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34 Cards in this Set
- Front
- Back
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What are 2 reasons that fungal infections are difficult to treat?
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1) In vitro testing does not usually provide clinically useful information
2) Fungal cells resemble mammalian cells at the subcellular level, increasing the risks of toxicity |
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What are the 2 classifications of antifungal agents?
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1) Systemic antifungals
-Amphotericin B, itraconazole, griseofulvin 2) Topical antifungals -Iodides, nystatin, natamycin |
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What is the mechanism of action of amphotericin B?
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Binding to ergosterols in fungal cell membranes results in the formation of membrane pores and disruption of the permeability and transport characteristics of the membrane, can't maintain osmotic balance--> death
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What is the spectrum of activity of amphotericin B?
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-Effective against a wide range of systemic mycoses
-No activity against dermatophytes |
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What is the charge of amphotericin B?
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Amphoteric with poor water solubility
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How is amphotericin B formulated?
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As deoxycholate colloid, small unilamellar vesicle (SUV) lipid complex
-Affects how it dissociates so it can minimizes binding to cholesterol -Minimizes nephrotoxicity |
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How is amphotericin B administered in most cases ?
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Negligible oral absorption, administered IV
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How is amphotericin B administered for fungal meningitis?
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Poorly distributed-intrathecal administration is necessary
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How is amphotericin B eliminated?
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Most is biotransformed, but some of the drug binds to the cholesterol in the kidney membranes so it slowly leeches out over time=biphasic elimination
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What is biphasic elimination?
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Initial elimination profile is relatively rapid & steep and then the elimination is slow
-Amphotericin B: dependent on the drug being released from cholesterol in the kidneys |
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What are the adverse effects of amphotericin B?
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Nephrotoxicity is inevitable
-Redubed by lipid-based formulation -Measure creatinine and BUN during therapeutic monitoring |
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What is the mechanism of action of itraconazole (same group as ketoconazole)?
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Inhibits the demethylation of lanosterol, a precursor of membrane ergosterol, resulting in disturbance of membrane permeability.
-The demethylase which is inhibited is a cytochrome-p45- dependent enzyme system |
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What is the spectrum of activity of itraconazole?
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-A wide range of systemic mycoses
-Active against dermatophytes |
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What is the charge of itraconazole?
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Highly lipophilic
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How is itraconazole administered?
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Oral absorption is improved by food
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Describe the distribution of itraconazole.
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Highly plasma protein bound, distribution extensive, except into fluids with low protein concentration (CSF)
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How is itraconazole eliminated?
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Metabolized by liver
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What are the adverse effects of itraconazole?
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1) Inhibition of cytochrome p450
-More specific for the cyt p450 that converts langosterol into ergosterol 2) GIT effects not usually not severe 3) Infrequent hepatotoxicity |
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Compare the spectrum of activity and safety of amphotericin B to itraconazole.
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-Itraconazole has a better spectrum of activity than amphotericin B, but amphotericin B is what your first choice for severe systemic mycoses because more potent
-Itraconazole is safe compared to amphotericin B, but can cause GI problems |
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What is the mechanism of action of griseofulvin?
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Interacts with spindle microtubules and disrupts the mitotic process
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What is the spectrum of activity of griseofulvin?
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Effective against dermatophytes
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Absorption of griseofulvin is variable, but can be aided by what?
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High-fat foods and decreasing the particle size
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Where is griseofulvin distributed in the body?
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High affinity for keratin results in deposition in skin, hair and nails, where it makes keratin resistant to fungal growth
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How is griseofulvin eliminated?
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Metabolized
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What are the adverse effects of griseofulvin?
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most likely effects:
-Teratogenicity in cats -Leukopenia -Anemia -Neurotoxicity |
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Is the theraeutic index of griseofulin wide or narrow?
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Fairy wide, but narrower in cats
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Compare the time of onset of griseofulvin to itraconazole.
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Itraconazole has a longer lag time
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What is the mechanism of nystatin?
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Similar to that of amphotericin B
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What is Nystatin used to treat?
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Candida spp.
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How is nystatin administered?
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Topical
Orally for GI treatment |
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What is the mechanism of action of iodides?
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Promote immune response?
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What are iodides used to treat?
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-Topical antifungal against dermatophytes
-Na & K iodides used to treat Actinomyces |
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What is the mechanism of action of natamycin?
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Action against fungal cell membrane
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What is natamycin used to treat?
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Topical antifungal for ringworm, yeast mastitis, mycotic keratitis
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