This document discusses several antifungal drugs including their mechanisms of action, uses, and side effects. It describes how pathogenic fungi contain chitin and ergosterol in their cell walls and membranes. Common antifungal classes mentioned are azoles, polyenes such as amphotericin B, and allylamines like terbinafine. Amphotericin B inserts into fungal membranes to form pores, while griseofulvin disrupts fungal cell division. Flucytosine is converted to a compound interfering with fungal DNA synthesis. The document provides details on administration, metabolism, and adverse effects of these antifungal agents.

1. S.Aishwarya
2nd M.Sc Biochemistry

2.  Pathogenic fungi of humans are generally filamentous molds or intracellular yeasts.
 Fungal cell wall contains chitin and polysaccharides making it rigid and act as barrier
for drug penetration.
 The cell membrane contains ergosterol which influences the efficacy and risk of drug
resistance.
 Most antifungal agents are fungistatic.
 Diseases caused by fungi include superficial infections of the skin by dermatophytes.
 These dermatophytic infections are named for the site rather than causative agent.
 Eg. Tinea capis (scalp) – M.canis
 Systemic infection- coccidioidomycosis – cocidioides immitis
 Oppurtunistic infection – Aspergillosis – Aspergillus sp target organs like lung,brain
and sinuses.

3.  1. Antibiotics
A. Polyenes - Amphotericin B , Nystatin.
B. Echinocandins – caspofungin , micafungin.
C. Heterocyclic benzofuran – griseofulvin.
 2. Antimetabolite flucytosine
 3. Azoles
A. Imidazoles
Topical – clotrimazole , econazole, miconazole, oxiconazole.
Systemic – ketaconazole
B. Triazoles
Systemic – fluconazole, itraconazole,voriconazole, posaconazole.

4.  4. Allylamine terbinafine
 5. Other topical agents : tolnaftate, benzoic acid, sodium thiosulfate, cicloproxolamine,
undecylenic acid.

5. Eg. Amphotericin B (AMB)
Chemistry
 Possess a macrocyclic ring , one side has several conjugated double bonds and is
highly lipophilic and other side is hydrophilic with OH groups.
 Insoluble in water and unstable in aqueous medium.
Mechanism
 Polyenes have high affinity for ergosterol in fungal cell wall membrane.
 They get inserted into the membrane and form micropore.
 Because of that cellular contents of fungi get leaked.

6. Antifungal spectrum
 Amb is active against wide range of fungi and yeast – candida albicans, Aspergillus etc
 Also active on leishmania protozoa.
Pharmacokinetics
Absorption and administration
 Not absorbed orally – can be given orally for intestinal candiasis without systemic toxicity.
Distribution
 Administered as I.v with suspension with deoxycholate, gets widely distributed in body but
CSF penetration is poor.
Metabolism
 Binds to sterol and stays longer
 t ½ is 15 days
 60% is metabolize in liver

7. Excretion
 Urine and bile
Dosage
 Oral administration 50 to 100mg for intestinal moniliasis and topically for vaginitis
 Ear drops 3% fungi zone
 Conventional form c- Amb is available as dry powder for systemic mycosis.
 Liposomal l- Amb to improve tolerability of i.v infusion of Amb, reduce its toxicity and
achieve targeted delivery.
Adverse effects
 Headache, fever, chills, anorexia, vomitting, muscle and joint pain
 Pain at site of infection
 Nephrotoxicity, hemolytic anaemia, allergy and convulsions.
Products - fungizone, abelcet

8. Interactions
 Flucytosine has supra-additive action with Amb in the case of fungi sensitive to both.
 Amninoglycosides, vancomycin, cyclosporine and other nephrotoxic drugs enhance
the renal impairment caused by Amb.

9. Eg. Griseofulvin
Introduction
 It is fungistatic against dermatophytes but not against candida and other fungi
causing deep mycosis.
 Bacteria are also insensitive
Mechanism of action
 Disrupts the mitotic spindle by interacting with polymerized microtubules
 Resulting in the production of multinucleate fungal cells.
 It also inhibits nucleic acid resulting in swelling, distortion and spiral curling of
hyphae.

10. Absorption
 Irregular G.I tract absorption because of its low water solubility.
 Absorption is improved by taking fats and microfining drug particle.
Distribution
 Deposited in keratin forming cells of skin, hair and nails.
 Especially in tinea infected cells.
Metabolism and excretion
 Largely metabolised by methylation
 Excreted in urine
 T1/2 24hours but present in skin

11. Adverse effects
 Headache
 Aplastic anaemia
Dosage
 125 – 250 mg QID with meals
 Scalp 4wks
 Toe nails 10-12 months
Uses
 Used orally for dermatophytic and effective in athletes foot
Interactions
 Induces cyt450 enzyme and hastens warfarin metabolism
 Phenobarbitone reduces oral absorption and metabolism induces drug failure
 Can cause intolerance to alcohol

12. Eg. Flucytosine (5FC)
Mode of action
 Is a pyrimidine antimetabolite
 Flucytosine is converted to cytosine deaminase in fungal cell to fluorouracil – interferes
with RNA and protein synthesis
 Flurouracil converted to 5 fluorodeoxyuridylic acid – inhibits thymidylate synthesis required
for DNA synthesis leading to fungal death
Administration
 Oral drug
Distribution
 Well absorbed and distributed
 CSF levels are 65-90% of plasma levels

13. Elimination
 Urine
Adverse effects
 GI tract upset, hepatic involvement increase in transaminase
 Anaemia , leucopenia
 Thrombocytopenia
Uses
 Active against cryptococcus neoformans, torula, and few strains of candida

14. Thankyou