DOCSLIB.ORG

Vol-7 (1) 2006 BSM.Pmd

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Vol-7 (1) 2006 BSM.Pmd J MEDICINE 2006; 7 : 20-31 REVIEW ARTICLES NON STEROIDAL ANTI INFLAMMATORY DRUGS- AN OVERVIEW M MATIUR RAHMAN1, MD. BILLAL ALAM2, LT. COL. MD. AZIZUL ISLAM3, AKM AMINUL HAQUE4 Epidemiology from the cell membrane phospholipids by a cascade of More than 20 million Americans use various different enzymes. The sequence starts with release of nonsteroidal anti-inflammatory drugs (NSAIDs) on a arachidonic acid from the cell membrane by regular basis, making this class of drugs one of the Phospholipase-A2. Arachidonic acid is then converted most commonly used. Approximately 1 to 2 percent by cyclo oxygenase to prostaglandins, prostacyclin, and of patients taking NSAIDS will develop serious thromboxanes 8. The Cox-1 gene was cloned and gastrointestinal toxicity, which has resulted in 100,000 sequenced in 1988 and in 1991, a second cyclooxygenase to 400,000 hospitalizations per year in the United gene was identified. Celecoxib, the first Cox-2 selective States at a cost of over 2 billion dollars 1-3. In the NSAID got the US FDA approval in 19988-9. United States, 10 to 20,000 peoples died every year of NSAID complications. There are at least 2600 excess Mechanism of action deaths in the United States each year related to Cyclooxygenase inhibition – The primary effect of NSAIDs gastrointestinal toxic reactions in patients with is to inhibit cyclooxygenase (prostaglandin synthase), Rheumatoid Arthritis (RA) who are treated with thereby impairing the ultimate transformation of NSAIDs 4-5. A variety of NSAIDs are readily available arachidonic acid to prostaglandins, prostacyclin, and (at least 20 in the United States and more elsewhere) thromboxanes. The extent of enzyme inhibition varies 6-7 and widely used throughout the world . Although, among the different NSAIDS, although there are no steroid and some other drugs (e.g. Tramadol) have studies relating the degree of cyclooxygenase inhibition value in reducing pain of RA, the content of this article with antiinflammatory efficacy in individual will be limited to NSAIDs only. patients 10. History Two related isoforms of the cyclooxygenase (COX) The first effective analgesic documented in history was enzyme have been described: COX-1 (PGHS-1); and the powder of dried myrtle leaves used in Egypt in COX-2 (PGHS-2). The most important differences 1500 BC. Hippocrates recommended the use of the juice between the two isoforms are the regulation and of the willow and poplar bark for this purpose. In 1763, expression of the enzymes in various tissues: Edward Stone established the efficacy of willow bark • COX-1 is expressed in most tissues, but variably. extract in relieving pain with the help of a clinical trial. It is described as a “housekeeping” enzyme, Salicylic acid was first synthesized in 1860 and it was regulating normal cellular processes (such as shown that all these myrtle leaves, willow and poplar gastric cytoprotection, vascular homeostasis, barks contained salicylic acid. Aspirin, the magic drug platelet aggregation, and kidney function), and of this age, was first synthesized in 1899. Several is stimulated by hormones or growth factors. reports published almost simultaneously in 1971 established that aspirin acted by reducing the • COX-2 is usually undetectable in most tissues; concentration of prostaglandins. More than 25 years its expression is increased during states of ago, Sir John Vane showed that NSAIDs inhibited the inflammation, or experimentally in response to biosynthesis of prostaglandins - mediators of mitogenic stimuli. COX-2 is constitutively inflammation, by inhibiting the key enzyme, expressed in the brain, kidney, bone, and probably prostaglandin endo peroxide synthase or in the female reproductive system. Another cyclooxygenase (Cox) and proposed this as their distinguishing characteristic of COX-2 is that its mechanism of action. He proposed that the same expression is inhibited by glucocorticoids. This mechanism was responsible for the various beneficial observation may contribute to the significant anti- and toxic effects of NSAIDs. Prostaglandins are derived inflammatory effects of the glucocorticoids. 