Anti fungal (amphotericin b)

fungus drug classification
only one drug discuse in this slideshare

1. Antifungals CLASSIFICATIONS OF ANTI-FUNGAL DRUGS:- Acc. To route of admin:- Topical Nystatin Clotrimazole Econazole Amphotericin – B Oral Miconazole Ketoconazole Fluconazole Itraconazole Flucytosine Grisofulvin Terbenafine 1

2. AMPHOTERICIN B isolated from Streptomyces nodosus Pharmacokinetics Poorly absorbed from GIT so oral ampho B is only used for fungi within lumen of the tract not for systemic disease I/V inj , topical 90% bound to PP Widely distributed in most tissue , but only 2-3% reaches CSF Some of it excreted in urine slowly over period of several days Severe t ½ = 15days Hepatic dis, renal disease and dialysis has little effect on drug conc. And dose adjustment is not required 2

3. MOA It binds to ergosterol (a cell membrane sterol) and form ampho. B associated pores in the cell membs and alters its permeability Pore allows leakage of intercellular ions & macromolecules and results in cell death Resistance If ergosterol binding is impaired either by ↓ conc. Of ergosterol or by modifying the sterol tagetting molecule to reduce its affinity for the drug.   3

4. Adverse effects Infusion-relate toxicity Cumulative toxicity Immediate :- / infusion related toxicity Include Fever, chills ,Muscle spasms Vomiting, headache, hypotension can be ameliorated by slowing infusion rate or ↓ daily dose Premedication by Antipyretics Antihistaminic corticosteroid 4

5. cumulative toxicity Renal toxicity More common with AMB Reversible, prerenal renal failure occur in almost all patients 80% dose dependent/t ↓ renal perfusion can be reduce by giving inf of N. saline with daily dose irreversible renal tubular acidosis severe K+ and Mg wasting creatinine Cl - drops and K+ lost with potentiated by hypo natremia K= loss can be reversed by KCl 5

6. hypochromic, normocytic anemia d/t ↓ production of erythropoietin Thrombocytopenia, Leukopenia Head ach. Nausea, vomiting, malaise Seizures Hepatic toxicity 6

7. Antifungal activity Broad spectrum fungicidal Candida albicans Cryptococcus neofromans Histoplasma capsultum B lastomycoses dermatitides , C occidioides immitis Aspergillus furnigatus 7

8. Clinical use I. All life threatening mycotic infections It is used initially for serious infections and then replace by azoles for chronic or preventive therapy Fungal pneumonia cancer patient with neutropenia who remain febrile on brad spectrum antibiotics 8

9. II. Systemic fungal disease → slow I/V infusion at dose of 0.5-1mg /kg/d and usually continued to the total dose of 1-2 mg → in AIDS given once daily to prevent relapse of cryptococcosis + histoplasmosis III. Intrathecal therapy For cryptococcal meningitis not responding to other drugs. IV. Local use Mycotic corneal ulcer and keratitis in form of drops and direct sub conj. Inj Fungal arthritis treated with adjunctive local inj. Direct in to joint. Candiuria respond to bladder irrigation with Amphotericin B 9