DOCSLIB.ORG

Aspirin and Other Anti-Inflammatory Drugs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Aspirin and Other Anti-Inflammatory Drugs Thorax 2000;55 (Suppl 2):S3–S9 S3 Aspirin and other anti-inflammatory drugs Thorax: first published as 10.1136/thorax.55.suppl_2.S3 on 1 October 2000. Downloaded from Sir John Vane Historical introduction inhibiting COX, thereby reducing prosta- Salicylic acid, the active substance in plants glandin formation, providing a unifying expla- used for thousands of years as medicaments, nation for their therapeutic actions and their was synthesised by Kolbe in Germany in 1874. side eVects. This also firmly established certain MacLagan1 and Stricker2 showed that it was prostaglandins as important mediators of eVective in rheumatic fever. A few years later inflammatory disease (see reviews by Vane and sodium salicylate was also in use as a treatment Botting7 and Vane et al8). COX first cyclises for chronic rheumatoid arthritis and gout as arachidonic acid to form prostaglandin (PG) well as an antiseptic compound. G2 and the peroxidase part of the enzyme then Felix HoVman was a young chemist working reduces PGG2 to PGH2. at Bayer. Legend has it that his father, who was taking salicylic acid to treat his arthritis, Discovery of COX-2 complained to his son about its bitter taste. Over the next 20 years several groups postu- Felix responded by adding an acetyl group to lated the existence of isoforms of COX. Then salicylic acid to make acetylsalicylic acid. Rosen et al,9 studying COX in epithelial cells Heinrich Dreser, the Company’s head of phar- from the trachea, found an increase in activity macology, showed it to be analgesic, anti- of COX during prolonged cell culture. This 3 pyretic, and anti-inflammatory. Bayer intro- increase in activity was not accounted for by an duced the new drug as “aspirin” in 1899 and increase in the known mRNA of 2.8 kb. They sales have increased ever since. found a second mRNA of 4.0 kb and suggested In the latter part of the 20th century several that this was derived from a distinct COX- other non-steroidal anti-inflammatory drugs related gene which encoded for a protein with (NSAIDs) were discovered, including antipy- COX activity. Needleman and his group10–12 rine, phenacetin, phenylbutazone and, more reported that bacterial lipopolysaccharide recently, the fenamates, indomethacin and (LPS) increased the synthesis of prostaglandins naproxen. Despite the diversity of their chemi- in human monocytes in vitro and in mouse cal structures, these drugs all share the same peritoneal macrophages in vivo. This increase, therapeutic properties. They alleviate the but not the basal level of enzyme, was inhibited swelling, redness and pain of inflammation, by dexamethasone and associated with de novo reduce a general fever, and cure a headache. synthesis of new COX protein. This gave rise to They also share, but not equally, a number of the concept of “constitutive” and “inducible” side eVects including damage to the gastric forms of COX. http://thorax.bmj.com/ mucosa, delay in the birth process, and damage The breakthrough came from molecular to the kidney. A particularly interesting “side biologists outside the field of prostaglandins. eVect”, now used prophylactically, is the Simmons et al,13 studying neoplastic transfor- anti-thrombotic eVect. Many clinical trials mation, discovered a second form of COX have shown that aspirin given once a day in induced by v-src, serum, or phorbol esters in doses as low as 75 mg will help to prevent heart chicken embryo cells.13 14 It was encoded by a attacks or strokes. 4.1 kb mRNA similar in size to that reported When a chemically diverse group of drugs by Rosen et al.9 They cloned the gene, deduced on October 1, 2021 by guest. Protected copyright. shares not only the same therapeutic qualities the protein structure, and found it homologous (which in themselves have not much connec- to COX but to no other known protein. tion with each other), but also the same side Herschman and colleagues15 independently eVects, it is a fairly safe bet that their actions are found a similar gene in the mouse, as did Sim- based on a single biochemical intervention. For mons et al,16 O’Banion et al,17 and Sirois and many years pharmacologists and biochemists Richards.18 searched for such a common mode of action COX-1 and COX-2 have molecular weights without finding one that was satisfactory. of 71 kd and a 60% homology. Glucocorticoids It was against this background that, using a inhibit the expression of COX-2 and this is an crude preparation of prostaglandin synthase additional aspect of their anti-inflammatory (now known as cyclo-oxygenase or COX), action. The levels of COX-2, normally very low Vane4 found a dose dependent inhibition of in cells, are tightly controlled by a number of prostaglandin formation by aspirin, salicylate, factors including cytokines, intracellular mes- and indomethacin but not by morphine. Two sengers, and by the availability of substrate. other reports from