1. Assistant Professor, Department of Medicine, Sir Salimullah Medical College, Dhaka. 2. Associate Professor, Department of Medicine, Dhaka Medical College, Dhaka. 3. Medicine Specialist, CMH, Bogra Cantonment, Bogra. 4. Associate Professor, Department of Medicine, Mymensingh Medical College, Mymensingh. JM Vol. 7, No. 1 Non Steroidal Anti Inflammatory-An Overview Thus, differences in the effectiveness with which a percent of patients who take both over-the- particular NSAID inhibits an isoform of counter (OTC) and prescription NSAIDs. cyclooxygenase may affect both its activity and • Nausea and vomiting – These symptoms may or toxicity. It has been proposed that the perfect NSAID may not be directly related to a local mucosal would inhibit the inducible COX-2 isoform (thereby irritation. The exact incidence with which they decreasing inflammation) without having any effect occur is unknown. on the constitutive COX-l isoform (thereby minimizing toxicity). Three selective COX-2 • Esophagitis – Esophagitis is a relatively common inhibitors, celecoxib, rofecoxib, and valdecoxib have problem that can lead to stricture formation. received approval from the Food and Drug • Peptic ulcers – Gastric ulcers are far more Administration (FDA). These drugs have at least 200 common than duodenal ulcers in patients treated to 300 fold selectivity for inhibition of COX-2 over with NSAIDs. The point prevalence rate for COX-1. COX-2 inhibitors have not been approved for gastric ulcers among NSAID users as use in children 10-13. determined by endoscopic trials is 15 to 30 percent, 10 times that for duodenal ulcers. Both Classification of NSAIDs types of ulcer are usually asymptomatic, and 1. Drug with analgesic and weak anti inflammatory many do not become clinically significant. effect – Aniline derivative. Paracetamol. • Gastrointestinal hemorrhage – The incidence of 2. Drugs with analgesic and mild to moderate anti- NSAID-induced gastrointestinal hemorrhage is inflammatory effect. difficult to define. The published NSAID-induced a. Propionic acid derivatives : Ibuprofen, gastrointestinal complication rate varies from Fenbufen, Fenoprofen, Ketoprofen, 0.1 to 4 percent per year 14; many of these Neproxen patients are bleeding because of NSAID use. b. Fenamic acid derivative : Mefenamic acid. • Gastrointestinal perforation – Perforation is the 3. Drugs with analgesic and marked anti- rarest of the NSAID-induced gastrointestinal inflammatory effect complications; the exact incidence is unknown. a. Salicylic acid derivatives : Aspirin, Salsalate, Mechanism of gastrodeudenal toxicity – An Sodium salicyclate understanding of the mechanism by which NSAIDs b. Pyrazolone derivatives : Azapropazone, induce gastrointestinal mucosal damage requires an Phenyl butazone understanding of normal gastric anatomy and c. Acetic acid derivatives : Diclofenac, Etodolac, physiology. The stomach is richly endowed with a Fenclofenac multilayered protective barrier which includes 17,20 d. Indole derivatives : Indomethacin, Sulindac • A thick layer of hydrophobic mucous. e. Oxicam derivative : Piroxicam • Substantial glutathione to scavenge any 4. Cox-2 Inhibitors : Celecoxib, Etoricoxib, superoxide radicals generated. Meloxicam • Bicarbonate secreted by the superficial lining Adverse effects cells which serves to buffer acid that penetrates The widespread use of these drugs has led to the through the mucous barrier. recognition of numerous associated adverse effects. The most important complications are: • Tight junctions between cells of the superficial lining. Gastroduodenal toxicity • A