DOCSLIB.ORG

Effect of Erenumab on Functional Outcomes in Patients with Episodic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Migraine J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324396 on 5 January 2021. Downloaded from Original research Effect of erenumab on functional outcomes in patients with episodic migraine in whom 2–4 preventives were not useful: results from the LIBERTY study Michel Lanteri- Minet,1,2 Peter J Goadsby ,3 Uwe Reuter,4 Shihua Wen,5 Peggy Hours- Zesiger,6 Michel D Ferrari,7 Jan Klatt 6 ► Additional material is ABSTRACT versus placebo in patients in whom 2–4 preventives published online only. To view Objective To evaluate the effect of erenumab on had not been useful from the Phase 3b LIBERTY please visit the journal online study on patient- reported, functional outcomes. (http:// dx. doi. org/ 10. 1136/ patient-reported, functional outcomes in patients with jnnp- 2020- 324396). episodic migraine (EM) in whom 2–4 preventives were These include outcomes assessing the impact of not useful from the Phase 3b LIBERTY study. migraine on everyday activities and work produc- 1Pain Department and FHU Methods As previously reported, 246 patients with tivity as well as those assessing, physical and func- InovPain, CHU Nice – Côte Azur EM with 2–4 prior failed preventives were randomised tional impairment. An improvement in these areas Université, Nice, France 2INSERM U1107 Migraine 1:1 to subcutaneous erenumab 140 mg or placebo every indicates improved quality of life for patients. and Trigeminal Pain, Auvergne 4 weeks for 12 weeks. This analysis evaluated Migraine University, Clermont- Ferrand, Physical Function Impact Diary (MPFID), Headache France METHODS 3 Impact Test (HIT-6) and Work Productivity and Activity King’s College London, NIHR/ Standard protocol approvals, registrations and Wellcome Trust King’s CRF, Impairment (WPAI) scores at Week 12. P values were London, UK nominal without multiplicity adjustment. patient consents 4Department of Neurology, Results Erenumab significantly improved MPFID- The LIBERTY study is registered with Clini- Charite Universitatsmedizin Physical Impairment (PI) and Everyday Activities (EA) calTrials.gov (NCT03096834). The final study Berlin, Berlin, Germany scores versus placebo (treatment difference (TD) (95% CI) protocol, informed consent form and accompa- 5Novartis Pharmaceuticals Corp, nying materials provided to study patients were copyright. East Hanover, New Jersey, USA MPFID-PI: −3.5 (−5.7 to –1.2) (p=0.003); MPFID-EA: 6Novartis Pharma AG, Basel, −3.9 (−6.1 to –1.7)) (p<0.001) at 12 weeks. Patients on reviewed and approved by an independent ethics Switzerland erenumab were more likely to have a ≥5- point reduction committee or relevant institutional review board 7 Department of Neurology, in MPFID score (OR vs placebo (95% CI) MPFID- EA: 2.1 at all participating sites. This study was conducted Leiden University Medical in accordance with International Council for Center, Leiden, the Netherlands (1.2 to 3.6); MPFID-PI: 2.5 (1.4 to 4.5)). A similar trend was observed for HIT-6 (TD: −3.0; p<0.001); significantly Harmonisation Good Clinical Practice guidelines. All patients provided written informed consent. All Correspondence to higher proportions of patients on erenumab reported Dr Michel Lanteri- Minet, Pain a ≥5- point reduction (OR (95% CI): 2.4 (1.4 to 4.1)). centres complied with local regulations. Department and FHU InovPain, In three out of four WPAI domains, erenumab showed Centre Hospitalier Universitaire improvement versus placebo. de Nice, Nice 06003, France; Study design Conclusion At 12 weeks, erenumab was efficacious on lanteri- minet. m@ chu- nice. fr This analysis was based on data from the Phase http://jnnp.bmj.com/ functional outcomes in patients with EM in whom 2–4 3b, 12- week, randomised, double- blind, placebo- Received 25 June 2020 preventives were not useful. controlled, multicentre, parallel group LIBERTY Revised 10 November 2020 Trial registration details ClinicalTrials. gov identifier: study conducted from 20 March 2017 until 27 Accepted 8 December 2020 NCT03096834. Published Online First 5 January October 2017, in 16 countries across Europe and 2021 Australia involving patients with EM in whom 2–4 preventives were not useful. The study design is 7 INTRODUCTION reported elsewhere. Briefly, the study included a on September 29, 2021 by guest. Protected Erenumab is a fully human monoclonal antibody screening phase (0 to 2 weeks), baseline phase (4 that inhibits the canonical calcitonin gene- related weeks), double-blind treatment phase (12 weeks), peptide (CGRP) receptor.1 Clinical studies have an ongoing open- label treatment phase (156 weeks) demonstrated the efficacy and safety of erenumab in and a safety follow-up phase (12 weeks). patients with episodic migraine (EM)2 3 and chronic Patients were randomised to receive placebo or migraine (CM)4 including