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

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 +/- 1.1 kg) were anesthetized by IV fentanyl (15 microg . kg(-1) . h(-1)) and midazolam (1.0 mg . kg(-1) . h(-1)). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6 degrees +/- 0.2 degrees C for 6 h and were then rewarmed and kept normothermic at 37.7 degrees +/- 0.3 degrees C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% +/- 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% +/- 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.
 ...
PMID:The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs. 1578 13

In the present study, we evaluated the effect of epidural analgesia on the alterations of gut barrier function elicited by endotoxin in rabbits. After the placement of an epidural catheter, 28 male rabbits were randomized into either 0.5% lidocaine (group E) or saline (group C) group. The solutions (0.4 mL/kg) were epidurally injected, followed by continuous infusion (0.1 mL . kg(-1) . h(-1)) throughout the study period. Under a continuous infusion of lipopolysaccharide (15 microg . kg(-1) . h(-1)), mean arterial blood pressure, intramucosal pH, and plasma thrombomodulin concentrations were measured. At 4 h, mean arterial blood pressure was lower (P < 0.05), intramucosal pH was higher (P < 0.01), and the progression of hemodilution more profound (P < 0.05) in group E versus group C, whereas plasma thrombomodulin levels were increased to a similar extent between the groups. With less wet-to-dry weight ratio of ileum, histopathological injury scores of gut mucosa were significantly less in group E versus group C (P < 0.01). In a separate series of experiments (n = 10 each group), mucosal permeability in group E was significantly less compared with group C (P < 0.05). Collectively, these studies showed that despite a significant decrease of perfusion pressure and arterial oxygen content, epidural analgesia minimized endotoxin-induced functional and structural injury of gut mucosa possibly through endothelium-independent mechanisms.
 ...
PMID:Epidural analgesia prevents endotoxin-induced gut mucosal injury in rabbits. 1597 43

This review discusses the role of dynamic medicinal chemistry in the design and development of more effective opioids for the treatment of pain. Human Phase II clinical studies have shown that morphine-6-glucuronide (M6G) has equivalent analgesic effects to morphine and an improved side effect profile particularly at reducing the tendency to cause nausea, vomiting, sedation and respiratory depression. Based on these clinical observations, a new class of pain medication could be developed. Despite the promise, M6G is not an ideal drug because bioavailability is low and hydrolysis occurs in the gut. The literature covered includes a comprehensive list of work that illustrates: (i) the role of drug metabolism and drug disposition concepts in M6G analog drug development, (ii) the use of dynamic medicinal chemistry in improving M6G pharmaceutical properties, and (iii) the role of drug metabolism in enhancing bioavailability of M6G. Using optimized dynamic medicinal chemistry procedures for drug design and development, understanding the use of drug development concepts in early drug development and applying new methods from other fields may help advance this field of drug development. This review summarizes studies that support the feasibility of elaborating longer-acting, less expensive pain medications with possibly a safer profile of side effects. Development of new pain medications for cancer and other diseases based on M6G could provide novel agents that could balance optimal analgesia with a decreased occurrence of adverse side effects.
 ...
PMID:Dynamic medicinal chemistry in the elaboration of morphine-6-glucuronide analogs. 1602 81

This retrospective study evaluated the efficacy of enteral nutrition for pediatric patients undergoing the challenging treatment of allogeneic bone marrow transplantation. During the period from January 1999 to May 2000, 15 patients were transplant recipients. On admission to the hospital, 87% of patients were above the 50th percentile for weight for age. Nasogastric tubes were inserted while platelet counts remained greater than 50 x 10(9) mL/L. A specialized elemental formula for pediatric patients was commenced. These feeds were administered continuously and were titrated until caloric requirement or tolerance level had been achieved. During hospitalization for bone marrow transplantation, enteral nutrition was the major form of nutritional support for all patients. Enteral feeds continued even during maximal gut toxicity and were supported with antiemetics and analgesia. There were insignificant weight fluctuations during hospitalization, with 80% of children above the 50th percentile weight for age being discharged. Enteral nutrition via a nasogastric tube was effective in the provision of nutrition during bone marrow transplantation and continues to have an important role in this unit.
 ...
PMID:Enteral nutrition and bone marrow transplantation. 1647 84

