The antimicrobial agent which inhibits the ergosterol biosynthesis is:
IMIDAZOLES AND TRIAZOLES: These are presently the most extensively used antifungal drugs. Four irnidazoles are entirely topical, while ketoconazole is used both orally and topically. Two triazoles fluconazole and itraconazole have largely replaced ketoconazole for systemic mycosis because of greater efficacy, longer tlh, fewer side effects and drug interactions. The imidazoles and triazoles have broadspectrum antifungal activity covering dermatophytes, Candida, other fungi involved in deep mycosis (except mucor), Nocardia, some grampositive and anaerobic bacteria, e.g. Staph. aureus, Strep. faecal is, Bac. fragilis and Leishmania. The mechanism of action of irnidazoles and triazoles is the same. They inhibit the fungal cytochrome P450 enzyme &;lanosterol l4--demethylase&; and thus impair ergosterol synthesis leading to a cascade of membrane abnormalities in the fungus. The lower host toxicity of triazoles compared to irnidazoles has correlated with their lower affinity for mammalian CYP450 enzymes and lesser propensity to inhibit mammalian sterol synthesis. However, because they are active against ceain bacteria as well (which do not have ergosterol), other mechanisms of action also appear to be involved. Ketoconazole (KTZ): It is the first orally effective broad-spectrum antifungal drug, useful in both dermatophytosis and deep myc osis. The oral absorption of KTZ is facilitated by gastric acidity because it is more soluble at lower pH. Hepatic metabolism is extensive; metabolites are excreted in urine and faeces. Elimination of KTZ is dose dependent: tlh varies from llh to 6 hours. Penetration in CSF is poor: not effective in fungal men ingitis. However, therapeutic concentrations are attained in the skin and vaginal fluid. ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:761,762
Ketoconazole
Amphotericin B
5-Flucytosine
Griseofulvin
Chemotherapy