antifungals Flashcards
fungi
generally resistant to antibacterials, relatively toxic, not many agents effective against pathogenic fungi in vivo, in many avascular skin nails hair, hard distribution
classification of mycoses
Systemic: debilitated or immunosuppressed patients- aspergillus, candida, phycomyces, cryptococcus, histoplasma
Geographically localized- blastomyces, histoplasma, coccidioides, sporothrix
Life threatining
Superficial: mucous membranes- candida, dermatophytic- trichophyton, microsporum, epidermophyton
Amphotericin B
MOA: lipophillic, binds ergosterol in fungal membranes producing membrane instability/ leakage
Uses: effective for broad spectrum systemic mycoses
Admin- not absorbed in GI tract given IV
total cumaltive dose important for renal toxicity
SE: fever, GI, headache, chills, hypotension, hypokalemia, tachypne, 90% will show nonpermanent nephrotoxicity, permanent renal damage can occur, related to total drug dose, reversible hypochromic, normocytic anemia
Flucytosine
MOA: fungi contain a cytosine deaminase not found in humans which converts 5-FC to 5FU, metabolites of 5FU then block nucleic acid synthesis
Uses: serious infections due to Candida, cryptococcus
used in conjunction with amphotericin
Admin: given with amphotericin B
toxicity: nausea, vomiting, diarrhea, enterocolitis, leukopenia, thrombocytopenia, reversible elevated hepatic enzymes, use extreme caution in those with renal insufficiency or bone marrow depression
imidazoles/triazoles
fluconazole, itraconazole, voriconazole
MOA: inhibit sterol 14 a-sterol demethylase (a fungal CYP450) which then blocks converstion of lanosterol to ergosterol and deprives the membranes of ergosterol
admin and elimination: oral or IV (fluconazole-oral), CNS penetration fluconazole none for itraconazole
elimination: fluconazole excreted unchanged in urine, itra and vori are metabolized by liver
SE: nausea, vomiting, rash diarrhea, headache, heptatotoxicity,inhibits metabolism of CYP3A and 2C of 70 percent of drugs
fluconazole
cryptococcus meningitis, candida (albicans) not candida krusei
Itraconazole
blastomyces, histoplasma, candida albicans and glabrata strains (not for CNS or urinary)
CX: when combo with CYP3A4 inhibitors, weakness and dizziness, potential for serious CV effects
Voriconazole
invasice aspergillus, Candida (not urinary
extended spectrum includes C. glabrata and krusei
CX: when combo with CYP3A4 inhibitors, visual disturbances and rash
caspofungin
MOA: inhibits fungal cell wall synthesis by non-competitvely blocking synthesis of B 1,3 D glucan, no cross resistance with imidazoles and triazoles
Uses: invasive aspergillus in pts intolerant of refractory to other drugs, candida esophageal and systemic, broad candida coverage
Toxicity : fever, nausea vomiting, rash, phlebitis at injection site
treatment of superficial candida mycoses
fluconazole- oral dose, vaginal candida (single oral dose) Candida in urinary tract and oropharynx
miconazole- topical use for vaginal candida
clotrimazole- vaginal candida- topical, orophyrngeal candida (oral toches), oral form toxicity (abnormal liver function test 15%)
itraconazole- oropharyngeal and esophageal candida- oral dose
nystatic- exclusively candida, mechanism similar to amphotericin B, Topical/oral for GI distress
amphotericin B- topical formulation for cutaneus or mucosal candida, not effective against dermatophytes
treatment of ophthalmic fungal infections
natamycin- fungal eye infections (conjunctivitis)-fusarium, cephalosporium, aspergillus
MOA same as amphotericin B
toxicity- conjunctival chemosis and hyperemia
treatment of dermatophytic infections
(trichophyton, epidermophyton, microsporum)-
topical preparations for commpn skin and hair infections
Miconazole, clotrimazole, tolnaftate (foot), terbinafine (lamisil)
topical treatments for nail dermatophytic infections
ciclopiros- topical Rx for mid to moderate fungal nail infection
oral preps for sever dermatophyte infections that are refractory to topical therapy
terbinafine (12 week therapy for nail infections shorter for other dermatophyte infections
MOA: inhibits fungal squalene epoxidase; non-competitvely; the accumuation of squalene damages fungal cell membranes, fungicidal
toxicity: diarrhea, dyspepsia, abdominal pain, rash, terbinafine inhibits CYP2D6
griseofulvin
for recalcitrant dermatophytic infections of skin hair nails that are beyond topical therapy
therapy for tinea captis
MOA: interferes with microtubule function/mitotic spindle mitosis
Toxicity: headache contraindicated in those with porphyria and advanced liver disease, increased metabolism of other drugs, caution penicillin allergies
