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)

The gut-stimulating principle in Croton penduliflorus seed oil isolated as white crystals (CP crystals) significantly reduced pentobarbitone-induced sleeping time in mice at doses of 3 and 6 mg/kg intraperitoneally. Indomethacin (4 mg/kg) and atropine (0.044 mg/kg) significantly reversed the action of CP crystals on pentobarbitone sleeping time with indomethacin having a profound reversal effect. CP crystals significantly reduced the mean onset of convulsions and the mean death time in mice treated with a surely convulsive dose of strychnine. CP crystals significantly reduced the intensity of morphine and pethidine analgesia and prolonged the duration of pethidine analgesia. Most actions of CP crystals suggest that it stimulates the CNS and reduces the intensity of opioids (except codeine) while prolonging their duration of analgesic action.
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PMID:Effects of the gut-stimulating principle in Croton penduliflorus seed oil on the central nervous system. 260 52

Ureteral colic occurs in 24 to 34 per cent of all patients following extracorporeal shock wave lithotripsy. Recent research has shown prostaglandin synthetase inhibitors to be effective in relieving the pain associated with ureteral colic. Our prospective, controlled, double-blind, randomized study was designed to test the efficacy of indomethacin in the prophylactic treatment of pain after extracorporeal shock wave lithotripsy. Patients undergoing extracorporeal shock wave lithotripsy were randomized into 2 groups. Group 1 received 100 mg. indomethacin suppositories twice daily and group 2 received placebo suppositories. After extracorporeal shock wave lithotripsy 2 analgesics were available to the patients: oral co-dydramol or intramuscular pethidine was offered in the normal manner by the nursing staff. The pre-extracorporeal shock wave lithotripsy x-ray was used to make a quantitative estimate of the total stone burden in each patient. The post-extracorporeal shock wave lithotripsy analgesic requirement was used to compare the 2 groups. Of 112 patients recruited to the study 55 received indomethacin and 57 received placebo. The request for analgesia in the 2 groups was not different (28 of 55 and 33 of 57, respectively). However, in the indomethacin group only 6 patients required pethidine (10 doses), compared to 18 (41 doses) in the placebo group. This difference is statistically significant (p less than 0.01). There was no difference between the 2 groups in the occurrence of ureteral steinstrasse. Indomethacin has been shown to be effective in the prophylactic treatment of ureteral colic after lithotripsy.
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PMID:Indomethacin as prophylaxis against ureteral colic following extracorporeal shock wave lithotripsy. 230 78

Fifty-four orthopaedic patients were given either indomethacin (25-50 mg bolus plus infusion, 5-7.5 mg h-1) or only lactated Ringer solution intravenously over 20 h in a randomized and double-blind fashion. The study was started at the casualty department as soon as possible after the decision to operate was made. The patients were given a spinal block with bupivacaine, and the evaluation included postoperative analgesia and IVY bleeding times. Indomethacin plasma concentrations were measured and found to be at a therapeutic level throughout the study. The oxycodone dose (mean +/- s.d.) during the postoperative observation was lower in the indomethacin group (17.4 +/- 13.7 mg) than in the control group (25.6 +/- 15.6 mg) (P = 0.05). Fewer patients in the indomethacin group needed oxycodone more than once during the follow-up period (P less than 0.001). The mean IVY bleeding time was prolonged in the indomethacin group after 20 h of infusion (P less than 0.05). No abnormal bleeding was observed immediately postoperatively. However, at the end of the infusion there were more patients who bled through their bandages and casts in the indomethacin group (4/28 vs. 1/26).
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PMID:The effect of continuous intravenous indomethacin infusion on bleeding time and postoperative pain in patients undergoing emergency surgery of the lower extremities. 264 50

To study the effect of intravenous indomethacin on blood pressure, heart rate, body temperature and post-operative bleeding we performed a double-blind, placebo-controlled study on 100 operated children, aged 1-16 years. At the end of operation intravenous indomethacin 0.35 mg/kg followed by an infusion of 0.07 mg/kg/h for 24 h combined with standard doses of morphine according to clinical needs resulted in better postoperative analgesia than morphine alone. During the two first hours the systolic and diastolic blood pressure and ventilation rate did not differ between the groups. The heart rate was significantly lower (p less than 0.001) in the indomethacin group. Indomethacin did not prolong the bleeding time. Mild to moderate bleeding was observed in 13 indomethacin--and five placebo-treated patients (p less than 0.05). The bleeding did not, however, require any intervention. The mean body temperature did not differ between the two groups in the evening following the operation, but was significantly lower (p less than 0.01) on the first postoperative morning in the indomethacin group. Six patients (12%) in the placebo group had fever over 38 degrees C and paracetamol was administered to four of them. Clinically diminished diuresis was not observed. Since prophylactic indomethacin infusion improves the postoperative analgesia in children and no clinically important unwanted effects were seen, it may be used in children, over one year of age in whom non-steroidal anti-inflammatory drugs are not contraindicated.
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PMID:Intravenous indomethacin as postoperative analgesic in children: acute effects on blood pressure, heart rate, body temperature and bleeding. 332 45

