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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benoxaprofen is a potent and long-acting anti-inflammatory and antipyretic compound. Its anti-inflammatory activity has been demonstrated in carrageenan-induced oedema, in cellulose pellet granuloma and in both developing and established adjuvant arthritis tests in rats. Its antipyretic activity is greater than either aspirin or paracetamol in tests inducing pyrexia with yeast of 'E' pyrogen in rats and rabbits. Benoxaprofen has analgesic activity in tests where pain is accompanied by inflammation but not in other experimental models of pain. The weak prostaglandin synthetase inhibiting properties of this compound differentiate it from other acid anti-inflammatory compounds. The low ulcerogenic potential of benoxaprofen seen in animal models may be related to its relative inability to inhibit PG synthetase.
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PMID:The pharmacology of benoxaprofen (2-[4-chlorophenyl]-alpha-methyl-5-benzoxazole acetic acid), LRCL 3794, a new compound with antiinflammatory activity apparently unrelated to inhibition of prostaglandin synthesis. 1 68

The isolated perfused rabbit heart has the capacity to rapidly synthesize, release, and inactivate prostaglandins (PGs) which can readily modulate coronary resistance and cardiac performance. Prostaglandin synthetase converts arachidonic acid to prostaglandin-like substance in one passage across the heart. There is little evidence of functional prostaglandin dehydrogenase activity. Arachidonic acid and bradykinin produce a concentration-dependent decrease in coronary resistance directly associated with PG-like substance biosynthesis and release. An inhibitor of bradykinin destruction, the nonapeptide SQ-20881, markedly enhanced both the coronary vasodilation and PG-like substance release produced by cardiac injection of bradykinin. Indomethacin inhibited both the myocardial prostaglandin biosynthesis and the decrease in coronary resistance induced by bradykinin and arachidonic acid. In addition to direct effects on coronary vascular smooth muscle, prostaglandins produced in the heart apparently exert a modulating influence on efferent autonomic and on afferent cardiovascular and pain reflexes.
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PMID:The synthesis and function of prostaglandins in the heart. 78 41

Prostaglandin synthetase inhibitors are used for the treatment of ureteric colic. However, there is controversy regarding the mechanism of action of these drugs. In this study, differential prostaglandin synthesis in the human renal pelvis, ureter and bladder was measured using specific radioimmunoassays and gas chromatography/mass spectrometry. There was a significant quantitative predominance of the smooth muscle constrictor eicosanoids, PGF2 alpha and TXA2 over the dilatory PGE2 in tissue from all sites--renal pelvis, ureter and bladder. The results indicate that prostaglandins play a direct role in smooth muscle activity of the upper urinary tract and the inhibition of this activity with indomethacin indicates a further mode of its action in pain relief in ureteric colic.
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PMID:Eicosanoid synthesis in the isolated human renal pelvis, ureter and bladder. 202 8

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug exhibiting optical isomerism. Only the racemate is in clinical use. In in vitro studies it has been demonstrated that only the S(+)-enantiomer inhibits the PG synthetase system. Nevertheless, it is widely believed that the sole use of the active isomer does not comprise any advantages since the inactive isomer is converted within the human body. In a triple cross-over study (300 mg S(+), 300 mg R(-), 600 mg racemic IBU; n = 8), we could show that the converted R(-)-IBU after racemate administration provides for only one third of the AUC of S(+)-IBU obtained after S(+)-application. Highest S(+)-peak plasma levels were reached after S(+)-IBU, lower ones after racemate. We, therefore, studied 4 patients with classical rheumatoid arthritis treated with 2-3 doses of 500 mg of S(+)-IBU/day over a two week period. Significant clinical recovery (Ritchie-index p less than 0.01; analogue scale pain p less than 0.05, motion p less than 0.01) was reached after one week. The results indicate that a reduction of dose and of metabolic load is possible if the S(+)-enantiomer is administrated.
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PMID:Pharmacological differences between R(-)- and S(+)-ibuprofen. 280 37

