ACQUIRED TOLERANCE TO AND CROSS TOLERANCE BETWEEN THE NITROUS AND NITRIC ACID ESTERS AND SODIUM NITRITE IN MAN’

The pharmacology of glyceryl trinitrate and allied substances is seldom discussed without reference to the tolerance developed by their prolonged use. During that period when glyceryl trini-trate was more commonly employed in conditions of high blood pressure than at present, the decreasing response which followed the continued administration of the drug was recognized as an obstacle to its successful therapeutic use. Tolerance to glyceryl trinitrate and other drugs of the “nitrite group ” has been discussed by several writers. Stewart (1) re-ports the case of a patient in whom 1 minim of a 1 per cent alco-holic solution of glyceryl trinitrate was the beginning dose; after the continuous use of the drug over a period of six months, this patient was obtaining less effect from 16 minims of a 10 per cent solution than with the original dose of 1 minim of a 1 per cent solution. In this case the dose was increased to 160 times that originally used without increasing its effectiveness. Matthew (2) observed acquired tolerance to glyceryl trinitrate in patients, but no acquired tolerance to erythrol tetranitrate, mannitol hexani-trate, or sodium nitrite. Laws (3), Ebright (4), and Heitz (5) all report tolerance to glyceryl trinitrate on the part of men en-gaged in the manufacture of dynamite. Nerertheless, no care-‘This contribution is part of an extended study of the pharmacology of the nitrates and nitrites undertaken under the direction of Professor A. S. Loevenhart (1878-1929). It is affectionately dedicated to his memory.-L. A. C., C. D. L., and C. W. M