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Anti Fungal by Mind Map: Anti Fungal
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Anti Fungal

Drugs for systemic infections

polyene macrolides

Amphotericin B, 4 formulas, C-AMB, L-AMB, ABLC, ABCD, mechanism, binds to ergosterol in the cell membrane, increases permeability, cell death, only binds to fungal sterol, not human cholesterol, pharmacokinetics, NOT absorbed orally, only IV, PPB more than 90%, long half life (15 days), does is 5mg/kg, does for C-AMB is 0.6mg/kg, advantages, life saving drug, high anti fungal activity, broad anti fungal spectrum, candida, albicans, histoplasma capsulatum, cryptococcus neoformans, coccidiodes species, sporothrix schenckii, aspergillus species, blastomyces dermatitidis, fungicidal activityh, negligible fungal resistance, disadvantages, nephrotoxicity, renal tubular acidosis and loss of K+ and Mg++, many weeks after therapy, infusion of normal saline helps, potassium supplement is required in 1/3 of patients on prolonged therapy, fever and chills, worst reaction: ABCD, least: L-AMB, 30-45 minutes, other side effects, headache, nausea, vomiting, hypotension, tachypnea, wight loss, azotemia (elevation of BUN) in 80% of patients, worst: C-AMB, less: ABLC, less: L-AMB, least: ABCD, anemia, due to bone marrow depression and decreased production of erythropoietin, therapeutic uses, all life threatening fungal infections, mucormycosis, cryptococcal meningitis (initial), severe histoplasmosis, blastomycosis, coccidioidomycosis, aspergillosis, sporotrichosis, fusariosis, trichosporonosis, patients with severe neutropenia and fever that did not respond to antibacterial agents for 5-7 days

pyrimidine antimetabolites

flucytosine, mechanism, impairs DNA synthesis, spectrum, cryptococcus neoformans, some candida, pharmacokinetics, complete & rapid absorption orally, minimal PPB, volume of distribution about total body water, 1-2 hours to active peak plasma concentration, dose is 50-150mg/kg/day (dividid by 4 doses), 80% excreted in urine unchanged, half life 3-6 hours, up to 200 hours with renal failure, dose reduced with renal failure, therapeutic uses, in combination with AMB, cryptococcal meningits, systemic candidiasis, in combination with fluconazole, AIDS patients with cryptococcosis, adverse effects, common, nausea, vomiting, diarrhea, rashes, bone marrow depression, leucopenia, thrombocytopenia

azoles

Imidazoles & triazoles, mechanism, inhibit fungal growth, spectrum, broad anti fungal spectrum, candida, cryptococcus neoformans, blastomyces, dermatitidis, histoplasma capsulatum, dermatophytes, coccidodes, some paracoccidodes, types, fluconazole, pharmacokinetics and dosage, completely absorbed from GIT, not altered with food or gastric acidity, half life 25-30 hours, elimination through kidney, diffuse to breast milk, sputum and CSF, dose 50-400mg once daily (oral or IV), therapeutic uses, candidiasis, systemic, oropharyngeal, esophageal, cryptococcal meningitis (after AMB), coccididal meningitis in AIDS patients, 400 mg daily dose for, allogeneic bone marrow transplant patients (to decrease incidence of deep candidiasis), treat candidemia (non immunosuppressed), special adverse effects, rashes, itraconazole, pharmacokinetics and dosage, oral absorption increases with food and gastric acid, PPB 99%, does not reach CSF, dosing, initial 200mg TID for three days, then 200mg twice a daily, therapeutic uses, lethargic non meningeal infections, B. dermatitidis, H. capsulatum, P. brasiliensis, C. immitis, invasive aspergillosis (outside CNS), oropharyngeal and eophageal candidiasis (if no response to fluconazole), special adverse effects (10% of patients), hypokalemia, hypertriglyceridemia, posaconazole, pharmacokinetics and dosage, bioavailability is enhanced with food, half life is 25-31 hours, PPB more than 98%, prophylaxis dose (above 8 y/o) 200mg TID, dose for active infection 200mg QID, therapeutic uses, refractory invasive aspergillosis, chromoblastomycosis, fusariosis, coccidioidomycosis, prophylaxis in chemotherapy or bone marrow transportation, voriconazole, pharmacokinetics and dosage, bioavailability is 96%, metabolized by CYP2C19 and CYP2C9, elimination half life is 6 hours, 80% of the metabolites excreted in urine, dosing, initial dose: 6mg/kg every 12 hours for 2 doses, followed by 3-4mg/kg every 12 hours, then 200mg every 12 hours, therapeutic uses, wider spectrum and better efficacy than fluconazole, invasive aspergillosis, esophageal candidiasis, special adverse effects, visual disturbance, hepatotoxicity, liver function should be monitored, prolongation of QT interval, general, common adverse effects, nausea, vomiting, diarrhea, headach, abdominal pain

