Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x kg(-1)) in a double blind, cross-over study. Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); this was prevented by ADL 8-2698 (P = .004). Postoperatively, 45 patients were randomly assigned in a double-blind fashion to receive ADL 8-2698 (4 mg) or placebo and intravenous morphine (0.15 mg/kg) or to receive oral and intravenous placebo. Analgesia and pupil constriction were measured. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002). We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of selective peripheral opioid anitagonism without affecting central opioid analgesia.
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PMID:ADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia. 1118 40

Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy (<3 complete bowel movements per week) compared with 7.6% in a control group. Of subjects who required laxative therapy, only 46% of opioid-treated patients (control subjects, 84%) reported achieving the desired treatment results >50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.
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PMID:Incidence, prevalence, and management of opioid bowel dysfunction. 1175 92

Alvimopan (ADL 8-2698; Adolor Corporation, Exton, PA, USA) is a novel, peripherally restricted opioid antagonist. After oral administration, it has activity specific to the gastrointestinal (GI) tract. ADL 8-2698 has low systemic absorption and a high affinity for mu-opioid receptors. In healthy subjects, ADL 8-2698 antagonized loperamide-induced changes in GI transit and prevented morphine-induced delays in oral-cecal transit time without antagonizing centrally mediated opioid effects, such as analgesia or pupillary constriction. In the treatment of opioid naive patients who underwent surgery and received opioids for acute pain, oral ADL 8-2698 (6.0 mg) improved the management of postoperative ileus (POI) by shortening the time to achieve normal bowel function and, ultimately, hospital stay. Postoperative nausea and vomiting and the overall incidence of all GI side effects were reduced in patients treated with ADL 8-2698 for POI. Analgesia was not compromised, because there were no changes in median opioid consumption or Visual Analog Scale (VAS) pain scores in patients treated with ADL 8-2698 versus patients treated with placebo. No drug-related side effects were observed in acute pain postsurgical patients in the initial POI study. In patients treated with opioids for chronic pain or opioid addiction, lower doses of oral ADL 8-2698 (0.5 to 3.0 mg) reversed opioid bowel dysfunction (OBD) and normalized GI activity. These effects were evident without compromising opioid analgesia or inducing central nervous system symptoms of withdrawal. Some chronic opioid patients receiving apparently supramaximal doses of ADL 8-2698 (> or = 3.0 mg) reported localized GI side effects, possibly indicative of a localized GI withdrawal response. The most common side effects of ADL 8-2698 in chronic pain patients with OBD were abdominal pain, flatulence, and diarrhea. These effects were not observed in most OBD patients receiving lower doses of ADL 8-2698. Overall, ADL 8-2698 was well tolerated in clinical trials. Further studies to evaluate the efficacy and safety of ADL 8-2698 in clinical practice are in progress.
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PMID:Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. 1175 94

Ileus is a common postoperative complication after major abdominal surgery. Surgical manipulation of the bowel and stimulation of opiod receptor are the main causes of ileus. An investigational drug (ADL 8-2698, Alvinopam) a selective opioid antagonist with a very low oral absorption was recently introduced to clinical medicine. Unlike other opioid antagonist its activity is restricted to GI tract, it is potent, has a long duration of action, is orally effective, does not readily cross the blood-brain barrier even after intravenous administration in animals. Two randomized controlled clinical studies tested its effects in humans. Liu et al.'s study confirmed peripheral restriction of ADL 8-2698 by its lack of central effect on morphine analgesia and pupil miosis. They also showed that ADL 8-2698 prevents increases in gastrointestinal transit time. Taguchi et al. concluded that high dose (6 mg) of ADL 8-2698 archived fast recovery of gastrointestinal function, without antagonising analgesic efficacy of systemic opioid. In summary, selective inhibition of gastrointestinal opioid receptor by a peripherally restricted oral antagonist speeds recovery of bowel function, shortens times of hospitalization and preserves the analgesic effects of opiods.
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PMID:Use of selective opiate receptor inhibitors to prevent postoperative ileus. 1202 75

Preclinical studies suggest that visceral afferents constitutively express kappa-opioid receptors (KORs) and that noxious visceral stimuli can be inhibited at a peripheral site by KOR activation. To test the relevance of these observations to humans, we infused, in a randomized, double blind manner, a peripherally selective KOR agonist (ADL 10-0101) or placebo into six patients with chronic pancreatitis and ongoing abdominal pain despite mu-opioid agonist therapy. Pain was assessed using a pain magnitude estimate, an open ended scale of each patient's choosing and compared to their rating of pain from a 1.6 cm(2) thermode applied to the skin and heated to 49 degrees C for 5s. Normalizing pain scores to this rating as 100, pain prior to study drug treatment was 4070, and was unaffected by placebo infusion in the two individuals receiving this therapy. In contrast, ADL 10-0101 infusion reduced pain score from 63+/-7.6 (mean+/-SE) prior to infusion to 23+/-15 4h after infusion (P<0.05 vs. baseline). One patient receiving placebo and one receiving ADL 10-0101 experienced a mild headache during the study. One patient receiving ADL 10-0101 experienced restlessness and another had assymptomatic transient dysrhythmia upon standing after the 4h study. Neither of the treatments affected blood pressure, heart rate, respiratory rate, or oxyhemoglobin saturation, and no patient experienced nausea during the study. These limited data support the hypothesis that human visceral afferents express KOR and that peripherally restricted KOR agonists produce analgesia in patients with chronic visceral pain.
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PMID:Analgesia from a peripherally active kappa-opioid receptor agonist in patients with chronic pancreatitis. 1250 3

Cancer pain appears as a complex pain and often progressive.WhenWHO pain management strategy and/or palliative care failed to relieve their pain, patients are given high dose opioids or anonymous adjuvant drugs and have no chance to meet specialized pain treatment. This section briefly covers the outline of neurolysis and spinal analgesia for these cancer patients with severe pain. Purpose of nerve block and neurolysis are to block the incoming signal of pain in order to reduce pain, reduce analgesic dose, recover ADL, and finally to be discharged from the hospital. However, autonomic nervous system, sensory nerves, and motor function could be impaired at the same time. Careful selection of candidate should be considered by the pain specialists. Spinal analgesia is indicated when, conservative pain treatment failed to reduce pain, wide range or multiple pain area, and when contraindicated for neurolysis. Epidural analgesia is preferred for in-hospital treatment and intrathecal analgesia for home care settings. Many cancer pain patients' life expectancy is not long enough to postpone the indication of these invasive techniques. If you seek to maintain patients' quality of life(QOL), one should consider these procedures at some point, although it may not be indicated.
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PMID:[Neurolysis and Spinal Analgesia in Cancer Pain Management]. 2842 5