the same laboratory lent 5 support to his findings. Smith and Willis COX-1 The William Harvey showed that aspirin prevented the release of COX-1 has three folding units: an epidermal Research Institute, prostaglandins from aggregating human plate- growth factor-like domain, a membrane bind- London EC1 6BQ, UK lets and Ferreira et al6 demonstrated that ing section, and an enzymatic domain. The JRVane aspirin-like drugs blocked prostaglandin re- sites for peroxidase and cyclo-oxygenase activ- Correspondence to: lease from the perfused, isolated spleen of the ity are adjacent but spatially distinct. The Sir John Vane dog. Vane4 proposed that all NSAIDs act by enzyme integrates into only a single leaflet of www.thoraxjnl.com S4 Vane the membrane lipid bilayer and thus the muscle cells, pulmonary endothelial cells, and Thorax: first published as 10.1136/thorax.55.suppl_2.S3 on 1 October 2000. Downloaded from position of the COX channel allows arachi- alveolar macrophages treated with LPS or donic acid to gain access to the active site from proinflammatory cytokines. In the carrageenin the interior of the bilayer.19 induced pleurisy model of inflammation, levels NSAIDs compete with arachidonic acid for of COX-2 protein increased maximally at two binding to the active site, thereby excluding hours in the cell pellets of pleural exudate.27 access for the substrate.20 Uniquely, aspirin However, lung tissue can also express COX-2 irreversibly inhibits COX-1 by acetylation of constitutively. COX-2 mRNA is weakly ex- serine 530. COX-1 has clear physiological pressed in unstimulated rat isolated perfused functions. Its activation leads, for instance, to lungs and is upregulated by nitric oxide (NO) the production of prostacyclin which, when donors.28 Human lungs obtained from accident released by the endothelium is victims29 and human cultured pulmonary anti-thrombogenic,21 and when released by the epithelial cells expressed more constitutive gastric mucosa is cytoprotective.22 COX-2 than constitutive COX-1.30 31 Interest- ingly, hypoxia induces COX-2 gene expression COX-2 in isolated perfused lungs of the rat without The structure of COX-223 closely resembles aVecting the mRNA for COX-1.28 This induc- that of COX-1 but, fortunately for the medici- tion of the COX-2 gene by hypoxia was inhib- nal chemist, the binding site for arachidonic ited by NO donors, which may represent one of acid (the COX channel) is slightly diVerent. the mechanisms of the beneficial eVect of The active site of COX-2 is a little larger and inhaled NO in pulmonary hypertension. can accommodate bigger structures than that Inflammatory stimuli cause diVerential re- of COX-1. A secondary internal pocket lease of prostaglandins from various regions of contributes significantly to the larger volume of the lungs. Human cultured pulmonary epithe- the active site of COX-2, although the central lial cells stimulated with LPS, interleukin (IL)- channel is also 17% bigger. 1á, tumour necrosis factor (TNF)á,ora Since COX-2 is induced by inflammatory mixture of cytokines synthesise mainly PGE2 stimuli and by cytokines in migratory and other together with smaller amounts of PGF2á, PGI2, cells, it is attractive to suggest that the and TXA2. This prostaglandin production can anti-inflammatory actions of NSAIDs result be suppressed by dexamethasone32 which indi- from the inhibition of COX-2, whereas the cates that it is caused by COX-2. unwanted side eVects such as damage to the Pollutants such as those in car exhausts can stomach lining are caused by inhibition of the also induce COX-2 in human cultured airway constitutive enzyme, COX-1. This general epithelial cells, resulting in an increased forma- 33 concept is now widely accepted. tion of PGE2 and PGF2á. PGE2 and TXB2,in addition to COX-2 protein, could be detected Functions of COX-1 and COX-2 in the inflammatory exudate produced by LUNGS injection of carrageenin into the rat pleural Prostacyclin is a potent vasodilator of the pul- cavity.34 Thus, it seems likely that COX-2 is monary circulation in humans and other upregulated in the inflamed lungs of asthmatic http://thorax.bmj.com/ species. This endothelium derived prostacyclin patients resulting in increased production of is well placed to function as a local vasodilator bronchoconstrictor prostaglandins which exert and to prevent the formation of micro- an exaggerated eVect on the bronchiolar thrombi.24 smooth muscle that has become hyperreactive Pulmonary blood vessels are constricted by to constrictor agents. PGF2á and thromboxane (TX) A2 but, in some species, they are dilated by PGE2. The ENDOTHELIUM vasoconstrictor responses to PGF2á are potenti- Endothelial cells generate prostacyclin which is on October 1, 2021 by guest. Protected copyright. ated by hypoxia. Mediators of inflammation anti-aggregatory and a vasodilator. They such as bradykinin, histamine, and clearly contain COX-1 but McAdam et al35 and 5-hydroxytryptamine all release prostaglandins Catella-Lawson et al,36 using the selective from lung tissue.
