STUDIES ON PHENOTHIAZINE VIII. ANTISEPTIC VALUE OF PHENOTHIAZINE IN URINARY TRACT INFECTIONS

¹ From the Food Research Division of the Bureau of Chemistry and Soils, U. S. Department of Agriculture, and the Departments of Medicine and Pharmacology, Stanford University School of Medicine, San Francisco, California

Thirty-three patients with chronic, and 16 patients with acute, urinary tract infections were treated with average daily doses of 1.33 grams phenothiazine during an average period of 7.4 days. The average total dose was 9.99 grams.

Ten patients with acute urinary tract infections were relieved permanently of symptoms, and pus and bacteria disappeared from the urine. Cystoscopic examination showed an increase in bladder capacity, and a decrease in hyperemia of the bladder mucosa. Five patients with chronic inflammation of the urinary tract were clinically cured, and 20 improved. Several patients included in the "improved" group were "cured" as long as they remained under observation, but they failed to report during the four-week period arbitrarily established as necessary before the patient was pronounced "cured."

Only 8 of the 49 patients failed to secure relief from symptoms of urinary tract inflammation following the administration of phenothiazine.

When the urine was acidified by administration of ammonium chloride, the thionol content, after a given dose of phenothiazine, was increased and the bactericidal action more pronounced. Twenty-five of 31 patients were symptomatically cured by an average dose of 6.76 grams phenothiazine given daily for an average period of 3 days. However, the 2 groups of patients were not directly comparable because of the higher incidence of acute infections in those treated with phenothiazine and ammonium chloride.

No undesirable effects from the drug could be demonstrated in the gastrointestinal tract, circulation, kidneys, or liver. The color in the indirect Van den Bergh test and the icterus index were elevated due to color from the dye in the blood serum. Anemia in only a few patients (3 out of 49), occurred after an average total dose of 23.3 grams, which was far beyond the average therapeutic dose. The anemia was apparently hemolytic in nature, since there was an early reticulocyte response and a rapid regeneration of the blood which would not have occurred, if there had been injury to the bone marrow.

1. Phenothiazine given orally for a limited period of time in daily doses of 1.5 to 2 grams appears to be an effective urinary antiseptic, especially when the pH of the urine is kept acid in a pH range of 4.5 to 5.5, by the administration of ammonium chloride.

2. Phenothiazine is capable of producing secondary anemia when the drug is used continuously in excessive or extra therapeutic doses. The experimental evidence indicates that this side action is similar to that produced by methylene blue.

3. The maximum total dose of phenothiazine should not exceed 15 grams without a rest period, but generally a therapeutic result will be obtained with much less, if benefit is to occur.

4. The blood should be examined periodically, in case medication is continued for long periods, and if there is evidence of anemia, a rest period is indicated.

5. This drug should not be used extensively until more exhaustive clinical trials, under controlled conditions, are obtained by several observers.

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