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117 Cards in this Set
- Front
- Back
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Three reasons for increasing incidence of fungal infection:
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immunosuppression, broad spectrum antibiotics, indwelling catheters
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Are fungi EUK or PRO?
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Similar structure to eukaryotes (toxicity)
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What are the targets of antifungals?
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Targets: cell wall (glucan, chitin, mannan) & cell membrane (ergosterol)
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POLYENES
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Amphotercin B
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MOA? Solubility?
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MOA: binds ergosterol to disrupt membrane. Complexed to deoxycholate for solubility. Deoxycholate is a bile acid.
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Therapeutic Indicator?
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TI: Systemic fungal infections. IV, intrathecally, bladder wash. Grandaddy of all antifungals.
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Adverse effects: amphoterrible, awfultericin, amphibian terrorist.
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Organ?
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Renal toxicity: generally reversible, follow BUN & creatinine. K+, Mg+, HCO3- wasting. Hydrate with normal saline to decrease this toxicity.
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Premedicate why? And with what?
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Infusion related: fever & rigors (common), myalgia, arthralgia, HA. Premedicate with APAP (acetaminophen), NSAIDs (aspirin, ibuprofen, many others), diphenhydramine (Benadryl), meperidine (an opioid), hydrocortisone (a steroid)
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Injection site?
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Thrombophlebitis at injection (swelling (inflammation) of a vein caused by ablood clot)
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Blood? Why?
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Anemia b/c suppresses erythropoietin. Monitor CBC.
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How is the new line of Amphotercin B different?
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Newer preparations complexed with lipids to decrease the nephrotoxicity, allow larger doses. $$$ expensive! Does nothing for the rigors, infusion affects.
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Nystatin
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MOA?
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MOA: binds ergosterol to disrupt membrane.
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Therapeutic Indicator?
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Therapeutic indications: topical for oral, vaginal & skin candidiasis. Swish and swallow for GI candidiasis. Not absorbed orally. Too toxic for IV.
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Adverse effects?
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Adverse effects: not many.
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PYRIMIDINES
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Flucytosine
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MOA #1?
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MOA #1: fungi have cytosine deaminase that metabolizes flucytosine to 5-fluorouridylic acid, which is incorporated into the RNA and busts up translation
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MOA #2?
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MOA #2: fungi have cytosine deaminase that metabolizes flucytosine to 5- fluorouridylic acid, which is further metabolized to 5-fluorodeoxyuridylic acid, a potent inhibitor of thymidylate synthetase. No thymidylate, no DNA.
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Therapeutic Indicator?
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Therapeutic indication: tag team partner for Amp B for cryptococcal meningitis. Never used alone, resistance develops quickly.
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Adverse effects?
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Adverse effects: bone marrow suppression, rash, N/V/D, enterocolitis, increased liver enzymes (reversible when end therapy).
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AZOLES
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MOA as a class?
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MOA: inhibits sterol-14-α-demethylase to impair the biosynthesis of ergosterol.
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TI as a class?
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Therapeutic indications: mostly topical.
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KETOCONAZOLE
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Administration and how this helps absorption?
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Oral administration, acidic environment helps absorption. Enzyme inhibitor.
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Adverse effects:
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Adverse effects: GI, LFTs, rash, hormonal (menstrual irregularities, gynecomastia, low libido, impotency).
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More on this drug in the endocrine abnormality Cushing’s Syndrome.
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ITRACONAZOLE
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Administration?
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Oral, IV. Enzyme inhibitor. T½ = 30 h. Protein bound parent and metabolite. Many interactions!
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Adverse effects?
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AE: GI, LFTs, rash, hypertriglyceridemia, hypokalemia. Fatal cardiac arrhythmias with cisapride & quinidine!
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FLUCONAZOLE (used a lot)
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Administration?
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Oral, IV. Enzyme inhibitor, but not a lot of drug interactions. Eliminated by kidney, not extensively protein bound.
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Contraindication?
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Therapeutic indication: kills candida really well.
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AE?
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AE: GI (N/V/tummy ache), hepatotoxicity, rash, reversible alopecia.
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VORICONAZOLE
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|
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Kinetics?
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Oral, IV. Enzyme inhibitor. Non-linear kinetics means half life is variable, depending on dose. Adjust dose for renal compromised patients. Many interactions!