echinocandins

general features, active against candidiasis and aspergillus (including the resistant to azoles), act by inhibiting synthesis of beta glucan (important for the cell wall) which causes cell lysis, given IV only (not absorbed orally)

types, caspofungin, metabolism, by hydrolysis and N-acetylation, excreted in urine and feces, therapeutic use, initial therapy of deeply invasive candidiasis, rescue therapy for invasive aspergillosis (failed to respond to AMB and voriconazole, esophageal candidiasis, suspected fungal infection in febrile neutropenic patients, dose, initially 70mg then 50mg daily, micafungin, metabolism, in the liver, arylsulfatase, COMT, therapeutic use, invasive & esophageal candidiasis, dose, 100 mg daily over 1 hour, anidulafungin, treatment of esophageal candidiasis, 100mg followed by 50mg daily

allylamines

terabinafine, inhibits synthesis of ergosterol, pharmacokinetics, well absorbed orally but goes first pass metabolism (bioavailability 40%), PPB 99%, accumulated in skin, nails, and fat, initial half life is 12 hours but extends to 200-400 hours in steady state, therapeutic uses, onychomycosis, candidiasis, dermatophytosis, pityriasis, tinea capitis, adult oral dose is 250mg daily

Drugs for topical infections

systemic drugs

griseofulvin, inhibits mitosis by binding to tubulin, effective in topical dermatophytosis, trichophytin, microsporum, epidermophyton, dosing (oral), children, 2-3mg/kg up to 500mg max, adults, 500-1000, in sever cases can be increased for a short period of time to 1.5-2g, adverse effects, nausea, vomiting, diarrhea, dry mouth, headache, peripheral neuritis, vertigo, lethargy, blurred vision, hepatotoxicity, neutopenia, leucopenia

lodide

topical drugs

nystatin, same action of AMB, obtained from streptomyces noursei, only topically due to to hight systemic toxicity, used for vaginal candidiasis

haloprogin, halogenated phenolic ether, spectrum, epidermophyton, trichophyton, microsporum, pityrosporum, candida, therapeutic use, tinea pedis, tinea cruris, tinea corporis, tinea manuum, tinea versicolor, twice a day on infected skiing for 2-4 weeks

tolnaftate, treatment of most cutaneous mycoses, trichophton rubrum, t. mentagrophytes, t. tonsurans, e. floccosum, microsporum gypseum, m. canis, m. audouinii, m. furfur, 1% preparation

naftifine, inhibits biosynthesis of ergosterol, broad spectrum, 1% cream or gel, used for, tinea curis, tinea corporis, cutaneous candidiasis, tinea versicolor

imidazoles, miconazole, 2% and 4% vaginal cream, used for, tinea pedis, tinea crusis, tinea versicolor, vulvovaginal candidiasis, or vaginal suppositories at bed time, 100 gm (7 days), 200 gm (3 days), 1200 gm (1 day), adverse effects, burning, itching, systemic absorption, less than 1% topically, 1.3% from vagina, econazole, deschloro derivative or miconazole, penetrates the stratum corneum - found in the mid dermis, less than 1% in blood, 1% cream, used for, tinea pedis, tinea crusis, tinea corporis, cutaneous candidiasis, tinea versicolor, clotrimazole, systemic absorption, less than 0.5% from skin, 3-10% from vagina, used for, oropharyngeal and vulvovaginal candidiasis, dermatophyte infections, remains in vagina for 3 days after application, available as, 1% cream, lotion, powder, solution, applied twice a day, 1% or 2% vaginal cream, vaginal tablets, once in bed time, 100gm for 7 days, 200mg for 3 days, 500mg for one day, adverse effects, mild burning, rare abdominal cramps after vaginal application, butoconazole, similar to clotrimazole, 2% vaginal cream, slower response during pregnancy, so a 6 days course is recommended in 2nd and 3rd trimester, tioconazole, for vulvovaginal candidiasis, single dose of 300mg at bed time