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[Effects of analgesic-antipyretics on the spinal reflex potentials in cats: an analysis of the excitatory action of aminopyrine].

The effects of some analgesic-antipyretics on the spinal reflex potentials were studied in spinal cats. Aminopyrine at 25-100 mg/kg, i.v. produced a marked increase in mono- and poly-synaptic reflex potentials (MSR and PSR), and a decrease in dorsal root reflex potentials (DRR) in a dose-dependent manner. The amplitude of DRR decreased by aminopyrine was reversed by diazepam at 0.2 mg/kg, i.v.; however, the increased amplitudes of MSR and PSR were not affected by diazepam. Pretreatment of semicarbazide at 200 mg/kg, i.v. did not influence the increasing effect of aminopyrine on MSR and PSR. DL-5-Hydroxytryptophan produced facilitation of the MSR and PSR. In DL-5-hydroxytryptophan-treated cats, the amplitude of MSR was further increased by aminopyrine. Methysergide at 1 mg/kg, i.v. antagonized this increasing effect of aminopyrine on MSR and PSR. These observations suggest that the excitatory action of aminopyrine may be partly related to 5-hydroxytryptamine and not connected to the GABAergic mechanism. Other pyrazolone derivatives were also studied. Isopropylantipyrine at 50 mg/kg, i.v. produced increases in MSR and PSR. Intravenous sulpyrine at 500 mg/kg, antipyrine at 50 mg/kg or 4-aminoantipyrine at 50 mg/kg did not affect the reflex potentials. The non-pyrazolones, acetaminophen and indomethacin, did not increase the MSR and PSR. These results suggest that the N-dimethyl or isopropyl residue at the 4 position of the pyrazolone structure plays an important role in the excitatory action of analgesic-antipyretics in cat spinal cord.

5-Hydroxytryptophan↗

Analgesic antipyretic drugs as antagonists of bradykinin.

The antagonism between analgesic antipyretic drugs and bradykinin was examined quantitatively, using the bronchoconstrictor response of guinea-pigs in vivo. The dose of bradykinin required to overcome antagonism by calcium acetylsalicylate increased with the dose of acetylsalicylate given, the ratio being roughly constant. Fifty times the quantity of acetylsalicylate which just antagonized bradykinin did not modify bronchoconstriction due to small doses of histamine, 5-hydroxytryptamine, or acetylcholine. A method of measuring the potency of this anti-bradykinin action was developed. Acetylsalicylic acid, phenylbutazone, amidopyrine, and phenazone had a high potency; paracetamol, cinchophen, sodium salicylate, and acetanilide had a moderate potency; and phenacetin, salicylamide, and 4-hydroxyisophthalic acid had little or none. Cortisone, hydrocortisone, aldosterone, amodiaquine, and morphine were ineffective or their action was non-specific. In sensitized guinea-pigs, an injection of antigen caused bronchospasm. This response was greatly lessened by pretreatment with mepyramine, but was not affected by calcium acetylsalicylate, lysergic acid diethylamide, or atropine. Acetylsalicylic acid, phenylbutazone, and amidopyrine did not specifically antagonize the action of bradykinin on the capillaries of guinea-pig skin in vivo, on guinea-pig ileum in vitro or on rat duodenum in vitro.

Acetaminophen↗

Cutaneous reactions to analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. Analysis of reports to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia.

We analyzed the cutaneous reactions to systemic analgesic-antipyretics and non-steroidal anti-inflammatory drugs reported to the spontaneous reporting system of the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED). The system has been active since 1988, with periodic intensive surveillance exercises, and 202 dermatologists have collaborated. Up to December 1991, 2,137 reactions had been collected, of which 713 were reactions to systemic analgesic-antipyretics and nonsteroidal anti-inflammatory drugs. A general profile of the reactions was identifiable. It included, in order of frequency, urticaria/angioedema, fixed eruptions, exanthemas, erythema multiforme and Stevens Johnson syndrome. Fixed eruptions and Stevens Johnson syndrome were reported with exceedingly high frequency in association with feprazone. Our system also revealed previously unreported reactions, including fixed eruption to nimesulide, fixed eruption to piroxicam and fixed eruption to flurbiprofen.

Adverse Drug Reaction Reporting Systems↗

Evaluation of analgesic, antipyretic and anti-inflammatory activity of spirobarbitunylphenothiazines in rodents.

Analgesic, antipyretic and anti-inflammatory activities of newly synthesized spirobarbitunylphenothiazines viz 10-[7, 11-Di(4-4' dimethoxphenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5.5] undecane 1, 5 dione] acetylphenothiazine (test drug A) and 10-[7, 11-Di (N.N-dimethylaminophenyl)-3-oxo-9-methylaminoimino-2, 4-diazaspiro [5, 5] undecane-1, 5 dione] acetylphenothiazine (test drug B) have been screened in Swiss mice and Wistar rats. The peripheral analgesic activity of test drugs A and B was investigated by acetic acid induced writhing test in Swiss mice while the central analgesic action was assessed by hot-wire (tail flick test) of the analgesiometer and tail-clip test in Wistar rats. Antipyretic activity was assessed on Brewer's yeast induced pyrexic model while antiinflammatory activity was seen on carrageenan induced hind paw oedema. Analgesic activity was found to be only of peripheral type as there was reduction of 66% in writhing responses by test drugs A and B in dose of 80 mg/kg in mice. No change in the tail flick responses was observed on analgesiometer or by tail clip by both the test drugs. Reduction of 1.5 to 2.0 degrees C in rectal temperature was observed in pyretic rats by test drugs A and B in dose of 80 mg/kg. 80% reduction in paw volume was noted in 80 mg/kg dose of both the test drugs which was comparable to the anti-inflammatory activity of 300 mg/kg, p.o. of phenylbutazone.

