ORAL NALOXONE ANTAGONIZES MORPHINE-INDUCE D CONSTIPATION

Introduction: Almost all patients treated with opioids suffer from con stipation. Numerous laxatives are used to overcome the problem, but no ne has yet been found to yield favourable results in all patients. Sev eral studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impa irment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied. Methods: Fifteen patient s suffering from opioid-induced constipation participated in the prese nt study. (1)Constipation had been present for 5 to 14 days despite th e use of laxatives. According to the results obtained in the animal ex periments [4], it was originally planned to administer oral naloxone a t a dose ratio of 1:1 with respect to morphine on day 1 and 2; reducin g it on day 3 and 4 to one-half and then to one-fourth of the initial dose on day 5 and 6. Results: Twelve patients experienced a strong lax ative effect with spontaneous bowel evacuation 1 to 4 h after the firs t intake of oral naloxone. Three patients had no laxative effects even after repeated doses. Eleven of the 15 patients reported an average l oss of 10%-15% of analgesia after oral naloxone as measured by visual analogue scales. Increasing the morphine dose by about 15% restored th e previous level of analgesia without reappearance of constipation. Ei ght of the 12 patients having a laxative effect experienced abdominal cramps, and therefore, the total dose of naloxone was reduced on day 2 to 2%-15% of that originally planned; this dose still produced a laxa tive effect. Four of the 15 patients had a withdrawal syndrome. A sing le dose of morphine equivalent to their daily morphine intake abolishe d the symptoms. Discussion: The medical history of the 3 patients in w hom naloxone failed to abolish constipation revealed neurological dist urbances. Treatment of these patients included the use of neuroleptics , antiemetics, and other drugs. In this context, it should be noted th at oral naloxone can be expected to abolish only opioid-induced consti pation. In conclusion, it was found that the treatment of opioid-induc ed constipation by administration of oral naloxone produced positive r esults. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.