Enhanced Action of Morphine in Experimental Nephrosis after Oral Ingestion of Magnesium Sulphate

Abstract

We have shown 1 , 2 , 3 that the oral administration of magnesium sulphate raises the plasma magnesium of animals and men with damaged kidneys, but not that of normal individuals.

In view of the old-time clinical teaching that one should exercise caution in the administration of morphine to severe nephritics and to old persons, we have tested the effects of morphine sulphate injections on rabbits whose kidneys were injured by the subcutaneous administration of 10 mg. HgCl₂/K. The plasma magnesium of these animals ranged from 1.89 to 2.17 mg. Mg. per 100 cc. and rose to 6.90 to 8.98 mg. Mg. Two hours after the oral administration of 2 gm. per kg. MgSO₄, 7H₂O, 30 mg. morphine sulphate per kilo was administered subcutaneously to 8 of these nephrotic rabbits. In 3 of these narcosis lasted 9 to 11 hours (av. 9 2/3 hours) and 5 animals died in deep narcosis in 1/2 to 5 hours after the injection. The 4 control animals receiving the same dose recovered from the narcosis after 3 to 4 hours. The narcosis of the controls was less intense than that of the nephrotic animals.

These results indicate that animals, whose plasma magnesium is only moderately elevated (7.0 to 8.70 mg. per 100 cc.) (as in the case in nephrotic patients who have received a single purgative oral dose of Epsom salts), are much more sensitive to morphine than are normal animals. These results are in striking contrast to the results obtained by MacKay and MacKay, 4 who found that “uraemic” (nephrectomized) rats are less sensitive to morphine than are normal rats. The level of the plasma magnesium is most probably the determining factor.