Analgesics↗

Antipyretic, analgesic and anti-inflammatory activities of ketoprofen beta-cyclodextrin inclusion complexes in animals.

Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) orally effective in treating fever, pain, and inflammation but gastrointestinal side effects were observed. Preparation of ketoprofen beta-cyclodextrin inclusion complexes was to increase the solubility and reduce the irritation. The complexes were prepared and preliminarily confirmed using X-ray diffraction and dissolution test. Antipyretic, analgesic and anti-inflammatory models were induced by 10% yeast using rabbits, 0.8% acetic acid using mice and 1% carrageenin using rats, respectively. Results showed that the dissolution rate of ketoprofen was significantly improved by complexation. X-Ray diffraction pattern of the complexes exhibited a diffuse pattern that differed from that of physical mixture of ketoprofen and beta-cyclodextrin. Ketoprofen markedly inhibited the fever reactions at a single dose of 2 mg/kg as follows: 64.53% (inhibition rate %) at 1 h for ketoprofen, 73.04% at 1 h for ketoprofen beta-cyclodextrin inclusion complexes, respectively. Alleviating pain reaction rates following a single dose of 8 mg/kg at 20 min were 39.25% for the inclusion complexes and 26.72% for ketoprofen, respectively. Inhibition rates to rat edema following a single dose of 5 mg/kg at 1 h were 39.47% for the inclusion complexes and 23.86% for ketoprofen. Results for antipyretic, analgesic and anti-inflammatory activities showed that the rapid and stronger effects were found in the treatment group of ketoprofen beta-cyclodextrin inclusion complexes in comparison with those of free ketoprofen.

Adjuvants, Pharmaceutic↗

Antipyretic analgesics: nonsteroidal antiinflammatory drugs, selective COX-2 inhibitors, paracetamol and pyrazolinones.

Antipyretic analgesics are a group of heterogeneous substances including acidic (nonsteroidal antiinflammatory drugs, NSAIDs) and nonacidic (paracetamol, pyrazolinones) drugs. Moreover, various selective cyclooxygenase-2 (COX-2) inhibitors with improved gastrointestinal tolerability as compared with conventional NSAIDs have been established for symptomatic pain treatment in recent years. The present review summarizes the pharmacology of all of these drugs with particular emphasis on their rational use based on the diverse pharmacokinetic characteristics and adverse drug reaction profiles. Referring to the current debate, potential mechanisms underlying cardiovascular side effects associated with long-term use of COX inhibitors are discussed.

Acetaminophen↗

Renal disease from habitual antipyretic analgesic consumption: an assessment of the epidemiologic evidence.

The quantitative evidence relating habitual antipyretic analgesic consumption to the development of renal disease is reviewed. For purposes of analysis, "abuse" of analgesics is defined as regular, usually daily consumption. The prevalence of habitual consumption demonstrates marked geographic variation for poorly defined reasons. Prevalence tended to be highest in those populations in which phenacetin was available and popular. The prevalence of nephropathy among habitual consumers also shows marked interpopulation variability. A highly significant linear relationship exists between the prevalence of habitual analgesic consumption in a given population and the prevalence of nephropathy in the subset of that population that habitually consumes analgesics. This relationship may represent a dose-response curve relating amount of analgesic intake to prevalence of nephropathy. Four cross-sectional studies, 1 longitudinal, and 1 case-control study have shown significant differences in prevalence of nephropathy between habitual users of phenacetin-containing analgesics and control populations. Conversely, 2 cross-sectional studies and 1 case control study showed no difference between habitual users of analgesics and control populations. However, those studies showing no difference were performed in populations with low prevalence of habitual consumption of compound analgesics and a lower prevalence of nephropathy than was found in those populations where differences were observed. The relative risk for developing various manifestations of analgesic nephropathy has been estimated in 4 studies and varies depending on which abnormality is considered. Data are available only for subjects consuming phenacetin-containing compound analgesics. The relative risk for elevated serum creatinine is in the range of 8 to 11, about twice that for an abnormal renal concentrating test (approximately 4). The relative risk for clinical papillary necrosis is approximately 18, and for cause-specific death (and by inference for end-stage renal disease) about 4. The difference in risk between most clinical manifestations of analgesic nephropathy and death (or end-stage renal disease) may be due to the fact that most patients with nephropathy do not progress to terminal renal failure. Rheumatology clinic studies indicate that the prevalence of nephropathy in habitual consumers of phenacetin-containing compounds is higher than that for habitual consumers of aspirin alone. Removal of phenacetin from compound analgesics in Scandinavian countries appears to have reduced the prevalence of papillary necrosis and death from interstitial nephritis.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗

The analgesic, antipyretic and anti-inflammatory activity of Diospyros variegata Kruz.

