DOCSLIB.ORG

Rheumatoid Arthritis Evaluation of Methods and a Comparison of Mefenamic and Flufenamic Acids with Phenylbutazone and Aspirin by R

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rheumatoid Arthritis Evaluation of Methods and a Comparison of Mefenamic and Flufenamic Acids with Phenylbutazone and Aspirin by R Ann Rheum Dis: first published as 10.1136/ard.26.5.373 on 1 September 1967. Downloaded from Ann. rheum. Dis. (1967), 26, 373 ASSESSMENT OF DRUGS IN OUT-PATIENTS WITH RHEUMATOID ARTHRITIS EVALUATION OF METHODS AND A COMPARISON OF MEFENAMIC AND FLUFENAMIC ACIDS WITH PHENYLBUTAZONE AND ASPIRIN BY R. M. MASON, D. E. BARNARDO*, W. R. FOXt, AND M. WEATHERALL+ From the Department ofPhysical Medicine and Rheumatology, the London Hospital, and the Department ofPharmacology, the London Hospital Medical College Relief of symptoms in patients with chronic The methods of clinical trials are still capable of rheumatoid arthritis is difficult. Conventional much improvement. Particularly in trials on out- analgesics such as aspirin, paracetamol, and phenyl- patients, the opportunities for undetected errors are butazone have limited efficacy and are not free from very great. Problems of measurement are also toxic effects. Any alternative which was more considerable, at least in rheumatoid arthritis, in effective, safer, or both would be welcome, but most which all of the many measurements which can be copyright. new remedies owe such success as they achieve to made appear to vary somewhat independently of therapeutic optimism which is a powerful but each other (American Rheumatism Association, transient potentiator of pharmacological effects. 1965), so that confidence in any one is limited. The accurate assessment of new drugs by properly One cannot decide which is the best of a number of controlled trials is indispensable. Two drugs which alternative procedures without testing all of them in have shown promise in laboratory studies and early parallel. The present trial has been extended clinical trials are mefenamic and flufenamic acids considerably beyond the needs of a simple compari- (Winder, Wax, Scotti, Scherrer, Jones, and Short, son of drugs in order also to be informative about 1962; Goodley, 1963; Young, 1962), derivatives of problems of method. xylylanthranilic acid with actions broadly resembling http://ard.bmj.com/ those of aspirin. We have submitted these drugs Methods to a controlled trial, which has already been briefly (1) Patients reported (Barnardo, Currey, Mason, Fox, and All were females over 18 years of age and were selected Weatherall, 1966). Since our trial began, several by the six participating physicians from the attenders other trials have been reported. Flufenamic acid at the Department of Physical Medicine and Rheuma- (600 mg./day) has been found to be less effective tology of the London Hospital between October, 1964, than prednisone (Fearnley and Masheter, 1966), and and September, 1965. Each had "definite" or "classical" on October 2, 2021 by guest. Protected comparable in effect to aspirin (2,700 mg./day) over rheumatoid arthritis (Ropes, Bennett, Cobb, Jacox, and to 6 months and Jessar, 1959) for more than one year, was not pregnant periods up (Simpson, Simpson, nor expected to become so during the trial, and had no Masheter, 1966) and also comparable with phenyl- history of cardiac failure, hepatic disease, or proven butazone (300 mg./day) over shorter periods peptic ulceration. Patients sensitive, or reacting un- (Rajan, Hill, Barr, and Whitwell, 1967). Mefenamic favourably to, either phenylbutazone or aspirin were acid (1,500 mg./day) has been found effective also in admitted and a provision was made as described below to osteo-arthritis (Cahill, Hill, Jessop, and Hume avoid their receiving the drug to which they were sensitive. Kendall, 1965). Patients receiving other well-stabilized treatment such as steroids or antimalarial drugs were not excluded and their treatment with these drugs was continued while they took * Present address: Gastro-intestinal Research Unit, Mayo Clinic, Rochester, Minn. part in the trial. The purpose ofthe trial was explained to t Present address: Research Dzpt., Potato Marketing Board, each patient and anyone who did not wish to take part or London, S.W.1. who would have had practical difficulties in co-operating + Present address: Wellcome Research Laboratories, Beckenham, Kent. was excluded. 