The levels of 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 xi-cyclo prostaglandin E2 (bicyclo PGEM), 13,14-dihydro-15 keto-prostaglandin F2 alpha (PGFM) and prolactin were measured in four serial plasma samples collected from thirty women undergoing therapeutic abortions in the first trimester by a suction curettage procedure. Eleven of these women received a preoperative loading dose of sodium meclofenamate, a PG synthetase inhibitor, before the abortion procedure was started and the rest received this medication after the last blood samples were drawn. Prolactin levels increased significantly during the procedure. Sodium meclofenamate treatment had no effect on this increase. Bicyclo PGEM levels did not increase during the procedure in untreated or treated women, whereas PGFM levels increased but only in untreated women. The lack of increase in treated women apparently was not a treatment effect because PGFM levels in corresponding samples of untreated and treated women were similar. Treatment significantly reduced the bicyclo PGEM levels immediately after completion of the procedure as compared to untreated women. This differential PG response to treatment is unprecedented and may be due to sodium meclofenamate inhibition of PGE2 and not PGF2 alpha synthesis. Nevertheless, these data demonstrate that sodium meclofenamate treatment of patients undergoing first trimester therapeutic abortion to relieve pain involves selective suppression of PGE2 synthesis.
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PMID:Peripheral prostaglandin metabolite levels in women undergoing therapeutic abortions in the first trimester with and without treatment with prostaglandin synthetase inhibitor. 311 7

In a randomized double-blind trial, the effect of ibuprofen on the pain produced by gallbladder disease and on gallbladder mucosa and muscle wall tissue PGE and PGF production was evaluated to determine if the pain of cholecystitis and prostaglandin formation were altered by administration of a prostaglandin synthetase inhibitor. To ascertain potential differences in extracellular and intracellular prostaglandin production rates, gallbladder mucosal cells and muscle tissues were maintained in tissue culture medium and then subsequently homogenized. PGE and PGF concentrations were measured in culture medium and homogenates utilizing radioimmunoassay. Gallbladder mucosa and muscle tissue produced nanogram per milligram protein amounts of PGE and PGF. As the histological estimation of the degree of inflammation increased, so also did the production of PGE. Increased inflammation was associated with unchanged PGF levels, resulting in an increased ratio of PGE/PGF with increasing inflammation. Oral ibuprofen administration was effective in decreasing PGE production by gallbladder mucosa and muscle and eliminating the significant correlation between PGE levels and the histologic degree of inflammation found in the placebo-treated patients. Ibuprofen significantly decreased the pain of cholecystitis when compared to placebo-treated patients. However, there was poor correlation between pain relief and changes in PGE production by gallbladder mucosa and muscle. PGE may play a mediator role in inflammation associated with cholecystitis. Prostaglandin synthetase inhibition decreases the pain associated with cholecystitis; however, the absence of correlation with decreased PGE formation suggests that other prostanoids may play an important role in producing the symptoms of cholecystitis.
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PMID:Effect of oral ibuprofen on formation of prostaglandins E and F by human gallbladder muscle and mucosa. 389 1

Recognition of a relationship between elevated levels of prostaglandins (PG) and dysmenorrhea represented a major advance. The PGs of most importance in primary dysmenorrhea are assumed to be PGF2alpha and PGE2. Oral contraceptives (OCs), which disrupt the normal sequence of hormonal dominance in the endometrium and reduce menstrual PG production, were the therapeutic agent for dysmenorrhea until the introduction of nonsteroidan antiinflammatory drugs (NSAIDs) with PG synthetase in the mid-1970s. 4 groups of NSAIDs have been evaluated: 1) indomethacin, 2) the fenamates, 3) the arylpropionic acids, and 4) aspirin. Ibuprofen and naproxen, 2 arylpropionic acids, are commonly used to treat dysmenorrhea and have fewer side effects than the other agents. The clinical effectiveness of NSAIDs is ascribed to their inhibition of PG synthestase activity; however, little is known about the pharmacology of these drugs. Reduction of menstrual PG release by ibuprofen or naproxen sodium was shown to produce good to excellent relief in 80% of treatment cycles in a clinical trial, in contrast to placebo therapy which afforded little or no relief. Moreover, in individual subjects there was a positive correlation between the severity of dysmenorrhea and levels of menstrual PG released during the corresponding period. A causal relationship between uterine contractions and dysmenorrheic pain has been demonstrated by other investigators. A current shortcoming of NSAIDs is their lack of specificity. They are assumed to be nonselective agents, affecting PG synthesis in all body tissues and inhibiting PG synthesis indiscriminately. Future research efforts should be directed toward development of a more uterine-selective agent that would produce fewer side effects.
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PMID:Prostaglandins and nonsteroidal antiinflammatory drugs in dysmenorrhea. 634 48

