Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Opioid treatment for postoperative or chronic pain is frequently associated with adverse effects, the most common being dose-limiting and debilitating bowel dysfunction. Postoperative ileus, although attributable to surgical procedures, is often exacerbated by opioid use during and following surgery. Postoperative ileus is marked by increased inhibitory neural input, heightened inflammatory responses, decreased propulsive movements and increased fluid absorption in the gastrointestinal tract. The use of opioids for chronic pain is characterised by a constellation of symptoms including hard dry stools, straining, incomplete evacuation, bloating, abdominal distension and increased gastroesophageal reflux. The current management of opioid-induced bowel dysfunction among patients receiving opioid analgesics consists primarily of nonspecific ameliorative measures. Intensive investigations into the mode of action of opioids have characterised three opioid receptor classes -mu, delta and kappa- that mediate the myriad of peripheral and central actions of opioids. Activation of mu-opioid receptors in the gastrointestinal tract is responsible for inhibition of gut motility, whereas receptors in the central nervous system mediate the analgesic actions of opioids. Blocking peripheral opioid receptors in the gut is therefore a logical therapeutic target for managing opioid-induced bowel dysfunction. Available opioid antagonists such as naloxone are of limited use because they are readily absorbed, cross the blood-brain barrier, and act at central opioid receptors to reverse analgesia and elicit opioid withdrawal. Methylnaltrexone and alvimopan are recently developed opioid antagonists with activity that is restricted to peripheral receptors. Both have recently shown the ability to reverse opioid-induced bowel dysfunction without reversing analgesia or precipitating central nervous system withdrawal signs in non-surgical patients receiving opioids for chronic pain. In addition, recent clinical studies with alvimopan suggest that it may normalise bowel function without blocking opioid analgesia in abdominal laparotomy patients with opioid-related postoperative ileus.
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PMID:Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. 1265 45

Cough is an important defensive reflex of the airway and a common symptom of respiratory disease. After an upper respiratory tract virus infection, cough is transient, but is more persistent with conditions such as asthma, rhinosinusitis, gastroesophageal reflux, chronic obstructive pulmonary disease (COPD) and lung cancer. Treatment directed at these conditions may improve cough, but there remains a need to control cough directly. The most effective antitussives are opioids, such as morphine, codeine or pholcodeine, but they produce side effects including drowsiness, nausea, constipation and physical dependence. Opioids such as k- and d-opioid receptor agonists, non-opioids such as nociceptin, neurokinin and bradykinin receptor antagonists, vanilloid receptor VR(1) antagonists, blockers of sodium-dependent channels, and maxi-K calcium-dependent channel activators of afferent nerves may all represent novel antitussives and this needs to be confirmed in clinical trials.
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PMID:Current and future prospects for drugs to suppress cough. 1291 74

Opioid-induced bowel dysfunction (OIBD) comprises gastrointestinal symptoms such as constipation, anorexia, nausea, vomiting, gastro-oesophageal reflux, delayed digestion, abdominal pain, bloating, hard stool and incomplete evacuation that significantly deteriorate patients' quality of life and compliance. Approximately one third of patients treated with opioids do not adhere to the opioid regimen or simply quit the treatment due to OIBD. Several strategies are undertaken to prevent or treat OIBD. Traditional oral laxatives are used but their effectiveness is limited and they display adverse effects. Other possibilities comprise opioid switch or changing the administration route. New therapies target opioid receptors in the gut that seem to be the main source of OIBD. One is a combination of an opioid and opioid antagonist (oxycodone/naloxone) in prolonged-release tablets, and another is a purely peripherally acting opioid receptor antagonist (methylnaltrexone) available in subcutaneous injections. The aim of this article is to review the pathomechanism and possible treatment strategies of OIBD.
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PMID:The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities. 2378 66