DOCSLIB.ORG

Assessment of Anti-Inflammatory Drugs in the Rat Using Subcutaneous Implants of Polyurethane Foam Impregnated with Dead Tubercle Bacilli

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Assessment of Anti-Inflammatory Drugs in the Rat Using Subcutaneous Implants of Polyurethane Foam Impregnated with Dead Tubercle Bacilli Ann. rheum. Dis. (1975), 34, 326 Ann Rheum Dis: first published as 10.1136/ard.34.4.326 on 1 August 1975. Downloaded from Assessment of anti-inflammatory drugs in the rat using subcutaneous implants of polyurethane foam impregnated with dead tubercle bacilli A. K. CLARKE, B. VERNON-ROBERTS, AND H. L. F. CURREY From the Bone andJoint Research Unit, The London Hospital Medical College, Turner Street, London, El 2AD Clarke, A. K., Vernon-Roberts, B., and Currey, H. L. F. (1975). Annals ofthe Rheumatic Diseases, 34, 326-331. Assessment of anti-inflammatory drugs in the rat using subcuta- neous implants of polyurethane foam impregnated with dead tubercle bacilli. The fluid and cellular phases of inflammatory response have been measured using a technique employ- ing subcutaneous implantation of polyurethane foam cubes impregnated with heat-killed Mycobacterium tuberculosis. Phenylbutazone, azathioprine, aspirin, cyclophosphamide, and prednisolone suppressed fluid response, whereas sodium aurothiomalate, hydroxy- chloroquine, and D-penicillamine had no effect. All the drugs used suppressed the infiltration of inflammatory cells into the cubes. copyright. Laboratory tests of the anti-inflammatory action of in these models has been largely centred upon the drugs are based upon the suppression of some feature later, fibrotic, stages of the inflammatory reaction of the inflammatory response such as the migration (Bole and Heath, 1967; Kaltiala and Heikkinen, of leucocytes, changes in blood flow, and vascular 1971). This report describes the effects of a variety of permeability, or the formation of granulation tissue anti-inflammatory agents, commonly used in the http://ard.bmj.com/ and oedema. The weight ofgranulation tissue formed treatment of rheumatic diseases, on the cellular and and the effects of drugs in suppressing it are the basis fluid phases of the inflammatory response to polyure- of the granuloma pouch test (Selye, 1953) and thane cubes impregnated with heat-killed Myco- techniques employing the implantation of cotton bacterium tuberculosis. pellets (Meier, Schuler, and Desaulles, 1950), poly- vinyl sponges (Boucek and Noble, 1955), and other Materials and methods irritant materials. These techniques, and those which on September 24, 2021 by guest. Protected rely on the measurement of oedematous tissue swell- ANIMALS Female Wistar or Sprague-Dawley rats weighing 150 to ing after the injection ofirritants such as carrageenan, 250 g were used. Unless otherwise specified, each test dextran, ovalbumin, formalin, etc., fail to separate group contained 8 animals. the relative contributions of fluid and cellular exuda- tion to the inflammatory reaction. PREPARATION OF CUBES We have attempted to obtain this important infor- Polyurethane foam (Dunlopillo grade D12, Dunlop) was mation by implanting subcutaneously in the rat poly- cut into cubes measuring slightly less than 1 cm3 and urethane foam cubes impregnated with an irritant. weighing 17 mg. Some ofthe cubes were then impregnated Such implants can be recovered after various intervals with heat-killed M. tuberculosis (TBC) (Tuberculin and processed in different ways for separate Section, Ministry of Agriculture, Fisheries and Food) by analysis immersingandcompressing them in anaqueous suspension of the fluid exudate and the infiltrating cells. In pre- of TBC (0 5 mg/ml) followed by drying overnight at 37°C vious studies in which pieces of foam have been (to constant weight). Each cube then contained approxi- implanted subcutaneously in experimental animals it mately 0-33 mg dry TBC, and microscopical examination has beenthe irritant