Postoperative ileus (POI) is frequently experienced by many patients undergoing abdominal operations and other surgical procedures. Postoperative ileus causes physical discomfort and may increase risk for prolonged hospital length of stay. Despite its prevalence, there is currently no accepted standard definition of POI and, consequently, no standardized mode of prevention or treatment; it is no wonder that a variety of management approaches for POI have been developed. Some of these include alternative surgical techniques such as laparoscopic or endoscopic procedures to minimize trauma and help lessen the release of endogenous mediators of POI. Others have evaluated alternate analgesic regimens such as thoracic epidural anesthetics to avoid stimulating opioid receptors in the gut. These approaches have had varying results. Other pharmacologic attempts to reduce POI have focused on the blockade of opioid receptors to prevent opioid-induced GI-related adverse effects. A new class of agents, peripherally acting mu-opioid-receptor antagonists such as methylnaltrexone and alvimopan, may improve the pharmacologic management of POI and reshape the current paradigm of multimodal management of POI. Protocols that incorporate these agents may offer yet another avenue to mitigate the adverse effects of POI, and thus help improve surgical outcomes. To date, alvimopan has been shown in phase 3 clinical trials to significantly reduce the duration of POI while maintaining satisfactory analgesia and reducing length of hospital stay. Combinations of strategies with demonstrated effectiveness such as early feeding, epidural analgesia, laparoscopic surgery, and peripherally acting mu-opioid-receptor antagonists may help transform the management of POI into an effective multimodal paradigm that targets the diverse etiologic factors leading to this common clinical problem. Clearly, all surgical team members are crucial in the optimal implementation of such multimodal approaches.
 ...
PMID:Current choices--good or bad--for the proactive management of postoperative ileus: A surgeon's view. 1659 34

Opioid analgesics are the mainstay in the treatment of moderate-to-severe pain, yet their use is frequently associated with adverse effects, the most common and debilitating being constipation. Opioid-induced motor stasis results from blockade of gastrointestinal peristalsis and fluid secretion, and reflects the action of the endogenous opioid system in the gut. Methylnaltrexone and alvimopan are new investigational drugs that selectively target peripheral mu-opioid receptors because they are poorly absorbed in the intestine and do not enter the brain. Clinical studies have proved the concept that these drugs prevent opioid-induced bowel dysfunction without interfering with analgesia. As reviewed in this article, opioid receptor antagonists with a peripherally restricted site of action also hold therapeutic promise in postoperative ileus and chronic constipation due to the fact that they have been found to stimulate intestinal transit.
 ...
PMID:Treatment of opioid-induced gut dysfunction. 1724 38

There is a compelling body of evidence that N-methyl-d-aspartate receptors (NMDA-R) play a critical role in the development and maintenance of pain hypersensitivity. However, long-term treatments with NMDA-R antagonists are limited by unacceptable side effects. Since polyamines modulate the functioning of NMDA-R and mainly originate from normal dietary intake and bacterial metabolism in the gut, we developed a nutritional therapy based on dietary polyamine deficiency. Here, we reported that a polyamine deficient diet (PD diet) for 7 days prevented the enhancement of tyrosine phosphorylation of the spinal NR2B subunit-containing NMDA-R associated with inflammation in rats. Based on these data, we studied the ability of PD diet to prevent long-lasting pain hypersensitivity associated with tissue injury on one hind paw by evaluating long-lasting changes in both mechanical nociceptive threshold and weight bearing. A PD diet strongly reduced long-lasting hyperalgesia induced by inflammation or incision, especially in fentanyl-treated rats. Moreover a PD diet also prevented the exaggerated hyperalgesia induced by a second inflammation performed 7 days after the first one. A PD diet also opposed paradoxical hyperalgesia induced by non-nociceptive environmental stress in rats with pain and opioid experiences. A PD diet reversed pain hypersensitivity associated with monoarthritis or neuropathy and restored the analgesic effect of morphine. Since PD diet was devoid of any noticeable side effects, this nutritional therapy could be part of an effective and safe strategy for pre-emptive analgesia and for reducing the transition from acute to chronic pain and its outcomes in various pain syndromes.
 ...
PMID:Polyamine deficient diet to relieve pain hypersensitivity. 1790 Aug 9