Load more

Recommended publications
  • Non-Steroidal Anti-Inflammatory Agents – Benefits and New Developments for Cancer Pain
    Carr_subbed.qxp 22/5/09 09:49 Page 18 Supportive Oncology Non-steroidal Anti-inflammatory Agents – Benefits and New Developments for Cancer Pain a report by Daniel B Carr1 and Marie Belle D Francia2 1. Saltonstall Professor of Pain Research; 2. Special Scientific Staff, Department of Anesthesiology, Tufts Medical Center DOI: 10.17925/EOH.2008.04.2.18 Pain is one of the complications of cancer that patients most fear, and This article surveys the current role of NSAIDs in the management of its multifactorial aetiology makes it one of the most challenging cancer pain and elucidates newly recognised mechanisms that may conditions to treat.1 A systematic review of epidemiological studies on provide a foundation for the next generation of NSAIDs for analgesia cancer pain published between 1982 and 2001 revealed cancer pain for cancer patients. prevalence rates of at least 14%.2 A more recent systematic review identified prevalence rates of cancer pain in as many as one-third of Mechanism of Analgesic Effects patients after curative treatment and two-thirds of patients NSAIDs are a structurally diverse group of compounds known to undergoing treatment regardless of the stage of disease. The wide prevent the formation of prostanoids (prostaglandins and variation in published prevalence rates is due to heterogeneity of the thromboxane) from arachidonic acid through the inhibition of the populations studied, diverse settings, site of primary cancer and stage enzyme cyclo-oxygenase (COX; see Table 1). COX has two isoenzymes: and methodology used to ascertain prevalence.1 COX-1 is found ubiquitously in most tissues and produces prostaglandins and thromboxane, while COX-2 is located in certain A multimodal approach to the treatment of cancer pain that deploys tissues (brain, blood vessels and so on) and its expression increases both pharmacological and non-pharmacological methods may be during inflammation or fever.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,955,504 Wechter Et Al
    USOO5955504A United States Patent (19) 11 Patent Number: 5,955,504 Wechter et al. (45) Date of Patent: Sep. 21, 1999 54 COLORECTAL CHEMOPROTECTIVE Marnett, “Aspirin and the Potential Role of Prostaglandins COMPOSITION AND METHOD OF in Colon Cancer, Cancer Research, 1992; 52:5575–89. PREVENTING COLORECTAL CANCER Welberg et al., “Proliferation Rate of Colonic Mucosa in Normal Subjects and Patients with Colonic Neoplasms: A 75 Inventors: William J. Wechter; John D. Refined Immunohistochemical Method.” J. Clin Pathol, McCracken, both of Redlands, Calif. 1990; 43:453-456. Thun et al., “Aspirin Use and Reduced Risk of Fatal Colon 73 Assignee: Loma Linda University Medical Cancer." N Engl J Med 1991; 325:1593-6. Center, Loma Linda, Calif. Peleg, et al., “Aspirin and Nonsteroidal Anti-inflammatory Drug Use and the Risk of Subsequent Colorectal Cancer.” 21 Appl. No.: 08/402,797 Arch Intern Med. 1994, 154:394–399. 22 Filed: Mar 13, 1995 Gridley, et al., “Incidence of Cancer among Patients With Rheumatoid Arthritis J. Natl Cancer Inst 1993 85:307-311. 51) Int. Cl. .......................... A61K 31/19; A61K 31/40; Labayle, et al., “Sulindac Causes Regression Of Rectal A61K 31/42 Polyps. In Familial Adenomatous Polyposis” Gastroenterol 52 U.S. Cl. .......................... 514/568; 514/569; 514/428; ogy 1991 101:635-639. 514/416; 514/375 Rigau, et al., “Effects Of Long-Term Sulindac Therapy On 58 Field of Search ..................................... 514/568, 570, Colonic Polyposis” Annals of Internal Medicine 1991 514/569, 428, 416, 375 11.5:952-954. Giardiello.et al., “Treatment Of Colonic and Rectal 56) References Cited Adenomas With Sulindac In Familial Adenomatous Poly U.S.