nature ofthefoam itselfwhichhas of suitably stained sections showed this to be distributed provoked an inflammatory response and the interest evenly through the cube. Before implantation cubes were Accepted for publication October 24, 1974. Correspondence to: Professor H. L. F. Currey. Ann Rheum Dis: first published as 10.1136/ard.34.4.326 on 1 August 1975. Downloaded from Assessment ofanti-inflammatory drugs 327 sterilized in ethylene oxide. Control (nonimpregnated) cubes were processed similarly except that the TBC were omitted. IMPLANTATION OF CUBES Under ether anaesthesia and using a sterile technique, E cubes were implanted (one into each flank) through a a,0-7-/ dorsal midline incision. Each animal received an intra- peritoneal injection of 20 mg chloramphenicol to prevent -n 0*5// bacterial infection. O 0'4// 03 ASSESSMENT OF INFLAMMATORY FLUID EXUDATE 0*l- */Controls When cubes were removed, care was taken not to squeeze 02/ out any of the contained fluid. Cubes were then dried at 1 37°C overnight (to constant weight). The difference between the initial and final dry weight of each cube was 0~~~~~~~~l2 3 4 5 6 7 12/18 9 10 11 12 13 14 recorded as the 'dry weight gain'. Preliminary studies in Days after implontation which rats were implanted with a TBC-impregnated cube FIG. 2 Comparison ofdepth ofcellular invasion into cubes in one flank and a nonimpregnated cube on the opposite impregnated with tubercle bacilli and into nonimpregnated side established that there was a reproducible and pro- cubes examined at various intervals after implantation gressive daily increase in the dry weight gain ofthe irritant implant, while the dry weight gain ofthe nonirritant cubes and impregnated cubes on day +5. Preliminary studies had remained relatively constant for the first 6 days (Fig. 1). also established that this method of assessing the cellular This consideration led to the choice of 5 days for the infiltration correlated well with results obtained by actually duration of the experiments described below. Further counting the numbers ofcells in chosen fields. preliminary studies employing trypsinization and separate analysis of the cellular and fluid contents had established ADMINISTRATION OF DRUGS that on day +5 cells accounted for only about 12-5 % ofthe Sodium aurothiomalate (Myocrisin, May and Baker) was dry weight gain in the impregnated cube, and for about given by intramuscular injection on alternate days. 2-5 % in the nonirritant implants. Prednisolone suspended in arachis oil was given by copyright. intraperitoneal injection. The remaining drugs were ASSESSMENT OF INFLAMMATORY CELLULAR administered as a single daily dose via oral tube. The EXUDATE following preparations were employed. On the fifth day after implantation, cubes complete with Drug Preparation Vehicle overlying skin and underlying body wall were removed, Hydroxychloroquine Plaquenil, Winthrop Distilled water fixed in formol-saline, and embedded in wax. 5 ,um sections D-Peniclll_mine Distamine, Dista Deionized water Phenylbutazone Butazolidin, Geigy 025 Y/, carboxymethyl- were cut through the central part of each cube and were cellulose Azathioprine Imuran, Wellcome 0-251% carboxymethyl- stained with and A http://ard.bmj.com/ haematoxylin eosin. calibrated eye- cellulose piece was used to measure the depth of cellular invasion Aspirin Aspirin, B.P. Distilled water from the cube at on Cyclophosphamide Endoxana, Ward edge ofthe three points the superficial Blenkinsop Distilled water surface, three points on the deep surface, and two points Nil (controls) Nil 0-25V% carboxymethyl- on each of two remaining surfaces. The mean of these ten cellulose measurements gave the 'depth of cell invasion' for each cube. Preliminary experiments, similar to those described Results above, had indicated the progressive changes in this measurement after implantation (Fig. 2) and had shown EFFECT OF VARIOUS DRUGS ON DRY WEIGHT that there was a marked difference between the control GAIN OF CUBES IMPREGNATED WITH M. TUBER- on September 24, 2021 by guest. Protected CULOSIS (TABLES I AND II; FIG. 3) 110I 901 100- L -2..UflJ rui '-4 , AZR - ASP 3 90- a E~ 80 PRE .E- 70 cr c 60' ' 6o -6 50' a ' 40Q 3; 50 a' 40 > 30' 0 O 20' . TBC 30. 