Anti-Fungal Agents Flashcards
Bacterial derivative of Amphotericin B
Streptomyces nodosus
MOA of Amphotericin B
Binding to ergosterol to create pores leading to increased cell permeability and lysis
Therapeutic uses of amphotericin B
Used as induction regime and treatment of all life-threatening mycotic infections; immunosuppressed individuals
Adverse effects of amphotericin B
Nephrotoxicity (decreased EPO) causing anemia; infusion related toxicity
New AMB Formulations
AMB Lipid Complex (ABLC)
AMB colloidal dispersion (ABCD)
Liposomal AMB
Drug of choice for nearly all life-threatening mycotic infections
New AMB formulations
New AMB formulation that deliver AMB to reticuloendothelial cells in the liver and spleen
Liposomal AMB
These drugs produce lower AMB levels
ABLC and ABCD
Polyene macrolide active against Candida spp.
Nystatin
Therapeutic usage of nystatin
Oropharyngeal thrush, vaginal candidiasis and intertriginous candidal infections
Pharmacokinetics of nystatin
use only as topical agent “swish and spit or swish and swallow”
MOA of azoles
inhibit lanosterol 14-demethylase leading to decreased ergosterol synthesis
Azole type with lesser degree of specificity causing higher drug interactions and side effects
Imidazole
Azole type with lower toxicity and less propensity to inhibit mammalian sterol synthesis
Triazole
Common effect of azole groups
Both groups affect CYP450 causing a drug-drug interaction
Azole with 3 nitrogen atoms with good oral absorption and high propensity to inhibit mammalian CYP450
Ketoconazole
Adverse effects of Ketoconazole
Reduction in testosterone synthesis and suppression of estradiol synthesis
Drugs that decrease absorption of ketoconazole
H2 blockers, PPI, and antacids
Drugs that decrease efficacy and induce metabolism of ketoconazole
Rifampicin
Phenobarbital
Carbamazepine
Phenytoin
Drugs that cause torsades des pointes with Ketoconazole
Terfenadine
Astemizole
Cisapride
Fluorinated bistriazole that does not require an acidic environment
Fluconazole
Only renal triazole
Fluconazole
Therapeutic use of Fluconazole
Treatment and secondary prophylaxis of cryptococcal meningitis
Adverse effects of fluconazole
reversible alopecia
Synthetic triazole with 2 enantiomeric pairs each possessing 3 chiral centers
Itraconazole
Therapeutic use for Itraconazole
For aspergillus; most systemic mycosis not associated with meningitis
Drug of choice for paracoccidioidomycosis and chromomycosis
Itraconazole
MOA of flucytosine
Inhibits thymidylate synthesis which is an important component of DNA
Therapeutic use of flucytosine
Used as part of combination regimen with:
Amphotericin B for cryptococcal meningitis
Itraconazole for chromoblastomycosis
Adverse effect of flucytosine
Bone marrow toxicity
This anti-fungal drug is derived from Penicillium and is active against dermatophytes
Griseofulvin
MOA of griseofulvin
Binds to microtubules leading to defective cell wall formation and binds to keratin protecting the skin from new infection
Therapeutic use of griseofulvin
Oral fungistatic agent used in systemic treatment of dermatophytosis
Water-soluble, semisynthetic lipopeptide synthesized from the fermentation product of Glurea lozonensis
Terbinafine
MOA of terbinafine
noncompetitive inhibition of squalene monooxygenase to prevent ergosterol synthesis; squalene accumulation
Adverse effect of terbenafine
Steven-Johnson Syndrome
Topical used for ringworm, tinea versicolor, and mucocutaneous candidiasis
Triazoles
Ketal triazole similar to ketoconazole and clotrimazole
Terconazole and Butoconazole
Topical anti-fungal used for Candida vulvovaginitis
Tioconazole
Topical anti-fungal used for common pathogenic dermatophytes
Oxiconazole, Sulconazole, Sertaconazole
Topical anti-fungal that penetrates the stratum corneum and is found in effective concentration down to the mid-dermis
Econazole
Topical anti-fungal where fungicidal concentration remains in the vagina for as long as 3 days
Clotrimazole
Close chemical congener of econazaole that penetrates stratum corneum for more than 4 days
Miconazole
Drug used to treat seborrheic dermatitis of the scalp
Ciclopirox olamine
Halogenated phenolic ether used to treat tinea pedis, cruris, manuum, and versicolor
Haloprogin
Thiocarbamate fungicidal ineffective against Candida and is associated with pruritus
Tolnaftate
An allylamine that inhibits squalene 2,3-epoxidase that inhibits synthesis of ergosterol
Naftifine
Drug used for treatment of tinea cruris and tinea corporis
Naftifine