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PubMedDate not supplied

[Use of nabumetone in the treatment of primary dysmenorrhea. Report of 100 cases].

The aim of the study was to assess the efficacy and tolerability of nabumetone, a new nonsteroid anti-inflammatory agent with analgesic and antipyretic functions, in the treatment of primary dysmenorrhea in 100 patients. Treatment was administered at a dose of 1 g per day for slight and moderate cases and 2 g per day for severe forms, starting from the onset of painful symptoms and lasting while they persisted. Side effects were observed in 7% of cases but were limited to the gastroenteric tract. The analysis of results confirms that with regard to the remission of symptoms, treatment was efficacious from the second month and that a further improvement was obtained with continued treatment. However, the Authors observed that, although the remission of symptoms was partial in the majority of cases, there was a greater response in cases of moderate or severe dysmenorrhea and their duration was shorter in comparison to those months in which patients had not received nabumetone treatment.

Adult↗
PubMed2003

Acute hepatic failure in the course of alcohol-paracetamol syndrome--case report.

Acetaminophen belongs to the antipyretic and analgesic drugs most commonly used all over the world. In western Europe, primarily in Great Britain, as well as in the US, increasing incidence of acute liver failure due to the overdose of the drug has been reported. The report presents a description of alcohol-paracetamol syndrome, which led to the development of acute hepatic failure with numerous complications. Intensive symptomatic and causal treatment with N-acetylcysteine resulted in complete recovery.

Acetaminophen↗
PubMed2004

A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland.

BACKGROUND: Metamizole is a common analgesic and antipyretic drug. However, its use has been associated with a risk of side-effects involving agranulocytosis and aplastic anemia. These reactions are rare and unpredictable. The aim of this prospective study was to evaluate the risks of these complications in Poland, where this medication is available without prescription. MATERIAL/METHODS: Six hematological centers, serving approximately 40% (ca. 15 million people) of the country's population, participated in the study. All cases of agranulocytosis and aplastic anemia were recorded and their severity and association with the use of drugs, especially metamizole sodium, were evaluated. All the patients receiving cytostatic or immunosuppressive drugs were excluded. RESULTS: During the 12 months of the study, 2 cases of aplastic anemia and no cases of agranulocytosis were confirmed which may have been associated with the use of metamizole. Overall, we recorded 16 cases of agranulocytosis and 27 cases of aplastic anemia. The two cases of metamizole sodium-induced aplastic anemia were non-fatal in character. CONCLUSIONS: Considering the consumption of 112,300,094 tablets of metamizole in Poland a year, the figures obtained result in an incidence of 0.25 cases of aplastic anemia per 1 million persons per day of treatment; this value being less than that for other nonsteroidal anti-inflammatory drugs. Nevertheless, caution is recommended in the application of metamizole, particularly over long periods and in large doses.

Administration, Oral↗
PubMed2004

Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error?--Not as easy as 1, 2, 3.

A continued need to develop safe and effective analgesics and anti-inflammatory drugs fuels the ongoing investigations of cyclooxygenase (COX). In addition, a long unanswered question in the biomedical arena revolves around the mechanism of action of acetaminophen leading to its analgesic and antipyretic activity. Upon the discovery of COX in 1971, alternative enzyme forms were initially suggested. With the development of molecular biology, the discovery of two major cyclooxygenase genes (COX-1 and COX-2) was heralded in 1990, which has subsequently led to the clinical use and development of selective COX-2 inhibitors. Splice variants of both COX-1 and COX-2 were first encountered in the early 1990s, as were single nucleotide polymorphisms of COX-1 and 2. There have been some recently well-publicized investigations of COX-1 and -2 enzyme variants that may assist in our eventual conceptual understanding of the mechanisms of action of acetaminophen. The term "COX-3" has been utilized by some scientists and in the media. The evidence for "COX-3" in terms of various COX-variants and possible scientific and therapeutic implications of COX variant enzymes are described.

Acetaminophen↗
PubMed2004

[Development of a simple method of detecting acetaminophen using 96 well microplate readers].