373 Ann Rheum Dis: first published as 10.1136/ard.26.5.373 on 1 September 1967. Downloaded from 374 ANNALS OF THE RHEUMATIC DISEASES (2) Design and Procedure replication was achieved by an appropriate instruction to the pharmacist and did not involve the physician in Patients differ considerably from one another. Varia- breaking the code. tion in the severity of any given patient's arthritis is The trial proper was preceded by a short pilot study in likely to be less than the variation between patients. which the trial procedure was tested and practised and The trial was therefore designed so that drugs were the physicians obtained experience in the completion of compared within patients. Each patient was to receive the forms designed for keeping records in the trial. both new drugs and an appropriate standard treatment. Seven patients were admitted to the pilot study, which The choice of a standard presented some difficulty. revealed no appreciable faults of planning. A further Many drugs have been shown to be more effective than 36 patients were admitted; four among these failed to a placebo in rheumatoid arthritis, so the use of a dummy complete three periods of treatment and a corresponding would have raised ethical problems. Besides, one object additional number were admitted to make a complete of the trial was to compare the new remedies with balanced set as designed. While the results from this standard treatments, of which aspirin and phenylbuta- set were being analysed, further patients were admitted zone seemed most appropriate. Some patients are, or with a view to completing a second complete set of 36. believe themselves to be, sensitive to one or other of these The results on the first 36 indicated that no substantial drugs. It is for such patients that a new alternative difference was appearing between treatments, and the analgesic is particularly needed. The trial therefore had second set was therefore not completed. In all 68 to be arranged so that such patients could be included, patients were admitted, including the seven in the pilot without risk of being exposed to the drug to which they study and eight who completed less than three periods. were perhaps sensitive. This objective was achieved Analyses of comparison between drugs are mostly based by designing the trial so that aspirin served as the standard on the balanced set of 36 patients. Other analyses were treatment for half the patients and phenylbutazone for based on all the patients studied. the other half. Ordinarily the choice depended on the statistical design, but if a patient was believed to react Many clinical trials are conducted with fixed dosage of unfavourably to either drug the physician requested drugs. The conclusions which can be drawn from single instead a sequence omitting the drug in question. This fixed-dose studies are very limited. If one drug produces request was made on four occasions, but the allotted better results than another, the difference may be due entirely to the doses chosen, and an otherwise identical copyright. sequence was, in fact, inappropriate and had to be trial with different doses might produce exactly the altered only once. opposite result. If each drug is administered at two or During three consecutive periods, each of 4 weeks' more levels of dosage, and if the larger dose has larger duration, all patients were supposed to receive mefenamic average effects than the smaller, a reasonable basis of acid, flufenamic acid, and either phenylbutazone or comparison is possible between the dose-response lines aspirin in capsules of a different colour. Three kinds for each drug. But it is seldom possible in practice to of coloured capsule were used (blue, blue and white, achieve a graded response, because the range between the and red and yellow) and each drug was dispensed equally apparently ineffective dose and the evidently toxic dose often in one kind of capsule as another. It was therefore is usually too small. evident to patients that they were receiving different To avoid this difficulty, doses in the present trial were http://ard.bmj.com/ remedies in successive periods, but communication selected not by an arbitrary weight of drug but by the between patients or staff about the efficacy of different- response of the patient to treatment. Initially the doses looking remedies (Asher, 1948) would not lead to prescribed were 720 mg. aspirin, 100 mg. phenylbutazone, collective judgements related to a particular drug. Each 500 mg. mefenamic acid, or 200 mg. flufenamic acid, of the twelve possible orders of treatment was allocated each given three times daily. In order to adjust the dose to three patients and the three capsule colours were to each individual patient, all patients were seen at the arranged in a Latin square design over each such group. end of the first week in each period; their progress was A complete replicate of the design thus required 36 briefly reviewed and the physician had the option of on October 2, 2021 by guest. Protected patients. When a physician admitted a patient to the decreasing or increasing the daily dose by one third (by trial, the pharmacist took note of any specific request to altering the frequency of medication to twice or four avoid a sequence containing either aspirin or phenyl- times daily) if it seemed desirable on grounds of thera- butazone and then gave the patient the next available peutic response and toxic manifestations. Provision suitable trial number. Thereafter the pharmacist was also made for discontinuation of a drug if worsening dispensed the appropriate capsules, leaving both the of symptoms or toxic effects were severe. In such a case patient and the physician unaware of the identity of the the patient proceeded immediately to the drug planned treatment. for the next period. Occasionally a short period without When patients failed to complete three periods, treatment was adopted before resuming the trial sequence.