The diagram of the mortality of acute pancreatitis is characterized by two distinct peaks, in a similar manner to other generalized acute inflammatory responses. In the first phase, which is characterized by "hyper-inflammatory" mechanisms, death occurs due to overwhelming SIRS and subsequent multi-organ failure. The second peak of death is usually detected much later, at least two weeks after the onset of acute pancreatitis. Infection in necrotising pancreatitis is frequently observed in this so-called "compensatory antiinflammatory" phase. Since there has been no effective therapy evolved to prevent the activation of inflammatory and proteolytic cascades, the treatment of acute pancreatitis is merely symptomatic. Adequate fluid resuscitation and analgesia are the mainstays of treatment. In case of development of multi-organ failure, extensive medical and ventilatory supportive therapy is usually necessary. However, recent studies suggested certain methods might decrease the incidence of infection in pancreatic necrosis, which is usually due to bacterial translocation from the gut. Numerous attempts have been published in the literature to decrease the frequency of septic complications. Furthermore, the outcome of studies favouring antibiotic prophylaxis in acute pancreatitis were debatable. The development of multi-resistant strains of Gram-positive bacteria and Candida, due to long-term antibiotic use, is a strong argument against the indication of prophylactic antibiotic use. Recently, various clinical studies aimed to decrease bacterial translocation, including probiotic use and enteral feeding as part of the treatment. This paper provides a systematic review on data available in the evidence based literature on the use of antibiotics and the role of alternative and supportive therapy in the treatment of severe acute pancreatitis.
 ...
PMID:Preventive strategies for septic complications of acute pancreatitis. 1796 33

Advances in understanding the physiology and pharmacology of the endogenous cannabinoid system have potentiated the interest of cannabinoid receptors as potential therapeutic targets. Cannabinoids have been shown to modulate a variety of immune cell functions and have therapeutic implications on central nervous system (CNS) inflammation, chronic inflammatory conditions such as arthritis, and may be therapeutically useful in treating autoimmune conditions such as multiple sclerosis. Many of these drug effects occur through cannabinoid receptor signalling mechanisms and the modulation of cytokines and other gene products. Further, endocannabinoids have been found to have many physiological and patho-physiological functions, including mood alteration and analgesia, control of energy balance, gut motility, motor and co-ordination activities, as well as alleviation of neurological, psychiatric and eating disorders. Plants offer a wide range of chemical diversity and have been a growing domain in the search for effective cannabinoid ligands. Cannabis sativa L. with the known plant cannabinoid, Delta(9-)tetrahydrocannabinol (THC) and Echinacea species with the cannabinoid (CB) receptor-binding lipophilic alkamides are the best known herbal cannabimimetics. This review focuses on the state of the art in CB ligands from plants, as well their possible therapeutic and immunomodulatory effects.
 ...
PMID:CB receptor ligands from plants. 1828 87

Calcitonin operates predominantly to regulate acute hypercalcemic states. The response to calcium challenges is lowest in elderly women; however, the contribution of calcitonin to the etiology of osteoporosis is unclear. The calcitonin receptor is a member of a supergene family consisting of G-protein-linked receptors with seven domains spanning the cellular membrane. These receptors are distributed in calcium-responsive tissues, gut, and hypothalamus and mediate calcitonin's known clinical effects of hypocalcemia, enhanced gastric motility, and analgesia. Therapeutic use of calcitonin is indicated in both perimenopausal and postmenopausal women with contraindications or intolerance to estrogen replacement therapy, Paget's disease, painful vertebral compression fractures, and steroid-induced osteopenia.
 ...
PMID:Calcitonin. 1907 52


<< Previous 1 2 3 4 5 6 7 Next >>