Acetaminophen (APAP: N-Acetyl-p-aminophenol) has been widely used as a relatively safe antipyretic and analgesic drug. However, APAP is known as a major causative agent of fulminant hepatic failure, in a dose and a blood concentration dependent manner, in Western countries. The APAP toxicity should be expected to increase in proportion as the increasing of the clinical use in Japan. Therefore, a simplified method which determines the concentration of APAP would be valuable for clinical use. We have modified the APAP determination method developed by Yasojima. Our method enabled to measure APAP concentration with a small volume of samples by using 96-well microtiter plate, which can handle multiple samples simultaneously. From 10 microg/ml to 320 microg/ml of APAP was quantitatively measured by our method, which is suitable for diagnostics of the APAP toxicity. APAP levels below the lethal concentration of 160 microg/ml can be determined with one plate.

Acetaminophen↗
PubMed2004

Screening of inhibitors of uridine diphosphate glucuronosyltransferase with a miniaturized on-line drug-metabolism system.

Inhibition of uridine diphosphate glucuronosyltransferase (UGT), a major drug-metabolyzing enzyme, has been studied using an on-line drug-metabolism system integrated into capillary electrophoresis. Microsomes isolated from rat liver were encapsulated in tetramethoxysilane (TMOS)-based silica matrices within a capillary in a single step under mild conditions. This microsome-immobilized capillary column allows both the metabolism of drugs and determination of the metabolites in a single capillary simultaneously, just by injecting the substrate-coenzyme mixture onto the column. Glucuronidation of acetaminophen, a widely used pharmaceutical analgesic and antipyretic agent, was investigated using this system. The glucuronidation was inhibited by 4-nitrophenol (4NP) or probenecid that was injected onto a column along with the substrate-coenzyme mixture. On the other hand, valproate did not inhibit the metabolizing reaction. The extents of inhibition using encapsulated UGT were almost the same as those obtained using free UGT. On the other hand, this electrophoretic enzyme-inhibitor assay in microfabricated devices consumes 10(4) less sample and 10(3) less microsome per experiment compared to the conventional reaction schemes. These results demonstrate that this on-line system can circumvent laborious procedures for the isolation and determination of drug metabolites from the reaction mixtures required in the conventional schemes and can provide an attractive alternative technique for the analysis of drug interactions in the metabolic pathways.

Animals↗
PubMed2004

[Is there a future for COX-2 inhibitors?].

The two cyclooxygenase isoforms (COX-1 and COX-2--coxibs) have overlapping functions and both are involved in the regulation of homeostatic and inflammatory processes in the various tissues. Treatment with highly selective COX-2 inhibitors is associated with significantly fewer serious adverse gastrointestinal events than is treatment with the dual inhibitors--the non-selective NSAIDs. Of the two coxibs, rofecoxib was shown to be much more selective than celecoxib and with less interaction with other drugs. Various clinical studies have demonstrated that the coxibs are equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator non-selective NSAIDs in osteoarthritis, rheumatoid arthritis, post surgery pain and dysmenorrhea. Perioperative use of coxibs reduces pain, opioid consumption and the risk of bleeding caused by the non-selective NSAIDs. The coxibs show similar tolerability for renal, liver and cardiothrombotic events as compared to the non-selective NSAIDs. Coxibs are contraindicated in pregnancy, in nursing mothers and pediatric patients and should be used with caution in patients with asthma. The impact of the coxibs on the cardiovascular system is controversial. However, coxibs should be used in caution and at the lowest recommended dose in patients with hypertension, ischemic heart disease and heart failure. These drugs do not interfere with the aspirin anti-platelet aggregation activity. Emerging evidence suggest that the coxibs may also find potential use as supportive therapy in various malignant tumors and intestinal polyps where COX-2 is overly expressed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

[Toxicological analyses over the past five years at a single institution].

