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)

The efficacy and tolerability of a new, controlled-release indomethacin (75 mg) tablet was compared to that of a sustained-release diclofenac sodium (100 mg) tablet in 84 patients with rheumatoid arthritis. The study was designed as a double-blind, double-dummy crossover trial, patients being allocated at random to receive 1 active tablet and 1 placebo tablet of the alternative medication at night for 4 weeks before being crossed over to the alternative treatment for a further 4 weeks. Patient and clinical assessments on entry and at the end of each treatment period showed that pain scores for day and night, duration of morning stiffness, requirement for escape analgesia (paracetamol) and treatment preference were similar for both treatments. Both preparations also significantly improved the degree of joint tenderness compared to baseline (p less than 0.001), as measured by a modified Ritchie Articular Index. Incidence and severity of side-effects were comparable, with a significant improvement in degree of constipation reported for both treatments compared to baseline (p less than 0.05). The incidence and severity of headache was statistically significantly worse (p less than 0.05) for controlled-release indomethacin; however, there was no difference in any other parameter of tolerability. It was concluded that controlled-release indomethacin tablets (75 mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100 mg).
 ...
PMID:Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of rheumatoid arthritis: a comparative controlled clinical trial. 227 88

Oral morphine is increasingly recognized as the pharmacologic standard for cancer pain management. Yet for the primary care physician and oncologist alike, misconceptions of the safety and efficacy of oral morphine along with lack of recognized guidelines for use have often resulted in inadequate cancer pain therapy. Use of controlled-release oral morphine sulfate (MSC) requires additional guidelines for optimum analgesia. Proposed are ten principles of dosing oral morphine, especially MSC, which were followed in a clinical trial involving cancer patients. MSC dosed at 8-, 10-, and 12-hour intervals was compared with immediate-release morphine (IRMS) dosed every four hours, and with prestudy analgesics. Patients achieved satisfactory analgesia at daily doses (mean +/- SE) of 118.0 +/- 8.6 mg and 111.4 +/- 12.6 mg (P greater than .05) for IRMS and MSC, respectively. Dosing endpoints were determined by titration with IRMS and MSC to a minimal and equivalent amount of supplemental short-acting analgesic. Side effects were typical for opioids and tolerated except for one dropout on IRMS (nausea and constipation). The ten principles have been incorporated into a dosing scheme as a practical guide for MSC therapy.
 ...
PMID:Principles of cancer pain management. Use of long-acting oral morphine. 264 96

The pattern of sensitivity of mice from three inbred strains were compared on measures of morphine-induced analgesia (hot plate), locomotor activity, hypothermia, Straub tail (muscular rigidity), antidiuresis and constipation. The DBA/2J strain emerged as the most sensitive strain for analgesia, retention of a water load (antidiuresis) and hypothermia. In addition, the DBA/2J mice had lower concentrations of morphine in the brain 30 min after injection and had the lowest Kd and the highest Bmax for naloxone as measured by in vitro receptor binding. In contrast, mice of the C57BL/6J strain were most sensitive when locomotor activity, Straub tail and constipation were measured. The C3H/HeJ mice were generally intermediate in their sensitivity to morphine. The observed strain differences indicate a rather high degree of genetic control for most of the effects studied, however, the low consistency of rank order among the three strains across these measures suggests that the genetically determined mechanisms are largely different between these measures of morphine sensitivity.
 ...
PMID:Genetic dissociation of multiple morphine effects among C57BL/6J, DBA/2J and C3H/HeJ inbred mouse strains. 281 56

The purpose of these investigations was to determine 1) whether peripherally located mu, delta and kappa opioid receptors can inhibit the rate of gastrointestinal transit and, if so, 2) do peripheral opioid receptors mediate the constipation caused by systemic morphine? and 3) whether constipation can be separated from analgesia on the basis of different sites of action. We studied the effects of peripherally administered (s.c.) mu, delta and kappa opioid receptor selective agonists on the rate of gastrointestinal transit in mice. We used peptidergic agonists with high peripheral selectivity (limited ability to cross the blood-brain barrier) including [MePhe3,D-Pro4]morphiceptin (PL017) (mu), [D-Pen2,D-Pen5]enkephalin (DPDPE) (delta) and Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg (dynorphin 1-9) (kappa). As peripheral selectivity is dose-related, we included the hot-plate test as an index of that dose at which each compound lost its peripheral selectivity and entered the central nervous system. When given s.c., [MePhe3,D-Pro4]morphiceptin inhibited transit (IC50 = 0.37 mg/kg s.c.) at doses much lower than those needed to produce analgesia (A50 = 30 mg/kg s.c.), indicating that peripheral mu receptors can inhibit transit independently of central mu receptors. The independence of peripheral mu antitransit receptors from central receptors was demonstrated further as the lack of antagonism of s.c. [MePhe3,D-Pro4]morphiceptin antitransit effects by simultaneous i.c.v. administration of the mu receptor antagonist D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) (1 microgram i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Peptide opioid antagonist separates peripheral and central opioid antitransit effects. 282 48