10' *-* Controls 5 10 o00 I0 I io 6 7 14 Daily dose in mg/kg (log scale) Days after implantation FIG. 3 Graphillustratingrelativesuppression ofdry weight FIG. 1 Dry weight gain (mean ±2 SE) ofpolyurethane gain of tubercle-impregnated cubes by increasing doses of foam cubes impregnated with tubercle bacilli compared with prednisolone (PRED), cyclophosphamide (CY), azathio- dry weightgain ofnonimpregnatedcubes prine (AZ), phenylbutazone (PBZ), and aspirin (ASP) Ann Rheum Dis: first published as 10.1136/ard.34.4.326 on 1 August 1975. Downloaded from 328 Annals ofthe Rheumatic Diseases Table I Effect ofvarious anti-inflammatory agents on dry weight gain ofpolyurethane cubes impregnated with heat-killed M. tuberculosis Drug Route of Frequency of Daily dose (mg/kg) Dry weight gain ofcubes administration administration (mg + SE) (day 0 = day ofcube implantation) Sodium aurothiomalate Intramuscular Alternate days 12-5 84-7+3-2 -10 to +4 25 85-6±2-6 50 848 ±2-7 100 85-3 3-3 Hydroxychloroquine Oral Daily 6-25 87-0 3-7 -10 to +4 12-5 86-9 + 2-5 25 80-1 ± 1*8 50 86-5 + 2-6 D-Penicillamine Oral Daily 25 78-5+2-0 -10 to +4 50 79-3 + 2-2 100 69-7 + 3-5* 200 75-6 + 3-6 Phenylbutazone Oral Daily 37-5 69-3 ± 1-9: 0 to +4 75 64-9 + 1-91: 150 63 5 ± 191: 300 60-8±3-01 Azathioprine Oral Daily 25 80-5+2-0 0 to +4 50 75-4 3-9 100 60-0 3-61 copyright. 200 54-96-1: Aspirin Oral Daily 100 78-9 + 2-0 0 to +4 200 70-3 + 2-0t 400 63-9 + 2-21: 800 53-6 ± 091: Cyclophosphamide Oral Daily 6-25 77-2 + 2-1 0 to +4 12-5 63-1 + 2-0t 25 540± 1-31: http://ard.bmj.com/ 50 49-0 ± 2-4: Prednisolone Intra- Daily 6-25 66-1 + 1-6t peritoneal 0 to +4 12-5 52-4 ± 2-3: 25 39-0 ± 1-3: 50 41-4 + 2-5$ Controls - 82-1 +2-7 on September 24, 2021 by guest. Protected *P = < 0-05; tP - < 0-01; $P = < 0-001. Groups of rats (8 in each group) were given one of the established that neither azathioprine nor phenyl- drugs in the range of doses shown in Table I.
Load more

Recommended publications
  • Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic
    Sys Rev Pharm 2020; 11(5): 464 468 A multifaceted review journal in the field of pharmacy E-ISSN 0976-2779 P-ISSN 0975-8453 Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic Agus Purnomo1, Arya Pradana Wicaksono2, Dodit Hendrawan2, Muhammad Thohawi Elziyad Purnama3* 1Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, DI Yogyakarta, 55281, Indonesia 2Postgraduate Studies, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia 3Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia *Corresponding author E-mail: [email protected] Article History: Submitted: 26.02.2020 Revised: 16.04.2020 Accepted: 21.05.2020 ABSTRACT This study aimed to evaluate the efficacy of flunixin, ketoprofen and multiple range test. The results showed a significant alleviation in all phenylbutazone on serum biochemistry, plasma catecholamines and observed variables on Day 13, although the use of various NSAIDs serum cortisol in Delman horses with mild colic. During the study showed no significant difference. period, 32 horses were evaluated due to mild colic. Flunixin, Keywords: serum biochemical, catecholamine, cortisol, colic, NSAIDs ketoprofen, and phenylbutazone were administered intravenously at Correspondence: the recommended dose rates of 1.0; 2.2 and 4.4 mg/kg, respectively. Muhammad Thohawi Elziyad Purnama Administration of the NSAIDs commenced on Day 1 and continued Department of Veterinary Anatomy, Faculty of Veterinary Medicine, every 12 h for 12 days. Blood samples collected between days 2, 5, 9 Universitas Airlangga, Surabaya, 60115, Indonesia and 13 to evaluate AST, ALP, GGT, creatinine, urea, epinephrine, E-mail: [email protected] norepinephrine, and cortisol level.
