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 analgesic efficacy of oral naproxen and its sodium salt was compared with that of aspirin and codeine in two separate trials involving 140 and 90 patients, respectively, with postpartum uterine pain in a single-dose, parallel, stratified, randomized, placebo-controlled, double-blind design. With 300 or 600 mg naproxen and with 275 mg naproxen sodium, significant analgesia, measured subjectively by pain intensity differences (PID), was prolonged at least 7 or 8 hr; onset tended to be delayed 2 hr or more. With 650 mg aspirin analgesia began within 1 hr and continued until the fifth hour, while with 60 mg codeine responses were indistinguishable from placebo responses throughout the 8-hr time course. Although time-effect patterns with naproxen sodium and aspirin were different, summed analgesic effects (SPID) showed equal efficacy and superiority over placebo (p less than 0.005). With each of the 2 doses of naproxen, SPID separation from placebo was comparable to that above (p less than 0.02 and 0.005, respectively), but analgesic dose response, though measurable, was not significant. Side effects were not significant with any of the treatments. It appears that naproxen and naproxen sodium are analgesics with efficacy equal to aspirin and may prove to be rational substitutes for currently available analgesics in some painful states in which longer pain relief would be desireable.
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PMID:Naproxen, aspirin, and codeine in postpartum uterine pain. 32 Nov 77

Mice were given single s.c. injections of morphine sulphate (M.S.), heroin hydrochloride (H.HCl) and the sparingly-soluble diheroin pamoate (H.Pam) and 3,5-di-tert-butyl-2,6-dihydroxybenzoate (H.Bnz) in three vehicles, saline, peanut oil, or a slow-release vehicle (SRV) and tested for analgesia by both the tail-clip and hotplate techniques. Duration of analgesia as assessed by the tail-clip method was always longer than that by the hotplate when equivalent doses were used in any vehicle. The H.Pam and H.Bnz salts significantly prolonged the analgesia: the mean duration in mice injected with equivalent amounts of heroin base was 3.0 hr for the group receiving heroin HCl in saline and 7.8 hr after H.Bnz in slow-release vehicle. An inverse relationship was evident between the degree of dissociation of H from the three salts, at pH 7.3 and their durations of analgesia in vivo. This was statistically significant (p less than 0.01) at the higher dose level. All mice were challenged with naloxone hydrochloride (1 mg/kg) 24 hr after the injection of each narcotic agonist preparation. The jumping behaviour elicited by naloxone was not consistently related to dose, salt form, or vehicle employed for the injection of agonists, but from 12.5 too 54.2% of all the mice did jump at that time. The durations of analgesia observed and the intensity of the jumping response correlated significantly with the mean number of jumps per mouse after the naloxone challenge.
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PMID:Analgesia duration and physical dependence in mice after a single injection of three heroin salts and morphine sulphate in various vehicles. 56 22

With improving standards of antenatal care, severe pre-eclampsia dn eclampsia are becoming less common and experience in the management of these conditions is lessening. Co-ordinated plans for the care of patients should be established by obstetricians and anaesthetists working as a team. A suitable regime for drug therapy in severe pre-eclampsia or eclampsia is the following: Initial management Diazepam 10 mg slowly i.v. Pethidine 100-150 mg i.m. or i.v. in incremental dosage, or extradural blocks, if analgesia is also required. Hydrallazine 20 mg i.v. initially, followed by 5 mg at intervals of 20 min until the diastolic pressure is less than 110 mm Hg. Then, preferably by syringe pump in a concentration of 2 mg/ml, at a rate of 2-20 mg/h. If vomiting occurs this can be controlled by administration of atropine. Subsequent management Sedation and anticonvulsant therapy. Continue diazepam and, in severe cases, institute chlormethiazole infusion. Continue analgesia with pethidine or extradural block. Control of hypertension by adjusting the dose of hydrallazine. If tachycardia exceeds 120 beat/min give propanolol 2-4 mg i.v. Plasma protein depletion with groww oedema is treated by administration of salt-free albumin or plasma protein fraction. Diuretic therapy is indicated if there is gross oedema or signs suggestive of acute renal failure. Oliguria associated with increased blood urea may be a result of renal failure or dehydration. The latter should be evident from the patient's condition and central venous pressure, but i.v. fluids and frusemide 20-40 mg can be used as a therapeutic test. Mannitol reduces cerebral oedema and may be given if diuresis has been first produced with frusemide. Potassium chloride is given if the plasma potassium decreases to less than 3 mmol/litre. Heparin therapy is considered if there is clinical evidence of disseminated intravascular coagulation.
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PMID:The management of severe pre-eclampsia and eclampsia. 83 44

Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model.
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PMID:Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699. 140 95

Ketorolac is a new chiral nonsteroidal anti-inflammatory drug (NSAID) which is marketed for analgesia as the racemate. The drug is administered as the water soluble tromethamine salt and is available in tablets or as an intramuscular injection. The absorption of ketorolac is rapid, Cmax being attained between 20 to 60 min. Its oral bioavailability is estimated to range from 80 to 100%. The drug is extensively bound (> 99%) to plasma proteins and has a volume of distribution (0.1 to 0.3 L/kg) comparable with those of other NSAIDs. Only small concentrations of ketorolac are detectable in umbilical vein blood after administration to women in labour. The elimination half-life is between 4 and 6h and is moderate in comparison with other NSAIDs. The area under the plasma concentration-time curve of ketorolac is proportional to the dose after intramuscular administration of therapeutic doses to young healthy volunteers. Ketorolac is extensively metabolised through glucuronidation and oxidation; little if any drug is eliminated unchanged. Most of the dose of ketorolac is recovered in the urine as conjugated drug. Although ketorolac is excreted into the breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure. Little stereoselectivity was present in the pharmacokinetics of ketorolac in a healthy volunteer receiving single intravenous or oral doses. The elderly exhibit reduced clearance of the drug. Renal insufficiency appears to cause an accumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics.
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PMID:Clinical pharmacokinetics of ketorolac tromethamine. 2751 22

Most peptides do not enter the central nervous system because of their hydrophilic character and the presence of peptidolytic enzymes in the lipoidal blood-brain barrier. To achieve brain delivery of a peptide conjugate, an opioid peptide (enkephalin) was placed in a molecular environment that disguises its peptide nature and provides biolabile, lipophilic functions to penetrate the blood-brain barrier by passive transport. The strategy also incorporates a 1,4-dihydrotrigonellinate targetor that undergoes an enzymatically mediated oxidation to a hydrophilic, membrane-impermeable trigonellinate salt. The polar targetorpeptide conjugate that is trapped behind the lipoidal blood-brain barrier is deposited in the central nervous system. Analgesia was observed with "packaged" enkephalin but not with the unmodified peptide or lipophilic peptide precursors.
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PMID:A strategy for delivering peptides into the central nervous system by sequential metabolism. 152 56

Extracorporeal shock wave lithotripsy (ESWL) is successful in fragmenting gallstones, but less than 28 per cent of patients with gallstone disease fulfil the conventional criteria for treatment. However, no data exist to substantiate these selection criteria. In this study, the selection criteria were broadened to include patients with radiolucent stones of any size and number, and radio-opaque stones less than 3 cm in diameter. To date; 108 symptomatic patients with gallstones have received treatment. All patients received up to six outpatient sessions of ESWL (6000 shock waves per session) without sedation or analgesia. The dissolution therapy consisted of combined bile salt and terpene administration. The clearance rates were 9 per cent within 2 months, 21 per cent at 2-4 months, 38 per cent at 4-8 months, 60 per cent at 8-12 months, and 78 per cent at 12-18 months. Of patients with a successful outcome only 19 (18 per cent) would have satisfied traditional selection criteria. There have been no significant complications except in one patient who developed mild acute pancreatitis, which settled on conservative treatment, and two patients who developed acute cholecystitis. This study would suggest that the previously accepted selection criteria underestimate the number of patients suitable for gallstone ESWL and dissolution therapy.
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PMID:Piezoelectric lithotripsy for gallstones: analysis of results in patients with extended selection. 201 62