    [Show full text]
  • Synthesis of Aspirin
    SYNTHESIS OF ASPIRIN I. OBJECTIVES AND BACKGROUND You will: synthesize acetylsalicylic acid (aspirin) by carrying out a simple organic reaction, separate your product from the reaction mixture by vacuum filtration, purify your product by recrystallization, perform a chemical test to identify the change in functional group from reactant to product, and determine the success of your synthesis by calculating the percentage yield of your product. INTRODUCTION Aspirin is one of the most widely used medications in the world. It is employed as an analgesic (pain relief), an anti-pyretic (fever control) and an anti-inflammatory. More recently, studies have indicated that daily intake of small doses of aspirin can lower the risk of heart attack and stroke in high-risk patients. The history of aspirin and its precursor dates back to ancient times. Documents attributed to Hippocrates, the father of modern medicine, from the 4th century B.C. refer to the alleviation of pain by chewing on the bark of a willow tree or ingesting a powder made from the bark and leaves of the willow. This remedy was passed on from generation to generation. Fast forward now to the 19th century, where the field of organic chemistry began to experience tremendous growth. By 1838, chemists had managed to isolate, purify and identify the component of willow bark that provided the analgesic benefit. The compound was named salicylic acid, which was based on the genus name of the willow. Efforts to market salicylic acid met with failure, due to an unfortunate side effect-- prolonged ingestion of salicylic acid led to stomach pain, and in some cases, ulcers.
    [Show full text]
  • Pharmacokinetics of Salicylic Acid Following Intravenous and Oral Administration of Sodium Salicylate in Sheep
    animals Article Pharmacokinetics of Salicylic Acid Following Intravenous and Oral Administration of Sodium Salicylate in Sheep Shashwati Mathurkar 1,*, Preet Singh 2 ID , Kavitha Kongara 2 and Paul Chambers 2 1 1B, He Awa Crescent, Waikanae 5036, New Zealand 2 School of Veterinary Sciences, College of Sciences, Massey University, Palmerston North 4474, New Zealand; [email protected] (P.S.); [email protected] (K.K.); [email protected] (P.C.) * Correspondence: [email protected]; Tel.: +64-221-678-035 Received: 13 June 2018; Accepted: 16 July 2018; Published: 18 July 2018 Simple Summary: Scarcity of non-steroidal anti-inflammatory drugs (NSAID) to minimise the pain in sheep instigated the current study. The aim of this study was to know the pharmacokinetic parameters of salicylic acid in New Zealand sheep after administration of multiple intravenous and oral doses of sodium salicylate (sodium salt of salicylic acid). Results of the study suggest that the half-life of the drug was shorter and clearance was faster after intravenous administration as compared to that of the oral administration. The minimum effective concentration required to produce analgesia in humans (16.8 µL) was achieved in sheep for about 0.17 h in the current study after intravenous administration of 100 and 200 mg/kg body weight of sodium salicylate. However, oral administration of these doses failed to achieve the minimum effective concentration as mentioned above. This study is of significance as it adds valuable information on pharmacokinetics and its variation due to breed, species, age, gender and environmental conditions.
    [Show full text]
  • What Are the Acute Treatments for Migraine and How Are They Used?
