Antifungal agents

Pharmacology - Antifungal agents

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

7. 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.

8. 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.

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

10. 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.

11. 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