SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Two new series of 2-aryletenylthiazolo-4-acetic (IV-XII) and 4-carboxylic (XIII-XXI) acids substituted with alkoxy groups in the benzene ring were synthesized. The compounds were subjected to comparative tests of antiinflammatory, analgesic and antipyretic activity.
Explore the source record for details and available documents.
The metabolism of antipyrine and oxazepam has been measured in twelve healthy subjects. Antipyrine, an analgesic and antipyretic drug, is extensively metabolized by oxidation at various sites and oxazepam, a benzodiazepine, is almost exclusively metabolized by conjugation with glucuronic acid. Comparing the plasma clearance rates and the plasma half lives of the two drugs, correlation coefficients of r = 0.766 (P less than 0.01) and r = 0.966 (P less than 0.01) have been obtained. The data suggests that in man the processes of oxidation and glucuronidation are linked by a common control which regulates the metabolic rates of the two reactions.
The treatment of lepra reactions constitutes one of the most serious problems in leprosy. For this reason, the first reports in 1965 of the favourable results obtained with thalidomide aroused considerable interest and led WHO, in 1967, to carry out a trial with the co-operation of four centres. A short-term double-blind trial was designed to study the effect of thalidomide, in comparison with acetylsalicylic acid, in the treatment of acute lepra reactions in male lepromatous patients. Acetylsalicylic acid was used instead of a placebo because of its antipyretic and analgesic activity. Because of the severe adverse reactions that may be caused by thalidomide, mainly the teratogenic effects, only males were included in the trial.The results of this short-term study seem to confirm previous reports of the efficacy of thalidomide and indicate that acetylsalicylic acid also seems to be helpful in the management of certain symptoms of lepra reactions.
The synthesis of 5H-indeno[1,2-c]pyridazine (V) and of some derivatives were reported. The compounds synthesised generally retained the antiinflammatory activity exhibited by the 4,4a-dihydro derivatives of this class, previously tested. Moreover (V) showed analgesic and antipyretic properties higher than those of acetylsalicylic acid.
The metabolism of 2-(4-isobutylphenyl)-propio-hydroxamic acid (ibuproxam, Ibudros), a new molecule with anti-inflammatory, antipyretic and analgesic activity was studied by its administration orally and rectally to the rat. The analysis, carried out with gas chromatographic method and thin-layer chromatography, showed that the drug is present in blood as 2-(4-isobutylphenyl)-propionic acid (ibuprofen), an anti-inflammatory drug which is commonly used and the metabolites of which are already known. Using the same methods, it was observed that only a few traces of the hydroxamic acid appear in the urines of rats treated with ibuproxam, whilst the ibuprofen metabolite is absent. Therefore, we conclude that the drug ibuproxam changes rapidly into ibuprofen, following afterwards the same known metabolic process as the latter drug.
The acute, subacute, and chronic toxicity of gamma-oxo[1,1'-biphenyl]-4-butanoic acid (fenbufen), a new orally and parenterally effective non-steroidal antiinflammatory, analgesic, and antipyretic agent, was investigated in mice, rats, and dogs. In these studies, the gastrointestinal and renal changes associated with toxic doses of fenbufen resembled those described for this class of drug. In coadministration studies, there were no evidences of specific adverse interactions when fenbufen was given with dicoumarol or with triamcinolone; however, coadministration of acetylsalicylic acid (ASA) and fenbufen resulted in decreased plasma concentrations of fenbufen-related materials and a possible increase in the incidence of gastrointestinal hemorrhages or ulcers.
Aspirin remains the agent of first choice, but ibuprofen, fenoprofen, naproxen and tolmetin are useful drugs in rheumatoid arthritis. Ibuprofen and fenoprofen are also approved for use in osteoarthritis. Each shares anti-inflammatory, analgesic and antipyretic properties with aspirin, phenylbutazone and indomethacin. The nonsteroidal anti-inflammatory agents have fewer minor side effects than aspirin and fewer major side effects than indomethacin or phenylbutazone. The patient must understand that drugs are but one part of a comprehensive management program.
The synthesis of imidazo [2,1-b]-1,3,4-thiadiazole derivatives and preliminary pharmacological screening are reported. The compounds studied showed mainly antiphlogistic, antipyretic and analgesic activity. From the results it appears that analgesic activity is peripheral.
Imidazole 2-hydroxybenzoate is a new antiphlogistic compound with analgesic and antipyretic properties undergoing clinical investigations. The purpose of this pilot study was to evaluate new methods for the quantitation of imidazole, salicylic acid and salicyluric acid in plasma and urine. Imidazole metabolites caused considerable methodologic difficulties in plasma and urine. They were below the detectable limit. Salicylic acid metabolites were present in plasma also under the limit of detection (0.5 microgram/ml). In urine the metabolite salicyluric acid was measured in considerable quantities, whereas gentisinic acid was under the limit of detection. Three healthy volunteers were given a single p.o. dose of 750 mg imidazole 2-hydroxybenzoate in order to examine the practicability of these new methods a well as to evaluate the pharmacokinetics. The data are presented and interpreted. Further studies in this respect are advised.
The analgesic and antipyretic effect of paracetamol and phenacetin is to be traced back to the same pharmacologic active substance. When no therapeutic doses are applied, paracetamol causes severe lesions of the liver parenchyma with often fatal termination. It is reported on the paracetamol intoxication of a 38-year-old landlady, in whom as a sequel of the intoxication a severe lesion of the liver parenchyma and an acute toxic renal failure developed. The understanding of the paracetamol-conditioned lesions takes the knowledge of the course of the reaction of its biotransformation for granted. Since the pharmacokinetics underlies numerous influence factors, there is no foreseeable correlation between toxicity and doses. It seems that also in therapy paracetamol does not cause less side-effects than phenacetin. The discussed use of paracetamol instead of phenacetin is, therefore, critically to be considered.
