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PubMed2006

Use of nonsteroidal anti-inflammatory drugs in patients with aspirin hypersensitivity : safety of cyclo-oxygenase-2 inhibitors.

This article provides information on the pathogenesis of aspirin hypersensitivity, cross-sensitivity, and cross-tolerance of different NSAIDs in patients with respiratory types of reactions. Hypersensitivity to aspirin may affect 5-20% of patients with chronic asthma and an unknown fraction of patients with chronic urticaria-angioedema. These patients develop cross-reactions to other, chemically non-related, NSAIDs with strong inhibitory activity towards cyclo-oxygenase (COX)-1 (e.g. indomethacin, naproxen, ketoprofen). Avoidance of aspirin and all cross-reacting NSAIDs as well as education of patients are crucial. As an alternative antipyretic or analgesic drug, aspirin-sensitive asthmatic patients may take acetaminophen (paracetamol) in low or moderate doses (<1000mg). Preferential COX-2 inhibitors (nimesulide, meloxicam) are tolerated by the majority but not all hypersensitive patients. Selective COX-2 inhibitors (celecoxib and rofecoxib [withdrawn from the market]) are well tolerated by almost all aspirin-sensitive asthmatic patients. In patients with coronary artery disease requiring treatment with aspirin, desensitization to aspirin may be an alternative approach. Thus, for the majority of patients with asthma and hypersensitivity to aspirin or other NSAIDs, an alternative anti-inflammatory drug can be found. However, in each individual case physicians must consider the choice of an alternative NSAID carefully.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Novel insights and therapeutical applications in the field of inhibitors of COX-2.

The discovery of the two isoenzymes COX-1 and COX-2 and the knowledge of their function, localisation and regulation has initiated the development of COX-2 selective inhibitors (coxibs). Inducible COX-2 at the peripheral site of inflammation has been detected in the early 1990s, the involvement of recently detected spinal COX-2 has led to new insights into mechanisms of pain and may explain analgesic and antipyretic properties of COX-2 selective inhibitors. The coxibs rofecoxib and celecoxib have been introduced into therapy and seem to offer some advantages over the classical non-selective NSAIDs. The search for new COX-2 inhibitors is going on, the development of etoricoxib and lumiracoxib is a step ahead concerning efficacy, tolerability and safety. Until today COX-2 selective inhibitors have found their place in therapy of arthritis, osteoarthritis, dysmenorrhea and acute pain. A new paradigm in pain therapy seems to justify their use in perioperative settings in a preemptive or multimodal therapeutical strategy. In the future COX-2 selective inhibitors as opioid sparing agents could become an important tool in pain therapy. Even a therapeutical benefit of COX-2 selective inhibitors in the treatment of Alzheimer's Disease or in the prevention or treatment of colorectal or prostate cancer is presently intensely investigated. Recently some authors reported on COX-3, a splicing variant of COX-1. If COX-3 really represents the target for acetaminophen must be called into question.

Animals↗
PubMed2004

Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases.

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase (COX), a prostaglandin-synthesizing enzyme. It has also been revealed that NSAIDs exert inhibitory effects on the generating system of nitric oxide radicals and modulating effects on transcription factors which are related to inflammatory reactions including cytokine expression. Recently, a number of studies have been conducted focusing on the neuroprotective effects of NSAIDs, since it has been reported that inflammatory processes are associated with the pathogenesis of several neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. In the experimental model of Parkinson's disease, NSAIDs have also exerted neuroprotective effects which are based not only on their COX-inhibiting effects but also on other properties: inhibitory effects on nitric oxide synthesis, action as agonists for peroxisome proliferator-activated receptor gamma, and some unknown pharmacological effects. In this article, various pharmacological effects of NSAIDs except their inhibitory action on COX are reviewed, and possible neuroprotective effects of NSAIDs have been discussed on neurodegenerative diseases, especially Parkinson's disease.

