Action of Dilaudid on the Gut. ∗

Abstract

David 1 has reported a comparative study of metabolic and other effects of dihydromorphinone hydrochloride (“Dilaudid” N.N.R.) and its parent substance, morphine. This new keto-derivative has a narcotic potency 5 to 10 times that of morphine, but apparently its use is not attended by freedom from the undesirable side-effects of morphine to quite the extent suggested by Alvarez. 2 Study of the relative addiction tendencies of the 2 drugs in human subjects is of great importance but will require competent clinical observation over an extended period because of the intrinsic difficulties in such a comparison. Meanwhile it is of interest to investigate the more easily measurable physiological side-actions of the new agent, as has been done for certain subjective and objective effects by David.

In regard to the effect of dilaudid on the gastro-enteric tract, David found no marked difference from morphine in the occurrence of nausea, vomiting, diarrhea, and constipation in student volunteers to whom there was administered subcutaneously a dose equivalent in narcotic efficacy to a therapeutic dose of morphine. Of 74 subjects receiving 0.01 to 0.04 mg. per kg. of dilaudid, 58% were nauseated, 20% vomited, 8% showed diarrhea and 30% constipation in comparison with 63% nausea, 27% vomiting, 3% diarrhea and 37% constiption respectively in 41 subjects receiving 0.14 to 0.22 mg./kg. of morphine sulphate.

Vomiting and nausea, which occur after the 2 drugs, are of central origin and it seems in humans that dilaudid does not vary much from morphine in the ratio of emetic dose to therapeutic dose. Leake³ found that 10 mg./kg. of morphine sulphate causes emesis in dogs within 12 minutes, while we caused vomiting in only one of 4 dogs injected with 2 mg./kg. of dilaudid, although marked salivation and licking of chops were present in all. With subcutaneous dilaudid in dogs, the vomiting center may be too rapidly depressed, as with intravenous morphine, for emesis to occur regularly. That dilaudid definitely depresses the vomiting center after a slight initial stimulation, as demonstrated for morphine by Leake,³ is shown by the fact that 1 mg./kg. of apomorphine HCl subcutaneously one hour after the administration of dilaudid failed to elicit any symptoms of vomiting whatsoever.