Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Clinical studies report a low incidence of intestinal side effects with transdermally administered fentanyl (TTS-fentanyl) in comparison with oral morphine. To support these clinical data, analgesic and intestinal effects of both opioids were compared in rats. After subcutaneous injection, analgesia in the tail withdrawal reaction test was obtained at a peak effect dose of 0.032 mg/kg with fentanyl and 8.0 mg/kg with morphine. This analgesic dose exceeded the ED50 for inhibition of castor oil-induced diarrhea only slightly (1.1 x) in the case of fentanyl (0.028 mg/kg) but markedly (36 x) in the case of morphine (0.22 mg/kg). To reverse completely the antidiarrheal effect of equivalent analgesic doses of the opioids (their ED50S for analgesia lasting 2 hours), much more naloxone was required in the case of morphine (5.4 mg/kg) than in the case of fentanyl (0.19 mg/kg). After oral administration, the difference between both opioids was less pronounced. Analgesia was obtained at 0.85 mg/kg with fentanyl and 32 mg/kg with morphine. This analgesic dose only slightly (1.7 x) exceeded the antidiarrheal dose in the case of fentanyl (0.49 mg/kg) but significantly (6.2 x) in the case of morphine (5.2 mg/ kg). To reverse completely the antidiarrheal effect of equivalent analgesic oral doses of the opioids (their ED50S for analgesia lasting 2 hours), more naloxone was required in the case of morphine (11 mg/kg) than in the case of fentanyl (2.0 mg/kg). Rapid penetration of fentanyl into the brain is thought to be responsible for small dissociation between the analgesic and intestinal effect of this lipophilic opioid. The present data provide preclinical evidence to support the relatively low incidence of intestinal side effects observed clinically with the use of TTS-fentanyl in comparison with orally administered morphine.
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PMID:Comparison of the analgesic and intestinal effects of fentanyl and morphine in rats. 960 Nov 61

The effectiveness of a combined regimen of mifepristone and vaginal misoprostol for termination of pregnancies of 9-13 weeks of gestation was investigated in 120 UK abortion patients (median age, 22.1 years; median duration of amenorrhea, 10.3 weeks). Each woman received a single oral dose of 200 mg of mifepristone 36-48 hours before admission, at which time 800 mcg of misoprostol was administered vaginally. Where indicated, a further two doses of 400 mcg of misoprostol (vaginal or oral) were provided every 3 hours. All 120 women aborted on the day of prostaglandin administration; however, 6 women (5%) required exploratory curettage after the procedure for retained placenta. The median prostaglandin dose was 1200 mcg (range, 800-1600 mcg). The median time from misoprostol administration to abortion was 4.33 hours (range, 1.3-16.0 hours). 60 women (50%) required oral analgesics and 26 (22%) received parenteral analgesia. Diarrhea occurred in 38 women (32%). The median duration of bleeding after abortion was 12.5 days (range, 3-43 days). In questionnaires administered to 73 women, only 3 (4%) expressed dissatisfaction with medical abortion, because of pain or prolonged bleeding. The relatively high dose of misoprostol used in this study and the vaginal route of administration are presumed to account for the 95% success rate. Extension of medical abortion to later gestation times would decrease the need for surgery and expand women's choice of methods of pregnancy termination.
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PMID:Termination of pregnancy at 9-13 weeks' amenorrhoea with mifepristone and misoprostol. 971 62

Postnatal day-14 (P14) infant rats remained naive or were implanted with osmotic minipumps infusing saline or fentanyl (50 microg kg(-1) h(-1)). Fentanyl was administered 72 h later for measurement of antinociception in the tail-flick test. The potency of fentanyl was 3.0-fold lower in fentanyl-infused compared to saline-infused P17 rats. Fentanyl-infused P17 rats injected with naloxone underwent withdrawal characterized by increases in spontaneous activity, wall climbing, diarrhea, abdominal stretching, forepaw treading/tremors, wet-dog shakes, jumping, ptosis, rhinorrhea and hypothermia. Other naive, saline-infused and fentanyl-infused P17 rats not challenged with fentanyl or naloxone were housed until maturing into P42 juveniles. Fentanyl's potency was equal among each treatment group. However, morphine's potency was reduced in juveniles tolerant to fentanyl as infants. Morphine was also less potent in P90 adults tolerant to fentanyl as infants. Thus, chronic opiate exposure during infancy may affect the developing central nervous system, and desensitize animals and humans to opiate analgesia throughout life.
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PMID:Long-term alterations in opiate antinociception resulting from infant fentanyl tolerance and dependence. 988 76