Animals↗
PubMed2006

Chloroquine resistance reversal agents as promising antimalarial drugs.

The development and spread of resistance to antimalarial drugs poses a severe and increasing public health threat. Failures of prophylaxis or treatment with quinolines, hydroxynaphthoquinones, sesquiterpene lactones, antifolate drugs and sulfamides are involved in a return malaria-related morbidity and mortality. Resistance is associated with a decrease in accumulation of drugs into the vacuole, which results from a reduced uptake of the drug, an increased efflux or a combination of both. A number of candidate genes in P. falciparum have been proposed to be involved in antimalarial resistance, each concerned in membrane transport. Weaker or stronger associations are seen in P. falciparum between the resistance to quinolines or artemisinin derivatives and codon changes in Pfmdr1, a gene which encodes Pgh-1, an ortholog of one of the P-glycoproteins expressed in multi-drug resistant human cancer cells (ABC transporter). Further analysis has revealed a new gene, Pfcrt, encoding a PfCRT protein, which resembles an anion channel. Codon changes found in the Pfcrt sequence in drug resistant isolates could facilitate the drug efflux through a putative channel. It has been proposed that the reversal of quinoline resistance by verapamil is due to hydrophobic binding to the mutated PfCRT protein. Several compounds have demonstrated in the past decade a promising capability to reverse the antimalarial drug resistance in vitro in parasite isolates, in animal models and in human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic and antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and anthracenic derivatives. Here we summarize the progress made in biochemical and genetic basis of antimalarial resistance, emphasizing the recent developments on drugs, which interfere with trans membrane proteins involved in drug efflux or uptake.

Animals↗
PubMed2006

A computational view of COX-2 inhibition.

Selective inhibition of COX-2 provided a new class of anti-inflammatory, analgesic and antipyretic drugs with significantly reduced side effects and could also be an important strategy for preventing or treating a number of cancers. This review illustrates the molecular modeling methods used for the knowledge of the molecular mechanism of inhibition as well as for the design of selective compounds.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Action of drugs and chemical agents on rat liver regeneration.

Chemical agents and drugs of widely differing pharmacological activity have been administered to partially hepatectomized male rats and the extent of liver regeneration ascertained over a period of 10 days. Of the large number investigated, the following fed ad lib in diets supplemented in a basal ration at the weight percentages indicated, proved to be hepatotrophic: anticonvulsants - mephenytoin (0.15), methsuximide (0.15), phensuximide (0.15) and primidone (0.10); benzodiazepines - clobazam (0.10), flurazepam hydrochloride (0.12), halazepam (0.070), oxazepam (0.030) and temazepam (0.10); anti-inflammatory agents - benoxaprofen (0.040), ibuprofen (0.10 and 0.20), naproxen (0.040) and sulindac (0.075); sedatives and hypnotics - ethinamate (0.75), glutethimide (0.075), methaqualone (0.030 and 0.10) and methprylon (0.30) and the analgesic and antipyretic, aminopyrine (0.15); antifungal - griseofulvin (0.50); anti-androgen - cyproterone acetate (0.020 and 0.050); uricosuric - sulfinpyrazone (0.050 and 0.20); skeletal muscle relaxant - chlorzoxazone (0.20); hydrocholeretic - florantyrone (0.30); anti-hypertensive - prazosin hydrochloride (0.010) and the thyroid inhibitor, methimazole (0.025). The feeding of several of the stimulants at the given levels to intact males elicited wet and dry liver enlargement. Most of the current test agents as screened in operated rats, had little effect on the regeneration and in fact, tended to depress the process when higher levels were fed or injected.

Animals↗
PubMed1992

Kinetic and inhibitor studies of acetaminophen and zidovudine glucuronidation in rat liver microsomes.

