LAsparaginase

The enzyme l-asparaginase (Elspar) is derived from the bacteria Escherichia coli and Erwinia carotovora. It catalyzes the hydrolysis of l-asparagine to aspartic acid and ammonia. l-Glutamine also can undergo hydrolysis by this enzyme, and during therapy, the plasma levels of both amino acid substrates fall to zero. Tumor cells sensitive to l-asparaginase are deficient in the enzyme asparagine synthetase and therefore cannot synthesize asparagine. Depletion of exogenous asparagine and glutamine inhibits protein synthesis in cells lacking asparagine synthetase, which leads to inhibition of nucleic acid synthesis and cell death.

The half-life of l-asparaginase in human plasma is 6 to 30 hours. The drug remains primarily in the intravas-cular space, so its volume of distribution is only slightly greater than that of the plasma. Metabolism and disposition are thought to occur through serum proteases, the reticuloendothelial system, and especially in patients with prior exposure to the drug, binding by antibodies. The drug is not excreted in urine, and very little appears in the CSF.

The major indication for l-asparaginase is in the treatment of acute lymphoblastic leukemia; complete remission rates of 50 to 60% are possible. Lack of cross-resistance and bone marrow toxicity make the enzyme particularly useful in combination chemotherapy. l-Asparaginase also can be used in the treatment of certain types of lymphoma. It has no role in the treatment of nonlymphocytic leukemias or other types of cancer.

Since it is a foreign protein, l-asparaginase may produce hypersensitivity reactions, including urticarial skin rashes and severe anaphylactic reactions. One-third of patients have nausea, anorexia, weight loss, and mild fever. Almost all patients develop elevated serum transaminases and other biochemical indices of hepatic dysfunction. Severe hepatic toxicity occurs in fewer than 5% of cases. Patients receiving l-asparaginase may develop symptoms of CNS toxicity, including drowsiness, confusion, impaired mentation, and even coma. Pancreatitis occurs in 5 to 10% of cases. Hyperglycemia, possibly due to inhibition of insulin synthesis, also may occur. L-Asparaginase differs from most cytotoxic drugs in its lack of toxicity to bone marrow, gastrointestinal tract, and hair follicles.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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