Opioid-induced Constipation

Argoff, Charles E.

doi:10.1097/ajp.0000000000000852

Cited by 40 publications

(7 citation statements)

References 37 publications

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“…With the exception of digestive disorders, these other disorders are not involved in the toxicological effects of these drugs. While constipation can result from the consumption of opioids [ 45 ], it is unlikely to be part of an acute poisoning event that results in a call to the APCC. There were greater odds of a call being related to both opioids and cannabinoids when the owner reported that the dog had cardiovascular, general, and nervous disorders.…”

Section: Discussionmentioning

confidence: 99%

Comparing the diagnostic performance of ordinary, mixed, and lasso logistic regression models at identifying opioid and cannabinoid poisoning in U.S. dogs using pet demographic and clinical data reported to an animal poison control center (2005–2014)

et al. 2023

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Researchers have begun studying the impact of human opioid and cannabinoid use on dog populations. These studies have used data from an animal poison control center (APCC) and there are concerns that due to the illicit nature and social stigma concerning the use of these drugs, owners may not always be forthcoming with veterinarians or APCC staff regarding pet exposures to these toxicants. As a result, models derived from APCC data that examine the predictability of opioid and cannabinoid dog poisonings using pet demographic and health disorder information may help veterinarians or APCC staff more reliably identify these toxicants when examining or responding to a call concerning a dog poisoned by an unknown toxicant. The fitting of epidemiologically informed statistical models has been useful for identifying factors associated with various health conditions and as predictive tools. However, machine learning, including lasso regression, has many useful features as predictive tools, including the ability to incorporate large numbers of independent variables. Consequently, the objectives of our study were: 1) identify pet demographic and health disorders associated with opioid and cannabinoid dog poisonings using ordinary and mixed logistic regression models; and 2) compare the predictive performance of these models to analogous lasso logistic regression models. Data were obtained from reports of dog poisoning events collected by the American Society for the Prevention of Cruelty to Animals’ (ASPCA) Animal Poisoning Control Center, from 2005–2014. We used ordinary and mixed logistic regression models as well as lasso logistic regression models with and without controlling for autocorrelation at the state level to train our models on half the dataset and test their predictive performance on the remainder. Although epidemiologically informed logistic regression models may require substantial knowledge of the disease systems being investigated, they had the same predictive abilities as lasso logistic regression models. All models had relatively high predictive parameters except for positive predictive values, due to the rare nature of calls concerning opioid and cannabinoid poisonings. Ordinary and mixed logistic regression models were also substantially more parsimonious than their lasso equivalents while still allowing for the epidemiological interpretation of model coefficients. Controlling for autocorrelation had little effect on the predictive performance of all models, but it did reduce the number of variables included in lasso models. Several disorder variables were associated with opioid and cannabinoid calls that were consistent with the acute effects of these toxicants. These models may help build diagnostic evidence concerning dog exposure to opioids and cannabinoids, saving time and resources when investigating these cases.

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Section: Discussionmentioning

confidence: 99%

Comparing the diagnostic performance of ordinary, mixed, and lasso logistic regression models at identifying opioid and cannabinoid poisoning in U.S. dogs using pet demographic and clinical data reported to an animal poison control center (2005–2014)

et al. 2023

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“…In a study of using PAMORAs to treat OIC in adults, the 2 PAMORAs methylnaltrexone and naldemedine showed significant improvements in the quality of life using constipation-specific patient-reported outcomes. Of the PAMORAs, subcutaneous methylnaltrexone is the only medication approved for treating OIC in patients with advanced illness or active cancer pain 57,68. There are no specific guidelines for which specific PAMORA to choose for adults with OIC because of noncancer pain.…”

Section: Discussionmentioning

confidence: 99%

Management of Opioid-induced Constipation in Older Adults

Horrigan

Bhumi

Miller³

et al. 2022

Journal of Clinical Gastroenterology

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Opioid-induced constipation (OIC) is a common condition in older adults who may not be responsive to traditional laxative therapy. OIC is defined as new or worsening constipation symptoms that occur with initiation of or altering the dose of opioid analgesia. For adult patients with OIC and noncancer pain, we recommend considering nonpharmacologic interventions (eg, dietary measures, increased physical activity, and biofeedback training) and over-the-counter laxatives, followed by prescription opioid receptor antagonists (methylnaltrexone, naloxegol, and naldemedine) if traditional over-the-counter laxatives fail. Other options may include lubiprostone, linaclotide, plecanatide, and prucalopride; however, these are not indicated for OIC specifically or studied in older adults. Because of the complex nature of absorption, distribution, metabolism, and excretion in the aging population, all agents used to treat OIC must be evaluated individually and reevaluated as patients continue to age. This review will serve as a guide to managing OIC in older adults.