The antiviral drug zidovudine (ZDV) and the analgesic and antipyretic agent acetaminophen (AP) are both biotransformed in the liver of humans to ether glucuronides. A previous clinical trial of ZDV suggested the potential for a clinically significant interaction between AP and ZDV, probably based upon competing hepatic metabolism. To study the mechanism of this potential competition between AP and ZDV as substrates for uridine diphosphoglucuronyltransferase (UDPGT), enzyme kinetic studies were performed using rat liver microsome preparations. Cross inhibition studies demonstrated that AP glucuronidation was competitively inhibited by ZDV, while ZDV glucuronidation was slightly inhibited by AP in a noncompetitive interaction.

Acetaminophen↗
PubMed1978

Pharmacological properties of diclofenac sodium and its metabolites.

Diclofenac sodium (Voltaren) is a non-steroid anti-inflammatory agent of a new chemical structure, which is animal experiments shows a high degree of anti inflammatory, analgesic, and antipyretic activity in various pharmacological models. It inhibits prostaglandin biosynthesis in vitro and in vivo, and this inhibitory effect at least partly explains the mechanism of action of the preparation. In animal experiments diclofenac sodium is characterised by a broad therapeutic range. Also, its gastrointestinal tolerability is better than that of other highly effective non-steroid anti-inflammatory agents. Two of the metabolites produced during the biotransformation of diclofenac sodium in man are also biologically active. The activity of these two metabolites, however, is very much weaker than that of unchanged diclofenac sodium and is comparable to that of phenylbutazone.

Animals↗
PubMed1996

Parvovirus B19 infection. Associated diseases, common and uncommon.

Parvovirus B19 infection is common worldwide but is often asymptomatic. However, the virus has been implicated in numerous disorders, including aplastic crisis in patients with chronic hemolytic anemia, erythema infectiosum, arthropathy, arthritis, and fetal infections. Diagnostic tests are not routine, but several are available through commercial reference laboratories. Treatment ranges from analgesics and antipyretics for mild and self-limited illness to administration of commercial immunoglobulin preparations and blood transfusion for more serious conditions.

Erythema Infectiosum↗
PubMed2001

Principles of appropriate antibiotic use for acute pharyngitis in adults: background.

The following principles of appropriate antibiotic use for adults with acute pharyngitis apply to immunocompetent adults without complicated comorbid conditions, such as chronic lung or heart disease, and history of rheumatic fever. They do not apply during known outbreaks of group A streptococcus.1. Group A beta-hemolytic streptococcus (GABHS) is the causal agent in approximately 10% of adult cases of pharyngitis. The large majority of adults with acute pharyngitis have a self-limited illness, for which supportive care only is needed.2. Antibiotic treatment of adult pharyngitis benefits only those patients with GABHS infection. All patients with pharyngitis should be offered appropriate doses of analgesics and antipyretics, as well as other supportive care.3. Limit antibiotic prescriptions to patients who are most likely to have GABHS infection. Clinically screen all adult patients with pharyngitis for the presence of the four Centor criteria: history of fever, tonsillar exudates, no cough, and tender anterior cervical lymphadenopathy (lymphadenitis). Do not test or treat patients with none or only one of these criteria, since these patients are unlikely to have GABHS infection. For patients with two or more criteria the following strategies are appropriate: a) Test patients with two, three, or four criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results; b) test patients with two or three criteria by using a rapid antigen test, and limit antibiotic therapy to patients with positive test results or patients with four criteria; or c) do not use any diagnostic tests, and limit antibiotic therapy to patients with three or four criteria. 4. Throat cultures are not recommended for the routine primary evaluation of adults with pharyngitis or for confirmation of negative results on rapid antigen tests when the test sensitivity exceeds 80%. Throat cultures may be indicated as part of investigations of outbreaks of GABHS disease, for monitoring the development and spread of antibiotic resistance, or when such pathogens as gonococcus are being considered.5. The preferred antibiotic for treatment of acute GABHS pharyngitis is penicillin, or erythromycin in a penicillin-allergic patient.

Acute Disease↗
PubMed1977

Acetaminophen.

