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127 Cards in this Set
- Front
- Back
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polyene antifungals
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amphotericin B
lipid amphotericin products |
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Azole antifungals
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fluconazole
itraconazole voriconazole posaconazole |
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echinocandins
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caspofungin
micafungin anidulafungin |
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what should you consider when treating with amphotericin
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whether its conventional or liposomal amphotericin B
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MOA of amphotericin B
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binds to ergosterol in the cell wall resulting in alteration of membrane permeability which allows leakage of the cellular contents and causes cell death
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what else is affected by amphotericin
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sterols in mammalian cells
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what type of antifungal is amphotericin
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fungicidal
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resistance mechanisms for amphotericin
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intrinsic resistance
decrease in ergosterol content in cell -replacement of some of the polyenebinding sterols -masking of exisiting ergosterol |
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bug with intrinsic amphotericin resistance
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C lusitaniae
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absorption of amphotericin
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all IV poor oral absorption
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distribution of amphotericin
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widely distributed especially in liver and spleen
extensive binding to tissue |
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metabolism of amphotericin
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extensive
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how long can amphotericin be detected in the body
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up to 7 wks after discontinuation
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what is terminal half life of amphotericin
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15 days
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antifungal activity of amphotericin
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candida sp
aspergillus sp cryptococcus neoformans histoplasma, blastomyces, coccidioides, paracoccidiodes |
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infusion related adverse reactions of amphotericin
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shaking chills and fever
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infusion reactions of amphotericin are mediated by what and how do you treat this
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mediated by prostaglandins
premedicate with acetaminophen+diphenhydramine+merperidine |
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how can you help the thrombophelbitis reaction from amphotericin
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treat with hydrocortisone
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worst and most serious adverse reaction with amphotericin
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nephrotoxicity
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patients with nephrotoxicity from amphotericin present with what
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renal tubular acidosis
hypokalemia hypomagnesemia |
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other adverse reactions of amphotericin
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anemia due to decreased erythropoietin production
lipid products and toxicity |
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azole antifungals
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ketoconazole
fluconazole itraconazole voriconazole posaconazole |
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triazoles
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fluconazole
itraconazole voriconazole posaconazole |
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MOA of azoles
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inhibit the cytochrome p450 dependent enzyme 14-alpha-demethylase which disrupts membrane synthesis
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what type of antifungals are azoles
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fungistatic mostly
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what is the additional MOA of voriconazole
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alos inhibits 24-methylene dihydrolanasterol demthylase which may explain its increased activity against certain molds
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resistance mechanisms for azoles
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alteration of 14-alpha-demethylase
efflux pumps decreased permeability of membrane |
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which azole is renally excreted
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fluconazole
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half life of azoles longest to shortest
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itraconazole=64
posaconazole=24 fluconazole=24+/-9 voriconazole=6 |
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bioavailability of azoles longest to shortest
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fluconazole=93
voriconazole=90 itraconazole=55 |
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azoles with excellent absorption
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fluconazole
voriconazole |
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itraconazole capsule form is best absorbed with what
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food
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intraconazole solution is best absorbed
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on a empty stomach
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posaconazole requires what for absorption
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high fat meal
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which azole distributes widely and into CSF
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fluconazole
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which azole does not appear in urine or csf
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intraconazole
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what azole is metabolized by 34A and also inhibits that system
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itraconazole
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what azoles are metabolized by 2C19, 2C9, and 3A4 and also inhibit that system
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voriconazole
posaconazole |
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Azole with minimal hepatic metabolism
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fluconazole
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eliminated 90% in urine
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fluconazole
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azole that require renal dose adjustment
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fluconazole
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half lives of azoles are generally what
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long
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azoles usually require what type of dosing
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loading
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spectrum for fluconazole
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candida albicans, cryptococcus neoformans
histoplasma capsulatum bastomyces dermatitidis coccidioides immitis paracoccidioides brasiliensis |
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spectrum for itraconazole
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candida albicans
aspergillus cryptococcus neoformans histoplasma capsulatum bastomyces dermatitidis coccidioides immitis paracoccidioides brasiliensis sporothrix schenckii phaeohyphomycetes dermatophytes |
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spectrum for voriconazole and posaconazole
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candida sp
aspergillus sp cryptococcus neoformans histoplasma capsulatum bastomyces dermatitidis coccidioides immitis paracoccidiodes brasiliensis |
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adverse reactions with fluconazole
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GI distress
rash headache transient increase in LFT's |
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adverse reactions with intraconazole
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GI distress
rash headache, dizziness increase in LFT's |
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what adverse reaction is reported with itraconazole capsules
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CHF and pulmonary edema
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itraconazole capsules should not be given to who
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patients with evidence of ventricular dysfunction such as congestive heart failure or a history of CHF
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IV itraconazole should be given to who
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patients who creatinine clearance is less than 30mL/min
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ocular effects of voriconazole
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increased brightness, blurred vision, altered visual perception, photophobia, altered color perception, ocular discomfort
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cardiac effects of voriconazole
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high dose associated with prolonged QT interval in animals
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liver effects of voriconazole
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hepatic toxicity listed
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what is recommended monitoring while on voriconazole
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prior to therapy
within first 2wks every 2-4 wks |
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what appears to be the relationship between increased LFT's and voriconazole
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duration of treatment
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skin effects of voriconazole
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rash
may progress to stevens-johnson photosensitivity |
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infusion reactions of voriconazole
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anaphylactoid type reactions
flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, and rash |
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whic azole is least likely for drug interactions
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fluconazole
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itraconazole is contraindicated with what drugs
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dofetilide, quinidine, pimozide, midazolam, triazolam, lovastatin, simvastatin
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drugs which decrease gastric acidity may affect what with itraconazole
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absorption