significant blood supply, which maintains the NSAIDs can induce both unimportant and important highly metabolic activity of the superficial lining, effects in the gastroduodenum 14-22. A variety of cells. symptoms and signs are commonly associated with NSAID-induced gastrointestinal toxicity. In addition, prostaglandins modulate the amount of gastric acid generated, regulate the integrity of the • Dyspepsia – Some believe that dyspepsia is the mucous barrier, the amount of bicarbonate and most common problem, affecting up to 50 glutathione generated, and the amount of mucosal 21 JM Vol. 7, No. 1 Non Steroidal Anti Inflammatory-An Overview blood flow. Thus, it is not surprising that ulcer are also infected with Helicobacter pylori. There prostaglandin inhibition by a NSAID might lead to is little correlation between the majority of gastrointestinal toxicity. symptoms induced by NSAIDs and pathologic changes 24. However, local esophageal disease due to NSAIDs The NSAIDs are all weak organic acids except for appears to be correlated with symptoms 25. nabumetone. As a result, most of the NSAIDs that are not enteric coated are uncharged in the acid Risk of gastrointestinal toxicity – One important milieu of the stomach lumen. They are therefore determinant is the duration of therapy. The able to rapidly penetrate the hydrophobic mucous administration of NSAIDs for a short period of time barrier and enter the superficial lining cells 17,20. (less than one week) in healthy people is unlikely to Inhibition of prostaglandin synthesis in the mucosa result in any significant gastroduodenal toxicity 25- allows these drugs to degrade the integrity of the 30. In contrast, longer duration of therapy is barrier that normally prevents gastric acid from associated with an increased risk of developing reaching the cells, to reduce
Load more

Recommended publications
  • Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-Ones and 1,3,4- Oxadiazole-2-Thiones
    Scientia Pharmaceutica (Sci. Pharm.) 71,331-356 (2003) O Osterreichische Apotheker-Verlagsgesellschaft m. b.H., Wien, Printed in Austria Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4- Oxadiazole-2-thiones Aida A. ~l-~zzoun~'*,Yousreya A ~aklad',Herbert ~artsch~,~afaaA. 2aghary4, Waleed M. lbrahims, Mosaad S. ~oharned~. Pharmaceutical Sciences Dept. (Pharmaceutical Chemistry goup' and Pharmacology group2), National Research Center, Tahrir St. Dokki, Giza, Egypt. 3~nstitutflir Pharmazeutische Chemie, Pharrnazie Zentrum der Universitilt Wien. 4~harmaceuticalChemistry Dept. ,' Organic Chemistry Dept. , Helwan University , Faculty of Pharmacy, Ein Helwan Cairo, Egypt. Abstract A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate) , antiinflammatory (carrageenin induced rat's paw edema) and ulcerogenic effects as well as plasma prostaglandin E2 (PGE2) level. The highest analgesic activity was achieved with compound 5a (0.5 ,0.6 ,0.7 mrnolkg b.wt.) in respect with mefenamic acid (0.4 mmollkg b.wt.). Compounds 6h, 61 and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat's paw edema at dose level of O.lrnrnol/kg b.wt, compared with 58% inhibition of mefenamic acid (0.2mmoll kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE2 level was displayed also with 6h, 61 and 5g (71, 70,68.5% respectively, 0.lmmolkg b.wt.) compared with indomethacin (60%, 0.01 mmolkg b.wt.) as a reference drug.
    [Show full text]
  • United States Patent (19) 11 4,360,518 Rovee Et Al
