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10 Cards in this Set
- Front
- Back
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Itraconazole
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- Oral or IV
- 40:1 (hydroxylpropyl cyclodextrin:itraconazole --> accumulation is bad in people with kidney problems - drug absorption is increased by food and low gastric pH - poor CNS penetration - hepatic elimination through the bile - drug interactions due to incompatibility with P450 - Rifampin and Rifabutin = decreased bioavailability - used for skin infections |
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Amphotericin B
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- poorly soluble in water --> prepared as suspension with sodium desoxycholate
- polyene macrolide = contains many double bonds - amphoteric molecule = has + and - charges associated with it |
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Amphotericin B
MOA & Resistance |
MOA
- cidal effect - binds to ergosterol (cell membrane sterol) and alters the permeability of the cell - forms amphotericin pores = leakage of small molecules out of fungal cell = death Resistance - impaired ergosterol binding - decrease membrane concentration of ergosterl - modifying the sterol target molecule to decrease affinity |
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Amphotericin B
Spectrum of Action & PK |
PK
- IV suspension (slow infusion) - poor CNS penetration - 90% bound to plasma proteins - increased tissue binding - relatively slow urinary excretion - no dose change in renal or hepatic failure Spectrum of Action - broad spectrum - used to treat a variety of infections - skin, respiratory tract, GI tract, systemic infections (caused by Candida, Cryptococcus, aspergillus) - immuno-compromised patients --> induction therapy to decrease fungal burden then stop |
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Amphptericin B
Adverse Reactions |
- fever, chills, HA, hypotension --> infusion related
- decrease dose of slow the infusion rate to decrease symptoms - more severe= pre-treat with anti-pyretic, antihistamine, corticosteroid - impaired renal function (dose dependent) - toxicity (infusion related) |
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Fluconazole
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- water soluble
- good CNS penetration - high oral bioavailability (no effect of food on abs) - few interactions = widest therapeutic index = can raise dose - excreted via kidneys - GI toxicity = N/V (doesn't cause discontinuation) - Interactions: Phenytoin, AZT, cyclosporin, warfarin (increase concentrations) - Avoid in pregnancy - not effect vs aspergillus - prophylactic treatment of cryptococcal meningitis or candiasis infection w/ skin |
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Voriconazole
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- in oral bioavailability
- increase CNS penetration - hepatic elimination - inhibitor of CYP3A4 --> decrease dose of meds - cyclosporin, tacromilus, statins (HMG-CoA reductase inhibitors) Adverse Rxns - skin rash - elevated hepatic enzymes = liver toxicity - visual disturbances (common) - primary use = treatment of aspergillus and candida infections |
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Flucytosine
PK & Adverse Reactions |
- water soluble
- given orally - widely distributed (CNS) - renal excretion through glomerular filtration (decrease dose with renal impairment) Adverse Reactions - bone marrow toxicity (anemia, leukopenia, thrombocytopenia) --> more common in patients with HIV - narrow therapeutic index = increased risk of toxicity Flucytosine/ AmphoB - cryptococcal meningitis Flucytosine/Itraconazole = chronic skin infections caused by blastomycosis |
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Flucytosine
MOA and Resitance |
MOA
- taken up by fungal cells by cytosine permease - converted into 5-FU then to FdUMP and FUTP to inhibit DNA and RNA respectively Resistance - develops rapidly in monotherapy - decrease in permease - decrease in cytidine deaminase - decrease in UMP pyrophosphate Synergistic effect when given with Amphotericin B |
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Caspofungin
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- IV formulations only
- water soluble and highly protein-bound - excreted via the kidneys and GI tract - dosage adjustments are required only for severe hepatic insufficiency MOA - inhibit the synthesis of Beta(1-3)glucan --> disruption of the fungal cell wall and cell death Adverse Rxns - well tolerated - GI side effects and flushing - fever - Phlebitis (problems with veins due to IV) - not a lot of potential for drug interactions - used to treat: mucocutaneous and dissemented candida infections, invasive aspergillus infections - second choice in patients who don't respond to AmphoB |
