Management of Opioid‐Induced Gastrointestinal Effects in Patients Receiving Palliative Care

Abstract

Opioid-induced gastrointestinal side effects, namely, nausea and constipation, are bothersome yet often easy to manage. Due to their widespread frequency, it is imperative that prophylactic and treatment modalities be understood. Although many pharmacotherapeutic agents are available with which to prevent or treat these side effects, few randomized, placebo-controlled studies have been conducted in terminally ill patients, thus limiting most treatment decisions to empiric therapies based on extrapolated data. A strong understanding of the pathophysiology of the sequelae is therefore paramount. Common agents administered for nausea are butyrophenones, phenothiazines, metoclopramide, and serotonin-receptor antagonists. Those given to manage constipation are stimulant laxatives and stool softeners, individually or in combination.

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

“…However, when given orally a substantial amount of the drug reaches the [Meissner et al 2000] Significant improvement in bowel function compared to oxycodone as assessed by BFI, number of complete SBMs, and PAC-SYM score. Laxative use reduced [Burness and Keating, 2014;Löwenstein et al 2009;Simpson et al 2008] Only marketed in oral formulation in combination with oxycodone Does not allow for opioid rotation or as add on to existing therapy Methylnaltrexone Peripherally acting, competitive µ-opioid receptor antagonist [Herndon et al 2002] Effective in inducing laxation in opioid treated patients within four hours of administration compared to placebo Only available in subcutaneous formulation and only approved in palliative care in patients with advanced illness Alvimopan Peripherally acting, competitive µ-opioid receptor antagonist [Camilleri, 2005;Schmidt, 2001] Significant increase in weekly SBMs compared to placebo. Improvement in a number of OIBD-related symptoms [Webster et al 2008] Cardiovascular safety concerns Only approved in the USA following partial small or large bowel resection with primary anastomosis in hospitalized patients Naloxegol Peripherally acting, competitive µ-opioid receptor antagonist [Corsetti and Tack, 2015;Eldon et al 2007] Significantly higher response rates for a composite primary endpoint compared with placebo.…”

Total temporomandibular joint alloplastic reconstruction

“…The consequence of constipation along time is related to increased morbidity and mortality and worsening of patients' quality of life. Chronic constipation results in effort to evacuate, formation of hemorrhoids, rectal region pain and burning sensa-tion, intestinal obstruction with risk of rupture and death 4 . Decreased intestinal mobility results from the activation of mu receptors in the gastrointestinal tract, acting directly on the enteric nervous system or decreasing parasympathetic autonomic flow 5 .…”

Recent Developments in the Management of Cancer Pain in Japan: Education, Clinical Guidelines and Basic Research

“…Nausea and vomiting are controlled by the 'vomiting center' in the medulla oblongata (45), which receives signals from the chemoreceptor trigger zone (CTZ) in the area postrema, the gastrointestinal tract, the vestibular apparatus in the temporal lobe and the cerebral cortex (46). Opioids exert an emetogenic effect by stimulating the CTZ and the vestibular apparatus, and by inhibiting gut motility (47). Although the stimulation of the CTZ by opioids involves m-and d-opioid receptors (48), signals from the CTZ to the vomiting center mainly involve dopamine D 2 and serotonin (5-HT 3 ) receptors.…”