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voriconazole is substrate inhibitor of what
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CYP2C19, 2C9, 3A4
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echinocandins
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caspofugin
micafungin anidulafungin |
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MOA of echinocandins
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non-competitive inhibition of 1,3 beta D glucan synthase which forms glucan polymers in fungal cell wall
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what type of antifungal are echinocandins
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fungistatic
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echinocandins are referred to as what
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the penicillins of antifungals
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absorption of echinocandins
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IV only
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elimination of echinocandins
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excreted in feces and urine only 1.4% is unchanged
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spectrum for echinocandins
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aspergillus funigatus, flavus, terreus
candida sp pneumocystis carinii emerging molds |
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studies so synergy with echinocandins and what
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amphotericin or voriconazole
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adverse reactions of echinocandins
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fever, NV, phlebitis at injection site, facial flusing during infusion
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drug abnormalities with echinocandins
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increases in alkaline phosphatase, eosinophilia, urine protein, urine RBCs,
decrease in serum potassium |
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what does cyclosporin do to caspofungin levels
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increase by approximately 35%
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what does caspofungin do to tacrolimus
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decrease levels by 20-25%
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MOA of terbinafine
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interferes with ergosterol biosynthesis by inhibiting the enzyme squalene epoxidase whic leads to accumulation of sterol squalene which is toxic to the cell
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absorption of terbinafine
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good absorption but bioavailable decreaed 40% due to first pass
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terbinafine distribution
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accumulation occurs in skin, nails, and adipose tissue
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elimination of terbinafine
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renally eliminated
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is renal dose adjustment necessary with terbinafine
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yes
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half life of terbinafine
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approx 24hr
terminal half life of approx 200 t0 400 hrs |
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spectrum for terbinafine
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dermatophytes
candida albicans some synergy with other agents on emerging molds |
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adverse reaction of terbinafine
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liver failure
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terbinafine should be avoided where
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patients with creatine clearance of less than 50mL/min
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other adverse reactions with terbinafine
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ocular changes
transient decrease in absolute lymphocytes severe skin reactions including steven johnson and toxic epidermal necrolysis |
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increased drug reactions with terbinafine
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warfarin
medications metabolized by CYP2D6 |
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what clearance in increased with terbinafine
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cyclosporine clearance increased
rifampin increases clearance of terbinafine |
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MOA of flucytosine
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inhibits fungal protein synthesis by replacing uracin with 5-flurouracil in fungal RNA
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how is flucytosine alway administered
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in combination
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absorption of flucytosine
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good from GI tract
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distribution of flucytosine
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widely
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elimination of flucytosine
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renally approx 80% unchanged in urine
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is renal dose adjustment necessary with flucytosine
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yes
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spectrum for flucytosine
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candida sp
cryptococcus neoformans aspergillus sp |
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adverse reactions of flucytosine
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bone marrow toxicity
hepatotoxicity GI |
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drug interactions of flucytosine
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synergy and risk of toxicity with amphotericin B
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macrolides
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erythromcyin
clarithromycin azithromycin |
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erthromycin is degraded in the stomach to what
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hemiketal and spiroketal intermediates
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what happens to clarithromycin in the stomach
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more acid stable and prevents degradation in stomach
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characteristics of azithromycin
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more acid stable, increased half life, increases tissue penetration, broadens spectrum
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MOA for macrolides
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inhibits bacterial RNA dependent protein synthesis by binding to 50s subunit of the 70s subunit
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macrolides are what type of anitbiotic
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bacteriostatic
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resitance mechanisms for macrolides
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modifications of ribosomal binding site
efflux pumps production of exterases that hydrolyze macrolides |
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macrolides have cross resistance with what
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gram positive organisms
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IV erythromycin
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erthromycin lactobionate
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Oral erythromycin
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erythromycin base, estolate, stearate, ethylsuccinate
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clarithromycin IV
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none
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what forms does clarithromycin come in
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oral only
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what forms does azithromycin come in
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IV and oral
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bioavailability of macrolides
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erythro=15-45
clarithro=50 azithro=37 |
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half life of macrolides
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erythro=2
clarithro=3-5 azithro=10->40 |
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macrolide that is hepaticly metabolized
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azithro
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macrolide that needs renal dose adjustment
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clarithro
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effects of food on macrolide absorption
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decreases erythro and azithro
increases bio of clarithro clarithro should be taken with food |
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distribution of macrolides
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everywhere except csf
azi and clari in PMNs and macrophages |
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metabolism of macrolides
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CYP 3A4
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active metabolite of clarithro
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14 hydroxyclarithromycin
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excretion of macrolides
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erythro=bile
clarithro=partially in urine azithro=feces |
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gram + spectrum for macrolides
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streptococci including S pneumoniae
staphylococcus excluding MRSA |
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gram - spectrum for macrolides
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atypical respiratory
-legionella, mycoplasma, chlamydia n. gonorrhoeae, treponema pallidum, c trachomatis clarithromycin, azithromycin, mycobacterium, helicobacter pylori, borrelia burgdoferi |
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clarithro can have what taste
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metallic taste
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GI of macrolides
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NVD
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erthromycin estolate can cause what
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cholestatic hepatitis
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rapid IV of erythromycin can cause
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reversible hearing loss
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erythromycin associated with what cardiac side effect
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prolongation of QT interval and torsades de pointes
usually with high IV doses |
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erythro is what pregnancy class
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b
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clarithro is what pregnancy class
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C
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possible drug interactions with erythromycin and clarithromycin
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warfarin
theophyiline cyclosporine/tacrolimus carbamazepine phenytoin protease inhibitors HMG-CoA reductase inhibitors |