Arylacetic acid antiinflammatory drugs can be metabolically produced by beta-oxidation of a 6-arylhex-5-enoic acid side chain. Such a mechanism provides for an in vivo sustained release of the active principle indomethacin from 6-[N-(p-chlorobenzoyl)-2-methylindol-3-yl]hex-5-enoic acid (7). Similarly, biphenylacetic acid was produced from both 6-(4'-biphenylyl)hex-5-enoic acid and its lower even homologue, 4-(4'-biphenylyl)but-3-enoic acid. The indole derivative produced sustained analgesia in a yeast-induced hyperalgesia model over a 12-h period. Indomethacin plasma levels of 2 micrograms/mL were observed for up to 24 h. Such levels were less than those achieved for the analogous case in which biphenylacetic acid was produced from biphenylylhex-5-enoic acid, suggesting metabolic discrimination between hex-5-enoic substrates. When indomethacin was dosed in equipotent analgesic levels, the level of circulating drug was considerably higher than that seen for metabolically derived drug. Hence 6-hex-5-enoic acid derivatives of indomethacin are metabolized to indomethacin in vivo to give sustained analgesia at low apparent circulating plasma levels of free drug. The possibility of tissue compartmentalization enhancing biological efficacy is suggested by these observations.
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PMID:Metabolic synthesis of arylacetic acid antiinflammatory drugs from arylhexenoic acids. 2. Indomethacin. 366 13

Indomethacin 0, 15, 25 and 35 mg t.i.d. was given in randomized order for two weeks to eight outpatients with rheumatoid arthritis in a double-blind study. At the end of each treatment period the clinical response was evaluated by subjective and objective methods and the plasma indomethacin concentration was measured by GLC-mass fragmentography. Compared with non-treatment periods, indomethacin had a statistically significant therapeutic effect as judged by global assessment, duration of morning stiffness, use of escape analgesia, articular index and pain score, but there was no relation between the clinical effect and the size of the dose or the plasma concentration of the drug. Technetium uptake over the affected joints did not change during indomethacin therapy, which might reflect a lack of effect on the local activity of the disease. Lower doses than those currently prescribed are probably sufficient to alleviate symptoms in this disease.
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PMID:Double-blind dose-response study of indomethacin in rheumatoid arthritis. 699 34

Although results obtained in baboons and rats have demonstrated that the fatty acid cyclo-oxygenase inhibitor indomethacin reduces cerebral blood flow (CBF) under control conditions and markedly attenuates the CBF response to hypercapnia, nonconfirmatory results have been obtained in rabbits and cats. Since these latter studies were carried out under barbiturate anesthesia, we tested the effect of indomethacin (10 mg kg-1) on CBF and cerebral oxygen consumption in rats anesthetized with 150 mg kg-1 of phenobarbital. At normocapnia the barbiturate reduced CBF, measured with a 133Xe modification of the Kety-Schmidt technique, to about 50% of nitrous oxide control values as previously determined with a similar technique. At this CBF level, indomethacin induced a small, albeit highly significant decrease in CBF. We suggest that a reduction of this magnitude will escape detection with some CBF techniques in current use. Indomethacin induced a highly significant decrease in CBF during hypercapnia, demonstrating that the barbiturate does not eliminate the effect of indomethacin on CO2 responsiveness. The magnitude of the reduction in CO2 response was so large that is should be detected with most methods for measuring CBF. A comparison with previous data on animals under 70% N2O demonstrated that phenobarbital reduced the CO2 responsiveness. defined as the ratio deltaCBF/deltaPCO2, to 39% of that observed under nitrous oxide analgesia. With both types of anesthesia, indomethacin curtailed the CO2 responsiveness 4- to 5-fold.
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PMID:Effects of indomethacin on cerebral blood flow and oxygen consumption in barbiturate-anesthetized Normocapnic and hypercapnic rats. 732 33