    [Show full text]
  • Non-Steroidal Anti-Inflammatory Drugs (Nsaids)
    NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ANALYSIS IN MILK BY QUECHERS AND LC-MS: LOW AND HIGH RESOLUTION DETECTION AND CONFIRMATION APPROACHES A. Rúbies1, L. Guo2, I. Beguiristain1, F. Centrich1, M. Granados2 1. Laboratori Agència de Salut Pública de Barcelona, 2. Departament de Química Analítica - Universitat de Barcelona. * INTRODUCTION NON-STEROIDAL ANTI-INFLAMATORY DRUGS (NSAIDs) Non-steroidal anti-inflammatory drugs (NSAIDs) are used as anti-inflammatory, analgesic and OXICAMS ANTHRANILIC ACID DERIVATIVES ACETIC ACID antipyretic drugs in medicine and veterinary. Their action mechanism is based on the blocking of PROPIONIC ACID DERIVATIVES DERIVATIVES the biosynthesis of prostaglandins. NSAIDs are highly effective and extensively used, but they have some adverse side effects, such as hepatotoxicity, renal disorders or allergic reactions. In the European Union, to assure food safety and protect consumers, maximum residue limits have been established for some authorised NSAIDs in food products. Therefore, high throughput and reliable analytical methodology is required for the effective control of NSAIDs in food from animal Flufenamic acid origin. Liquid chromatography (LC) coupled to mass spectrometry (MS) is currently the technique of choice in confirmatory analysis of NSAIDs residues. We present a new method for the determination of representative NSAIDs in milk based on QuEChERS methodology, LC-MS/MS and UHPLC-HRMS. Meloxicam Ketoprofen Diclofenac EU Maximum Residue Limits (MRLs) Recommended NSAIDs concentrations for NSAIDs in milk.
    [Show full text]
  • Nonsteroidal Anti-Inflammatory Agents Differ in Their Ability to Suppress
    Oncogene (2004) 23, 9247–9258 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $30.00 www.nature.com/onc Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-jB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation Yasunari Takada1, Anjana Bhardwaj1, Pravin Potdar1 and Bharat B Aggarwal*,1 1Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Introduction aspirin have been shown to suppress transcription factor NF-jB, which controls the expression of genes such as Owing to its analgesic and anti-inflammatory effects, cyclooxygenase (COX)-2 and cyclin D1, leading to aspirin (acetylsalicylic acid), first synthesized in 1897, inhibition of proliferation of tumor cells. There is no was approved for the treatment of rheumatoid arthritis systematic study as to how these drugs differ in their ability in 1899 (Botting, 1999). Since then several other to suppress NF-jB activation and NF-jB-regulated gene nonsteroidal anti-inflammatory drugs (NSAIDs) have expression or cell proliferation. In the present study, we been synthesized and approved for human use. The anti- investigated the effect of almost a dozen different commonly inflammatory and analgesic effects of NSAIDs have used NSAIDs on tumor necrosis factor (TNF)-induced NF- been shown to be due to their ability to inhibit the jB activation and NF-jB-regulated gene products, and on enzymatic activity of cyclooxygenases (COXs), which cell proliferation. Dexamethasone, an anti-inflammatory convert arachidonic acid to prostaglandins (PGs) (Vane, steroid, was included for comparison with NSAIDs.