Acetaminophen is an effective mild analgesic and antipyretic agent. In double-blind, controlled experimental pain studies of short duration, acetaminophen is superior to placebo and produces analgesia comparable to that produced by aspirin. The frequency of adverse reactions to therapeutic doses of acetaminophen is low, as is that of aspirin. Overdosage with acetaminophen, however, may result in irreversible hepatotoxicity. Since clinical manifestations of intoxication can be of slow onset, physicians may tend to delay initiation of definitive therapy. Intravenous cysteamine, and possibly oral methionine, appear to be effective in preventing hepatotoxicity if they are administered with 10 h of drug ingestion. Physicians should be aware of the potential danger of acetaminophen overdosage and alerted to its clinical manifestations.

Acetaminophen↗
PubMed1986

Anti-inflammatory activity of 6MFA, a compound obtained from fungus Aspergillus ochraceus.

6MFA, an interferon-inducing substance obtained from fungus, Aspergillus ochraceus, has shown anti-inflammatory activity both in acute and chronic animal models of inflammation. It was found that 6MFA was equally effective in inhibiting both exudative as well as granulative phase of inflammation. The compound suppressed also cellular migration during inflammatory process and potentiated significantly the anti-inflammatory activity of indomethacin. The compound was devoid of analgesic or antipyretic activity. The probable mechanism of action of this compound is not fully understood. However, the possibility of triggering the induction of endogenous anti-inflammatory substance(s) along with interferon(s), or interaction of induced interferon(s) directly or indirectly with the prostaglandin system has been attributed.

Animals↗
PubMed1998

A study on hemostasis parameters in the neurosurgery of cerebral aneurysms.

BACKGROUND: This prospective study was accomplished with 14 patients, 10 women and 4 men, where some pre-, intra- and immediate postoperative parameters of hemostasis were analyzed and compared to a control group of normal individuals. METHODS: The patients included in this study were admitted to the Hospital das Clinicas at Unicamp in the 1990-1993 period. All the accepted patients have had their latest bleeding at least 30 days before surgery, therefore, after the acute bleeding phase, because in this phase there are alterations in hemostasis. In this period only dipyrone was used in all patients as analgesics and antipyretics. Opiates were used in all the anesthetic proceedings. The following parameters were determined: coagulation; prothrombin time, (PT), thrombin time, (TT), activated partial thromboplastin time, (APTT), platelets (PQ), fibrinogen, (FG) factor V, (F V), protein C, (P C), protein S (PS), antithrombin III (AT III); fibrinolysis, plasminogen (PLG), C 1 inhibitor (C 1), alfa 2 macroglobulin (A2M), prekallikrein (PK), euglobulin lysis time (ELT), lysis area in fibrin plates (LAFP), in 5 of these 14 patients. Activity of both plasminogen tissue activator (t-PA) and plasminogen activator inhibitor (PAI-1) were also determined. For analyze the hepatic function pre-albumin (PRE ALB) was determined. RESULTS AND CONCLUSIONS: In this study, the analysis of LAFP and ELT in the different surgical times suggests that the patients submitted to cerebral aneurysm surgery are head to hypofibrinolysis from the intraoperative to the immediate postoperative period and this evidence do not related whit PAI-1.

Adult↗
PubMed1978

Meseclazone, 5-chlorosalicylic acid and acetylsalicylic acid. Comparison of their effects on in vitro and ex vivo platelet aggregation.

Meseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on pletelet aggregation were evaluated in vitro and ex vivo with acetylsalicylic acid (ASA). In vitro, meseclazone and ASA exhibited almost identical inhibitory potency of secondary phase ADP aggregation while 5-CSA was less effective. Moreover, collagen aggregation was inhibited by all three agents: ASA greater than meseclazone greater than 5-CSA. Thrombin-induced aggregation was inhibited to approximately the same extent by 5-CSA and ASA while meseclazone was inactive. The in vitro effects on the release-inducing aggregants were confirmed by ex vivo experiments in rats. These demonstrated that ASA and meseclazone inhibited collagen-induced aggregation 1 and 4 hr after oral administration although ASA was three to four times more active. ASA, but not meseclazone, was still effective 24 hr after administration. Bleeding times in rats 1 and 4 hr following oral administration of meseclazone and ASA were not altered. It is concluded that meseclazone and/or 5-CSA inhibit in vitro and ex vivo platelet aggregation initiated by the release reaction similar to ASA and other non-steroidal anti-inflammatory drugs.

Adenosine Diphosphate↗
PubMed2000

Nonsteroidal anti-inflammatory drugs: new perspectives on a familiar drug class.

Nonsteroidal anti-inflammatory drugs are among the most commonly used and lethal drug classes. The anti-inflammatory, analgesic, and antipyretic effects result from the inhibition of cyclooxygenase (COX), which is the critical enzyme in the synthesis of prostaglandins. The most common adverse effects are gastrointestinal, but renal and platelet effects are also important. Recent discovery that there are two forms of cyclooxygenase (COX-1 and COX-2) has led to hypothesis that the newly marketed COX-2 selective inhibitor can provide beneficial effects without these adverse effects. Patient monitoring and education are nursing functions essential to the safe use of these agents.

Analgesia↗
PubMedDate not supplied

Preparation of mefenamic acid sustained release beads based on kappa-carrageenan.

Mefenamic acid (MA) is a nonsteroidal anti-inflammatory drug used as analgesic and antipyretic drug. Available conventional pharmaceutical forms are capsules and film-coated tablets given three times a day (t.t.d.). Natural polymers such as sodium alginate, pectin, chitosan and carregeenan, used as barriers to effect the drug release, are those of the main interest of researchers. The aim of the present study was to formulate sustained release MA-beads based on kappa-carrageenan in order to reduce daily dose and to minimize gastrointestinal disturbances caused by the drug.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Defining COX-2 inhibitors.

Arachidonic acid metabolism is governed by 2 isoforms of cyclooxygenase (COX), the constitutively expressed COX-1 and the inducible COX-2. Antiinflammatory, analgesic, and antipyretic effects of nonsteroidal antiinflammatory drugs (NSAID) are explained by the capacity of these agents to inhibit COX-2, whereas the serious gastrointestinal side effects are caused by inhibitors of COX-1. The first of a new class of COX inhibitors, the COX-2 specific inhibitors, has just been approved for the treatment of osteoarthritis (OA) and rheumatoid arthritis (RA). As the clinical outcomes of specific COX-2 inhibitors are considerably different than those of NSAID, it is essential for the clinician to understand the basis of classification of those new, effective, and safer therapeutic agents for the treatment of OA and RA.

Animals↗
PubMed2000

Somatic and skeleton development of rat foetuses following in-utero exposure to isopropylantipyrine (propyphenazone) during the second trimester of gestation.

Isopropylantipyrine (IPA, propyphenazone) is a pyrazolone derivative, widely used as an antipyretic and analgesic drug. The aim of the study was to evaluate the influence of propyphenazone on rat development. IPA was administered to pregnant rats from day 8 to day 14 of pregnancy once a day, orally by a stomach tube at doses of 2.10 (R1), 21.0 (R2), and 210.0 mg/kg/day (R3). The dams were sacrificed on day 21 of gestation and corpora luteum, implants, resorptions, and live foetuses were counted. The weight of foetuses and placentas, the length of foetuses and their tails were checked. The foetuses were fixed in alcohol and skeletons were stained with alizarin. There was a statistical difference in body length in R1, R2 and numbers of subcutaneous ecchymose in R1. External and skeletal examination of the foetuses revealed no evidence of teratogenesis. It can be concluded that IPA has no harmful effects on the prenatal development of the rat offspring at doses used in the present study.

Animals↗