ANTIFUNGAL DRUGS

dr. Agung Wiwiek Indrayani, M.Kes

Pharmacology Department Faculty of Medicine

dr. Agung Wiwiek Indrayani, M.Kes

Pharmacology Department Faculty of Medicine

Problems

+ a polyene

ergosterol

ergosterol withpore

Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450

enzymes

Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450

enzymes

Clinical UseMany candida species, Crytococcus neoformans , the endemic mycoses (blastomycosis, coccidiodomycosis, histoplasmosis, the dermatophytes,

aspergillus infections

Clinical UseMany candida species, Crytococcus neoformans , the endemic mycoses (blastomycosis, coccidiodomycosis, histoplasmosis, the dermatophytes,

aspergillus infections

Acetyl CoA

Squalene

Lanosterol

(ergosterol)

Allylaminedrugs

Azoles

Squalene-2,3 oxide

Squalene monooxygenase

14--demethylase

VORICONAZOLENewest triazole

Intravenous and oral formulations

Dosage 400 mg/d

Intravenous and oral formulations

Dosage 400 mg/d

Well absorbed, bioavaibility 90 %,

inhibition of P450 low

Visual disturbances 30 % patient

Less toxic > Amphotericin B

Candida species, invasive aspergillosis

Echinocandins the newest antifungal agent

Only intravenous form, a single loading dose 70 mg, dailly dose 50 mg

Water soluble, highly protein bound T1/2 9-11 hours Excretion kidneys and GIT Dosage adjustment hepatic

insufficiency Disruption cell wall inhibiting synthesis

of B (1-3) glucan Invasive aspergillosis, candida

Very insoluble ,fungistatic, from penicillium

Oral form absorption with fatty food, 1 g/d

It binds to keratin, protecting from new infection

2-6 weeks for skin and hair infectionNail infection for monthsSerum sickness, hepatitis, drug

interaction ( warfarin and phenobarbital ),

replaced by azoles and terbinafine

A synthetic allylamine , fungicidal, oral formulation, 250 mg/d

Dermatophytoses, onychomycosis Keratophilic, inhibit ergosterol

biosynthesis Accumulation of the sterol squalene

toxic organism One tablet daily 12 weeks cure rate 90

%

Acetyl CoA

Squalene

Lanosterol

(ergosterol)

Allylaminedrugs

Azoles

Squalene-2,3 oxide

Squalene monooxygenase

14--demethylase

RATIONALE FUNGAL DRUGS

THANK YOUTHANK YOU