The critical care patient population has much to gain from properly administered neural blockade. Effective analgesia alone may make the difference between a patient who is able to compensate for their acute insult and one who cannot. A good example is the patient with multiple fractured ribs, who, after intercostal nerve blocks, no longer requires intubation and mechanical ventilation. The authors believe that effective analgesia is just the beginning of the beneficial effects of neural blockade, because blockade of the afferent limb of sympathetic and sensory nerves may circumvent the neuroendocrine response to acute injury. There is evidence that the stress response is not beneficial in the hospital setting and in fact may be detrimental. Some of the effects include elevated plasma catecholamines, ADH, cortisol, and blood glucose, which contribute to tachycardia, hypertension, increased myocardial work and oxygen consumption, salt and water retention, and a catabolic state with negative nitrogen balance. Whether these changes result in reduced morbidity and mortality has been the subject of several studies, but more studies are needed. It would seem that critically ill patients with little physiologic reserve might be the best population to study because even a small improvement may improve survival. A small beneficial effect in healthy postoperative patients may not be clinically apparent. Most would agree that neural blockade used intraoperatively results in reduced blood loss and a lower incidence of postoperative thromboembolism. The continuation of these techniques into the postoperative period may reduce morbidity and mortality in high-risk patients. A word of caution is in order. The indiscriminate application of the techniques described in this article to critically ill patients would not be in the patients' best interest. Nerve blocks are only safe in the hands of those physicians specifically trained to perform them. In addition, local anesthetics have a low therapeutic ratio, and their administration requires continual observation. The use of epidural or intrathecal opioids alone or in combination with other agents also has potentially serious side effects, and requires continual patient monitoring. The proper performance and maintenance of these techniques requires a large commitment of time, manpower, equipment, and a multidisciplinary approach to include physicians, nursing, and support staff. Nerve blocks and other sophisticated techniques started in the operating room or critical care unit should not necessarily be discontinued when the patient is transferred to a ward bed because the full benefit of this therapy may not have been fully realized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nerve blocks in the critical care environment. 218 9

Angiotensin II (AII), arginine vasopressin (AVP) and prolactin (PRL) were measured by radioimmunoassay in plasma and cerebrospinal fluid (CSF) in concurrent daily samples from conscious unrestrained steers. Packed cell volume, [Na+] and osmolality were also measured from these samples. Salt appetite was assessed during a 5-min daily session of operant conditioning. Food and water was always available. Unilateral parotid duct fistulation was effected under xylazine analgesia and halothane/O2 anaesthesia. To prevent a sodium deficit developing from loss of [Na+] in the extruded saliva, 0.3 M NaHCO3 was available ad libitum so that each animal could ingest sufficiently to balance the salivary loss. A week later epidural cannulae were implanted in the cisternae magna using the same anaesthesia. Three days afterwards when the saliva [Na] was 78 mmol/1, the 0.3-M NaHCO3 supplement was withdrawn for 7 days so that sodium deficiency developed to a degree which evoked salt appetite. When the NaHCO3 supplement was restored ad libitum, all aspects of [Na+] deficiency and salt appetite were completely ameliorated within 2-3 days. Packed cell volume increased and body weight decreased (p less than 0.05) during depletion, but rapidly returned to normal on day 2 of repletion. Both plasma and CSF osmolality were reduced during depletion as were plasma [Na+] (p less than 0.01) and CSF [Na+] (p less than 0.001). From a basal value of 64.7 +/- 9.35 fmol/ml on day 0, plasma AII increased to 229.2 +/- 46.65 fmol/ml (p less than 0.001) on day 3, prior to the onset of salt appetite on days 4-7. In marked contrast to plasma AII during sodium depletion, CSF AII was unchanged during salt appetite. There was no correlation between plasma and CSF AII during behavioural salt appetite.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation of endogenous systemic and brain angiotensin II, arginine vasopressin and prolactin with the genesis of salt appetite in cattle. 284 67

We evaluated the anxiolytic property of a brain-specific gamma-aminobutyric acid delivery system (GABA-CDS) in male rats by means of a drink-foot shock conflict procedure. Brain-specific delivery of the active compound was achieved by combination of GABA benzyl ester with an interconvertible dihydropyridine in equilibrium pyridinium salt carrier, which is "locked in" to the brain upon its oxidation. Pharmacokinetic studies revealed that the hydrophilic pyridinium salt form (G-Q+) of the GABA-CDS formed in situ remained in the brain for 12 h but was cleared from the blood and other peripheral tissues by 0.5-4 h. While the lipophilic form (G-DH) of the GABA-CDS caused a marked and sustained anxiolytic response when administered systemically, GABA and the charged pyridinium salt (G-Q+ form) of the GABA-CDS were ineffective. G-DH was injected at either 0, 4, 10 or 25 mg/kg IV in DMSO after rats were water and food deprived. After either 0.5, 2, 4, 8 or 24 h, rats were permitted 10 s of shock-free drinking of 10% sucrose, then given a 35 mA (DC) current through the drinking tube. Drinking time was recorded for 3 min. All doses of G-DH caused a significant increase in anxiolysis over control levels through 8 h. An increase (4 to 7-fold) in anxiolytic activity was observed through the 10 mg/kg dose with the 25 mg/kg dose causing no additional increase. No sedation or analgesia was observed at 2 h with any anxiolytic-producing dose of G-DH. These results suggest that G-DH elicits anxiolysis with minimal sedation, through the local brain action the G-Q+ or subsequent to the release of GABA.
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PMID:Anxiolytic activity of a brain delivery system for GABA. 288 84


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