antifungal drugs Flashcards
Flucytosine
MOA
inhibits DNA, RNA, synthesis
Flucytosine
clinical use and side effects
Flucytosine
CU: systemic infection d/t cryptococcus neoformans and some candida spp. excellent CNS penetration- meningitis caused by cryptococcus
Side effects: Bone marrow suppression leading to leukopenia and thrombocytopenia
Griseofulvin
MOA
Griseofulvin
inhibits microtubule function, disrupt mitosis
Griseofulvin
Clinical use
Griseofulvin
Not for systemic infection- used systemically (oral) for treating dermatophytosis (ringworm, tinea) of the scalp, torso, inguinal, foot, and nail.
terfinabine is the DOC for tinea infections, azoles are the alternative
Griseofulvin
Side effects
serious reactions are rare
GI- N/V/D/bleeding
Hepatotoxicity: avoid in a patient with compromised liver fuction
photosensativity
CYP450 drug inducer
Terbinafine
MOA
Terbinafine
ergosterol synthesis inhibitor
Inhibits the synthesis of squalene epoxide by inhibiting the enzyme “squalene epoxidase”
this leads to the accumulation of squalene which is toxic to fungal cells
Terbinafine
Side effects
well tolerated
Pregnancy category B
Terbinafine
Clinical Use
Terbinafine
DOC for treating dermatophytosis (tinea infections): topical use for cruris and corporis
Onychomycosis (tinea unguinum- nail fungus)
oral administration and prolonged therapy
“-azoles”
MOA
“-azoles”
ergosterol synthesis inhibitors
inhibit the synthesis of ergosterol from lanosterol by inhibiting CYP450 enzymes
“-azoles”
Clinical Use
“-azoles” broad spectrum of action including candida spp, cryptococcus neoformans, endemic mycoses, dermatophytes, even aspergillus
Ketoconzole:
Clinical Use
Side effects
Ketoconzole:
dermatophytosis
not for systemic use dt its narrow therapeutic index and side effects.
Side effects:
potent CYP450 inhibition
inhibits adrenal steroidogenesis causing adreanal insufficiency
hepatotoxicity
Fluconazole
major clinical use
Fluconazole
Cryptococcal meningitis (good CSF penetration)
Itraconazole
Major clinical use
Itraconazole:
candida, cryptococcus, blastomycosis
vorconazole
Vorconazole
DOC Aspergillus
Amphotericin B/Nystatin
MOA
Amphotericin B/Nystatin
Cell membrane integrity inhibitors
bind to ergosterol and forms pores in membrane to allow the leakage of electrolytes
Polyenes
Amphotericin B:
Clinical Uses
Amphotericin B:
DOC for most severe and/or life-threatening infections, systemic infections
topical use for candida albicans infection
Amphotericin B:
Side Effects
Amphotericin B:
Side effects
immediate toxicity: fever/chills, muscle spasms, vomiting, headache, hypotension. Treated by slowing infusion or prevent with antipyretics, antihistamine, meperidine, corticosteroids
cumulative toxicity: renal toxicity dt constriction of afferent arterioles and disruption of the membrane permeability. Renal tubular acidosis and renal wasting of K+ and Mg+
Nystatin:
Clinical Use
Nystatin
topical use only (too toxic for systemic use)
cutaneous, mucocutaneous, and oral infections normally caused by candida spp.
“swish and swallow” for thrush
topical for diaper rash or vaginal candidiasis
Nystatin
Side effects
Nystatin
Not absorbed from GI, skin, or vagina so has little toxicity
Echinocandins
Suffix
MOA
Echinocandins “-fungin”
Inhibit cell wall synthesis
inhibit synthesis of beta- glucan a component of the cell wall
Echinocandins
Clinical use
Echinocandins
Candida and Aspergillus
emperic antifungal therapy during febrile neutropenia
Echinocandins
Side effects
Echinocandins
Minor GI upset and flushing
v. expensive ($400/day)