    [Show full text]
  • Topical NSAID for Osteoarthritis Safe and Effective (Print)
    The Horse: Study: Topical NSAID for Osteoarthritis Safe and Effective (print) Study: Topical NSAID for Osteoarthritis Safe and Effective by: Stacey Oke, DVM, MSc February 26 2009 Article # 13686 Move over, Bute. In a new independent study, researchers at Colorado State University's Gail Holmes Equine Orthopaedic Research Center concluded that diclofenac liposomal cream (1% diclofenac sodium, trade name Surpass) is safer and more effective than phenylbutazone for treating discomfort associated with osteoarthritis in horses. Phenylbutazone, commonly known as "Bute," is a non-steroidal anti-inflammatory (NSAID) drug administered systemically (i.e., intravenously or orally) to help control the pain and inflammation caused by osteoarthritis in horses. "Considering that phenylbutazone and other NSAIDs are known to have important adverse effects in horses when used long-term and that these drugs are not able to alter the course of OA but only help control clinical signs, alternatives are needed," explained researcher David Frisbie, DVM, PhD, Dipl. ACVS. One such alternative is diclofenac liposomal cream--an NSAID that is applied to the skin overlying the affected joint(s) to control pain and inflammation of the tarsal, carpal, metacarpophalangeal, metatarsophalangeal and proximal interphalangeal joints. This product is approved by the Food and Drug Administration and is the first product of its kind manufactured for horses. Results of this study were presented at the 2007 annual American Association of Equine Practitioners' conference and were recently published in the study, "Evaluation of topically administered diclofenac liposomal cream for treatment of horses with experimentally induced osteoarthritis," in the February edition of the American Journal of Veterinary Research.
    [Show full text]
  • List Item Frequently Asked Questions on Phenylbutazone in Horsemeat
    15 April 2013 Frequently asked questions on Phenylbutazone in horsemeat 1. What is phenylbutazone? 2. What is the situation regarding phenylbutazone in food in the EU? 3. Why was phenylbutazone banned for use in food-producing animals? 4. What are the known toxic effects of phenylbutazone? 5. What is the likelihood of consumers being exposed to phenylbutazone in horsemeat? 6. What were EFSA and EMA asked to do by the European Commission? 7. What information did EFSA and EMA consider in their risk assessment of phenylbutazone? 8. What are the main conclusions of the joint statement? 9. What did the report conclude with regard to the potential risk for consumers? 10. What recommendations did EFSA and EMA make to further reduce the risk of phenylbutazone entering the food chain? 11. What is EFSA’s role with regards to the management of issues such as the contamination of beef products with horsemeat? 12. What is EMA’s contribution to this joint risk assessment regarding the public health implications of phenylbutazone in horsemeat? 1. What is phenylbutazone? Phenylbutazone – sometimes also referred to as “bute” – is a substance that falls into the class of drugs known as non steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are routinely used as painkillers in human and veterinary medicine. Phenylbutazone was introduced in 1949 as a human medicine for the treatment of rheumatoid arthritis and gout. These days it is used only under specialist supervision in patients who suffer from a severe form of arthritis where other treatments have not worked. Phenylbutazone is used for the treatment of pain and fever in horses and dogs.
    [Show full text]
  • Original Paper Enhancement of Chemotherapeutic Drug Toxicity To
    European Journal of Cancer, Vol. 34, No. 8, pp. 1250±1259, 1998 # 1998 Elsevier Science Ltd. All rights reserved Pergamon Printed in Great Britain 0959-8049/98 $19.00+0.00 PII: S0959-8049(98)00045-8 Original Paper Enhancement of Chemotherapeutic Drug Toxicity to Human Tumour Cells In Vitro by a Subset of Non-steroidal Anti-in¯ammatory Drugs (NSAIDs) C.P. DuVy, C.J. Elliott, R.A. O'Connor, M.M. Heenan, S. Coyle, I.M. Cleary, K. Kavanagh, S. Verhaegen, C.M. O'Loughlin, R. NicAmhlaoibh and M. Clynes National Cell and Tissue Culture Centre, Dublin City University, Glasnevin, Dublin 9, Ireland The eVect on cytotoxicity of combining a range of clinically important non-steroidal anti-in¯amma- tory drugs (NSAIDs) with a variety of chemotherapeutic drugs was examined in the human lung cancer cell lines DLKP, A549, COR L23P and COR L23R and in a human leukaemia line HL60/ADR. A speci®c group of NSAIDs (indomethacin, sulindac, tolmetin, acemetacin, zomepirac and mefenamic acid) all at non-toxic levels, signi®cantly increased the cytotoxicity of the anthracyclines (doxorubicin, daunorubicin and epirubicin), as well as teniposide, VP-16 and vincristine, but not the other vinca alkaloids vinblastine and vinorelbine. Asubstantial number of other anticancer drugs, including methotrexate, 5-¯uorouracil, cytarabine, hydroxyurea, chlorambucil, cyclophosphamide, cisplatin, carboplatin, mitoxantrone, actinomycin D, bleomycin, paclitaxel and camptothecin, were also tested, but displayed no synergy in combination with the NSAIDs. The synergistic eVect was concentration dependent. The eVect appears to be independent of the cyclo-oxygenase inhibitory ability of the NSAIDs, as (i) the synergistic combination could not be reversed by the addition of prostaglandins D2 or E2; (ii) sulindac sulphone, a metabolite of sulindac that does not inhibit the cyclooxygenase enzyme, was positive in the combination assay: and (iii) many NSAIDs known to be cyclo-oxygenase inhibitors, e.g.