Pharmacological studies were conducted with the hexane extract of the dry stem of Diospyros variegata Kruz. (Ebenaceae) on experimental animals for evaluating the analgesic, antipyretic and anti-inflammatory activities. In the analgesic test, the hexane extract elicited inhibitory intensity on acetic acid-induced writhing response and on the late phase of formalin test but possessed only a weak effect on the tail-flick response and on the early phase of formalin test. The hexane extract also elicited antipyretic action when tested in yeast-induced hyperthermia in rats. In addition, the hexane extract showed an anti-inflammatory effect when tested in ethyl phenylpropiolate (EPP)- and arachidonic acid (AA)-induced rat ear edema.

Acetic Acid↗

Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta.

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia.

Animals↗

Antipyretic, analgesic and muscle relaxant activities of pueraria isoflavonoids and their metabolites from Pueraria lobata Ohwi-a traditional Chinese drug.

We evaluated the antipyretic, analgesic, and muscle relaxant activities of Pueraria isoflavonoids and their metabolites in mice. The glycosides daidzin and genistin significantly reduced fever induced by lipopolysaccharide (LPS). Their metabolites, daidzein and p-ethylphenol, also significantly reduced fever induced by LPS. In addition, daidzin, daidzein, dihydrodaidzein, and p-ethylphenol showed analgesic activity as assessed by the acetic acid-induced writhing test. Furthermore, equol and p-ethylphenol showed muscle relaxant activity in the rotarod and horizontal wire test. These results suggest that these compounds play a major role in the therapeutic activity of Pueraria isoflavonoids.

Analgesics↗

History of antipyretic analgesic therapy.

The use of naturally occurring plant materials for the relief of pain dates back to 3,000 B.C., although rapid advances in antipyretic analgesic therapy have been made more recently. Salicylic acid was synthesized in 1860, and the pyrazolone group, first represented by antipyrine, in 1883. Phenacetin was developed in 1886. Acetaminophen has been in use since the 1890s.

Acetaminophen↗

Analgesic, antipyretic and anti-inflammatory effects of essential oil of Lippia multiflora.

The essential oil of Lippia multiflora Moldenke (Verbenaceae) produced by conventional hydrodistillation was analyzed and studied for its analgesic, antipyretic and anti-inflammatory activities in rats and mice. At the doses used (2, 4 and 8 ml/kg o.s.) the essential oil of L. multiflora showed significant and dose-dependent analgesic effect on acetic acid-induced writhing in mice. Only the dose of 8 ml/kg of essential oil, antagonized hyperexia induced by brewer's yeast. No effect on granuloma formation was observed.

Acetic Acid↗

[Densitometric determination of propyphenazone, paracetamol, guaiacol glycerol ether, caffeine and acetylsalicylic acid in analgesic-antipyretic preparations with thin-layer chromatography].

Optimum conditions for a simultaneous determination of propyphenazone, paracetamol, guaiacol glycerol ether, caffeine and acetylsalicylic acid were described for preparations with analgesic-antipyretic activity, which don't allow a direct determination of the active principle because of interference phenomena. Using an external standard for calibration the determination was carried out by adsorption measurement (reflectance detection) in situ. Beside the determination of the drug content the method can be used to identify substances according to their RT and RF-values as well as by on-plate spectra taken.

Acetaminophen↗

[Pain therapy with antipyretic analgesics].

The pharmacotherapy of musculoskeletal pain remains of high importance in Western countries. The present review concentrates on the use of acidic (nonsteroidal anti-inflammatory drugs) and nonacidic (paracetamol, selective cyclooxygenase-2 inhibitors) antipyretic analgesics in the therapy of musculoskeletal pain disorders with particular emphasis on the diverse pharmacokinetic properties and unwanted side effects of these substances.

Analgesics, Non-Narcotic↗

Mutagenicity studies with x-ray-contrast media, analgesics, antipyretics, antirheumatics and some other pharmaceutical drugs in bacterial, Drosophila and mammalian test systems.

As part of our investigation into mutagenic effects of environmental compounds, we studied 21 pharmaceuticals most frequently sold in West Germany: 6 X-ray-contrast media, 13 analgesics, antipyretics and antirheumatics, 1 central stimulant, and 1 antidepressant. They were studied in different bacterial, Drosophila and mammalian test systems. 4 of these 21 compounds could be detected as mutagens in one of the test systems. namely: 1,2-dichloroethane induced an increase in the frequency of recessive sex-linked lethal mutations in Drosophila melanogaster, quinine dihydrochloride and dimethylaminophenazone were mutagenic in the Salmonella typhimurium tester strain TA98 in the presence of S-9 liver fraction derived from Aroclor-induced rats, and trilithium citrate caused a significant effect in the micronucleus test on bone marrow of NMRI mice.

Analgesics↗