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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