Evolving paradigms in the treatment of opioid-induced bowel dysfunction

Abstract

Abstract:In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

“…21 Opioid treatment results not only in constipation, but a range of other symptoms such as reflux, bloating, abdominal distension and cramping, nausea, anorexia and therefore the term OIBD is more appropriate. 28,29 As the abdominal symptom subscale score covers symptoms as discomfort in the stomach, bloating, and stomach cramps that are consistent with the more broadly description of the pan-intestinal effects of opioids, it appears the participants are better treated with PR naloxone than macrogol. However, these abdominal symptoms may also be ascribed to side effects from the macrogol treatment.…”

Treatment with Naloxegol Versus Placebo: Pain Assessment in Patients with Noncancer Pain and Opioid‐Induced Constipation

“…The analgesic effect of opioids occurs via actions at receptors in both the central nervous system (CNS) and the peripheral nervous system . However, because opioid analgesics also act at receptors in the gastrointestinal (GI) tract that mediate a variety of functions, including GI motility and secretion, individuals who take these agents are at risk for experiencing opioid‐induced bowel dysfunction . One significant manifestation of such is opioid‐induced constipation (OIC), a condition in which gut motility and secretions are reduced, leading to a variety of symptoms, including hard, dry stools; rectal straining; and incomplete evacuation .…”

Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic low back pain with a neuropathic component: a blinded end point analysis of randomly selected routine data from 12-week prospective open-label observations

“…Nonopioid analgesics were the most frequently used treatments reported by 98.9% (n=258/261) of patients as the prior index medication, followed by nonsteroidal anti-inflammatory drugs (96.2%, 251/261), antidepressants (70.1%, 183/261), WHO Step II opioids (69.3%, n=181/261), and antiepileptic agents (37.5%, 98/261). Around 37.2% (97/261), a third of patients, presented with advanced pain chronification (Stage III) according to the Mainz Pain Staging System,35 and 59.0% (n=154/261) suffered from a high disability with either moderate (Grade III; n=100/261, 38.3%) or severe (Grade IV; n=54/261, 20.7%) limitations according to the von Korff pain grading scale 36. For both assessments, OXN patients showed significantly stronger impairments compared to those treated with TAP.…”

“…Although most of these AEs are transient and can be prevented or at least diminished by appropriate countermeasures, OIC often persists over time and evolves – with a prevalence of 40% in opioid-treated patients – into the most common and most burdensome complication of long-term treatment with opioid analgesics, resulting in an increased use of health care resources and a significant loss of productivity 19–26. Recommended countermeasures to treat or even prevent this opioid-related AEs (eg, fluid and fiber intake, laxatives, and stool softeners) suffer from a lack of high-quality evidence regarding efficacy and safety27–30 and have proven ineffective for the majority of patients, as they are not able to address the underlying OIC mechanisms adequately 31–36…”