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“…Opioid-induced constipation (OIC) is a condition associated with abdominal discomfort and pain and is a common adverse event of opioid use. 1–3 Patients often develop tolerance to other side effects of opioid use, such as nausea and vomiting, but some patients do not develop tolerance to constipation with opioid use. 4 Additionally, OIC is associated with disruption of opioid therapy when patients skip or discontinue opioid doses, longer duration of opioid therapy, greater use of healthcare resources, and higher healthcare costs.…”

Section: Introductionmentioning

confidence: 99%

“…OIC is believed to occur because of opioid binding to peripheral μ-opioid receptors in the gastrointestinal tract, leading to abnormal modulation of mucosal secretion and fluid absorption. 1 Peripherally acting μ-opioid receptor antagonists (PAMORAs) block µ-opioid receptors in the gastrointestinal tract. PAMORAs have limited ability to cross the blood–brain barrier, thereby reversing μ-opioid binding in the gut without compromising the effects of opioid analgesia.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients with Advanced Illness

Mehta,

Slatkin,

Israel

et al. 2023

JPR

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Purpose We evaluated the impact of baseline patient characteristics on safety and efficacy of methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, in patients with advanced illness with opioid-induced constipation (OIC). Patients and Methods This analysis pooled data from 2 randomized, double-blind, placebo-controlled studies (study 302: NCT00402038; study 4000: NCT00672477) in patients with advanced illness, including cancer, and OIC. Patients were randomized to receive subcutaneous methylnaltrexone (study 302: 0.15 mg/kg; study 4000: 8 or 12 mg based on weight) or placebo every other day for 2 weeks. The proportions of patients achieving rescue-free laxation within 4 or 24 hours after the first dose of study drug were assessed in patient subgroups stratified by baseline age, Eastern Cooperative Oncology Group (ECOG) performance status, cancer status, laxative type, and opioid requirement. Treatment-emergent adverse events (TEAEs) were evaluated. Results Overall, 363 patients were included in this analysis (methylnaltrexone, 178; placebo, 185). Mean (SD) age was 66.3 (13.7) years and 48.5% were men overall. A significantly greater proportion of patients receiving methylnaltrexone versus placebo achieved rescue-free laxation within 4 hours (111/178 [62.4%] vs 31/185 [16.8%]; P <0.0001) and 24 hours (135/178 [75.8%] vs 81/185 [43.8%]; P <0.0001) of the first dose. These trends were consistent across all subgroups. Most patients experienced ≥1 TEAE in the overall population (methylnaltrexone, 82.1%; placebo, 76.2%), which remained consistent when stratified by baseline characteristics. More than half of TEAEs were gastrointestinal in nature. Abdominal pain was more common in patients receiving methylnaltrexone than placebo across baseline characteristic subgroups. Conclusion Methylnaltrexone treatment was superior to placebo in achieving rescue-free laxation within 4 and 24 hours after the first dose, irrespective of patients’ cancer status, baseline ECOG performance status, or baseline opioid or laxative use. The methylnaltrexone safety profile remained consistent across baseline characteristic subgroups.

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Opioid-induced Constipation

Cited by 40 publications

References 37 publications

Comparing the diagnostic performance of ordinary, mixed, and lasso logistic regression models at identifying opioid and cannabinoid poisoning in U.S. dogs using pet demographic and clinical data reported to an animal poison control center (2005–2014)

Comparing the diagnostic performance of ordinary, mixed, and lasso logistic regression models at identifying opioid and cannabinoid poisoning in U.S. dogs using pet demographic and clinical data reported to an animal poison control center (2005–2014)

Management of Opioid-induced Constipation in Older Adults

Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients with Advanced Illness

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