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AE?
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AE: visual changes, cardiovascular, CNS, rash, hepatotoxicity
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More antifungals
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|
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CASPOFUNGIN
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|
|
|
MOA?
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MOA: Inhibits the cell wall synthesis of b 1,3 glucan.
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|
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Administration?
|
IV, polyphasic T½, highly protein bound. Cyclosporine increases levels of caspofungin.
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|
|
TI?
|
Therapeutic indications: systemic aspergillus & candida infections.
|
|
|
AE?
|
AE: headache, hepatotoxicity, histamine related infusion reactions at injection site.
|
|
|
GRISEOFULVIN
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|
|
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MOA?
|
MOA: binds to human keratin and inhibits fungal cell mitosis there. New keratinized tissue grows free of fungus.
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What does it increase the metabolism of?
|
Orally absorbed best with fatty foods, T½ = 1 day, renal elimination. Enzyme inducer that increases the metabolism of warfarin, oral contraceptives.
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|
TI?
|
Therapeutic indications: mycoses of hair, skin & nails.
|
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AE?
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AE: headache, hepatotoxicity, hematologic, GI, rash, photosensitivity.
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TERBINAFINE
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MOA?
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MOA: Inhibits squalene epoxidase and leads to a deficiency in ergosterol within the fungal cell membrane and results in fungal cell death
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½ LIFE?
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T½ can reach 400 h (!) at steady state because the drug accumulates in the skin, nails, fat & releases slowly from these tissues.
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|
TI?
|
Therapeutic indications: mycoses of the nails, ringworm. Pulse therapy.
|
|
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What increases the level of Terbinafine?
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AE: not many. Cimetidine may increase level of Terbinafine.
|
|
|
Three reasons for increasing incidence of fungal infection:
|
immunosuppression, broad spectrum antibiotics, indwelling catheters
|
|
|
Are fungi EUK or PRO?
|
Similar structure to eukaryotes (toxicity)
|
|
|
What are the targets of antifungals?
|
Targets: cell wall (glucan, chitin, mannan) & cell membrane (ergosterol)
|
|
|
POLYENES
|
|
|
|
Amphotercin B
|
|
|
|
MOA? Solubility?
|
MOA: binds ergosterol to disrupt membrane. Complexed to deoxycholate for solubility. Deoxycholate is a bile acid.
|
|
|
Therapeutic Indicator?
|
TI: Systemic fungal infections. IV, intrathecally, bladder wash. Grandaddy of all antifungals.
|
|
|
Adverse effects: amphoterrible, awfultericin, amphibian terrorist.
|
|
|
|
Organ?
|
Renal toxicity: generally reversible, follow BUN & creatinine. K+, Mg+, HCO3- wasting. Hydrate with normal saline to decrease this toxicity.
|
|
|
Premedicate why? And with what?
|
Infusion related: fever & rigors (common), myalgia, arthralgia, HA. Premedicate with APAP (acetaminophen), NSAIDs (aspirin, ibuprofen, many others), diphenhydramine (Benadryl), meperidine (an opioid), hydrocortisone (a steroid)
|
|
|
Injection site?
|
Thrombophlebitis at injection (swelling (inflammation) of a vein caused by ablood clot)
|
|
|
Blood? Why?
|
Anemia b/c suppresses erythropoietin. Monitor CBC.
|
|
|
How is the new line of Amphotercin B different?
|
Newer preparations complexed with lipids to decrease the nephrotoxicity, allow larger doses. $$$ expensive! Does nothing for the rigors, infusion affects.
|
|
|
Nystatin
|
|
|
|
MOA?
|
MOA: binds ergosterol to disrupt membrane.
|
|
|
Therapeutic Indicator?
|
Therapeutic indications: topical for oral, vaginal & skin candidiasis. Swish and swallow for GI candidiasis. Not absorbed orally. Too toxic for IV.
|
|
|
Adverse effects?
|
Adverse effects: not many.
|
|
|
PYRIMIDINES
|
|
|
|
Flucytosine
|
|
|
|
MOA #1?
|
MOA #1: fungi have cytosine deaminase that metabolizes flucytosine to 5-fluorouridylic acid, which is incorporated into the RNA and busts up translation
|
|
|
MOA #2?