We investigated 352 patients with acute poisoning, 145 males and 207 females, who were sent to the Department of Emergency and Critical Care Center between June 1999 and March 2004. The insurance application rate averaged 72.5%. The causative agents included 98 prescribed drugs, 23 pesticides and herbicides, cyanide, arsenic and boric acid. Hypnotic and psychotropic drugs accounted for 192 cases (47.5%); antipyretics and analgesics, 93 (23.0%); pesticides and herbicides, 65 (16.1%); amphetamine-like drugs, 6 (1.5%); boric acid, 4 (1.0%); cyanide, 3 (0.7%); arsenic, 1 (0.2%); and other agents, 40 (9.9%). In young people, the most prevalent cause of poisoning was hypnotic,or psychotropic drugs prescribed in psychiatry clinics. In people older than 30, poisoning due to pesticides and herbicides was increased, reaching a peak among those in their 40s. Of 23 patients who died, 20 took Paraquat and Diquat, 2 took organophosphates and 1 took an overdose of antidepressants. The other 329 were transferred to different medical departments or were discharged from our hospital after recovery.

Acute Disease↗
PubMed2004

[Parents' and caregivers' theoretical and practical knowledge of first aid in case of accidents and minor injuries in children].

Accidents and injuries cause most serious health problems in pediatric group of patients in Poland. We asked a group of 93 parents and tutors (11 men and 82 women) to complete a questionnaire containing 20 questions. It referred to their knowledge on first aid treatment. We have analyzed the answers using statistical methods and couched our conclusions. 1. The results of the enquiry show a great extent of self-satisfaction in the questioned group of parents. Most of them (64.5%) think they know first aid rules, although only 35 people (37.6%) were ever trained in this field. Parents declare they known, how to deal with such conditions as bums, slight contusions and injuries, fractures, torsions, choking and high temperature. 2. Most parents (71%) have already treated minor injuries and dealt with minor accidents which took place while they took care of a child. Most common health problems were: high temperature--23.9%, slight contusions--22.4%, minor injuries--16.1%, hemorrhage--8.8%, scalding--8.3%, choking--7.3%. Accidents occur mainly during playground activities or cycling (63%) and at home (17%). 3. When an accident involving children occurs, 29.2% of parents call for medical help, 63.8% of them do it only if very serious injuries occur and 9% always try to treat a child themselves. In our enquiry most parents knew the names of popular analgesic and antipyretic drugs. They also knew how to deal with a slight burn or scald. 4. In questioned adults' opinion health care professionals do not give enough first aid information to the society. In our examined group, 58.1% of parents try to read and learn themselves. This shows the need for training people who take care of children in first aid treatment. As the best places for such training enquired parents pointed schools, kindergartens, pediatric and obstetric clinics.

Acute Disease↗
PubMed2005

[Aspirin--the prodigious panacea? Molecular mechanisms of the action of acetylsalicylic acid in the organism].

Aspirin (acetylsalicylic acid) is a commonly used non-steroidal anti-inflammatory drug capable of acetylating proteins in the course of a simple, non-enzymatic chemical reaction. Its main physiological effect is inhibiting prostanoid synthesis. Cyclooxygenases, COX-1 and COX-2, are crucial in the metabolic pathway leading to the generation of prostanoids. Both enzymes are major cellular targets for aspirin. The physiological spectrum of the biological activity of the prostanoids is very broad, and underlies the high clinical effectiveness of aspirin as an anti-inflammatory, antipyretic, and analgesic drug. Apart from the inhibition of prostanoid synthesis aspirin shows a variety of pharmacological activities, including reduction of ATP storage pools, increased extracellular adenosine, lowered inducible nitric oxide synthase activity, modulation of mitogen-activated protein kinases, and the expression of a plethora of genes induced under conditions of cell stress via the regulation of transcription factor NFkappaB activity. Such multipotent action explains its wide use in clinical practice. Regardless of the accumulated evidence on the molecular mechanisms of aspirin's action, the rationale of the appropriate dosing and monitoring of aspirin therapy and prophylaxis remains obscure. Hence, an evaluation and reasonable weighing of the cost/benefit ratio of aspirin therapy in various diseases seems appropriate.