    United States Patent (19) 11 4,360,518 Rovee et al. 45) Nov. 23, 1982 54 TOPICAL ANTI-INFLAMMATORY DRUG Primary Examiner-Stanley J. Friedman THERAPY . 57) ABSTRACT 75) Inventors: David T. Rovee, Bridgewater; John A pharmaceutical composition for topical treatment of R. Marvel; James A. Mezick, both of cutaneous disorders or disruptions characterized by East Brunswick, all of N.J. skin inflammation or hyperproliferative epidermal ac 73) Assignee: Johnson & Johnson, New Brunswick, tivity comprises the combination of a topically active N.J. anti-inflammatory corticosteroid and a non-steroidal 21 Appl. No.: 244,569 anti-inflammatory agent which is an inhibitor of prosta glandin synthetase selected from the group consisting of 22 Filed: Mar. 17, 1981 the hydratropic acid derivatives; acetylsalicylic acid; the pyrazolone derivatives; the fenamic acid deriva Related U.S. Application Data tives; the aroyl-substituted pyrroles and the substituted 60) Division of Ser. No. 64,311, Aug. 6, 1979, abandoned, arylacetohydroxamic acids in a pharmaceutically ac which is a division of Ser. No. 788,453, Apr. 20, 1977, ceptable topical vehicle. Treatment of above cutaneous Pat. No. 4,185, 100, which is a continuation-in-part of disorders may also be effected by concurrent therapy Ser. No. 685,942, May 13, 1976, abandoned. using separate applications of corticosteroid and non 51) Int. Cl. ...................... A61K 31/19; A61K 31/56 steroid. (52) U.S. Cl. ..................................... 424/240; 424/317 58) Field of Search ................................ 424/317, 240 18 Claims, No Drawings 4,360,518 1 2 Ziboh, V. A. and Snyder, D. S. 1974 Naturally occur TOPICAL ANTI-NFLAMMATORY ORUG ring and synthetic inhibitors of prostaglandin synthetase THERAPY of the skin.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,221,377 B1 Meyer (45) Date of Patent: Apr
    USOO6221377B1 (12) United States Patent (10) Patent No.: US 6,221,377 B1 Meyer (45) Date of Patent: Apr. 24, 2001 (54) ADMINISTRATION MEDIA FOR (56) References Cited ANALGESIC, ANTI-INFLAMMATORY AND ANT-PYRETC DRUGS CONTAINING FOREIGN PATENT DOCUMENTS NITROUS OXDE AND PHARMACEUTICAL 2 277 264 10/1994 (GB). COMPOSITIONS CONTAINING SUCH MEDIA AND DRUGS OTHER PUBLICATIONS (75) Inventor: Petrus Johannes Meyer, Randburg Chemical ABstracts AN 1985:464783, Hertz et al., Jan. (ZA) 1985.* Chemical Abstracts AN 1978:44978, Berkowitz et al., Jan. (73) Assignee: Pitmy International N.V., Bonaire 1977.* (NL) International Publication No. WO93/25213, published Dec. 23, 1993. (*) Notice: Subject to any disclaimer, the term of this Mikrochim. Acta, vol. 2, No. 5-6, 1980 pp. 464–474, Stahl patent is extended or adjusted under 35 et al., Extraction of natural Substances using Supercritical U.S.C. 154(b) by 0 days. and liquified gases. (21) Appl. No.: 09/068,543 Reynolds J.E.F. et al., “Martindale', 1989, The Pharmaceu tical Press. (22) PCT Filed: Nov. 13, 1996 Science, vol. 194, No. 4268, 1976, pp. 967–968, Berkowitz (86) PCT No.: PCT/IB96/01366 et al., "Nitrous oxide “analgesia': resemblance to opiate action'. S371 Date: May 13, 1998 Steinegger et al., “Lehrbuch der Pharmakognosie und Phy S 102(e) Date: May 13, 1998 topharmazie', Edition 4, 1988. (87) PCT Pub. No.: WO97/17978 * cited by examiner PCT Pub. Date: May 22, 1997 Primary Examiner Jyothsna Venkat (30) Foreign Application Priority Data ASSistant Examiner-Grace Hsu (74) Attorney, Agent, or Firm-Arent Fox Kintner Plotkin Nov. 13, 1995 (ZA) ...................................................
    [Show full text]
  • Objective Salicylate Propionic Acid Derivatives Acetic Acid
    Semester-IV Sub Name-medicinal chemistry-I (sub code-BP-402T) Objective Sodium salicylate, Aspirin, Mefenamic acid*, Meclofenamate, Indomethacin, Sulindac, Tolmetin, Zomepriac, Diclofenac, Ketorolac, Ibuprofen*, Naproxen, Piroxicam, Phenacetin, Acetaminophen, Antipyrine, Phenylbutazone. 1. INTRODUCTION A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti- inflammatory agents block certain substances in the body that cause inflammation. They are used to treat many different conditions. Some anti-inflammatory agents are being studied in the prevention and treatment of cancer. 