Indomethacin, a typical cyclo-oxygenase inhibitor, acts as an analgesic by preventing the hyperalgesia induced by prostaglandins during inflammation. Analgesics of the dipyrone type directly block the sensitization of nociceptors. In the present investigation, the analgesic effect of diclofenac was compared with that of indomethacin in two algesimetric tests which permit discrimination between the two types of analgesic: the rat knee joint incapacitation and the rat paw hyperalgesia tests. The analgesics were given either pre- or posttreatment relative to the induction of hyperalgesia with carrageenin or prostaglandin E2. In both tests intraperitoneal pretreatment with indomethacin was equally or slightly more potent than diclofenac. Posttreatment with diclofenac was more effective than posttreatment with indomethacin. This was particularly evident in the paw hyperalgesia test in which posttreatment with indomethacin was not effective while diclofenac caused dose-dependent analgesia. When nociception was induced by PGE2 in both tests, the administration of indomethacin directly into the knee joint or rat paw had no effect while diclofenac continued to cause dose-dependent analgesia. Thus, diclofenac has a direct effect on ongoing hyperalgesia in addition to its ability to block cyclo-oxygenase. Naloxone and N-methyl-nalorphine did not affect diclofenac analgesia, thus indicating that the analgesic effect of the latter is independent of a central or peripheral opioid effect. Local administration of agents which inhibit the formation of nitric oxide (NG-monomethyl-L-arginine) or inhibit the activation of guanylate cyclase by nitric oxide (methylene blue) abolished diclofenac-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of diclofenac analgesia: direct blockade of inflammatory sensitization. 790 38

Because of the lack of information about effective analgesics in non-mammalian vertebrates, the potency of various non-opioid agents were tested in a model of analgesia by using Northern grass frogs (Rana pipiens). This alternative model has been used widely for investigating opioid analgesic action. Potential non-opioid analgesics tested included antipsychotic, benzodiazepine, barbiturate, antihistamine, non-steroidal anti-inflammatory (NSAID), and partial opioid agents. Northern grass frogs were acclimated to lab conditions in individual cages. Drugs were administered systemically through the dorsal lymph sac, and analgesic effects were estimated by using the acetic acid test (AAT). The AAT is done by placing logarithmic dilutions of acid dropwise on the dorsum of the animal's thigh until a wiping response is obtained. At various doses, chlorpromazine and haloperidol (antipsychotics), chlordiazepoxide (a benzodiazepine), buprenorphine (a partial opioid agonist), and diphenhydramine (a histamine antagonist) produced moderate to strong analgesic effects. Indomethacin and ketorolac (NSAIDs), butorphanol (a partial opioid agonist), and pentobarbital (a barbiturate) produced weaker but noticeable analgesic effects. Our results are the first to document the effectiveness of a wide array of pharmacologically active agents in a novel amphibian model for analgesia. These findings provide needed data regarding the use of alternative, non-opioid agents for the treatment of pain in amphibians and other poikilothermic species.
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PMID:Testing and comparison of non-opioid analgesics in amphibians. 1145 91

We have previously shown in rats that both intrathecal and systemic analgesia regimens attenuate surgery-induced increases in tumor susceptibility. The current study used indomethacin to assess the role of prostaglandins and inflammation-associated pain in mediating the deleterious effects of surgery on immunity and tumor susceptibility. Male and female Fischer 344 rats were anesthetized with halothane and were either subjected or not to experimental laparotomy, followed by the administration of indomethacin or vehicle. Tumor susceptibility was assessed by the lung retention assay using the syngeneic MADB106 mammary adenocarcinoma cell line, a natural killer (NK)-sensitive tumor that colonizes only in the lungs. Surgery resulted in a 2- to 3.5-fold increase in lung tumor retention, and indomethacin administration significantly reduced this effect in both sexes without affecting unoperated animals. Indomethacin also attenuated the reductions in rearing behavior evident after surgery, suggesting that it relieved abdominal discomfort. Surgery increased interleukin-6 levels and suppressed NK activity per milliliter blood. Indomethacin restored NK activity in both male and female rats but attenuated surgery-induced interleukin-6 increases only in the male rats. These findings further support our previous work implicating pain in mediating the tumor-enhancing effects of surgery and implicate prostaglandins in mediating this effect. If similar relationships occur in humans, controlling postoperative pain and inflammation must become a priority in the management of cancer patients undergoing surgery.
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PMID:Indomethacin attenuates the immunosuppressive and tumor-promoting effects of surgery. 1462 54


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