    [Show full text]
  • Non Steroidal Anti-Inflammatory Drugs
    Non Steroidal Anti‐inflammatory Drugs (NSAIDs) 4 signs of inflammation • Redness ‐ due to local vessel dilatation • Heat ‐ due to local vessel dilatation • Swelling – due to influx of plasma proteins and phagocytic cells into the tissue spaces • Pain – due to local release of enzymes and increased tissue pressure NSAIDs • Cause relief of pain ‐. analgesic • Suppress the signs and symptoms of inflammation. • Exert antipyretic action. • Useful in pain related to inflammation. Esp for superficial/integumental pain . Classification of NSAIDs • Salicylates: aspirin, Sodium salicylate & diflunisal. • Propionic acid derivatives: ibuprofen, ketoprofen, naproxen. • Aryl acetic acid derivatives: diclofenac, ketorolac • Indole derivatives: indomethacin, sulindac • Alkanones: Nabumetone. • Oxicams: piroxicam, tenoxicam Classification of NSAIDs ….. • Anthranilic acid derivatives (fenamates): mefenamic acid and flufenamic acid. • Pyrazolone derivatives: phenylbutazone, oxyphenbutazone, azapropazone (apazone) & dipyrone (novalgine). • Aniline derivatives (analgesic only): paracetamol. Clinical Classif. • Non selective Irreversible COX inhibitors • Non slective Reversible COX inhibitors • Preferential COX 2 inhibitors • 10‐20 fold cox 2 selective • meloxicam, etodolac, nabumetone • Selective COX 2 inhibitors • > 50 fold COX ‐2 selective • Celecoxib, Etoricoxib, Rofecoxib, Valdecoxib • COX 3 Inhibitor? PCM Cyclooxygenase‐1 (COX‐1): -constitutively expressed in wide variety of cells all over the body. -"housekeeping enzyme" -ex. gastric cytoprotection, hemostasis Cyclooxygenase‐2 (COX‐2): -inducible enzyme -dramatically up-regulated during inflammation (10-18X) -constitutive : maintains renal blood flow and renal electrolyte homeostasis Salicylates Acetyl salicylic acid (aspirin). Kinetics: • Well absorbed from the stomach, more from upper small intestine. • Distributed all over the body, 50‐80% bound to plasma protein (albumin). • Metabolized to acetic acid and salicylates (active metabolite). • Salicylate is conjugated with glucuronic acid and glycine. • Excreted by the kidney.