|
MOA #2: fungi have cytosine deaminase that metabolizes flucytosine to 5- fluorouridylic acid, which is further metabolized to 5-fluorodeoxyuridylic acid, a potent inhibitor of thymidylate synthetase. No thymidylate, no DNA.
|
|
|
Therapeutic Indicator?
|
Therapeutic indication: tag team partner for Amp B for cryptococcal meningitis. Never used alone, resistance develops quickly.
|
|
|
Adverse effects?
|
Adverse effects: bone marrow suppression, rash, N/V/D, enterocolitis, increased liver enzymes (reversible when end therapy).
|
|
|
AZOLES
|
|
|
|
MOA as a class?
|
MOA: inhibits sterol-14-α-demethylase to impair the biosynthesis of ergosterol.
|
|
|
TI as a class?
|
Therapeutic indications: mostly topical.
|
|
|
KETOCONAZOLE
|
|
|
|
Administration and how this helps absorption?
|
Oral administration, acidic environment helps absorption. Enzyme inhibitor.
|
|
|
Adverse effects:
|
Adverse effects: GI, LFTs, rash, hormonal (menstrual irregularities, gynecomastia, low libido, impotency).
|
|
|
|
More on this drug in the endocrine abnormality Cushing’s Syndrome.
|
|
|
ITRACONAZOLE
|
|
|
|
Administration?
|
Oral, IV. Enzyme inhibitor. T½ = 30 h. Protein bound parent and metabolite. Many interactions!
|
|
|
Adverse effects?
|
AE: GI, LFTs, rash, hypertriglyceridemia, hypokalemia. Fatal cardiac arrhythmias with cisapride & quinidine!
|
|
|
FLUCONAZOLE (used a lot)
|
|
|
|
Administration?
|
Oral, IV. Enzyme inhibitor, but not a lot of drug interactions. Eliminated by kidney, not extensively protein bound.
|
|
|
TI?
|
Therapeutic indication: kills candida really well.
|
|
|
Contraindication?
|
Never in pregnancy, will give skeletal and cardiac deformities!
|
|
|
AE?
|
AE: GI (N/V/tummy ache), hepatotoxicity, rash, reversible alopecia.
|
|
|
VORICONAZOLE
|
|
|
|
Administration?
|
Oral, IV. Enzyme inhibitor. Non-linear kinetics means half life is variable, depending on dose. Adjust dose for renal compromised patients. Many interactions!
|
|
|
Kinetics?
|
|
|
|
AE?
|
AE: visual changes, cardiovascular, CNS, rash, hepatotoxicity
|
|
|
More antifungals
|
|
|
|
CASPOFUNGIN
|
|
|
|
MOA?
|
MOA: Inhibits the cell wall synthesis of b 1,3 glucan.
|
|
|
Administration?
|
IV, polyphasic T½, highly protein bound. Cyclosporine increases levels of caspofungin.
|
|
|
TI?
|
Therapeutic indications: systemic aspergillus & candida infections.
|
|
|
AE?
|
AE: headache, hepatotoxicity, histamine related infusion reactions at injection site.
|
|
|
GRISEOFULVIN
|
|
|
|
MOA?
|
MOA: binds to human keratin and inhibits fungal cell mitosis there. New keratinized tissue grows free of fungus.
|
|
|
Administration?
|
Orally absorbed best with fatty foods, T½ = 1 day, renal elimination. Enzyme inducer that increases the metabolism of warfarin, oral contraceptives.
|
|
|
Best absorption environment?
|
|
|
|
What does it increase the metabolism of?
|
|
|
|
TI?
|
Therapeutic indications: mycoses of hair, skin & nails.
|
|
|
AE?
|
AE: headache, hepatotoxicity, hematologic, GI, rash, photosensitivity.
|
|
|
TERBINAFINE
|
|
|
|
MOA?
|
MOA: Inhibits squalene epoxidase and leads to a deficiency in ergosterol within the fungal cell membrane and results in fungal cell death
|
|
|
½ LIFE?
|
T½ can reach 400 h (!) at steady state because the drug accumulates in the skin, nails, fat & releases slowly from these tissues.
|
|
|
TI?
|
Therapeutic indications: mycoses of the nails, ringworm. Pulse therapy.
|
|
|
AE?
|
AE: not many. Cimetidine may increase level of Terbinafine.
|
|
|
What increases the level of Terbinafine?
|
|