Analgesics↗
PubMed1992

Oxaprozin: a new NSAID.

Oxaprozin, a propionic acid derivative, is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its spectrum of anti-inflammatory activity has been demonstrated in both in vitro and in vivo models.1 The majority of published clinical trials have focused on the use of oxaprozin (from Searle) in the treatment of osteoarthritis and rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

[Paracetamol dosage for children--different from that for adults].

Paracetamol (acetaminophen) has become the most widely used antipyretic and analgesic drug for children in Denmark. However, there is a wide discrepancy between the consumption of the drug and our knowledge of children's pharmacokinetics and pharmacodynamics. Dosage, therapeutic intervals and toxic potential are different for children and adults. In this review we look at the published guidelines for treating children with paracetamol and the evidence supporting them.

Acetaminophen↗
PubMed1975

[Biology of prostaglandins with reference to therapeutic aspects].

Prostaglandins are highly potent derivatives of unsaturated fatty acids with multiple biological activities. They are synthesized and metabolized in almost all tissues studied so far. The E- und F-type prostaglandins may be regarded as local modulators of hormonal effects on cell function and--in some cases (kidney, uterus-corpus luteum)--as regional or tissue hormones. Thus they seem to be involved in the regulation of neurotransmission, kidney function, triglyceride metabolism in adipose tissue and progesterone biosynthesis. Apart from their influence on renal blood flow prostaglandins of the A-type possibly have an additional function as circulatory hormones regulating blood pressure. Second messenger-systems (cAMP, Ca++-cGMP) which mediate the effects of most non-steroidal hormones are also involved in the action of prostaglandins, at least of the E-and F-types. Disturbances in prostaglandin metabolism (increased or decreased biosynthesis) are discussed to play a role in the pathogenesis of inflammation, pain, fever, hypertension, bronchial asthma and gastric or duodenal ulcer formation. Drugs with antiinflammatory, analgesic and antipyretic activity have been shown to be potent inhibitors of prostaglandin formation. The correlation of a local prostaglandin deficit or the therapeutic use of single effects of prostaglandins by administration of exogenous compounds (natural prostaglandins or modified derivatives) has so long been less satisfactory because of their large number of biological actions which lead to undesired side effects. Extensive experience have been obtained in the successful induction of therapeutic abortion. This effect is based on the stimulatory action of E- and F-type prostaglandins on the smooth muscles of the pregnant uterus which is resistent to the influence of other stimuli, e. g. oxytocin. Here the incidence of side effects could be reduced by local administration of low doses of prostaglandins into the uterine cavity. A general improvement of the therapeutic usefulness of prostaglandins will however only be achieved, if modified derivatives with more specific actions on the desired "target" tissues are available.

Animals↗
PubMedDate not supplied

Juvenile idiopathic arthritis: an update on clinical and therapeutic approaches.

Juvenile idiopathic arthritis represents a heterogeneous group of autoimmune diseases. It arises before 16 years of age and lasts more than 6 months. We can distinguish many arthritis sub-types. A serious problem in juvenile idiopathic arthritis is skeletal growth retardation, osteopenia and greater risk of developing fractures. Juvenile idiopathic arthritis diagnosis is an exclusion diagnosis. Many conditions can simulate it. First-choice drugs in juvenile idiopathic arthritis treatment are nonsteroidal anti-inflammatory drugs, analgesic and antipyretic drugs. The second-choice drugs are "slow-acting" antirheumatic drugs, like methotrexate. The use of glucocorticoids is strongly influenced by their side effects, in particular the inhibition of statural growth and the premature appearance of osteoporosis. Recent findings on the central role of tumor necrosis factor-alpha, in particular damage pathogenesis in the course of juvenile idiopathic arthritis, have permitted the development of new therapeutic strategies (infliximab, etanercept), aimed at blocking this cytokine.

Adolescent↗
PubMed2006

Acute generalized exanthematous pustulosis induced by nimesulide.