Load more

Recommended publications
  • Colitis Caused by Non-Steroidal Anti-Inflammatory Drugs
    Postgrad Med J: first published as 10.1136/pgmj.62.730.773 on 1 August 1986. Downloaded from Postgraduate Medical Journal (1986) 62, 773-776 Colitis caused by non-steroidal anti-inflammatory drugs S. Ravi', A.C. Keat2 and E.C.B. Keat1 'Cuckfield Hospital, Cuckfield, West Sussex, and2Westminster Hospital, Horseferry Road, London SWIP2AP, UK. Summary: Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse. Introduction Ulcerative colitis is a disease of unknown aetiology Case reports with characteristic clinical features and a protracted course. A similar clinical picture, but running a shorter Case I and usually benign course, is occasionally seen follow- ing the administration of certain drugs. This was first A 77 year old woman was referred with intermittent noticed following the administration of antibiotics, bleeding per rectum for 6 months, associated for the often with pseudomembrane formation. Later, this last 2 months with bloody diarrhoea up to eight times was shown to be associated with infection by toxigenic daily. Previously, she had had troublesome symptoms Clostridium difficile. Until 1978, most cases were from osteoarthritis of her back and knees for which copyright. associated with treatment with clindamycin but since she had been prescribed flufenamic acid 200 mg thrice that time nearly all antibiotics have been implicated. daily. Her general health had remained good but she Other drugs capable of causing proctocolitis, though appeared pale and her haemoglobin was reduced to by different mechanisms, include phenindione (Keat & 8 g/dl.
    [Show full text]
  • Investigating the Influence of Polymers on Supersaturated
    Page 1 of 45 Molecular Pharmaceutics 1 2 3 4 5 6 7 Investigating the Influence of Polymers on 8 9 10 11 12 Supersaturated Flufenamic Acid Cocrystal Solutions 13 14 15 16 1 1 2 2 1 17 Minshan Guo , Ke Wang , Noel Hamill , Keith Lorimer and Mingzhong Li * 18 19 20 1School of pharmacy, De Montfort University, Leicester, UK 21 22 23 2Almac Science, Seagoe Industrial Estate, Craigavon, UK 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment 1 Molecular Pharmaceutics Page 2 of 45 1 2 3 4 5 6 7 Table of contents graphic 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment 2 Page 3 of 45 Molecular Pharmaceutics 1 2 3 Abstract 4 5 6 7 The development of enabling formulations is a key stage when demonstrating the effectiveness 8 9 10 of pharmaceutical cocrystals to maximize the oral bioavailability for poorly water soluble drugs. 11 12 Inhibition of drug crystallization from a supersaturated cocrystal solution through a fundamental 13 14 understanding of the nucleation and crystal growth is important. In this study, the influence of 15 16 17 the three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and a copolymer 18 19 of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the flufenamic acid 20 21 22 (FFA) crystallization from three different supersaturated solutions of the pure FFA and two 23 24 cocrystals of FFA-NIC CO and FFA-TP CO has been investigated by measuring nucleation 25 26 induction times and desupersaturation rates in the presence and absence of seed crystals.