Acetaminophen is an effective analgesic and antipyretic agent with few adverse effects when used in recommended dosages. The drug is metabolized mainly in the liver, and the several end products have no harmful effects. An intermediate compound in a minor metabolic pathway, however, is toxic; it is normally inactivated by glutathione. In the case of an acetaminophen overdose the hepatic stores of glutathione seem to become depleted, leaving the toxic intermediate free to damage liver tissue. Such damage is unlikely to occur unless the plasma concentration of acetaminophen peaks above 150 micrograms/mL--a level far in excess of the 5 to 20 micrograms/mL achieved with therapeutic doses of the drug. Long-term therapeutic use of acetaminophen does not appear to be associated with liver damage, although some case reports suggest the possibility. Acetaminophen poisoning follows an acute overdose and, if untreated, is manifested clinically by an initial phase of nonspecific signs and symptoms, a latent period in which the liver transaminase levels rise and then, 3 to 5 days after the ingestion, signs of more serious hepatic dysfunction. Most patients do not progress beyond the first or second phase. They and those who survive the third phase recover with no residual injury to the liver. Appropriate antidotal therapy markedly reduces the severity of the initial damage.
The paper reports the inhibitory activity (ID50) of a series of 2-phenylpyrazolo [1,5-a]pyrimidines on prostaglandin synthetase of guinea-pig lung homogenate in comparison with indomethacin. In vivo studies showed that some of these compounds possess interesting antiinflammatory, antipyretic and analgesic properties, as compared to those of classic non steroid antiinflammatory drugs like aspirin or phenylbutazone.
The mechanism of the antiinflammatory activity of 2-(5-ethylpyridin-2-ly)benzimidazole (KB-1043), a new benzimidazole derivative with antiinflammatory, analgesic and antipyretic activities, is described. KB-1043 inhibits the emigration of leucocytes and the exudation of protein into the site of injury. KB-1043 possesses also a potent membrane stabilizing activity. Although KB-1043, in vitro, did not inhibit the enzyme activity, the increase of enzyme activity at the site of injury was inhibited by the oral administration of KB-1043. The inhibitory effect of KB-1043 on prostaglandin synthesis was slightly weaker than that of acetylsalicylic acid (ASA). The antiinflammatory effect of DB-1043 was observed also in adrenalectomized rats and spinalectomized rats.
A benzophenone derivative, 4-butyl-2'-fluorobenzophenone (KC-8973), having anti-inflammatory effects has been studied pharmacologically and toxicologically. On the carrageenin-induced paw edema, KC-8973 had the most potent activity of the tested commercial non-steroidal anti-inflammatory drugs. KC-8973 had a moderate effect on bradykinin-induced capillary permeability and lesser effect on dextran-, egg white- and serotonin-induced paw edemas in rats, respectively. From the detailed studies of prophylactic and therapeutic effects on the adjuvant-induced arthritis in rats, it was demonstrated that KC-8973 has an immuno-suppressive activity in addition to an anti-inflammatory effect. KC-8973 had a local-analgesic and antipyretic effect on the rat paw edema induced by brewer's yeast. KC-8973 caused no undesirable side effect at pharmacologically effective dose in the 1-month sub-acute toxicological study.
The reproductive toxicology of gamma-oxo[1,1-biphenyl]-4-butanoic acid (fenbufen), a new non-steroidal antiinflammatory, analgesic and antipyretic agent was investigated in rats, rabbits and mice after oral administration. This drug showed no evidence of teratogenic or other embryotoxic effects in these three species when administered during organogenesis at dosages as high as 40 mg/kg/day. In male rats no effects on fertility and general reproductive performance were noted except those related to the ulcerogenic effect of this compound. In female rats there were no apparent effects on gonadal function, estrus cycle, mating behavior or fertility. Maternal dystocia and increased mortality of offspring (stillbirths) were observed in rats at doses of 20 mg/kg/d and greater. Increased duration of gestation and prolonged parturition were seen also in rats. Prostaglandin inhibition has been produced in vitro and in vivo by fenbufen and/or its metabolite, biphenyl acetic acid. This suggests that fenbufen shares with other non steroidal antiinflammatory agents the potential for inhibiting prostaglandin-mediated reproductive processes in the human.
Acetaminophen is a widely available and frequently recommended over-the-counter analgesic and antipyretic. Chronic doses in excess of 5 Gm. per day and acute doses of as little as 7 Gm. have caused hepatic damage in adults. Larger doses may be fatal. The hepatotoxicity, which is due to metabolic transformation of the acetaminophen to an alkylating agent, can be palliated or avoided by prompt treatment. Blood levels over 200 micrrograms per mL. four hours after ingestion correlate with severe hepatotoxicity. Clinical trials have shown N-acetylcysteine (NAC) to be a specific antidote when administered within eight hours of an acute ingestion.
Toxicity of meta or 3-hydroxyacetanilide was evaluated in mice. The LD50 was 1025 mg/kg when given intraperitoneally (i.p.). The drug in doses greater than 400 mg/kg i.p. caused significant sedation. 3-Hydroxyacetanilide, 900 mg/kg i.p., did not cause hepatic necrosis evaluated by either histology or changes in plasma glutamate pyruvate transaminase activity. Acetaminophen (4-hydroxyacetanilide, paracetamol) caused significant liver glutathione depletion two hours after dosing. In contrast, liver glutathione was only slightly decreased by 600 mg/kg i.p. of 3-hydroxyacetanilide at 2 or 4 hours after the dose. It is suggested that the meta-substituted acetanilide derivatives might be safer analgesics and antipyretics than acetaminophen.