1.1 CLASSIFICATION NSAIDs can be classified based on their chemical structure or mechanism of action. Older NSAIDs were known long before their mechanism of action was elucidated and were for this reason classified by chemical structure or origin. Newer substances are more often classified by mechanism of action. Salicylate • Aspirin (acetylsalicylic acid) • Diflunisal (Dolobid) • Salicylic acid and its salts Propionic acid derivatives • Ibuprofen • Dexibuprofen • Naproxen • Fenoprofen • Ketoprofen • Dexketoprofen Acetic acid derivatives • Indomethacin • Tolmetin • Sulindac • Ketorolac • Diclofenac • Aceclofenac • Nabumetone (drug itself is non-acidic but the active, principal metabolite has a carboxylic acid group) Enolic acid (oxicam) derivatives • Piroxicam • Meloxicam • Tenoxicam • Droxicam • Lornoxicam • Isoxicam (withdrawn from market 1985) • Phenylbutazone Anthranilic acid derivatives (fenamates) The following NSAIDs are
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,852,615 B1 Harrison Et Al
    USOO8852615B1 (12) United States Patent (10) Patent No.: US 8,852,615 B1 Harrison et al. (45) Date of Patent: *Oct. 7, 2014 (54) CLEAR, GREASELESS SKIN-CARE 4,935,224 A 6, 1990 Russo et al. COMPOSITIONS 4,997,853. A 3, 1991 Bernstein 5,013,726 A 5/1991 Ivy et al. 5,082,661 A 1/1992 Melnik et al. (75) Inventors: James Jeffries Harrison, West Hills, 5,124,320 A 6/1992 Ivy et al. CA (US); Nohemi Harrison, West Hills, 5,607,980 A 3, 1997 McAtee et al. CA (US) 5,759,529 A 6/1998 LeGrow et al. 5,856,361 A 1/1999 Holt et al. 5,916,548 A 6/1999 Hutchins et al. (73) Assignee: Chemsil Silicones, Inc., Chatsworth, CA 5,993,837 A 11/1999 Calello et al. (US) 6,103,266 A 8/2000 Tapolsky et al. 6,106,820 A 8/2000 Morrissey et al. (*) Notice: Subject to any disclaimer, the term of this 6,124,490 A 9/2000 Gormley et al. patent is extended or adjusted under 35 6,296,880 B1 10/2001 Murad U.S.C. 154(b) by 0 days. 6,338,855 B1 1/2002 Albacarys et al. 6,348,501 B1 2/2002 Holt et al. This patent is Subject to a terminal dis 6,372,234 B1 4/2002 Deckers et al. claimer. 6,383,523 B1 5, 2002 Murad 6,384,023 B2 5/2002 Singleton et al. 6,403,069 B1 6/2002 Chopra et al. (21) Appl.
    [Show full text]
  • Solubility and Dissolution Thermodynamic Data of Mefenamic Acid Crystals in Different Classes of Organic Solvents
    Article pubs.acs.org/jced Solubility and Dissolution Thermodynamic Data of Mefenamic Acid Crystals in Different Classes of Organic Solvents Siti K. Abdul Mudalip,†,‡ Mohd R. Abu Bakar,*,§ Parveen Jamal,† and Fatmawati Adam‡ † Department of Biotechnology Engineering, Kulliyyah of Engineering, International Islamic University Malaysia, 50728 Kuala Lumpur, Malaysia ‡ Department of Chemical Engineering, Faculty of Chemical Engineering & Natural Resources, University Malaysia Pahang, Gambang, 26300 Kuantan, Pahang, Malaysia § Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia ABSTRACT: Different classes of solvents provide different polarity values, which influence the solubility of pharmaceutical solids. In this article, the solubility of mefenamic acid in different classes of organic solvents, including polar protic, dipolar aprotic, and apolar aprotics at a range of temperatures from (298 to 323) K are reported. It has been found that mefenamic acid shows high solubility in dipolar aprotic solvents (N,N-dimethylacetamide, N,N-dimethylformamide, ethyl acetate, and propanone), moderate solubility in polar protic solvents (ethanol and propan-2-ol), and poor solubility in apolar aprotic solvents (hexane, heptane, and cyclohexane) and water. ■ INTRODUCTION gravimetrically12 or using spectroscopy.13 Some variations of the 2-[(2,3-Dimethylphenyl)amino]benzoic acid (C H NO , me- technique are also available, which are described in detailed 15 15 2 elsewhere.11,14 Another experimental technique for the solubility fenamic acid) is a widely used nonsteroidal anti-inflammatory determination involves heating up a suspension of solid and and analgesic agent for the treatment of pain caused by 1,2 solvent to dissolution and detecting the clear point, which is menstrual disorders.
