Amphotericin B

Amphotericin B

·        Amphotericin A & B are antifungal antibiotics.

·        Amphotericin A is not used clinically.

·        It is a natural polyene macrolide

·        (polyene = many double bonds )

·        (macrolide = containing a large lactone ring )

Pharmacokinetics

·        Poorly absorbed orally, is effective for fungal infection of gastrointestinal tract.

·        For systemic infections given as slow I.V.I.

·        Highly bound to plasma protein.

·        Poorly crossing BBB.

·        Metabolized in liver

·        Excreted slowly in urine over a period of several days.

·        Half-life 15 days.

Mechanism of action

·        It is a selective fungicidal drug.

·        Disrupt fungal cell membrane by binding to ergosterol, so alters the permeability of the cell membrane leading to leakage of intracellular ions & macromolecules (cell death).

Adverse Effects

1-    Immediate reactions (Infusion –related toxicity).

·        Fever, muscle spasm, vomiting, headache, hypotension.

·        Can be avoided by :

A.  Slowing the infusion

B.    Decreasing the daily dose

C.   Premedication with antipyretics, antihistamincs or corticosteroids.

D.  A test dose. A test dose of 1 mg per 20 mL 5% dextrose in
water infused over 30 minutes should be given

2-    Slower toxicity

·        Most serious is renal toxicity (nearly in all patients).

·        Hypokalemia

·        Hypomagnesaemia

·        Impaired liver functions

·        Thrombocytopenia

·        Anemia

Clinical uses

·        Has a broad spectrum of activity & fungicidal action.

·        The drug of choice for life-threatening mycotic infections.

·        For induction regimen for serious fungal infection.

·        Also, for chronic therapy & preventive therapy of relapse.

·        In cancer patients with neutropenia who remain febrile on broad –spectrum antibiotics.

Routes of Administration

1-    Slow I.V.I. For systemic fungal disease.

2-    Intrathecal for fungal C.N.S. infections.

3-    Topical drops & direct subconjunctival injection for Mycotic corneal ulcers & keratitis.

4-    Local injection into the joint in fungal arthritis.

5-    Bladder irrigation in Candiduria.

Liposomal preparations of amphotericin B

Amphotericin B is packaged in a lipid- associated delivery system to reduce binding to human cell membrane, so reducing:

A. Nephrotoxicity

B. Infusion toxicity

Also, more effective and more expensive