Primary dysmenorrhea is a common gynecologic disorder. Dysmenorrheic pain normally has an onset of from 2-12 hours before the start of menses and tapers over the next one to two days. Although the exact etiology is unknown, this condition is associated with an increase in prostaglandin F2 alpha. In the past, nonspecific treatments such as heat and exercise were tried, with poor results. Little relief was offered by antispasmodics or low-dose aspirin. Currently, effective therapy for primary dysmenorrhea includes oral contraceptives and prostaglandin synthetase inhibitors. Oral contraceptives should be prescribed only for women who desire contraception and who are candidates for this type of therapy. Prostaglandin synthetase inhibitors can be given to women who do not desire oral contraceptives or those who do not respond to hormonal therapy. Secondary dysmenorrhea should be suspected in women who do not respond to either treatment modality.
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PMID:Therapeutic management of primary dysmenorrhea. 642 Jan 34

Using microtransducer, the author has studied the uterine contraction in various menstrual phases and during dysmenorrhea, and also the effect of the administration of PG synthetase inhibitors. The results obtained can be summarized as follows: 1) In normal non-gravid uterus, the contraction was 25.6mmHg in amplitude and 19.9/10min. in frequency in the proliferative phase, 12.4 and 28.4 in the early half of secretory phase, 28.3 and 11.5 in the latter half, and 42.3 and 12.9 during menstruation. In other words, while the contractions were the most pronounced during menstruation, no difference was found between proliferative and the latter half of secretory phase, and they were the weakest during the early half of secretory phase with the ripple like small waves. 2) During the proliferative phase, relatively regular contractions were found in various kinds of patients, - that is - , patients with normal menstrual cycles, with organic disorders but without dysmenorrhea, with functional dysmenorrhea, or with organic dysmenorrhea. 3) Compared to other menstrual phases, the contractions were weak in the early half of secretory phase. However, the patients with organic dysmenorrhea had stronger contractions than other patients. 4) In the latter half of secretory phase, the patients with organic disorders or organic dysmenorrhea showed stronger contractions than in those without the organic changes, and the contractions were approximately 55mmHg in amplitude in patients with organic change, -almost twice higher than in patients without organic change. 5) During menstruation, patients with dysmenorrhea, functional or organic, showed contractions with the average amplitude of 87mmHg, -more than twice the height found in the patients without dysmenorrhea. 6) When the amplitude was higher then 140mmHg, all the patients complained of pain. 7) In patients with dysmenorrhea, the administration of PG synthetase inhibitors, such as Indomethacin, Naproxen, etc., caused the reduction of contraction amplitude, resulting in the relief of pain.
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PMID:[Contraction of non-gravid human uterus in various menstrual phases (author's transl)]. 706 50

Control and abolition of pain during and after surgical procedures is crucial point in the practice of anaesthesiology. In the last years the concept of multimodal analgesia (the use of different analgesic and techniques to relieve pain), has developed and non-steroidal anti-inflammatory drugs (NSAIDs) have a major role in it, because they have an opioid sparing effect. Moreover, they are very effective on somatic and breakthrough pain. NSAIDs can be divided functionally in four classes: salicylates, acetaminophen, non-specific inhibitors (i.e. ibuprofen, ketorolac, etc.) and cyclooxygenase2-inhibitors (coxibs). The target of action of these drugs is the different isozymes of the Prostaglandin G/H synthase, called Cyclooxygenases (COX). At least three different types of COX have been identified, which are probably organ specific. These isozymes play a crucial role in the developing of the inflammatory cascade, and in the genesis of various pain mediators released from tissue injury. Their most important side effects affect mainly gastrointestinal system, the kidney and the coagulation system. Less important are the effects on the liver and the immunologic system (asthma). The analgesic nephropathy and the coagulopathy must be taken into account in the surgical patient, for the possibility of increase perioperative morbidity. Very recently the newest class of coxibs, although they reduce g.i. bleeding and coagulopathy, have proved to increase the risk of cardiovascular accidents both in long term therapy than postoperatively in cardiac surgical patients. Many data are needed, but in patients at high risk of cardiac disease other NSAIDs should be considered.
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PMID:Analgesia in PACU: nonsteroidal anti-inflammatory drugs. 1630 56


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