China
Africa
Explore chapters and articles related to this topic
Development of palliative medicine in the United Kingdom and Ireland
Published in Eduardo Bruera, Irene Higginson, Charles F von Gunten, Tatsuya Morita, Textbook of Palliative Medicine and Supportive Care, 2015
Alvimopan is an orally administered peripherally restricted mu-opioid receptor antagonist approved for short-term use in hospitalized patients for the management of postoperative ileus in patients undergoing bowel resection. It is not approved for management of opioid-induced constipation. While several studies in chronic noncancer pain patients have suggested benefit, Â 27,28 a recent double-blind, placebo-controlled trial conducted over 12 weeks in 485 patients with noncancer pain found no statistically significant difference in the proportion of patients with spontaneous bowel movements (primary outcome) between the three groups: alvimopan 0.5mg once daily (63%), alvimopan 0.5mg twice daily (63%), or placebo (56%,p>0.05).29
Pharmacology of opioids
Published in Pamela E. Macintyre, Stephan A. Schug, Acute Pain Management, 2014
Pamela E. Macintyre, Stephan A. Schug
Alvimopan is a μ-receptor antagonist which was developed for the prevention and/or treatment of opioid-induced ileus and constipation subsequent to bowel resection. It shows very limited oral bioavailability and also no penetration of the blood–brain barrier. Its main effect is on opioid receptors in the gut wall, where it has a higher affinity than naloxone. It has an adverse effect profile similar to placebo, but accelerates recovery of GI function after surgery (ANZCA and FPM, 2010). In view of an increased risk of myocardial infarction, the FDA has limited its use to short-term under strict precautions (Food and Drug Administration, 2013).
Complications
Published in J. Richard Smith, Giuseppe Del Priore, Robert L. Coleman, John M. Monaghan, An Atlas of Gynecologic Oncology, 2018
Following laparotomy, a postoperative ileus occurs routinely. Small bowel motility and absorption generally returns within a few hours of surgery followed by stomach emptying which begins after 24 hours. The colon remains inactive for approximately 48 to 72 hours. This process is controlled by the autonomic nervous system. Occasionally a paralytic ileus may develop that can last from days to weeks. A paralytic ileus is associated with bowel mucosal injury secondary to bowel manipulation, hypoxia, endotoxins, and/or hypoperfusion, and all bowel segments are affected. Pain and opioid use can prolong both postoperative and paralytic ileuses. Techniques to reduce the risk of ileus include gentle handling of tissue, appropriate intraoperative fluid management, minimizing opioid use, epidural infusion of local anesthetics for pain management, and use of peripherally acting gastrointestinal opioid receptor antagonist. Alvimopan, approved by the FDA for postoperative use, has been found to shorten the time to return of bowel function without compromising pain control in patients undergoing bowel resection and radical hysterectomy. Concern has been raised regarding a potential association between use of COX 2 inhibitors and impaired intestinal healing following bowel resection. Patients with a paralytic ileus develop abdominal bloating, anorexia, nausea, and vomiting if early feeding is initiated. Abdominal cramping and pain in excess of that anticipated by the patient’s postoperative state are usually absent. Physical exam reveals a distended, tympanitic abdomen without bowel sounds. Obstruction series imaging will show a nonspecific bowel gas pattern with dilated loops of small and often large bowel. It can often be difficult radiographically to distinguish an ileus from an early obstruction. It is important to rule out infectious and metabolic causes such as peritonitis, abscess, and electrolyte abnormalities such as hypokalemia and hypomagnesemia. Patients are kept nil per orum (NPO) and observed with supportive measures instituted. For patients with persistent nausea and vomiting, a nasogastric tube should be inserted. However, nasogastric tubes have not been shown to shorten the duration of an ileus. If possible, narcotic use should be minimized. No currently available medications have been demonstrated to relieve a postoperative ileus once it is established. Watchful waiting with periodic obstruction series imaging to exclude an obstruction and blood work to exclude infection and metabolic derangement is recommended. For a prolonged ileus lasting more than 1 week, hyperalimentation should be considered. We have anecdotally found that hunger develops shortly before flatus and that diarrhea is common during the first 24 hours following the onset of bowel movements.
Investigational opioid antagonists for treating opioid-induced bowel dysfunction
Published in Expert Opinion on Investigational Drugs, 2018
Shilan Mozaffari, Shekoufeh Nikfar, Mohammad Abdollahi
Management of OIC is currently of concern since traditional treatment options are not sufficiently effective [8,9]. PAMORAs provide more benefits in OIC through a novel targeted approach [12]. There are Phase II clinical trials evaluating efficacy, safety, and tolerability of TD-1211 as a new PAMORA. The results indicate promising effectiveness with no serious adverse effects so far [23]. Four agents have been approved for OIC treatment by FDA. These agents have passed Phase IV of clinical trials and have been released into market (Table 2). More recently developed targeted agents are methylnaltrexone, naloxegol, and naldemedine [13]. Another novel approach is the combination of an opioid to control pain and a PAMORA to prevent OIC [13,43]. Although naloxone is not a PAMORA, oxycodone and naloxone oral tablets have been approved for patients with chronic pain [4]. Oxycodone-induced bowel dysfunction is a notable issue in chronic pain treatment. Addition of oral naloxone with opioid antagonizing properties provides a valuable combination. Prolonged release oxycodone-naloxone oral tablets exhibit a positive effect on pain management with minimized OIC in patients with cancer or non-cancer chronic pain [43,44]. Except for oxycodone-naltrexone and ADL5945 which are discontinued, all developed and developing agents show beneficial effects over placebo in patients with OIC [3]. No reduction in opioid-induced analgesia or withdrawal symptoms, have been reported. These agents have mild to moderate GI-related adverse effects, generally. Oral route of administration in newer agents increases patient’s compliance in comparison to injectable formulations. Alvimopan is another PAMORA that is not effective in OIC treatment, as it can cause serious cardiovascular adverse effects in patients with OIC [45].
A meta-analysis of naldemedine for the treatment of opioid-induced constipation
Published in Expert Review of Clinical Pharmacology, 2019
Xuesong Song, Dunwei Wang, Xiaoyu Qu, Naifu Dong, Shiyong Teng
Furthermore, OIC occurs not only in patients with chronic pain but also in postoperative patients. A related but separate entity is postoperative ileus, opioid-induced bowel dysfunction after surgery. Several studies reported PAMORAs alvimopan might be effective in treating opioid-induced bowel dysfunction and postoperative ileus without reversing analgesia [21–23]. Naldemedine as a novel PAMORAs might have similar effects on postoperative ileus where further studies are needed.
An update on the use of pharmacotherapy for opioid-induced bowel dysfunction
Published in Expert Opinion on Pharmacotherapy, 2023
Taraneh Mousavi, Shekoufeh Nikfar, Mohammad Abdollahi
Alvimopan is not recommended in patients with gastric or pancreatic anastomosis or those undergoing surgery for complete bowel obstruction. Use is also contraindicated in patients who have been under opioid therapy for more than seven consecutive days immediately before alvimopan initiation; since they might be more sensitive to alvimopan GI side effects.