Acupuncture has been used for various gastrointestinal (GI) conditions. Voluminous data support the effect of acupuncture on the physiology of the GI tract, including acid secretion, motility, neurohormonal changes, and changes in sensory thresholds. Much of the neuroanatomic pathway of these effects has been identified in animal models. A large body of clinical evidence supports the effectiveness of acupuncture for suppressing nausea associated with chemotherapy, postoperative state, and pregnancy. Prospective randomized controlled trials have also shown the efficacy of acupuncture for analgesia for endoscopic procedures, including colonoscopy and upper endoscopy. Acupuncture has also been used for a variety of other conditions including postoperative ileus, achalasia, peptic ulcer disease, functional bowel diseases (including irritable bowel syndrome and nonulcer dyspepsia), diarrhea, constipation, inflammatory bowel disease, expulsion of gallstones and biliary ascariasis, and pain associated with pancreatitis. Although there are few prospective randomized clinical studies, the well-documented physiological basis of acupuncture effects on the GI tract, and the extensive history of successful clinical use of acupuncture, makes this a promising modality that warrants further investigation.
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PMID:Acupuncture for gastrointestinal and hepatobiliary disorders. 1010 29

Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor.
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PMID:Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. 1031 80

Anaesthesia and surgical procedures lead to a reduction of intestinal motility, and opioids may produce a postoperative ileus, that might delay postoperative feeding. The aim of this prospective randomised study is to test whether or not different kinds of epidural analgesia (Group A: morphine 0.0017 mg/kg/h and bupivacaine 0.125%-0.058 mg/kg/h; Group B: morphine alone 0.035 mg/kg/12h in the postoperative period) allow earlier postoperative enteral feeding, enhance intestinal motility a passage of flatus and help avoid complications, such as nausea, vomiting, ileus, diarrhoea, pneumonia or other infective diseases. We included in the study 60 patients (28 males and 32 females) with a mean age of 61.2 years (range 50-70) and with an ASA score of 2 or 3. All patients had hepato-biliary-pancreatic neoplasm and were candidates for major surgery. We compared two different pharmacological approaches, i.e., morphine plus bupivacaine (30 patients, Group A) versus morphine alone (30 patients, Group B). Each medication was administered by means of a thoracic epidural catheter for the control of postoperative pain. In the postoperative course we recorded every 6 hours peristaltic activity. We also noted morbidity (pneumonia, wound sepsis) and mortality. Effective peristalsis was present in all patients in Group A within the first six postoperative hours; in Group B, after 30 hours. Six patients in Group A had bowel motions in the first postoperative day, 11 in the second day, 10 in the third day and 3 in fourth day, while in Group B none in the first day, two in the second, 7 in the third, 15 in the fourth, and 6 in the fifth: the difference between the two groups was significant (p<0.05 in 1st, 2nd, 4th and 5th days). Pneumonia occurred in 2 patients of Group A, and in 10 of Group B (p < 0.05). We conclude that epidural analgesia with morphine plus bupivacaine allowed a move rapid return to normal gut activity and early enteral nutrition compared with epidural analgesia with morphine alone.
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PMID:Morphine plus bupivacaine vs. morphine peridural analgesia in abdominal surgery: the effects on postoperative course in major hepatobiliary surgery. 1097 18