    2. Acute Treatment CQ II-2-1 What are the acute treatments for migraine and how are they used? Recommendation The mainstay of acute treatment for migraine is pharmacotherapy. The drugs used include (1) acetaminophen, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans and (5) antiemetics. Stratified treatment according to the severity of migraine is recommended: use NSAIDs such as aspirin and naproxen for mild to moderate headache, and use triptans for moderate to severe headache, or even mild to moderate headache when NSAIDs were ineffective in the past. It is necessary to give guidance and cautions to patients having acute attacks, and explain the methods of using medications (timing, dose, frequency of use) and medication use during pregnancy and breast-feeding. Grade A Background and Objective The objective of acute treatment is to resolve the migraine attack completely and rapidly and restore the patient’s normal functions. An ideal treatment should have the following characteristics: (1) resolves pain and associated symptoms rapidly; (2) is consistently effective; (3) no recurrence; (4) no need for additional use of medication; (5) no adverse effects; (6) can be administered by the patients themselves; and (7) low cost. Literature was searched to identify acute treatments that satisfy the above conditions. Comments and Evidence The acute treatment drugs for migraine generally include (1) acetaminophens, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans, and (5) antiemetics. For severe migraines including status migrainosus and migraine attacks refractory to treatment, (6) anesthetics, and (7) corticosteroids (dexamethasone) are used (Tables 1 and 2).1)-9) There are two approaches to the selection and sequencing of these medications: “step care” and “stratified care”.
    [Show full text]
  • Use of Aspirin and Nsaids to Prevent Colorectal Cancer
    Evidence Synthesis Number 45 Use of Aspirin and NSAIDs to Prevent Colorectal Cancer Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-02-0021 Prepared by: University of Ottawa Evidence-based Practice Center at The University of Ottawa, Ottawa Canada David Moher, PhD Director Investigators Alaa Rostom, MD, MSc, FRCPC Catherine Dube, MD, MSc, FRCPC Gabriela Lewin, MD Alexander Tsertsvadze, MD Msc Nicholas Barrowman, PhD Catherine Code, MD, FRCPC Margaret Sampson, MILS David Moher, PhD AHRQ Publication No. 07-0596-EF-1 March 2007 This report is based on research conducted by the University of Ottawa Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0021). Funding was provided by the Centers for Disease Control and Prevention. The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment. This document is in the public domain and may be used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders.
    [Show full text]
  • WO 2009/145921 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 3 December 2009 (03.12.2009) W O 2009/145921 A l (51) International Patent Classification: (74) Agents: CASSIDY, Martha et al; Rothwell, Figg, Ernst A61K 31/445 (2006.01) 67UT37/407 (2006.01) & Manbeck, P.C., 1425 K Street, N.W., Suite 800, Wash A61K 31/4545 (2006.01) 67UT 37/79 (2006.01) ington, DC 20005 (US). 67UT 37/55 (2006.01) A61K 31/18 (2006.01) (81) Designated States (unless otherwise indicated, for every 67UT 37/495 (2006.01) 67UT 37/54 (2006.01) kind of national protection available): AE, AG, AL, AM, 67UT 37/60 (2006.01) A61P 17/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, 67UT 37/796 (2006.01) 67UT 45/06 (2006.01) CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, 67UT 37/405 (2006.01) EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) International Application Number: HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, PCT/US2009/003320 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, (22) International Filing Date: NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, 1 June 2009 (01 .06.2009) SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, (25) Filing Language: English UG, US, UZ, VC, VN, ZA, ZM, ZW.
