Procarbazine

Procarbazine (Matulane) may autooxidize spontaneously, and during this reaction hydrogen peroxide and hydroxyl free radicals are generated. These highly reactive products may degrade DNA and serve as one mechanism of procarbazine-induced cytotoxicity. Cell toxicity also may be the result of a transmethylation reaction that can occur between the N-methyl group of procarbazine and the N7 position of guanine.

Procarbazine is rapidly absorbed after oral administration and has a plasma half-life of only 10 minutes. The drug crosses the blood-brain barrier, reaching levels in CSF equal to those obtained in plasma. Metabolism is extensive and complex. Urinary excretion accounts for 70% of the procarbazine and its metabolites lost during the first 24 hours after drug administration.

When originally tested as a single agent in advanced Hodgkin's disease, procarbazine produced tumor regression responses that were brief, usually lasting only 1 to 3 months. The combination of procarbazine with mechlorethamine, vincristine, and prednisone in the MOPP regimen, however, resulted in an 81% complete remission rate in Hodgkin's disease. Most of these patients are considered cured. Procarbazine is also used in various combination chemotherapy protocols for non-Hodgkin's lymphomas and small cell anaplastic (oat cell) carcinoma of the lung. Limited antitumor effects have been observed against multiple myeloma, melanoma, and non-oat cell lung cancers.

The major side effects associated with procarbazine therapy are nausea and vomiting, leukopenia, and throm-bocytopenia. Skin rashes have been reported, as have rare cases of allergic interstitial pneumonia. Procar-bazine administration produces a high degree of chromosomal breakage, and the compound is mutagenic, ter-atogenic, and carcinogenic in experimental systems.

Procarbazine may potentiate the effects of tranquilizers and hypnotics. Hypertensive episodes can result if procarbazine is administered simultaneously with adrenomimetic drugs or with tyramine-containing foods. Rarely, a reaction to alcohol similar to that provoked by disulfiram may occur.

Getting to Know Anxiety

Getting to Know Anxiety

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