This document discusses antifungal agents used to treat fungal infections. It defines antifungal agents as drugs that selectively eliminate fungal pathogens with minimal toxicity. It classifies fungal infections and describes various antifungal drug classes including polyenes, azoles, allylamines, echinocandins, and pyrimidines. For each drug class, it provides examples of drugs, their mechanisms of action, pharmacokinetics, spectrum of activity, and common adverse effects.

3. INTRODUCTIONINTRODUCTION

4. DEFENITION:DEFENITION: An antifungal agent is a drug thatAn antifungal agent is a drug that
selectively eliminates fungal pathogens from a host withselectively 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.

6. TREATMENTTREATMENT

7. 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:

8. 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

9. Nystatin
Mechanism : Like Amphotericin B and has same mechanism of action.
 Adverse effects : Too toxic for parenteral
administration, and is only used topically.
Griseofulvin

10. 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

11. 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, Clotrimazole
Bioavailability is low by taking
orally.
Used topically.

12. Itraconazole
 Treatment of dermatophytoses and
onychomycosis
 The only agent with significant activity against
aspergillus species.
Fluconazole

13. VorionazoleVorionazole
 Metabolism is predominantly hepatic.
 Similar to itraconazole in its spectrum
of action, having good activity against
candida species.
 More effective than itraconazole.

14. AllylaminesAllylamines
 Allyl amines inhibit the enzyme
squalene
epoxidase, another enzyme required for
ergosterol synthesis:
 Terbinafine - marketed as Lamisil
 Amorolfine
Naftifine
 Butenafine

15. EchinocandEchinocand
inin
 Echinocandins inhibit the synthesis of glucan
in the cell wall, probably via the enzyme
1,3-βglucan synthase
 Anidulafungin
 Caspofungin

16. 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.

17.  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

18. CONCLUSION:CONCLUSION:

19. REFERENCESREFERENCES::