The kappa-opioid compound U-69,593 was studied in rats in vitro in binding assays to assess its selectivity at the single types of opioid sites and in vivo to assess its analgesic activity and effect on intestinal propulsion. In vitro the U-69,593 inhibition curve of [3H]-(-)-bremazocine binding suppressed at mu- and alpha-sites was biphasic and the inhibition constant (Kl) at the high-affinity site (10-18 nM) was two orders of magnitude smaller than the Kl at the low-affinity site. The Kl at mu- and alpha-sites were respectively 3.3 and 8.5 microM. Thus [3H]-(-)-bremazocine, suppressed at mu- and alpha-sites, may still bind more than one site, which U-69,593 might distinguish. In vivo U-69,593 i.p. prolonged the reaction time of rats on a 55 degrees C hot-plate and the dose of naloxone required to antagonize this effect was 40 times the dose that antagonized morphine-induced antinociception, suggesting the involvement of the kappa-receptor. In the intestinal transit test U-69,593 at doses between 0.5 and 15 mg/kg i.p. only slightly slowed intestinal transit of a charcoal meal in rats with no dose-relation; it partly but significantly antagonized morphine-induced constipation. These results suggest that the kappa-type of opioid receptor, with which U-69,593 interacts may induce analgesia, but has no appreciable role in the mechanisms of opioid-induced inhibition of intestinal transit in rats.
 ...
PMID:Interaction of U-69,593 with mu-, alpha- and kappa-opioid binding sites and its analgesic and intestinal effects in rats. 282 59

The opioid agonist-antagonists are a heterogeneous group of compounds capable of providing analgesia sufficient to treat moderate to severe acute pain. Pentazocine, butorphanol and nalbuphine produce subjective effects which are quite different from those of morphine. Lack of mood elevation and occasional dysphoria may contribute to a lower level of patient acceptance, but all of these analgesics are significantly safer than the pure agonists. Doses in the therapeutic range are unlikely to produce dangerous levels of respiratory depression in most patients. Other opioid side-effects such as nausea, constipation and biliary spasm appear to be less frequent as well. The mu partial agonist buprenorphine shares many of the safety advantages of the older drugs, and its subjective effects appear more morphine-like. It is not clear whether mu partial agonists have real clinical advantages over kappa-type analgesics. All of these drugs are opioid antagonists and are able to precipitate abstinence in individuals with significant prior exposure to opiates. Neither absolute potency nor the ratio of agonist to antagonist effect are predictors of therapeutic usefulness. There is now an enormous amount of clinical experience with the agonist-antagonists. In many, but not all, clinical situations they are acceptable alternatives to the morphine-like drugs.
 ...
PMID:The clinical usefulness of agonist-antagonist analgesics in acute pain. 289 87

The present study investigates the effects of ketamine on nociception towards chemical and thermic stimuli and on gastrointestinal transit in mice. The reversibility of these effects by the opioid antagonist naloxone (10 mg/kg) was also assessed. Ketamine promoted dose-related analgesia in both the acetic acid-induced writhing and hot plate tests. Analgesia was not influenced by pretreatment with naloxone. Contrasting the constipation induced by opioids, ketamine enhanced gastrointestinal transit in a dose-dependent manner and this was not modified by naloxone. These results suggest that although ketamine can elicit analgesia, it does not activate opioid mechanisms in subanesthetic doses.
 ...
PMID:Effects of ketamine on nociception and gastrointestinal motility in mice are unaffected by naloxone. 356 47

Morphine sulfate Contin (MSC) is an investigational matrix delivery system for oral morphine sulfate that allows for prolonged blood levels of morphine. Twenty-six patients with inadequately controlled cancer-related pain were examined in an open but controlled study using MSC. Initially, all patients were converted from the prestudy analgesic regimen to an equianalgesic amount of immediate-release morphine sulfate (IRMS) on a q4h dose schedule that was in turn titrated to the level of adequate pain relief. Patients then were switched to MSC q8h and eventually to q12h, starting at doses representing the same total daily amount of morphine that was in the final IRMS dose. Of the 18 patients who completed the study, all achieved satisfactory levels of analgesia on MSC, seven at q8h and 11 at q12h dosing intervals. All patients reported better analgesia while taking MSC compared with their previous regimen. Side effects associated with MSC included sedation and constipation but not nausea or respiratory difficulty. Significant drug tolerance did not develop during a mean follow-up period of four weeks (range, 1-18 weeks). MSC is an effective oral opioid analgesic that allows an increased dose interval without increased side effects or decreased potency. It can improve the quality of life of cancer patients by allowing them to be maintained without frequent dosing or parenteral medication.
 ...
PMID:Management of cancer pain with oral controlled-release morphine sulfate. 368 May 67

An oral formulation of meptazinol has been developed and marketed in the United Kingdom. The 200 mg tablet has a potency similar to dextropropoxyphene 32.5 mg/paracetamol 325 mg or pentazocine 50 mg. Nausea is the major side effect and constipation and dysphoria are virtually absent. Though a variable first pass metabolism restricts its potential for use in severe pain, oral meptazinol provides effective analgesia in mild or moderate pain.
 ...
PMID:Oral meptazinol--United Kingdom experience. 390 33

A dissociation of the effects of the newly synthesized quaternary ammonium narcotic antagonist, levallorphan allyl bromide (CM 32191) on morphine-induced analgesia and constipation in the mouse is reported. CM 32191 behaved as a pure morphine antagonist on the "in vitro" preparation of longitudinal muscle of guinea-pig ileum and antagonized dose-dependently the peripherally mediated morphine constipation (ID50:15.6 mg/kg) without significantly affecting morphine analgesia (ID50: greater than 80 mg/kg). Its peripheral selectivity was greater than that of another quaternary ammonium compound, N-methyl naloxone. It is proposed as a useful pharmacological tool to differentiate the peripherally mediated from the centrally mediated effects of opioids.
 ...
PMID:Pharmacological actions of levallorphan allyl bromide (CM 32191), a new peripheral narcotic antagonist. 618 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>