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27 Cards in this Set
- Front
- Back
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what are the 3 ways to approach antifungal therapy
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prophlactic, empiric, definitive
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Describe the ideal antimicrobial agent
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specific to pathogen- potent and nontoxic
broad spectrum |
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Which antifungals are directed at each of these fungal cell components
-cell wall -DNA synthesis -Plasma membrane |
cell wall= echinocandins
DNA synthesis= flucytosine Plasma membrane= polyenes, azoles, allyamines |
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Amphotericin B is funga cidal/static
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Amphotericin B is fungiCIDAL
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What is the mechansim of Amphotericin B
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binds to fungal membrane sterols (ergosterol) and alters permeability selectively to K+ and Mg2+
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Azoles are fungi cidal/static
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azoles are fungiSTATIC
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What is the mechanism of action of azoles
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azoles inhibit the synthesis of ergosterol by blocking demethylation of lanosterol
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Echinocandins are cida/static
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Cidal for Candida
Static for aspergillus |
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What is the mechanism of action of echinocandins
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echinocandins inhibit B 1,3 D- glucan synthase which forms glucan polymers in the cell wall
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what is the mechanism of action of Flucytocine (5-FC)
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a pyrimidine analog that inhibits thymidilate synthetase which inhibits DNA and makes abnormal RNA (FU in place of uracil) which disrupts protein synthesis
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What is secondary resistance and how does it relate to fungal therapy
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-development of resistance associated wit treatment pressure
-uncommon except with 5FC monotherapy -can occur with azoles and echinocandins with prolonged therapy |
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How does fungal resistance to 5FC occur
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mutations in permease and deaminase
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How does resistance to AmB occur
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changes in sterol content reducing amount of ergosterol target
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How does resistance to echinocandins occur
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mutations in glucan synthase gene (FKS1)
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which sites are particularly difficult to get antifungals to
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CNS and eye, pharmacologically protected
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What two organs are involved in antifungal elimination
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kidneys and liver
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Describe the role of polymorphism in the hepatic metabolism of voriconazole
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The hepatic metabolism is CYP 2C19 dependent homozygyous are extenisve metabolizers 4 fold lower, heterozygous are extensive metabolizers 2 fold lower, there are also poor metablizers
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How can the toxicity of AmB be reduced
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lipid formulation targets away from renal receptors, 10-20x less toxic but 5x less potent
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what drug used used initially for invasive candidiasis/ candidemia unless it's caused by C. parapsilosis or eye/ CNS
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echinocandin
for parapsilosis used fluconazole or LAmB for eye/CNS use LAmB then step down to fluconazole |
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what drug should be used to treat candiduria if systematic
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fluconazole
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What drug should be used to treat oral/ esophageal candidaisis
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1st fluconzole
2nd itraconazole 3rd echinocandin |
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what drug should be used to treate VVC
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topical therapy works well
fluconazole for glabrata- boric acid, topical 5FC, AmB suppository |
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What drugs should be used to treat Apergillosis
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-Voriconazole
-azole/ echinocandin -LAmB -posaconazole |
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What drugs should be used to treat systemic endemic fungi
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-LAmB step down to itraconzole
for CNS LAmB then voriconazole or fluconazole |
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What drugs should be used to treat crytococcus
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meningitis- LAmB step down to fluconazole
Lung- fluconazole or LAmB |
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What drugs are useful for treating dermatophyte infections
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itraconazole, terbinafine
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What are 6 things that you should think about when using fungal therapy
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1. spectrum of activity
2. Cidal therapy for sick pts 3. site of infection, dose, penetration 4. drug levels and optimization of exposure 5.drug interactions for triazoles 6. toxicity |