    [Show full text]
  • Indomethacin in Rheumatic Diseases a Controlled Clinical Trial By
    Ann Rheum Dis: first published as 10.1136/ard.23.3.218 on 1 May 1964. Downloaded from Ann. rheum. Dis. (1964), 23, 218. INDOMETHACIN IN RHEUMATIC DISEASES A CONTROLLED CLINICAL TRIAL BY J. WANKA, L. I. JONES, PHILIP H. N. WOOD,* AND ALLAN ST. J. DIXON From the Rheumatism Departments of St. Stephen's Hospital, St. Mary Abbots Hospital, and Hammersmith Hospital, London Indomethacin (l-(p-chlorbenzoyl)-5-methoxy-2- In trials of this drug on ourselves and in patients we methylindole-3-acetic acid) (Fig. 1) is a compound noticed that a disabling headache could sometimes which has been shown to have anti-inflammatory occur. and antipyretic action in experimental animals (I) THE DOUBLE-BLIND TRIAL (Hodgkinson, 1963). Enthusiastic but largely un- controlled studies of its action in rheumatoid 22 patients with definite rheumatoid arthritis arthritis and other disorders have been reported (see (A.R.A. criteria-Ropes, Bennett, Cobb, Jacox, and Proceedings of the American Rheumatism Associa- Jessar, 1957) with inflammation (as judged by heat, tion, 1963) and more recently reports of its thera- swelling, redness, and tenderness) of one or more peutic value have been published in Great Britain joints were admitted to the trial. They were (Hart and Boardman, 1963). This paper reports allocated at random to start treatment with either experiences with this drug over the last year in the placebo or indomethacin; fourteen patients (Cases 3, 4, 5, 8, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21) started treatment of rheumatoid arthritis and other condi- copyright. tions. The study was conducted in three parts: on active tablets and eight (Cases 1, 2, 6, 7, 9, 10, 17, 22) on placebo therapy (Fig.
    [Show full text]
  • Phenylbutazone
    Phenylbutazone Background Phenylbutazone is among the oldest and most commonly used non-steroidal anti-inflammatory (NSAID) in veterinary medicine.i It is assigned 4/C in the ARCI’s Uniform Classification of Foreign Substances. Phenylbutazone is administered orally or intravenously for its anti-inflammatory, analgesic, and antipyretic effects.ii It is frequently used to control inflammation and pain resulting from iii osteoarthritis, navicular disease, and synovitis. https://commons.wikimedia.org/wiki/File:Phen ylbutazone.png Phenylbutazone is a prescription medication and can only be dispensed by, or upon, the request of a veterinarian. It is commercially available as both a brand name and generic drug in a variety of formulations (injectable; and oral pastes, tablets, granules, and powders).iv Phenylbutazone can be administered intravenously and orally.v Doses range from 2.2 to 4.4 mg/kg every 12-24 hours for both the oral and parenteral routes.vi Phenylbutazone is a non-selective cyclooxygenase (COX) inhibitor.vii It acts by inhibiting the portion of the arachidonic acid pathway responsible for production of thromboxanes, prostacyclins, and prostaglandins. The anti-inflammatory, anti-pyretic, and analgesic effects of phenylbutazone are believed to be associated with a reduction in prostaglandin synthesis.viii Additionally, researchers in one study concluded that phenylbutazone interferes with the expression of pleiotrophin that regulates migration of certain gastrointestinal cells – which may, in part, be responsible for an increase in gastric ulceration associated with use of phenylbutazone.ix In addition to the indirect cellular effects that phenylbutazone has on gastrointestinal mucosa, one group of researchers observed direct effects of oral phenylbutazone in altering the anti-oxidant/oxidant balance that may lead to additional ulceration in the stomach.x When used judiciously, phenylbutazone can be beneficial in the treatment of, and recovery from, illness or injury.
    [Show full text]
  • Non Steroidal Anti Inflammatory Drugs (NSAIDS)
    Fact Sheet Fact Sheet ChokNon-Steroidale Anti- Choke is a relatively common condition seen in horses and ponies and is typically caused by obstruction of the oesophagus (food pipe)Inflammatory with food; occasionally a foreign Drugs body can be involved e.g. wood or plastic. FortunatelyNon-steroidal anti-inflammatory drugs (NSAIDs) are probably many cases of choke resolve quickly and spontaneouslysome of the most widely used drugs used in both human and only cases in which the obstruction lasts for longerand equine medicine. They act to reduce pain by inhibiting than 30 minutes are likely to require veterinary assistancthe einflammatory. pathways after injury. Common NSAIDs It is important to note that this is not the same as the used in human medicine include aspirin, paracetamol life-threatening condition in humans, where the term and ibuprofen. NSAIDs used in equine medicine include “choke” refers to blockage of the windpipe rather thanphenylbutazone the (bute), meloxicam, suxibuzone and flunixin. oesophagus. This difference means that unlike humans, horses with choke can still breathe. NSAIDs may be administered by injection, orally (as a powder, granules or paste given in feed or by mouth) or in a cream, ointment, gel or lotion to apply to the surface of inflamed tissues such as the skin. Clinical signs: • difficulty/repeated attempts at swallowing • stretching/arching of the neck • coughing NSAIDs are a benefit to the welfare of the equine • food & saliva discharging from the nose population through the control of pain and inflammation. • drooling • disinterest in food REGULAThe term R‘non-steroidal’ DENTAL EXAMIN is usedATIONS to distinguish AND these • occasionally a lump may be seen or felt TREdrugsATMENT from C steroidAN REDU anti-inflammatoriesCE THE RISK OF (cortisone).CHOKE on the left side of the neck.