    [Show full text]
  • Big Pain Assays Aren't a Big Pain with the Raptor Biphenyl LC Column
    Featured Application: 231 Pain Management and Drugs of Abuse Compounds in under 10 Minutes by LC-MS/MS Big Pain Assays Aren’t a Big Pain with the Raptor Biphenyl LC Column • 231 compounds, 40+ isobars, 10 drug classes, 22 ESI- compounds in 10 minutes with 1 column. • A Raptor SPP LC column with time-tested Restek Biphenyl selectivity is the most versatile, multiclass-capable LC column available. • Achieve excellent separation of critical isobars with no tailing peaks. • Run fast and reliable high-throughput LC-MS/MS analyses with increased sensitivity using simple mobile phases. The use of pain management drugs is steadily increasing. As a result, hospital and reference labs are seeing an increase in patient samples that must be screened for a wide variety of pain management drugs to prevent drug abuse and to ensure patient safety and adherence to their medication regimen. Thera- peutic drug monitoring can be challenging due to the low cutoff levels, potential matrix interferences, and isobaric drug compounds. To address these chal- lenges, many drug testing facilities are turning to liquid chromatography coupled with mass spectrometry (LC-MS/MS) for its increased speed, sensitivity, and specificity. As shown in the analysis below, Restek’s Raptor Biphenyl column is ideal for developing successful LC-MS/MS pain medication screening methodologies. With its exceptionally high retention and unique selectivity, 231 multiclass drug compounds and metabolites—including over 40 isobars—can be analyzed in just 10 minutes. In addition, separate panels have been optimized on the Raptor Biphenyl column specifically for opioids, antianxiety drugs, barbiturates, NSAIDs and analgesics, antidepressants, antiepileptics, antipsychotics, hallucinogens, and stimulants for use during confirmation and quantitative analyses.
    [Show full text]
  • Flufenamic Acid, Mefenamic Acid and Niflumic Acid Inhibit Single Nonselective Cation Channels in the Rat Exocrine Pancreas
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Volume 268, number 1, 79-82 FEBS 08679 July 1990 Flufenamic acid, mefenamic acid and niflumic acid inhibit single nonselective cation channels in the rat exocrine pancreas H. Gagelein*, D. Dahlem, H.C. Englert** and H.J. Lang** Max-Planck-Institutfir Biophysik, Kennedyallee 70, D-600 Frankfurt/Main 70, FRG Received 17 May 1990 The non-steroidal anti-inflammatory drugs, flufenamic acid, mefenamic acid and niflumic acid, block Ca2+-activated non-selective cation channels in inside-out patches from the basolateral membrane of rat exocrine pancreatic cells. Half-maximal inhibition was about 10 PM for flufenamic acid and mefenamic acid, whereas niflumic acid was less potent (IC,, about 50 PM). Indomethacin, aspirin, diltiazem and ibuprofen (100 /IM) had not effect. It is concluded that the inhibitory effect of flufenamate, mefenamate and niflumate is dependent on the specific structure, consisting of two phenyl rings linked by an amino bridge. Mefenamic acid; Flufenamic acid; Niflumic acid; Indomethacin; Non-selective cation channel; Rat exocrine pancreas 1. INTRODUCTION indomethacin, ibuprofen, diltiazem and acetylsalicylic acid (aspirin) were obtained from Sigma (Munich, FRG). The substances were dissolved in dimethylsulfoxide (DMSO, Merck, Darmstadt, FRG, Recently it was reported that the drug, 3 ’ ,5-dichloro- 0.1% of total volume) before addition to the measuring solution. diphenylamine-2-carboxylic acid (DCDPC), blocks DMSO alone had no effect on the single channel recordings. non-selective cation channels in the basolateral mem- 2.2. Methods brane of rat exocrine pancreatic cells [ 11.
