Amphotericin B is a broad-spectrum antifungal drug isolated from Streptomyces nodosus. It binds to ergosterol in fungal cell membranes, forming pores that cause leakage and cell death. Common adverse effects include infusion-related fever and chills, as well as cumulative renal toxicity. It is used for serious, life-threatening fungal infections like candidiasis, cryptococcosis, and aspergillosis.

1. Antifungals
CLASSIFICATIONS OF ANTI-FUNGAL DRUGS:-
Acc. To route of admin:-
1. Topical
– Nystatin
– Clotrimazole
– Econazole
– Amphotericin – B
2. Oral
– Miconazole
– Ketoconazole
– Fluconazole
– Itraconazole
– Flucytosine
– Grisofulvin
– Terbenafine
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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
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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.
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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
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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
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6. hypochromic, normocytic anemia d/t ↓ production of
erythropoietin
Thrombocytopenia, Leukopenia
Head ach. Nausea, vomiting, malaise
Seizures
Hepatic toxicity
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7. Antifungal activity
Broad spectrum fungicidal
i. Candida albicans
ii. Cryptococcus neofromans
iii. Histoplasma capsultum
iv. Blastomycoses dermatitides ,
v. Coccidioides immitis
vi. Aspergillus furnigatus
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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
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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
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