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96 Cards in this Set

  • Front
  • Back
Fungal infections are generally associated with what parts of the body?
Skin (athletes foot) and mucous membranes (thrush)
What are the three categories of antifungal agents?
Systemic antifungal agents for systemic infections
Systemic antigfungal drugs for mucocutaneous infections and antifungal drugs for topical infections
Fungal infections are fatal when?
When the immune system is compromised or when fungi gain access to systemic circulation
Are fungal infecitons benign or malignant?
Cell wall synthesis?
Membrane function
Aphotercin B
Nucleic Acid synthesis
Lanosterol synthesis
Terbinafine and Nattifine
Ergosterol synthesis
What are the individual systemic antifungal agents for systemic infections?
Amphotercin B
What are the systemic antifungal drugs for mucocutaneous infections?
Antifungal drugs for toical infection?
topical azoles
topical allyamines (terbinafine)
Name some characteristics of the Amphotercin Structure
conjugated double bonds
amphotercin B's solubility?
insoluble in water, conventionall prepared as a colloid suspension for IV injection
Ampotercin category?
polyene macrolide
What is the neewr formation of amphotercin B?
Desribe Amphotercin B's absorption
Poorly absorbed from the GI ( orally administered only for infection localized to GI lumen)
Amphotercin B's Distribution
widely distributed to most tissues, NOT in CSF
(sometimes used intrathecally for fungal meningitis)
Can Amphotercin B get into CSF?
Is Amphotercin B broad specturm or narrow spectrum?
Broad Spectrum
Name some fungus tha Amphotercin B kills?
Candida albicans
Cryptococcous neorformans, HIstoplasma capsulatum, blastomyces dermatidis, Aspergills fumigatus
What is ampotercin B's MOA?
Binds to a sterol moiety, primarily ergosterol that is present in teh membrane of sensitive fungi. Then, forms pores or channels that increase teh permeability of the membrane, allowing leakage of a variety of small molecules
What is Amphotercin B's selectivitiy?
predominant sterol in mammalian membrane: cholesterol
Name the two cause of resistance to Amphotercin B?
Decreased fungus membrane concentration of ergosterol and modification of polyene binding site on ergosterol
What is the main cause of resistance to Amphotercin b?
due to impaired ergosterol binding
What are the two main drug formulation for Amphotercin B?
conventional formulation and lipid formulation for IV infusion
Why is Amphotercin B's partical size relevant to pharmacy?
Paritcle size for suspension 0.4 micrometers in diameter. IV lines are normally 0.22 micometers in diameter; therefore, you need a bigger pore size filter when giving this drug.
The conventional formulation of Amphotercin B forms a ______ in water.
What conventional formulatiom of Amphotercin B is named?
Amphotercin B deoxycholate complex (C-AMB)
How many lipid formulations are in teh US?
The lipid carrier in Amphotercin B lipid formulation serves as what?
Amphotercin B reservoir, which reduces binding to human cell membrane
Name in order which has a higher affinity for Amphotercin B? ergosterol, cholesterol,and lipid vehicle
ergosterol>lipid vehicle> cholesterol
Why is there a lipid formulation for Amphotercin B?
allow for reduction in toxicity, clinical efficacy only moderately increased,
What is the problem with lipid formulation of Amphotercin B?
very expensive
What are the infustion related toxicities of Amphotercin B?
fever, chills, muscle spasms, vomiting, HA, hypotension
Are infustion related toxicities immeidate onset or slow onset?
immediate reaction
What causes the infustion related toxicities to stop?
decrese daily dose or infusion rate
What are the cumulative toxicties of Amphotercin B?
renal damage (reversible or irreversible), heptotoxicity, and sezuires, anemia
Is flucytosine narrow spectrum or broad spectrum compared to Amphotercin B?
narrow spectrum
What fungus is flucytosine restricted to?
Crptococcus neoformans and some canidida species
How is flucytosine administered?
Describe the absoprtion of Flucytosine.
well absorbed from GI
Distribution of Flucytosine?
Well distributed in tissue fluids, INCLUDING CSF
Elimination of Flucytosine?
