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::