    [Show full text]
  • Native State Stabilization by Nsaids Inhibits Transthyretin Amyloidogenesis from the Most Common Familial Disease Variants
    Laboratory Investigation (2004) 84, 545–552 & 2004 USCAP, Inc All rights reserved 0023-6837/04 $25.00 www.laboratoryinvestigation.org Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants Sean R Miller, Yoshiki Sekijima and Jeffery W Kelly Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA Transthyretin (TTR) tetramer dissociation and misfolding affords a monomeric amyloidogenic intermediate that misassembles into aggregates including amyloid fibrils. Amyloidogenesis of wild-type (WT) TTR causes senile systemic amyloidosis (SSA), whereas fibril formation from one of the more than 80 TTR variants leads to familial amyloidosis, typically with earlier onset than SSA. Several nonsteroidal anti-inflammatory drugs (NSAIDs) stabilize the native tetramer, strongly inhibiting TTR amyloid fibril formation in vitro. Structure-based designed NSAID analogs are even more potent amyloid inhibitors. The effectiveness of several NSAIDs, including diclofenac, diflunisal, and flufenamic acid, as well as the diclofenac analog, 2–[(3,5-dichlorophenyl) amino] benzoic acid (inhibitor 1), has been demonstrated against WT TTR amyloidogenesis. Herein, the efficacy of these compounds at preventing acid-induced fibril formation and urea-induced tetramer dissociation of the most common disease-associated TTR variants (V30M, V122I, T60A, L58H, and I84S) was evaluated. Homotetramers of these variants were employed for the studies within, realizing that the tetramers in compound heterozygote patients are normally composed of a mixture of WT and variant subunits. The most common familial TTR variants were stabilized substantially by flufenamic acid and inhibitor 1, and to a lesser extent by diflunisal, against acid-mediated fibril formation and chaotrope denaturation, suggesting that this chemotherapeutic option is viable for patients with familial transthyretin amyloidosis.
    [Show full text]
  • Sodium-Salicylate-European-Public-Mrl-Assessment-Report-Epmar-Committee-Veterinary
    27 October 2010 EMA/CVMP/562066/2007 Veterinary Medicines and Product Data Management Committee for Medicinal Products for Veterinary Use European public MRL assessment report (EPMAR) Sodium salicylate (turkeys) On 12 October 2010 the European Commission adopted a Regulation1 establishing provisional maximum residue limits for sodium salicylate in turkeys, valid throughout the European Union. These provisional maximum residue limits were based on the favourable opinion and the assessment report adopted by the Committee for Medicinal Products for Veterinary Use. In turkeys, sodium salicylate is intended for use orally as an antipyretic in the treatment of acute respiratory diseases. Sodium salicylate was previously assessed for the purpose of establishing maximum residue limits and was entered in Annex II of Regulation (EEC) No 2377/902 (no MRL required) for topical use in all food producing species except fish and for oral use in bovine and porcine species. Chevita Tierarzneimittel GmbH submitted to the European Medicines Agency on 4 January 2007 an application for the extension of existing entry in Annex II of Regulation (EEC) No 2377/90 for sodium salicylates to turkeys. On 12 December 2007 the Committee for Medicinal Products for Veterinary Use adopted an opinion recommending the amendment of the entry in Annex II of Regulation (EEC) No 2377/90 to include sodium salicylate for oral use in turkeys. The European Commission subsequently returned the opinion to the Committee to consider whether its opinion should be reviewed to take into account issues raised during the Commission’s inter service consultation and in particular to consider whether establishment of maximum residue limits for sodium salicylate in turkeys should be established.
    [Show full text]
  • Efficacy and Safety of Celecoxib
    ORIGINAL PAPER Nagoya J. Med. Sci. 77. 81 ~ 93, 2015 EFFICACY AND SAFETY OF CELECOXIB COMPARED WITH PLACEBO AND ETODOLAC FOR ACUTE POSTOPERATIVE PAIN: A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP, CONTROLLED TRIAL NAOKI ISHIGURO1, MD, PhD; AKIO HANAOKA2, MS; TOSHIYUKI OKADA2, MS; and MASANORI ITO3, PhD 1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 2Clinical Development 1, Astellas Pharma Inc., Tokyo, Japan 3Global Data Science, Astellas Pharma Global Development Inc., Northbrook, IL, US ABSTRACT Celecoxib is a nonsteroidal anti-inflammatory drug (selective cyclooxygenase-2 inhibitor) that is widely used. The efficacy and safety of celecoxib for treatment of acute postoperative pain were evaluated in Japanese patients. The objective was to assess whether celecoxib showed superiority over placebo treatment and non-inferiority versus etodolac (another selective cyclooxygenase-2 inhibitor) that has been widely used for the management of acute pain. A multicenter, double-blind, randomized, parallel-group, controlled study was performed, in which 616 patients with postoperative pain received celecoxib, etodolac, or placebo. Their impressions of study drug efficacy (overall assessment) and pain intensity were evaluated. Based on each patient’s overall assessment of pain, the efficacy rate was 63.7% in the placebo group, 76.2% in the celecoxib group, and 68.0% in the etodolac group, with these results demonstrating superiority of celecoxib to placebo and noninferiority versus etodolac. The efficacy rate was significantly higher in the celecoxib group than in the etodolac group. There were no adverse events specific to celecoxib, and the safety of celecoxib was similar to that of placebo. Celecoxib was superior to etodolac for controlling acute postoperative pain.
