Thiouracil in angina pectoris

Abstract

Of eight patients with angina treated with thiouracil, five were improved, two unimproved, and one, though showing some evidence of improvement, had not been observed long enough to permit classification of the result. The two that did not respond were treated for three months and six weeks respectively. One of these, with severe angina, showed a change in the basal metabolic rate from minus 15 to minus 18 per cent. The other, with mild angina, dropped from plus 1 to minus 2 per cent. The patient with the unclassified result had a mild angina, was treated for two months, the metabolism changing from plus 2 to minus 12 per cent. By contrast, the five who improved were treated for eight, six, seven, eight and six months, respectively, an average of seven months. Little if any improvement became manifest before two months had elapsed. The lowest basal metabolic levels reached in these patients were minus 24, 22, 23, 23 and 20 per cent. In patients B. W. and L. B. myxedema developed at four months and five months, respectively. Bilateral thyroid enlargement appeared in patient O. H. at the end of eight months' treatment. This constitutes valid evidence for the ability of thiouracil to suppress the normal thyroid if it is administered consistently over a long enough period of time. Toxic reactions to the drug offered little interference in the treatment of this small group. Patient M. C. developed gastric distress at the onset which disappeared quite promptly. Patient O. H. developed joint pains and headache on the sixth day, which cleared on stopping medication for one week and did not recur on a lower dosage level. Propyl-thiouracil, because of its lesser toxicity, was substituted for thiouracil in three patients after improvement had appeared. In patient L. B. three months' administration at 75 to 125 mg. daily failed to hold the gain made with thiouracil. One hundred mg. daily over a three months' period held the ground previously gained by patients O. H. and J. K. Four of the five improved patients continued symptom-free without further treatment: Patient B. W. for four months, patient M. C., three months, and patients O. H. and J. K. one month each. In accounting for this and the improvement in general, it may well be claimed that a period of time alone, comparable to that devoted to treatment with thiouracil, would be sufficient to permit development of enough collateral circulation to overcome the anoxia and pain. While this might account for the ultimate improvement and freedom from attacks after treatment had been terminated, it would make no allowance for the part played by the thiouracil in lowering the metabolism, reducing the demands on the heart muscle, and in decreasing the latter's sensitivity to adrenalin. This action, though slow in developing, is apparently instrumental in controlling the symptoms in angina while modification of existing circulatory deficiencies is being accomplished through improvement in the collateral circulation.