Amphotericin B toxicity can be lowered by?
|A||Toxicity decreased by incorporating it in liposomal complex|
|B||Reducing the dose|
|C||Combining with flucytosine|
|D||Injecting the drug with saline pre loading|
a. Pharmacologically, both amphotericin A and B are known. However, clinically, amphotericin B is most commonly useD. Isolated originally from streptomyces.
b. The drug exhibits a wide variety of toxic features. Most common side effect is chills and rigors. That occurs with almost with every infusion. It also causes hypokalemia, hyperkalemia and hypomagnesemiA.
c. Bone marrow depression can lead to anemiA. Major toxicity is nephrotoxicity. The drug is now a days available as liposomal amphotericin B. it is significantly less with the liposomal formulation.
d. It has been shown that Amp B (liposomal), used in doses of 3mg/kg/day IV is more effective and safer compared to usual Amp B in treatment of dimorphic fungi in seriously ill patients (CMDT’2010, pp-1392).
e. Amphotericin is typically nephrotoxic in doses of 2-3 grams. This causes severe vasoconstriction leading to distal tubular damage (distal tubular acidosis).
f. The drug causes resistant to ADH action and leads to nephrogenic diabetes insipidus (CMDT’2010, pp-821-22). Importantly, cyclosporine too can cause distal tubular damage due to vasoconstriction.
g. A number of other agents are known to be nephrotoxiC. These include vancomycin, cephradine, acyclovir. All of these drugs have been noted to cause acute tubular necrosis.
h. Amp B is most commonly used for systemic fungal infections. It is the drug of choice for cryptococcal meningitis (Dhikav V, Drugs of Choice’ 2010, 4th Edition, AITBS publishers).
i. It is safe during pregnancy. Dose of Amp B can be reduced when it is given with flucytosine. The reason is better penetration of drug (BG Katzung’ 10th Edition, 2010).