    [Show full text]
  • Crystallisation and Physicochemical Property Characterisation of Conformationally-Locked Co-Crystals of Fenamic Acid Derivatives
    Electronic Supplementary Material (ESI) for CrystEngComm. This journal is © The Royal Society of Chemistry 2015 Crystallisation and physicochemical property characterisation of conformationally-locked co-crystals of fenamic acid derivatives K. E. Wittering,a,b L. R. Agnew,a,b A. R. Klapwijk,a,b K. Robertson,a,b A. J. P. Cousen,a,b D. L. Cruickshank, *a and C. C. Wilson*a a Department of Chemistry, University of Bath, Bath, BA2 7AY b Engineering and Physical Sciences Research Council (EPSRC) Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC), University of Bath, Bath, BA2 7AY [email protected], [email protected] Supporting information Table S1. All variables investigated during the co-crystal screening studies* Crystallisation Ratio API Co-former Solvent temperature (API:co-former) (°C) Fenamic acid Urea§ 1:1 Methanol 4 Flufenamic acid Oxalic acid 2:1 Isopropanol 18 Mefenamic acid Isonicotinamide 1:2 Dimethylformamide 30 Tolfenamic acid Nicotinic acid§ Ethanol 50 4-aminobenzoic acid Acetone 2-aminobenzoic acid Tetrahydrofuran Pyridoxine§ Isonicotinic acid hydrazide§ 4,4’-bipiridyl 2,2’-bipridyl 2-aminopyridine §Classified as GRAS by the Select Committee on GRAS Substances (SCOGS) *Note. The crystallisations were prepared using the minimal solvent required for dissolution with the aid of a sonic bath (30 °C). All combinations of API, co-former and ratio stated in Table S1 were tested with one or more of the solvents listed dependant on solubility, so not all possible solvents were used for each combination. The maximum crystallisation temperature used was appropriate to the boiling point of the solvent used.
    [Show full text]
  • Protection Against Peroxynitrite Dependent Tyrosine Nitration and A1
    Annals ofthe Rheumatic Diseases 1996; 55: 383-387 383 Protection against peroxynitrite dependent Ann Rheum Dis: first published as 10.1136/ard.55.6.383 on 1 June 1996. Downloaded from tyrosine nitration and a1-antiproteinase inactivation by some anti-inflammatory drugs and by the antibiotic tetracycline Matthew Whiteman, Harparkash Kaur, Barry Halliwell Abstract physiological pH to give a range of noxious Objective-To examine in vitro the ability products with reactivities resembling those of of several drugs to protect against del- hydroxyl radicals (OH), nitrogen dioxide eterious effects of peroxynitrite, a cyto- (NO2%), and nitronium ion (NO2+).8 toxic agent formed by reaction of nitric Addition of peroxynitrite to tissues and oxide with superoxide radical, that may be biological fluids leads to nitration of aromatic generated in the rheumatoid joint and amino acid residues, and the presence of these could cause joint damage. may be a 'marker' of peroxynitrite mediated Methods-The ability of several drugs to (NO" dependent) damage in vivo.6 9-11 Indeed, protect against such possible toxic actions nitrotyrosine is present in plasma and synovial ofperoxynitrite as inactivation of Gl-anti- fluid from patients with RA, but it was not proteinase and nitration of tyrosine was detected in healthy control subjects.'2 Nitration evaluated. of tyrosine residues on proteins may interfere Results-Most non-steroidal anti-inflam- with cell signal transduction by tyrosine matory drugs were moderately (indo- phosphorylation/dephosphorylation.'3 Peroxy-
    [Show full text]
  • Prediction by Pharmacogenetics of Safety and Efficacy of Non-Steroidal Anti- Inflammatory Drugs: a Review
    Send Orders for Reprints to [email protected] 326 Current Drug Metabolism, 2014, 15, 326-343 Prediction by Pharmacogenetics of Safety and Efficacy of Non-Steroidal Anti- Inflammatory Drugs: A Review Victoria Rollason1,*, Caroline Flora Samer1,2, Youssef Daali1,2 and Jules Alexandre Desmeules1,2 1Division of Clinical Pharmacology and Toxicology, Multidisciplinary Pain Centre, University Hospitals of Geneva and University of Geneva, Switzerland; 2Swiss Centre for Applied Human Toxicology (SCAHT), University of Geneva, Switzerland Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used drugs, either on prescription or over-the- counter (OTC). Their daily dosage is based on randomised controlled trials and an empirical clinical assessment of their efficacy and tox- icity that allows dose adjustment. The individual response can however be altered by environmental and genetic pharmacokinetic and pharmacodynamic factors. This review summarizes the available pharmacogenetic data that explains part of the variability in response and occurrence of adverse drug reactions to NSAIDs treatment, with a thorough focus on CYP2C9, uridine diphosphate glucuronosyl- transferases (UGTs) and cyclooxygenases (COX1 and COX2). Other polymorphisms that are currently being studied and could also ex- plain the interindividual variability in the efficacy and safety of NSAIDs will also be considered. Keywords: COX, CYP2C8, CYP2C9, genetic polymorphism, NSAIDs, PTGS, UDP glucuronsyltransferases, UGT. INTRODUCTION efficacy and toxicity of NSAIDs have been reported for only some Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the of these PK and PD steps. We will evaluate in this review the class of drugs most commonly taken by patients, either on prescrip- pharmacogenetic data available for NSAIDs and their potential tion or over-the-counter (OTC).