The objectives of this prospective non-concurrent cohort study were to confirm the efficacy of vaginal misoprostol for early pregnancy termination and to determine whether the incidence of side effects is lower with prophylactic loperamide and acetaminophen. Two-hundred women with an intrauterine pregnancy < or =56 days gestational age seeking medical pregnancy termination in an ambulatory research clinic were enrolled in the study. One-hundred participants (group 1) ingested 4 mg of loperamide and 500 mg of acetaminophen before the vaginal placement of 800 mirog of misoprostol moistened with 2 mL of saline. If abortion had not occurred, the same regimen was repeated every 24 h (maximum three doses). One-hundred participants (group 2) from the same clinic who previously underwent the same misoprostol regimen without prophylactic medication served as a control group for comparison with respect to abortion success and the incidence of side effects. The rate of successful abortion was not statistically significantly different between the two groups (group 1 93%, group 2 89%). The incidence of opiate analgesic use was significantly less in group 1 (4%) compared with group 2 (16%) (OR 0.22, 95% CI 0.06-0.73, p = 0.01). There was a significantly lower incidence of diarrhea in group 1 (23%) compared with group 2 (44%) (OR 0.38, 95% CI 0.20-0.73, p = 0.003). There was no difference in the incidence of fever/chills or the incidence of emesis between the two groups. Vaginal misoprostol is effective for termination of pregnancy < or = 56 days and the incidence of diarrhea and the use of opiate analgesia is significantly reduced with prophylactic loperamide and acetaminophen.
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PMID:Early pregnancy termination with vaginal misoprostol combined with loperamide and acetaminophen prophylaxis. 1137 49

Continuous caudal anesthesia has been commonly used for intra- and post-operative analgesia in infants and children. However, it has a potential risk of bacterial infection, especially in infants in whom the catheter site is easily contaminated with loose stool. To avoid infection, the authors applied a new procedure using subcutaneous tunneling for continuous caudal anesthesia. In the 18 cases studied with subcutaneous tunneling, clinical signs of infection were absent and bacterial colonization was not found on the catheter tip after 3.9 +/- 1.4 days of catheterization. The incidence of catheter colonization after continuous caudal anesthesia without tunneling had been reported. In their reports, the incidence of catheter colonization ranged from 20% to 37%. Therefore, caudal catheterization with subcutaneous tunneling is a simple and safe method, and has proved very effective to reduce the risk of epidural infection.
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PMID:Decreased risk of catheter infection in infants and children using subcutaneous tunneling for continuous caudal anesthesia. 1168 51

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

Although laparoscopic fundoplication is now performed commonly in children, its long-term results in neurologically impaired (NI) children is unknown. We present a single surgeon's experience. During an 8.5 year period, 54 consecutive NI children (age 5 months to 16 years; weight 2.7 to 42 kg) who had failed medical treatment for severe gastroesophageal reflux (GER) underwent laparoscopic Nissen fundoplication without (7) or with (47) gastrostomy. Indications for surgery included failure to thrive and feeding difficulties in all, major vomiting in 42, recurrent chest infections in 44, and inability to take oral medication in 14. Hiatus hernia was present in 14 and delayed gastric emptying in 6 patients. Eight (15%) had undergone previous abdominal surgery. Access was modified according to individual anatomy and 4 or 5 cannulae were used in each patient. Postoperative epidural/morphine analgesia was used in the first 12 to 24 hours, and fluid intake and feeding were started on day 1 and 2, respectively. The average operating time for fundoplication was 2.2 hours (range 1.05 to 3) and for fundoplication and gastrostomy 2.3 hours (range 1.22 to 4.10). Three patients had conversion to open surgery (1 perforated esophagus, 1 hypercarbia and hepatomegaly, 1 camera failure). There were no other operative complications or mortality. One child with Down syndrome developed a food bolus obstruction 3 days postoperatively. The vast majority of patients were discharged home 3 to 4 days following fundoplication and 5 to 7 days following fundoplication and gastrostomy. Postoperative gas bloat was common, diarrhea developed in 4, dumping in 3, and major gastrostomy infection in 1 case. During follow-up (median 5.2, range 3 months to 8.6 years), 9 (16%) children showed signs of persistent/recurrent problems. Investigations showed a recurrent hiatus hernia in 1 (requiring re-operation) and minor reflux in 3 patients. To date 6 (11%) children have died of their background conditions. In NI children, laparoscopic fundoplication is safe and successful. Awareness of the differences in access and risks for NI and normal children is important. Compared with historical data for open technique, laparoscopic fundoplication produces lower mortality and morbidity and similar intermediate and long-term results.
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PMID:Results of laparoscopic antireflux procedures in neurologically impaired children. 1240 29


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