Opioids and the gut: pharmacology and current clinical experience

Schepper, Heiko U. De; Cremonini, Filippo; Park, M.‐I.; Camilleri, Michael

doi:10.1111/j.1365-2982.2004.00513.x

Cited by 195 publications

(155 citation statements)

References 105 publications

(106 reference statements)

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“…This study applied thermal pain to the skin and viscera at the same heating rate and morphine analgesia was prominent only in the skin (Figure 2) [5]. This reflects the clinical situation where visceral pain, in contrast to somatic pain, can be difficult to treat with traditional m opioid agonists [104].…”

Section: Mechanistic Aspectsmentioning

confidence: 99%

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Staahl

Olesen

Andresen

et al. 2009

Brit J Clinical Pharma

111

131

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AIMExperimental pain models may help to evaluate the mechanisms of action of analgesics and target the clinical indications for their use. This review addresses how the efficacy of opioids can be assessed in human volunteers using experimental pain models. The drawback with the different study designs is also discussed. METHODA literature search was completed for randomized controlled studies which included human experimental pain models, healthy volunteers and opioids. RESULTSOpioids with a strong affinity for the m-opioid receptor decreased the sensation in a variety of experimental pain modalities, but strong tonic pain was attenuated more than short lasting pain and non-painful sensations. The effects of opioids with weaker affinity for the m-opioid receptor were detected by a more narrow range of pain models, and the assessment methods needed to be more sensitive. CONCLUSIONThe way the pain is induced, assessed and summarized is very important for the sensitivity of the pain models. This review gives an overview of how different opioids perform in experimental pain models. Generally experimental pain models need to be designed with careful consideration of pharmacological mechanisms and pharmacokinetics of analgesics. This knowledge can aid the decisions needed to be taken when designing experimental pain studies for compounds entering phase 1 clinical trials.

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Section: Mechanistic Aspectsmentioning

confidence: 99%

Assessing analgesic actions of opioids by experimental pain models in healthy volunteers – an updated review

Staahl

Olesen

Andresen

et al. 2009

Brit J Clinical Pharma

111

131

View full text Add to dashboard Cite

show abstract

“…1,2 They result from binding of exogenous opioids to opioid-receptors in the enteric nervous system, consequently disturbing normal GI function and manifesting in symptoms including gastroesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation, and incomplete evacuation. 3 Severe adverse effects are often the reason patients discontinue opioid treatment, which naturally results in inadequate pain management.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Opioid Treatment on Regional Gastrointestinal Transit

Poulsen

Nilsson

Brock

et al. 2016

J Neurogastroenterol Motil

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Background/AimsTo employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GI transit times using the 3-dimensional (3D)-Transit system. MethodsTwenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. Adverse GI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab ® graphical user interface. ResultsGI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P = 0.001). No associations between questionnaire scores and segmental transit times were detected. ConclusionsSelf-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation.

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“…Although being a relatively common manifestation in patients under opioids, it is worsened by several other factors such as malnutrition, dehydration and simultaneous use of other drugs, which are especially present in metastatic oncologic patients under palliative care 8 . Constipation is a challenge for the oncologic practice because it is often neglected by health professionals and caregivers, although being associated to several other symptoms, such as discomfort, abdominal pain, nausea, vomiting, fecal impaction with or without anal injury 4,5 , which invariably impact global health and quality of life of cancer patients, in addition to increasing the use of other drugs for relief or symptomatic treatment of symptoms and the rate of complications and costs related to such interventions. Considering the relevance of the subject and that experience in the treatment of opioid-induced constipation in children is scarce, this study aimed at evaluating intestinal habits of cancer patients under morphine.…”

Section: Introductionmentioning

confidence: 99%

“…The World Health Organization (WHO) indicates morphine to treat moderate to severe pain of cancer patients 3 . However, although effective, the treatment with morphine is often associated to side effects, such as constipation 4,5 . There are few data in the literature about constipation secondary to morphine among pediatric cancer patients.…”

Section: Introductionmentioning

confidence: 99%