Nimesulide is a new nonsteroidal anti-inflammatory (NSAID) drug with antipyretic and analgesic properties. Because of its favorable tolerability profile it appears to be a preferred alternative, especially in NSAID-sensitive patients. We report a case of acute generalized exanthematous pustulosis (AGEP) in a 50-year-old woman that was attributed to the ingestion of nimesulide. To the best of our knowledge there have been no previous reports of AGEP induced by the ingestion of nimesulide in the medical literature. Nimesulide should be added to the list of agents associated with this serious adverse drug reaction.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Inhibitors of cyclooxygenases: mechanisms, selectivity and uses.

The prostaglandins are lipid mediators, discovered in the 1930s by von Euler in Sweden and Goldblatt in the United Kingdom. They are made by the bifunctional enzyme, cyclooxygenase, which has both cyclooxygenase and peroxidase activities in the same molecule. Prostaglandins are involved in physiological functions such as protection of the stomach mucosa, aggregation of platelets and regulation of kidney function. They also have pathological functions such as their involvement in inflammation, fever and pain. Vane in 1971 elegantly showed that the pharmacological actions of aspirin and similar drugs were due to the inhibition of cyclooxygenase. Thus, aspirin-like drugs exert their anti-inflammatory, antipyretic and analgesic effects by inhibition of cyclooxygenase. In 1991, Simmons and his colleagues identified a second cyclooxygenase enzyme, designated cyclooxygenase-2, derived from a separate gene from cyclooxygenase-1. Cyclooxygenase-2 is upregulated by inflammatory mediators and forms prostaglandins which intensify the inflammatory response. Cyclooxygenase-1 is, therefore, a 'housekeeping' enzyme making prostaglandins, which are important for maintaining physiological functions and cyclooxygenase-2 makes prostaglandins which are important in inflammation. The discovery of cyclooxygenase-2 and the establishment of its structure led to the development of selective inhibitors of this enzyme, such as celecoxib and rofecoxib, with potent anti-inflammatory actions but with reduced gastrotoxic effects. A putative cyclooxygenase-3, has also been characterised and cloned. This enzyme is a product of the cyclooxygenase-1 gene, but retains intron 1 after transcription and translates into a cyclooxygenase enzyme with 34 additional amino acids. It is more sensitive to inhibition by paracetamol, aspirin and some other non-steroid anti-inflammatory drugs than cyclooxygenase-1 or cyclooxygenase-2. A cyclooxygenase enzyme induced in cultured cells by some non-steroid anti-inflammatory drugs is also more sensitive to inhibition by paracetamol than cyclooxygenase-2 induced by bacterial lipopolysaccharide.

Animals↗
PubMed1991

5-substituted 4-isoxazolecarboxamides with platelet antiaggregating and other activities.

The synthesis of a series of 5-substituted 4-isoxazolecarboxamides by reaction of eight 5-substituted 4-isoxazolecarbonyl chlorides with pyrrolidine, piperidine, morpholine and 4-trifluoromethylaniline is described. Some of these amides showed platelet antiaggregating activity in vitro slightly inferior to that of acetylsalicylic acid, as well weak antiinflammatory, analgesic and antipyretic activities in rats and mice.

Aniline Compounds↗
PubMed1991

[Clinical study of the efficacy of and tolerance to nimesulide in suppository formulation in pain-inflammatory pathologies of the ear, nose, and throat].

The efficacy and tolerability of a new pharmaceutical form of the non-steroid anti-inflammatory drug. Nimesulide have been studied in a double blind study compared with flurbiprofen, in 98 patients aged between 18 and 75 suffering from pain-inflammatory pathologies of ENT nature. Both drugs, administered in a dose of one suppository twice a day for 7 days, showed marked anti-inflammatory, analgesic and antipyretic activity and produced a significant, progressive improvement in the typical symptoms of the inflammatory state up to their complete remission. Nimesulide evidenced greater speed and duration of therapeutic action. Assessment on the effectiveness and tolerability as expressed separately by the physician and patient were positive in almost all cases of both treatments.

Adult↗