex: Fluconazole Itraconazole Voriconazole PO, limited V/D; hepatic metabolized, low CSF (except fluconazole) Toxicity: GI, hepatotox, skin eruption, HEPATIC CYTP450 DRUG INTERACTION Resistance: Alterations in drugimport/processing/in target enzyme/in efflux pumps |
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Antimetabolites:
Target Examples |
Target: nucleic acid synthesis/cell division
5-FC (flucytosine) |
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What yeast strains account for the majority of candida infections?
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C. albicans (54%)
C. glabrata (16%) G. parapsilosis (15%) |
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What drugs are INDUCERS of CYP 3A4? What does this mean?
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Rifampin
Phenytoin Carbamazepine Phenobarbital Inducers turn the faucet on, i.e., drugs flow right through CYP450 system and don't have high [ ]plasma Need to give higher doses of azoles! |
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What drugs are INHIBITORS of CYP 3A4? What does this mean?
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Azoles!
ketoconazole Fluconazole Itraconazole Voriconazole Turn down the faucet, drug accumulates, need to give lower doses |
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Echinocandins:
Target Examples |
(echinocandins AKA beta-glucan inhibitors)
Target: Cell Wall Synthesis Capsonfungin Mycofungin Anidulafungin |
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Caspofungin:
Method of Administration Drug Category Pharmacokinetics Toxicity |
Echinocandins
Min renal excretion, modest hepatic metab/excretion (no effect on cytP450) , IV ONLY Side effects rare (Rifampin increases hepatic excretion so must increase dose) |
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What drug treats all strains of candida AND aspergillis?
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Caspofungin
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What strains of candida are susceptible to poleyenes, azoles, and flucytosine (5-FC)?
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C. albicans
C. tropicalis C. parapsilosis |
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Treatment for C. glabrata
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Fluco, Itrac (DD)
5-FC |
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Treatment for C. krusei
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Itrac DD
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Treatment for C lusitaniae
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Fluco, Itrac DD
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