    [Show full text]
  • Pms-IBUPROFEN
    PRODUCT MONOGRAPH Prpms-IBUPROFEN Ibuprofen Tablets, USP 600 mg tablets Nonsteroidal Anti-Inflammatory Drug, Analgesic, Antipyretic Agent Pharmascience Inc Date of Revision: 6111 Royalmount Avenue August 21, 2015 Montreal, Quebec H4P 2T4 www.pharmascience.com Submission Control No: 183725 pms-IBUPROFEN Product Monograph Page 1 of 36 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION ......................................................... 3 SUMMARY PRODUCT INFORMATION ........................................................................ 3 INDICATIONS AND CLINICAL USE.............................................................................. 3 CONTRAINDICATIONS ................................................................................................... 4 WARNINGS AND PRECAUTIONS ................................................................................. 5 ADVERSE REACTIONS ................................................................................................. 13 DRUG INTERACTIONS .................................................................................................. 16 DOSAGE AND ADMINISTRATION .............................................................................. 19 OVERDOSAGE ................................................................................................................ 19 ACTION AND CLINICAL PHARMACOLOGY ............................................................ 20 STORAGE AND STABILITY ........................................................................................
    [Show full text]
  • And Stereoselective Hydroxylation of Α-Ionone
    VU Research Portal Engineered cytochrome P450 BM3 mutants as biocatalysts for metabolite production: Applications in biotechnology and toxicology Venkataraman, H. 2014 document version Publisher's PDF, also known as Version of record Link to publication in VU Research Portal citation for published version (APA) Venkataraman, H. (2014). Engineered cytochrome P450 BM3 mutants as biocatalysts for metabolite production: Applications in biotechnology and toxicology. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: [email protected] Download date: 06. Oct. 2021 ENGINEERED CYTOCHROME P450 BM3 MUTANTS AS BIOCATALYSTS FOR METABOLITE PRODUCTION: APPLICATIONS IN BIOTECHNOLOGY AND TOXICOLOGY Harini Venkataraman Engineered cytochrome P450 BM3 mutants as biocatalysts for metabolite production: applications in biotechnology and toxicology Harini Venkataraman Printed by Ipskamp Drukkers Cover design by Dhwajal Chavan Copyright Harini Venkataraman, Amsterdam 2014. All rights reserved. No part of this thesis may be reproduced in any form or by any means without permission from the author.
    [Show full text]
  • Structural and Functional Basis of Cyclooxygenase Inhibition
    © Copyright 2007 by the American Chemical Society Volume 50, Number 7 April 5, 2007 PerspectiVe Structural and Functional Basis of Cyclooxygenase Inhibition Anna L. Blobaum and Lawrence J. Marnett* A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute for Chemical Biology and Center in Molecular Toxicology, Vanderbilt UniVersity School of Medicine, NashVille, Tennessee 37232 ReceiVed NoVember 13, 2006 I. Introduction acetic acid), 1963) were developed, although the mechanism of action was unknown. In 1971, John Vane showed that aspirin, Brief History. The use of medicinal substances for the indomethacin, and sodium salicylate all cause a dose-dependent treatment of pain and fever dates to ancient Egyptian and decrease in the synthesis of prostaglandins from cell-free Grecian civilizations, where dried myrtle leaves or bitter extracts homogenates of lung tissue.2 Vane was awarded the Nobel Prize from the bark of poplar trees were used to treat back and in physiology and medicine in 1982, in conjunction with Sune abdominal pain. The Ebers papyrus from ancient Egypt (1850 Bergstrom and Bengt Samuelson, for “discoveries on prosta- B.C.) is the oldest preserved medical text and contains the first glandins and related biologically active substances”. record documenting the use of plant remedies for the treatment Vane,2,3 concurrent with Smith and Willis,4 proposed of pain and inflammation. Other records show that in 400 B.C., that aspirin and other nonsteroidal antiinflammatory drugs Hippocrates prescribed the bark and leaves of the willow tree (NSAIDsa) inhibited the enzyme activity that converts polyun- to reduce fever and to relieve the pain of childbirth.
    [Show full text]