    [Show full text]
  • (CD-P-PH/PHO) Report Classification/Justifica
    COMMITTEE OF EXPERTS ON THE CLASSIFICATION OF MEDICINES AS REGARDS THEIR SUPPLY (CD-P-PH/PHO) Report classification/justification of - Medicines belonging to the ATC group M01 (Antiinflammatory and antirheumatic products) Table of Contents Page INTRODUCTION 6 DISCLAIMER 8 GLOSSARY OF TERMS USED IN THIS DOCUMENT 9 ACTIVE SUBSTANCES Phenylbutazone (ATC: M01AA01) 11 Mofebutazone (ATC: M01AA02) 17 Oxyphenbutazone (ATC: M01AA03) 18 Clofezone (ATC: M01AA05) 19 Kebuzone (ATC: M01AA06) 20 Indometacin (ATC: M01AB01) 21 Sulindac (ATC: M01AB02) 25 Tolmetin (ATC: M01AB03) 30 Zomepirac (ATC: M01AB04) 33 Diclofenac (ATC: M01AB05) 34 Alclofenac (ATC: M01AB06) 39 Bumadizone (ATC: M01AB07) 40 Etodolac (ATC: M01AB08) 41 Lonazolac (ATC: M01AB09) 45 Fentiazac (ATC: M01AB10) 46 Acemetacin (ATC: M01AB11) 48 Difenpiramide (ATC: M01AB12) 53 Oxametacin (ATC: M01AB13) 54 Proglumetacin (ATC: M01AB14) 55 Ketorolac (ATC: M01AB15) 57 Aceclofenac (ATC: M01AB16) 63 Bufexamac (ATC: M01AB17) 67 2 Indometacin, Combinations (ATC: M01AB51) 68 Diclofenac, Combinations (ATC: M01AB55) 69 Piroxicam (ATC: M01AC01) 73 Tenoxicam (ATC: M01AC02) 77 Droxicam (ATC: M01AC04) 82 Lornoxicam (ATC: M01AC05) 83 Meloxicam (ATC: M01AC06) 87 Meloxicam, Combinations (ATC: M01AC56) 91 Ibuprofen (ATC: M01AE01) 92 Naproxen (ATC: M01AE02) 98 Ketoprofen (ATC: M01AE03) 104 Fenoprofen (ATC: M01AE04) 109 Fenbufen (ATC: M01AE05) 112 Benoxaprofen (ATC: M01AE06) 113 Suprofen (ATC: M01AE07) 114 Pirprofen (ATC: M01AE08) 115 Flurbiprofen (ATC: M01AE09) 116 Indoprofen (ATC: M01AE10) 120 Tiaprofenic Acid (ATC:
    [Show full text]
  • Effects of Chronic Administration of Phenylbutazone on Reproduction in the Mare. Mareth Ellsworth Louisiana State University and Agricultural & Mechanical College
    Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1991 Effects of Chronic Administration of Phenylbutazone on Reproduction in the Mare. Mareth Ellsworth Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Ellsworth, Mareth, "Effects of Chronic Administration of Phenylbutazone on Reproduction in the Mare." (1991). LSU Historical Dissertations and Theses. 5116. https://digitalcommons.lsu.edu/gradschool_disstheses/5116 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps.
    [Show full text]