Reaction at Site of Injection of Mercurial Diuretics as Influenced by Theophylline

Abstract

The comparative toxicity of mercurial preparations has usually been studied from the point of view of “minimal toxic dose” in the sense of causing death in a fixed period of time. The literature on this subject has been fully reviewed by Fourneau and Melville. 1 However, very little attention has been paid to the local reaction at the site of injection. The frequent occurrence of venous thrombosis and necrosis from the use of mercurial diuretics is of considerable importance. v. Issekutz and v. Vegh 2 combined a mercurial diuretic with theophylline and suggested that the latter, having weak acidic properties, neutralized the alkaline reaction (responsible for the pain) that is produced upon hydrolysis of the mercurial salt. This combination was introduced as novurit, but is known in this country as mercupurin.∗ Recently Fulton and Bryan 3 found that in animals both salyrgan and mercupurin produced definite necrotic lesions, but the former was more severe in extent and degree of reaction. They noted that there was a striking absence of slough formation when a mercurial salt, to which 5% theophylline was added, was injected subcutaneously.

We have compared the local action of mercurial diuretics with and without theophylline and have attempted to establish a quantitative relationship. The preparations used were mercupurin, the theophylline-free mercurial salt contained in mercupurin, salyrgan, salyrgan plus aminophylline (so that the theophylline content was equivalent to that of mercupurin) and as a control—aminophylline, physiological saline and distilled water.∗ Equivalent amounts of the drugs as regards mercurial content were used. The following series of experiments were performed:

(1) Doses of 0.05 cc. of various dilutions (undiluted to 1:100) of the drugs were injected intracutaneously into the abdominal wall of 12 rabbits. Each rabbit was given at the same experiment the various dilutions of at least 3 diuretics and the control drugs.