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Winston-Salem, NC, United States

Most prescribed opioids exert their analgesic effects via activation of central μ-opioid receptors. However, μ-opioid receptors are also located in the gastrointestinal (GI) tract, and activation of these receptors by opioids can lead to GI-related adverse effects, in particular opioid-induced constipation (OIC). OIC has been associated with increased use of healthcare resources, increased healthcare costs, and decreased quality of life for patients. Nonpharmacologic (e.g., increased fiber uptake) and pharmacologic agents (e.g., laxatives) may be considered for the treatment and prevention of OIC. However, many interventions, such as laxatives alone, are generally insufficient to reverse OIC because they do not target the underlying cause of OIC, opioid activation of μ-opioid receptors in the GI tract. Therefore, there has been keen interest in antagonism of the μ-opioid receptor in the periphery to inhibit the effects of opioids in the GI tract. In this review, currently available pharmacologic therapies for the treatment and prevention of OIC are summarized briefly, with a primary focus on the administration of the peripheral μ-opioid receptor antagonist methylnaltrexone bromide in patients with OIC and advanced illness who are receiving palliative care. Also, clinical trial data of methylnaltrexone treatment in patients with OIC and other pain conditions (i.e., chronic noncancer pain and pain after orthopedic surgery) are reviewed. Data support that methylnaltrexone is efficacious for the treatment of OIC and has a favorable tolerability profile. © 2013 Springer International Publishing Switzerland.

Rauck R.,Center for Clinical Research | Coffey R.J.,Medtronic | Schultz D.M.,Medical Pain Clinics | Wallace M.S.,University of California at San Diego | And 4 more authors.
Anesthesiology | Year: 2013

Background: Oral gabapentin is approved as an anticonvulsant medication and to treat postherpetic neuralgia. Its nonopioid properties and presumed spinal site of analgesic action made the study on intrathecal gabapentin attractive to establish the minimum effective dose for a later, pivotal trial. Methods: The authors examined the safety and efficacy of intrathecal gabapentin in a randomized, blinded, placebocontrolled, multicenter trial in a heterogeneous cohort of candidates with chronic pain for intrathecal drug therapy. Results: Patients (N = 170) were randomized to receive continuous intrathecal gabapentin (0 [placebo], 1, 6, or 30 mg/ day) during 22 days of blinded treatment after implantation of a permanent drug delivery system. The highest dose, 30 mg/day, was selected to maintain a safety margin below the 100-mg/day dose that was explored in a phase 1 study. The authors found no statistically significant difference in the primary outcome measure, which was the numerical pain rating scale and response rate after 3 weeks, for any dose versus placebo. Physical functioning, quality of life, and emotional functioning also revealed no differences. Small, nonsignificant changes occurred in opioid medication use. The most frequent device-related adverse events were transient postimplant (lumbar puncture) headache, pain, and nausea. The most frequent gabapentin-related adverse events were nausea, somnolence, headache, dizziness, fatigue, and peripheral edema. Conclusion: Twenty-two days of intrathecal gabapentin did not demonstrate statistically significant or clinically meaningful analgesic effects. The study sponsor has no current plans for further studies. Drug-related adverse events were similar to those for oral gabapentin. Most device-related adverse events resulted from the implant surgery or anesthesia. Copyright © 2013, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Armstrong D.G.,University of Arizona | Hanft J.R.,Doctors Research Network | Driver V.R.,Boston University | Smith A.P.S.,APS Medcon | And 10 more authors.
Diabetic Medicine | Year: 2014

Aims: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and β-hydroxy-β-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. Methods: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and β-hydroxy-β-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. Results: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and β-hydroxy-β-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. Conclusions: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and β-hydroxy-β-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and β-hydroxy-β-methylbutyrate in these high-risk subgroups might prove clinically valuable. © 2014 The Authors.

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