Background: Opioids like morphine produce side effects ranging from nausea and vomiting, pruritus, over sedation, dizziness and urinary retention to respiratory depression. Particularly, on chronic administration, it leads to development of tolerance. Combining opioids with certain other drugs (adjuvant analgesics) like ketamine, which is an N-methyl-D-aspartate (NMDA) receptor antagonist, not ...

BACKGROUND AND PURPOSE For patients experiencing inadequate analgesia and intolerable opioid-related side effects on one strong opioid analgesic, pain relief with acceptable tolerability is often achieved by rotation to a second strong opioid. These observations suggest subtle pharmacodynamic differences between opioids in vivo. This study in rats was designed to assess differences between opio...

Opioid-induced constipation is a major side effect that persists with long-term opioid use. Previous studies demonstrated that nicotine-induced contractions are enhanced after long-term morphine exposure in guinea pig ileum. In the present study, we examined whether the increased sensitivity to nicotine could be observed in single enteric neurons after long-term morphine exposure, determined th...

The inhibitory effects of central and peripherally acting opioid agonists on intestinal permeability (PER) were evaluated during acute and chronic intestinal inflammation in mice. Inflammation was induced by the intragastric (p.o.) administration of one (acute) or two (chronic) doses of croton oil (CO), whereas controls received saline (SS). Intestinal PER was assessed by the blood-to-lumen tra...

In Reply:—I thank Dr. Barasch for his insightful comments and for this opportunity to clarify my statement regarding the priority for confirmatory research. Actually, we agree that both laboratory and clinical research findings are strengthened, challenged, or refuted by further studies, and that subtle effects or those which are heavily dependent on the exact conditions of the experiment absol...

Preliminary estimates of U.S. drug overdose deaths exceeded 60,000 in 2016 and were partially driven by a fivefold increase in overdose deaths involving synthetic opioids (excluding methadone), from 3,105 in 2013 to approximately 20,000 in 2016 (1,2). Illicitly manufactured fentanyl, a synthetic opioid 50-100 times more potent than morphine, is primarily responsible for this rapid increase (3,4...