    [Show full text]
  • 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]
  • Choice of Drugs in the Treatment of Rheumatoid Arthritis
    RHEUMATOLOGY IN GENERAL PRACTICE 7 Those with predominant but never exclusive involvement of the terminal finger joint, usually associated with changes in the nail of the same finger; they are serologically negative. There may be a swollen finger with loss of the skin markings-a sort of dactylitis, again serologically negative. (2) Those with a much more severe process which produces loss of movement in the spine and changes in the sacroiliac joints much the same as those in ankylosing spondylitis; unlike ankylosing spondylitis, it produces severe deformity often with ankylosis in peripheral joints. Many of the finger joints become deformed and ankylosed. (3) Those cases indistinguishable from rheumatoid arthritis although the majority are sero-negative. The Stevens Johnson syndrome produces acute effusions, particularly in large joints. It is sometimes associated with the rash of erythema multiforme, always with ulceration in the mouth and genital tract; the mouth ulcers are accompanied by sloughing, unlike those of Beh9et's syndrome which we come to next. BehCet's syndrome, originally described as a combination of orogenital ulceration with relapsing iritis, is now expanded to include skin lesions, other eye lesions, lesions of the central nervous system, thrombophlebitis migrans, and arthropathy (occurring in 64 per cent). The onset is acute, often affecting only a single joint and settling without residual trouble. Choice of drugs in the treatment of rheumatoid arthritis Dr Dudley Hart, M.D., F.R.C.P. (Consultant physician, Westminster Hospital and Medical School) There are many potential drugs for the treatment of rheumatoid disease, but what are we treating in this disorder? Pain in rheumatoid arthritis is but one of the symp- toms.
    [Show full text]
  • S1 Table. List of Medications Analyzed in Present Study Drug
    S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine
    [Show full text]
  • Pharmaceutical and Veterinary Compounds and Metabolites
    PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES High quality reference materials for analytical testing of pharmaceutical and veterinary compounds and metabolites. lgcstandards.com/drehrenstorfer [email protected] LGC Quality | ISO 17034 | ISO/IEC 17025 | ISO 9001 PHARMACEUTICAL AND VETERINARY COMPOUNDS AND METABOLITES What you need to know Pharmaceutical and veterinary medicines are essential for To facilitate the fair trade of food, and to ensure a consistent human and animal welfare, but their use can leave residues and evidence-based approach to consumer protection across in both the food chain and the environment. In a 2019 survey the globe, the Codex Alimentarius Commission (“Codex”) was of EU member states, the European Food Safety Authority established in 1963. Codex is a joint agency of the FAO (Food (EFSA) found that the number one food safety concern was and Agriculture Office of the United Nations) and the WHO the misuse of antibiotics, hormones and steroids in farm (World Health Organisation). It is responsible for producing animals. This is, in part, related to the issue of growing antibiotic and maintaining the Codex Alimentarius: a compendium of resistance in humans as a result of their potential overuse in standards, guidelines and codes of practice relating to food animals. This level of concern and increasing awareness of safety. The legal framework for the authorisation, distribution the risks associated with veterinary residues entering the food and control of Veterinary Medicinal Products (VMPs) varies chain has led to many regulatory bodies increasing surveillance from country to country, but certain common principles activities for pharmaceutical and veterinary residues in food and apply which are described in the Codex guidelines.
    [Show full text]
  • Drug and Medication Classification Schedule
