chemotherapy of fungal diseases
TRANSCRIPT
INTRODUCTIONINTRODUCTION
DEFENITION:DEFENITION: An antifungal agent is a drug that An antifungal agent is a drug that selectively eliminates fungal pathogens from a host with selectively eliminates fungal pathogens from a host with
minimal toxicity to the.minimal toxicity to the.
Fungal infections classification: Superficial infections:
Ringworm (tinea) → skin and mucous membrane. Incidence
rate is high.
Systemic infections: Candida albicans → opportunist infections.
. Fatality rate is high.
TREATMENTTREATMENT
Amphotericin BAmphotericin B Produced by Streptomyces nodosus.
Amphoteric polyene macrolide. Mechanism: binds to ergosterol in
fungi (cholesterol in humans and bacteria) to form pores
Pharmacokinetics:
Adverse Effect :
Infusion-Related Toxicity: fever, chills, muscle spasms, vomiting, headache, hypotension.
Slower Toxicity: Renal toxicity, K+↓, Mg2+↓.
Anemia: erythropoietin Abnormalities of liver function
Neurologic sequela
NystatinMechanism : Like Amphotericin B and has same mechanism of action. Adverse effects : Too toxic for parenteral
administration, and is only used topically.
Griseofulvin
AzolesAzoles Synthetic compounds. Classification: according to the number of
nitrogen atoms in the five-membered azole ring Imidazoles: Ketoconazole, Miconazole, Econazole,
Clotrimazole, Bifonazole Triazoles: Itraconazole, Fluconazol, Vorionazole →
systemic treatment
Mechanism of Action
Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes.Greater affinity for funfal than for human cytochrome P450 enzymes.Imidazoles exhibit a lesser degree of specificity than the triazoles, accounting for their higher incidence of drug interactions and side effects
KetoconazoleKetoconazole The first oral azole introduced into clinical use. Less selective for fungal P450
Inhibition of human P450 interferes with biosynthesis of adrenal and gonadal steroid hormones;
Alter the metabolism of other drugs. Best absorbed at a low gastric pH.
Miconazole, Econazole, ClotrimazoleBioavailability is low by taking orally. Used topically.
Itraconazole
Treatment of dermatophytoses and onychomycosis
The only agent with significant activity against aspergillus species.
Fluconazole
VorionazolVorionazolee
Metabolism is predominantly hepatic. Similar to itraconazole in its spectrum
of action, having good activity against candida species.
More effective than itraconazole.
AllylaminesAllylamines Allyl amines inhibit the enzyme
squaleneepoxidase, another enzyme required for
ergosterol synthesis: Terbinafine - marketed as Lamisil Amorolfine Naftifine Butenafine
EchinocaEchinocandinndin
Echinocandins inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-βglucan synthase
Anidulafungin Caspofungin
Pyrimidine Flucytosine ( 5-FC ) is a water-
soluble pyrimidine analog. Its spectrum of action is much
narrower than that of amphotericin B. Poorly protein-bound and penetrates
well into all body fluid aompartments, including the cerebrospinal fluid.
Mechanism 5-FC (taken up by fungal cells via the
enzyme cytosine permease) → 5-FU → F-dUMP and FUTP → inhibit DNA and RNA synthesis, respectively.
Adverse effects: result from metabolism to fluorouracil (5-FU) Bone marrow toxicity with anemia,
leukopenia, and thrombocytopenia
CONCLUSION:CONCLUSION:
REFERENCESREFERENCES::