Antifungal Agents Flashcards
For many years _____ drug was the only efficacious antifungal drug available for systemic use
Amphotericin B
Azole drugs comes with what formations?
Oral and parenteral
The only available route of administration of echinocandins
Parenteral administration
___ drugs are antifungal antibiotics produced by streptomyces nodosus
Amphotericin A and B
Amphotericin A is not in clinical use
___ is an amphoteric polyene macrolide.
Amphotericin B
Is effective only on fungi within the lumen of the tract an cannot be used for treatment of systemic disease
Oral amphotericin B
___ is a cell membrane sterol, is found in the cell membrane of fungi
Ergosterol
The predominant sterol of bacteria and human cell is?
Cholesterol
In what sterol does amphoericin B binds to?
Ergosterol
MOA of the drug:
Binds to ergosterol and alters the permeability of the cell by forming amphotericin B-associated pores in the cell membrane. The pore allows the leakage of intracellular ions and macromolecules, eventually leading to cell death
Amphotericin B
A drug that remains as the anti fungal agent with the broadcast spectrum of action. Has activity against candida albicans, cryptococcus neoformans, pathogenic molds.
Amphotericin B
A drug that remains a useful agent for all nearly life-threatening mycotic infections
Amphotericin B
Topical drops as well as direct subconjunctival injection of amphotericin B can cure?
Mycotic corneal ulcer and keratitis
Two broadcast categories of toxicity in amphotericin B
Infusion-related toxicity
- nearly universal and consists of fever, chills, muscle spasms, vomiting, headache
Cumulative toxicity
- renal damage, most significant toxic reaction
A potent antifungal agent that was discovered in 1957 during a search for novel antineoplastc agents. Its spectrum of action is much NARROWER that that of amphotericin B
Flucytosine
ROA of flucytosine
Only in oral formulation
MOA
Taken up by fungal cells via the enzyme cytosine permease. It is converted intracellularly first to 5-FU and then to 5-fluorodeoxyuridine monophosphate and fluoridine triphosphate, which inhibit DNA and RNA synthesis
Flucytosine
Enzyme that takes up flucytosine
Fungal cells via enzyme cytosine permease.
Conversion of flucytosine
- 5-fluroacil
- 5-fluorodeoxyuridine monophosphate (FdUMP)
- Fluorouridine triphosphate
Spectrum of activity of ____ is restricted to C neoformans and some candida sp
Flucytosine
Bone marrow toxicity, with anemia, leukopenia and thrombocytopenia
What drug has this kinds of common adverse effect?
Flucytosine
Are systemic compounds that can be classified as either imidazole or triazoles according to the number of nitrogen atoms in the five-membered azole ring
Azoles
Examples of imidazole
Ketoconazole
Miconazole
Clotrimazole
Examples of triazoles
Itraconazole
Fluconazole
Voriconazole
Isavuconazole
Posaconazole
The first oral azole introduced into clinical use, is is less selective for fungal P450 than are the newer azoles
Ketoconazole
Is the azole of choice for treatment of disease due to dimorphic fungi histoplasma, basltomyces and sporothrix
Itraconazole
An azole that is extensively used in the treatment of dermatophytoses and onychomycosis
Intraconazole
An azole that has the widest therapeutic index of the azoles , permitting more aggressive dosing in a variety of fungal infections
Fluconazole
The azole of choice in the treatment and secondary prophylaxis of cryptococcal meningitis
Fluconazole
An azole agent that is most commonly used for the treatment of mucocutaneous candidiasus
Fluconazole
Available forms of:
Keto
Itra
Fluco
Vori
Posa
Isavu
Keto - PO
Itra - PO, IV
Fluco - PO, IV
Vori - PO, IV
Posa - liquid oral formulation
Isavu - PO, IV
Treatment of choice for invasive aspergillosis and some environmental molds
Voriconazole
A similar spectrum of action in triazoles that has an excellent activity agaist candida sp and dimorphic fungi
Voriconazole and itraconzaole
An azole that was originally available only in liquid oral formulation.
IV form and sustained acting tabled are now available
Posaconazole
The broadest spectrum member of the azole family, with activity against most species of candida and aspergillus
Posaconazole
the first azole with significant activity against the agent of mucormycosis
Posaconazole
A prodrug o the newest triazole
Isavuconazole
___ has an antifungal spectrum similar to that of posaconzole
Isavuconazole
The newest class of antifungal agents to be developed. Theya re large cyclic peptides linked to a long-chain FA
Echinocandins
The only echinocandins that are only the licensed agents in the category of antifungals
Caspofungin, micafungin and anidulafungin
The only available form of echinocandins
IV formulation
Micafungin
Dose of 150mg/d treats?
Dose of 100mg treats?
Dose of 50mg treats?
150 - esophageal candidiasis
100 - candidemia
50 - prophylaxis of fungal infections
HL of
Caspofungin
Micafungin
Anidulafungin
C - 9-11hrs
M - 11-15 hrs
A - 24-48 hrs
MOA of echinocandins
Inhibits the synthesis of B(1-3) glucan resulting in desruption of the fungal cell wall and cell death.
Caspofungin is licensed for use in?
Invasive aspergillosis
Micafungin is licensed for use in?
Mucocutaneous candidiasis, candidemia and prophylaxis of candidal infections
Anidulafungin is approved for use in?
Esophagel candidiasis, invasive candidiasis, candidemia
Very insoluble fungistatic drug derived from species of penicillium
Griseofulvin
Griseofulvin is only use in the systemic treatment of?
Dermatophytosis
ROA of griseofulvin
Microcrystalline oral form
MOA
It is deposited in newly forming skin where it binds to keratin, protecting the sin from new infection
Griseofulvin
A synthetic allylamine that is used in the treatment of dermatophytoses especially onychomycosis
Terbinafine
MOA
Inhibits fungal enzyme squalene epoxidase, leads to the accumulation of the sterol squalene, which is toxic to the organism
Terbinafine
Like griseofulvin, terbinafine is a keratophilic medication, but unlike griseofulvin, it is ____
Fungicidal
A polyene macrolide much like amphotericin B, too toxic for parental administration and is only used topically
Nystatin
Nystatin is commonly used for suppression of __ infection
Local candidal infection
Two azole that are most commonly used topically are?
Clotrimazole and miconazole
Pleasant-tasting Alternative to nystatin, they are available for treatment of oral thrush.
Oral clotrimazole
Allymines available as topical creams. Bot are effective for treatment of tinea cruris and tinae corporis
Terbinafine and naftifine