    KENTUCKY HORSE RACING COMMISSION UNIFORM DRUG, MEDICATION, AND SUBSTANCE CLASSIFICATION SCHEDULE KHRC 8-020-1 (11/2018) Class A drugs, medications, and substances are those (1) that have the highest potential to influence performance in the equine athlete, regardless of their approval by the United States Food and Drug Administration, or (2) that lack approval by the United States Food and Drug Administration but have pharmacologic effects similar to certain Class B drugs, medications, or substances that are approved by the United States Food and Drug Administration. Acecarbromal Bolasterone Cimaterol Divalproex Fluanisone Acetophenazine Boldione Citalopram Dixyrazine Fludiazepam Adinazolam Brimondine Cllibucaine Donepezil Flunitrazepam Alcuronium Bromazepam Clobazam Dopamine Fluopromazine Alfentanil Bromfenac Clocapramine Doxacurium Fluoresone Almotriptan Bromisovalum Clomethiazole Doxapram Fluoxetine Alphaprodine Bromocriptine Clomipramine Doxazosin Flupenthixol Alpidem Bromperidol Clonazepam Doxefazepam Flupirtine Alprazolam Brotizolam Clorazepate Doxepin Flurazepam Alprenolol Bufexamac Clormecaine Droperidol Fluspirilene Althesin Bupivacaine Clostebol Duloxetine Flutoprazepam Aminorex Buprenorphine Clothiapine Eletriptan Fluvoxamine Amisulpride Buspirone Clotiazepam Enalapril Formebolone Amitriptyline Bupropion Cloxazolam Enciprazine Fosinopril Amobarbital Butabartital Clozapine Endorphins Furzabol Amoxapine Butacaine Cobratoxin Enkephalins Galantamine Amperozide Butalbital Cocaine Ephedrine Gallamine Amphetamine Butanilicaine Codeine
    [Show full text]
  • LEGISLATIVE ASSEMBLY Question on Notice
    LEGISLATIVE ASSEMBLY Question On Notice Thursday, 15 February 2018 2560. Ms M. M Quirk to the Minister for Police; I refer to the commencement of operation of the Road Traffic Amendment Act 2016 in March 2017 which introduced compulsory blood or urine samples to be taken from drivers involved in serious crashes, and I ask: (a) since March 2017 how many such samples have been taken; (b) for what specific substances are those blood or urine samples tested; (c) what are the results of those tests to date; and (d) what percentage of drivers have been found to have ingested more than one substance capable of impairing driving skills? Answer (a) The compulsory taking of blood from all drivers involved in serious crashes commenced on 10 March 2017. Between 10 March 2017 and 22 February 2018 (inclusive) a total of 398 blood test samples have been collected under the provision of the Road Traffic Amendment Act 2016. There have been no urine tests collected. (b) Please see attached table for a list of substances in blood sample that are identifiable in ChemCentre toxicology analysis (Paper Number). (c) Of the 398 blood samples collected, 48 are pending results of ChemCentre analysis. Of the 350 analysed, 259 samples had a specific substance(s) detected and 91 samples had no specific substance detected. d) Of the 259 samples with specific substance(s) detected, 92% were found to have multiple substances (more than one). Detectable Substances in Blood Samples capable of identification by the ChemCentre WA. ACETALDEHYDE AMITRIPTYLINE/NORTRIPTYLINE
    [Show full text]
  • Barbiturate Assay, Tracers, Immunogens, Antibodies and Kit
    Europaisches Patentamt J European Patent Office © Publication number: 0 457 21 3 A2 Office europeen des brevets EUROPEAN PATENT APPLICATION © Application number: 91107624.8 © intCiAGOIN 33/532, G01N 33/533, G01N 33/94, C07D 405/12 © Date of filing: 10.05.91 Priority: 16.05.90 US 524195 Inventor: Dubler, Robert Edward 5041 Adele Drive Date of publication of application: Gurnee, Illinois 60031 (US) 21.11.91 Bulletin 91/47 Inventor: Jonas, Patrick J. 1608 Alexander Court Designated Contracting States: Waukegan, Illinois 60085(US) AT BE CH DE ES FR GB IT LI NL Inventor: Grote, Jonathan 753 Durham Lane Applicant: ABBOTT LABORATORIES Grayslake, Illinois 60030(US) CHAD-0377, AP6D/2, One Abbott Park Road Inventor: Nelson, Jane Ann Abbott Park, Illinois 60064-3500(US) 623 Constitution Drive No.3 Palatine, Illinois 60074(US) Inventor: Adamczyk, Maciej 174 Quail Haven Court Gurnee, Illinois 60031 (US) Representative: Modiano, Guido et al Inventor: Cantarero, Luis A. MODIANO, JOSIF, PISANTY & STAUB 1319 Dunleer Drive Modiano & Associati Via Meravigli, 16 Mundelein, Illinois 60060(US) 1-20123 Milano(IT) © Barbiturate assay, tracers, immunogens, antibodies and kit. © The present invention is directed to a fluorescence polarization immunoassay for barbiturates, to the various components needed for preparing and carrying out such an assay, and to methods of making these compo- nents. Specifically, tracers, immunogens and antibodies are disclosed, as well as methods for preparing them and a reagent kit containing them. The tracers and the immunogens are made from substituted barbiturate compounds. A fluorescein moiety is included in the tracer, while a poly(amino acid) forms a part of the immunogen.
    [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]