PHARMACOKINETICS INVOLVED WITH KAPPA OPIOID RECEPTORS (Atena Editora)

Abstract

INTRODUCTION: The receptors, members of the opioid receptor family, whose main actions involve neuroendocrine activity and pain perception, such as spinal analgesia, ventilatory depression and sedation. Although they are widely used, opioids have several adverse effects, which requires a continuous search for drugs that mitigate these consequences. Thus, among several agonists of these receptors, there are eluxadoline and R-dihydroetorphine, used as an alternative to commonly used opioids. Furthermore, such receptors are also associated with the misuse. METHODOLOGY: PubMed literature review, with the descriptors kappa AND opioid receptor in the last 5 years. Eleven scientific articles were selected, including only clinical trials in English in humans and excluding those that do not fit the pre-established objectives. RESULTS: Opioids are essential for the treatment of moderate to severe pain in oncological and perioperative patients, however, it is necessary to pay attention to chemical dependence and respiratory depression. Activation of κ and δ receptors is suggested to counteract respiratory depression induced by μ receptor activation in traditional opioids such as morphine and fentanyl. Studies of R-dihydroetorphine showed high analgesic potential, mild side effects and respiratory stability. Eluxadoline is an efficient alternative in the treatment of abdominal pain and diarrhea in Irritable Bowel Syndrome (IBS), in addition to having a lower abuse potential than other μ receptor agonists, however, the intranasal route has aversive properties, such as bad taste. There was no association of single nucleotide polymorphisms of κ receptors or δ-opioids with morphine analgesia for any pain. The use of eluxidaline must be noted, given the intestinal constipation and changes in cardiac repolarization.

CONCLUSION: R-dihydroetorphine exhibited a plateau in respiratory depression but not in analgesia. Eluxadoline, well tolerated, had side effects, mostly in cholecystectomy patients, with higher dosage. Early clinical response to eluxadoline was associated with benefits for 6 months for IBS. Thus, the aforementioned findings suggest the safety of eluxadoline in patients with IBS.