    [Show full text]
  • New Restrictions on Celecoxib (Celebrex) Use and the Withdrawal of Valdecoxib (Bextra)
    Early release, published at www.cmaj.ca on April 15, 2005. Subject to revision. HEALTH AND DRUG ALERTS P RACTICE New restrictions on celecoxib (Celebrex) use and the withdrawal of valdecoxib (Bextra) Early release, published at www.cmaj.ca on Apr. 15, 2005. Subject to revision. Reason for posting: Coxibs, v. 0.5%; risk ratio 3.7, 95% CI the class of NSAIDs that selec- 1.0–13.5).2 Amid concerns about Table 1: The degree of inhibition of COX-2 relative tively inhibit cyclooxygenase 2 reports of severe cutaneous reac- to COX-1 for various NSAIDs (COX-2), were designed to re- tions (Stevens–Johnson syn- NSAID type COX-2 selectivity* duce joint pain and inflamma- drome, erythema multiforme, tion without causing the gastric toxic epidermal necrolysis) COX-2 selective inhibitors epithelial adverse effects typical among patients taking valde- Rofecoxib 80 of nonselective NSAIDs. Rofe- coxib,5 the drug was removed Etodolac 23 coxib (Vioxx) was withdrawn from the market. Meloxicam 11 from the market in September Celecoxib 9 2004 over concerns about car- What to do: COX-2 inhibitors Nonselective NSAIDs diovascular adverse effects, and appear to increase the risk of car- Diclofenac 4 key safety trials involving cele- diovascular adverse events in a Sulindac 3 coxib (Celebrex)1 and valdecoxib dose-related fashion, and all pa- Piroxicam 2 (Bextra)2 have recently been tients should be informed of this. Ibuprofen 0.4 published. Health Canada now Calculating the patient’s baseline Naproxen 0.3 recommends new restrictions on risk of cardiovascular disease Indomethacin 0.2 celecoxib use, and valdecoxib (e.g., with Framingham risk cal- Ketorolac 0.003 has been taken off the market.3 culators) may be wise, and cele- Note: COX = cyclooxygenase.
    [Show full text]
  • Nsaids: Dare to Compare 1997
    NSAIDs TheRxFiles DARE TO COMPARE Produced by the Community Drug Utilization Program, a Saskatoon District Health/St. Paul's Hospital program July 1997 funded by Saskatchewan Health. For more information check v our website www.sdh.sk.ca/RxFiles or, contact Loren Regier C/O Pharmacy Department, Saskatoon City Hospital, 701 Queen St. Saskatoon, SK S7K 0M7, Ph (306)655-8506, Fax (306)655-8804; Email [email protected] We have come a long way from the days of willow Highlights bark. Today salicylates and non-steroidal anti- • All NSAIDs have similar efficacy and side inflammatory drugs (NSAIDs) comprise one of the effect profiles largest and most commonly prescribed groups of • In low risk patients, Ibuprofen and naproxen drugs worldwide.1 In Saskatchewan, over 20 may be first choice agents because they are different agents are available, accounting for more effective, well tolerated and inexpensive than 300,000 prescriptions and over $7 million in • Acetaminophen is the recommended first line sales each year (Saskatchewan Health-Drug Plan agent for osteoarthritis data 1996). Despite the wide selection, NSAIDs • are more alike than different. Although they do Misoprostol is the only approved agent for differ in chemical structure, pharmacokinetics, and prophylaxis of NSAID-induced ulcers and is to some degree pharmacodynamics, they share recommended in high risk patients if NSAIDS similar mechanisms of action, efficacy, and adverse cannot be avoided. effects. week or more to become established. For this EFFICACY reason, an adequate trial of 1-2 weeks should be NSAIDs work by inhibiting cyclooxygenase (COX) allowed before increasing the dose or changing to and subsequent prostaglandin synthesis as well as another NSAID.
    [Show full text]