When should the dose of flucytosien be adjusted?
renal impairment becaues the drug is eliminated renally
What drug exhibits synergism with flucytosine?
Amphotercin B
Explain the synergism of Amphotercin B and flucytosine.
enhanced penetration of fucytosine through amphotercin B damaged membranes
To become an antifungal what does flucytosine need to be converted to?
5-flura uracil (5-FU)
Flucytosine is converted to___, then to ____, and further ______
5-fluorouracil, FdUMP, FUTP
Fucytosine inhibits?
DNA and RNA synthesis
Flucytosine is unable to affect human cells because?
human cells are unable to convert parent drug to 5-FU
Resistance of Flucytosine?
altered metabolism of flucytosine
What caued ADE of flucytosine?
due to metabolism to 5 FU
What are the ADE of flucytosine?
bone marrow toxicity and less frequently hepatotoxicity
Name the synthetic compounds that are derivatives of imidazoles:
miconazole (topical)
clotrimazole (topical)
Synthetic compounds that are derivated of Triazoles:
What is the MOA of Azoles?
inhinit fungal p450 enzymes involved in ergosterol synthesis
What is less selective for fungal p450s?
Azoles exhibit ___ affinity for fungal than human p450 enzymes
Are azoles broad spectrum or narrow spectrum?
broad spectrum
What fungus do Azoles kill?
Candida sp. Cryptococcus neoformans, endemic mycoses (blastomycosis, coccidiodmycosis, histoplasmosis) and Asperigillus
What are azoles prone to drug interaction?
effect on mammalian p450
How well tolerated are Azoles?
relatively well tolerated: minor GI distubrances and abnormallities in liver enzymes
What drug has the greatest propensity to inhibit mammalian p450 enzymes
Name the two ways Itraconaole is administered?
Orally and IV
Does itraconazole have high or low bioavailibity?
Which azole affect mammalizan cells more than itraconazole?
Does itraconazole perentrate into CSF?
penetrated poorly in CSF
Which drug has high oral bioavaiblity? itraconazoel or fluconazole
Which azole is least effet on mammalian p450s?
Does fluconzole penetrate into CSF?
What fungus is fluconazole not active against?
What drug has excellent oral bioavailability?
Name in order which has the greatest effect on mammalian cells? azole
Ketoconazole>itraconazole> voriconazole>fluconazole
Is voriconazole active against Asperigillus?
Which azole causes rash, hepatotoxicity, vision problems
What fungus are Echinocandins active against?
candida and aspergillus, NOT against cryptococous
Echinocandins are large cyclic peptides attatched to ____
fatty acid chain
Caspofungin, MIcafungin, anidulafungini are examples of what?
are examples of Echinocandins
Echinocandins are adminstered?
IV only
What is the MOA of Echinocandins?
disrupt fungal cell wall (inhibit synthesis of B (1-3) glucan
What are the ADEs of Echinocandins?
very well tolerated; can cause minor GI disturbances and flushing
Name two drugs that are systemic antifungal for mucocuntaneous infections?
Griseofulvin and Terbinafine
Name the three drugs used for topical antifunal therapy?
Nystatin, clotrimazole, miconazole, and topical terbinafine and naftifine
Oral absorption fo Griseofulvin is improved when given with______
fatty foods
Explain how Griseofulvin works?
MOA unkown; however deposited in newly formed skin (binds to keratin and protects skin from new infection)
What are the administration requirements for Griseofulvin?
requireds prolonged administration
How long should Griseofulvin be givin for hair and skin infections?
2-6 weeks
How long should Griseofulvin be given for nail infections?
What is the MOA for terbinafine?
binds to keratin and interferes with erogosterol synthesis by inhibiting fungal enzyme squalene epoxidase (toxic squalene accumulates in fungi
Does terinafine affect p450?
Name the ADEs of Terbinafine:
well tolerated (mild GI upset)
Why is Nystatin only used orally?
to toxic for parental administration
What is nystatin used for?
candidial infections
Nystastin is not absorbed from....
GI, Skin, and mucous membranes
What are clotrimazole and miconazole used for?
Used for vuvlvovaginal candidiasis and dermatophytic infections