Emerging treatments in neurogastroenterology: eluxadoline – a new therapeutic option for diarrhea‐predominant <scp>IBS</scp>

Lacy, Brian E.

doi:10.1111/nmo.12716

Cited by 38 publications

(29 citation statements)

References 45 publications

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“…8,9,12 This makes Rifaximin a clinically preferable option compared to other treatment options, and thereby again supporting the conclusion of Rifaximin being a preferable therapy.…”

Section: Discussionmentioning

confidence: 54%

“…8 These IBS-D patients also have the lowest score of QoL compared to other IBS patients because of the significant influence of diarrhea on their social activities and daily life. 9 Despite that in the year 2000, alosetron, a5HT 3 receptor antagonist, was the only approved medication for the condition and that too solely for women with severe diarrhea.…”

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

A Cost-Effectiveness Comparison of Alosetron, Eluxadoline, and Rifaximin in the Treatment of Irritable Bowel Syndrome with Diarrhea

Sansgiry¹

2016

PPIJ

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“…8,9,12 This makes Rifaximin a clinically preferable option compared to other treatment options, and thereby again supporting the conclusion of Rifaximin being a preferable therapy.…”

Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 95%

A Cost-Effectiveness Comparison of Alosetron, Eluxadoline, and Rifaximin in the Treatment of Irritable Bowel Syndrome with Diarrhea

Sansgiry¹

2016

PPIJ

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“…It has been demonstrated that local activation of µ-opioid receptors slows GI transit and reduces GI secretions. 15 In contrast, δ-opioid receptor antagonism is thought to increase colonic propulsion. Thus, the addition of a δ-opioidreceptor antagonist to a µ-opioid-receptor agonist should theoretically counteract excessive inhibition of gastrointestinal motility of unopposed µ-opioid-receptor agonism, resulting in potentially more normalized bowel function.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…There is also evidence to suggest that the combination of µ-opioid-receptor agonism and δ-opioid-receptor antagonism has synergistic analgesic effects. 15 The role of κ-opioid agonism is not well established, however, it may be involved in reducing visceral hyperalgesia.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…In the gut, there are three main opioid receptors, mu (µ), delta (δ), and kappa (κ), all of which are G-protein-coupled receptors. 15 These receptors are present in the enteric nervous system, smooth muscle cells, and interstitial cells of Cajal (ICC) where they are believed to play a major role in gut motility, secretion and visceral sensation. Eluxadoline is a µ-opioid and κ-opioidreceptor agonist/δ-opioid-receptor antagonist ( Figure 1).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

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The place of eluxadoline in the management of irritable bowel syndrome with diarrhea

Levio

Cash

2017

Therap Adv Gastroenterol

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain associated with defecation with altered stool frequency or stool form. The global prevalence of IBS ranges from 10% to 15% and total healthcare cost attributable to IBS is significant. Among individuals with IBS, the condition has dramatic effects on health-related quality of life, work and school productivity, and activities of daily living. It may be diagnosed with confidence, based on symptom-based diagnostic criteria, exclusion of alarm features and directed diagnostic testing. Management of IBS typically begins with dietary and lifestyle modifications, progressing to over-the-counter therapies, and then to prescription medications, both approved and nonapproved for IBS. This narrative summarizes the efficacy and safety of three US Food and Drug Administration (FDA)-approved prescription therapies for IBS with diarrhea (IBS-D), with a focus on the most recently marketed agent, eluxadoline, and its role in the treatment IBS-D.

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Insights into the Role of Opioid Receptors in the GI Tract: Experimental Evidence and Therapeutic Relevance

Galligan

Sternini

2016

Handbook of Experimental Pharmacology

100

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Opioid drugs are prescribed extensively for pain treatment but when used chronically they induce constipation that can progress to opioid-induced bowel dysfunction. Opioid drugs interact with three classes of opioid receptors: mu opioid receptors (MORs), delta opioid receptors (DOR), and kappa opioid receptors (KORs), but opioid drugs mostly target the MORs. Upon stimulation, opioid receptors couple to inhibitory Gi/Go proteins that activate or inhibit downstream effector proteins. MOR and DOR couple to inhibition of adenylate cyclase and voltage-gated Ca channels and to activation of K channels resulting in reduced neuronal activity and neurotransmitter release. KORs couple to inhibition of Ca channels and neurotransmitter release. In the gastrointestinal tract, opioid receptors are localized to enteric neurons, interstitial cells of Cajal, and immune cells. In humans, MOR, DOR, and KOR link to inhibition of acetylcholine release from enteric interneurons and motor neurons and purine/nitric oxide release from inhibitory motor neurons causing inhibition of propulsive motility patterns. MOR and DOR activation also results in inhibition of submucosal secretomotor neurons reducing active Cl secretion and passive water movement into the colonic lumen. Together, these effects on motility and secretion account for the constipation caused by opioid receptor agonists. Tolerance develops to the analgesic effects of opioid receptor agonists but not to the constipating actions. This may be due to differences in trafficking and downstream signaling in enteric nerves in the colon compared to the small intestine and in neuronal pain pathways. Further studies of differential opioid receptor desensitization and tolerance in subsets of enteric neurons may identify new drug or other treatment strategies of opioid-induced bowel dysfunction.

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Emerging treatments in neurogastroenterology: eluxadoline – a new therapeutic option for diarrhea‐predominant IBS

Abstract: This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed.

Cited by 38 publications

References 45 publications

A Cost-Effectiveness Comparison of Alosetron, Eluxadoline, and Rifaximin in the Treatment of Irritable Bowel Syndrome with Diarrhea

A Cost-Effectiveness Comparison of Alosetron, Eluxadoline, and Rifaximin in the Treatment of Irritable Bowel Syndrome with Diarrhea

The place of eluxadoline in the management of irritable bowel syndrome with diarrhea

Insights into the Role of Opioid Receptors in the GI Tract: Experimental Evidence and Therapeutic Relevance

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