This document discusses antifungal agents, specifically amphotericin B. It begins by classifying fungal infections as superficial or deep and lists common causative fungi. It then describes the classification of antifungal agents and provides details on the mechanism of action, uses, administration and dosage of amphotericin B. Key points are that amphotericin B is a broad-spectrum polyene antibiotic obtained from streptomyces nodosus, acts by binding ergosterol in fungal cell membranes, and is the gold standard treatment for many invasive fungal infections but has high toxicity including nephrotoxicity, anemia and acute reactions.

1. ANTI-FUNGAL AGENTS
SREEHARSHA.P
ROLL NO. 78
>CLASSIFICATION OF ANTIFUNGAL AGENTS
>AMPHOTERICIN B - M.O.A , USES & ADVERSE EFFECTS

2. ANTI-FUNGAL AGENTS
*Mycoses
*These are drugs used to treat fungal infections (superficial
& deep).
*Fungal infections may be primary or secondary.
*Mostly associated with use of -
- broad spectrum antibiotics
- corticosteroids , anticancer/immunosuppressants
- Indwelling catheters & implants
- immunocompromised patients(AIDS, D.M)

3. Deep mycosis
*Aspergillus
*Blastomyces
*Cryptococcus
*Coccidioides
*Candida
*Histoplasma
*Mucormycetes
*Sporothrix schenkii
Superficial mycosis
*Dermatophytes
-Epidermophyton
-Trichophyton
-Microsporum
*Candida
*Malassezia furfur

4. CLASSIFICATION OF ANTIFUNGAL AGENTS

5. AMPHOTERICIN B
*Amphotericin B is a polyene broad-spectrum
antibiotic.
*obtained from streptomyces nodosus.
* structure - macrolytic ring, 1 side has
doublebonds(lipophilic), other side has OH
groups(hydrophilic).
*All polyenes are unstable in water & unstable in aq.medium.
*AMB is one of the most toxic systemically used antibiotics.

6. MECHANISM OF ACTION

8. ANTIFUNGAL SPECTRUM
* active against most of the fungal infections - candida.albicans ,
H.capsulatum , C.neoformans , Blastomyces.dermatidis ,
Coccidioides.immitis , Torulopsis , Aspergillus , Sporothrix etc.
PHARMACOKINETICS
*Not absorbed orally
*administered i.v as suspension with deoxycholate, it is widely distributed.
*poor csf penetration.
*terminal elimination t1/2 = 15 days.
*60% is metabolized in liver.
*excretion- both urine and bile.
*no dose adjustment needed in kidney & liver diseased patients.

9. ADMINISTRATION & DOSAGE
*Oral - AMB 50-100mg QID - intestinal moniliasis
*Topical - vaginitis , otomycosis(FUNGIZONE OTIC 3% ear drops).
*I.V - Fungizone iv , Mycol 50mg vial(dose increased based on tolerance)
*Intrathecal injection - fungal meningitis
*Liposomal AMB
-Produced to improve tolerability of i.v infusion of AMB
-to reduce toxicity & achieve target delivery
-consists of 10% AMB incorporated with liposomes
-Special features - mild acute reaction,lower nephrotoxicity,minimal
anemia, delivers to RE cells.
-Specifically indicated for critically ill deep mycoses cases, kala azar,
febrile neutropenic pts not responding to antibacterial antibiotics.

10. USES -
*Gold standard of antifungal
therapy.
*Oral,vagina,cutaneous
candidiasis.
*fungal corneal ulcer,
*otomycosis.
*febrile neutropenia
*leishmaniasis

11. ADVERSE EFFECTS-
*Toxicity is high
*Acute reaction - chills,fever,aches,nausea,vomiting,dyspnea(2-5 hrs)
*Nephrotoxicity- azotemia, reduced GFR, acidosis,hypokalaemia,inability
to concentrate urine. It reverses slowly after stoppage of therapy.
*Anaemia - slowly progressing, due to B.M depression.(reversible)
* CNS toxicity - only in intrathecal inj. - headache, vomiting, nerve palsies
etc.

12. DRUG INTERACTIONS
*Flucytosine (5-FC) - has supra additive action with AMB in case of fungi
is sensitive to both. AMB increases penetration of 5-FC
*Aminoglycosides,vancomycin,cyclosporine - enhance renal impairment
caused by AMB.
Reference - textbook of pharmacology - KD TRIPATI , SHANBAG