in those with prior erenumab 140 mg subcutaneously in a 1:1 ratio, preventive migraine treatment failures.5 6 Results once every 4 weeks for 12 weeks. Patients who © Author(s) (or their from the Phase 3b LIBERTY study confirmed that completed the 12-week double-blind treatment employer(s)) 2021. Re- use permitted under CC BY-NC . No erenumab is a potential treatment for the manage- phase of the LIBERTY study were eligible to partici- commercial re-use . See rights ment of patients with EM in whom 2–4 preventives pate in an ongoing open- label treatment phase. The and permissions. Published were not useful.7 results of the extension phase will be reported sepa- by BMJ. An important component of migraine manage- rately. This article reports results from the 12- week To cite: Lanteri- Minet M, ment is to evaluate headache- related functional double-blind treatment phase. Goadsby PJ, Reuter U, et al. J impairment reported by patients and measured by Patients completed PRO questionnaires using an Neurol Neurosurg Psychiatry patient- reported outcomes (PROs).8 The aim of electronic diary (eDiary) platform. PRO question- 2021;92:466–472. this analysis was to evaluate the effect of erenumab naires were administered to patients either at home 466 Lanteri- Minet M, et al. J Neurol Neurosurg Psychiatry 2021;92:466–472. doi:10.1136/jnnp-2020-324396 Migraine J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324396 on 5 January 2021. Downloaded from or during visits to the clinic at baseline and during the double- daily activities because of headache, feeling ‘fed up’ or irritated blind treatment phase. because of headache and headaches limiting ability to concen- trate or work on daily activities. No recall period is specified for Inclusion criteria and previous preventive failures the first three items, while the past 4 weeks is used for the last Patients aged 18 to 65 years, with EM (4 to 14 migraine days three items. HIT-6 scores are categorised into four grades, repre- per month)9 were included in the LIBERTY study.7 Eligible senting little or no impact (49 or less), some impact (50 to 55), patients had (1) failed 2–4 prior preventive treatments: propran- substantial impact (56 to 59) and severe impact (60 to 78) due olol/metoprolol, topiramate, flunarizine, valproate/divalproex, to headache; higher scores suggest negative impact. The thresh- amitriptyline, venlafaxine, lisinopril, candesartan or other olds for minimally important intergroup differences are well 14 15 locally approved preventives (cinnarizine in the Czech Republic; established;­−1.5­for­EM ­and­−2.3­for­CM. In an individual indoramine in France; nadolol in Spain; oxetorone in France; patient, a reduction of 5 points is usually considered clinically 16 and pizotifen in Austria, the Czech Republic, France, the Nether- meaningful with negative change indicating improvement. lands, Sweden and the UK); (2) failed or were not suitable for at Functional impairment in patients with migraine was measured least one of: propranolol/metoprolol, topiramate or flunarizine; using change in HIT-6 score from baseline to Week 12, and and (3) failed or were not suitable for valproate/divalproex. percentage­of­patients­with­a­≥5-­point­reduction­in­total­HIT-6­ Efficacy failure was defined as no meaningful reduction in score between baseline and Week 12. frequency of migraine attacks after administration of drugs for 10 at least 2 to 3 months, at generally accepted therapeutic doses Work Productivity and Activity Index within the 5 years before screening. Tolerability failure was The Work Productivity and Activity Index (WPAI) (change from defined as documented discontinuation due to adverse events at baseline at Week 12), a commonly used scale that assesses work any previous time. For the purposes of this study, being deemed productivity and economic consequences of various disease unsuitable for treatment was defined as a patient being consid- states, was also evaluated. Although a headache-specific version ered to be ineligible for a treatment for medical reasons such exists, few trials have used the WPAI to assess the effects of as contraindications or precautions included in local labels, preventive treatment.17 national guidelines or other locally binding documents, or other In the WPAI- Headache tool, patients are asked six questions medically relevant reasons as confirmed by the treating physi- about work and activity impairment due to headache, including cian. Treatment failure and unsuitability were assessed on the hours worked and hours missed in the last 7 days. WPAI scores 7 basis of the patient’s medical history and medical judgement. are based on 1-item (presenteeism, activity impairment), 2-items (absenteeism) and multiple items (overall work productivity); a Outcomes score cannot be calculated if there is a missing response to the copyright. The primary and secondary efficacy endpoints of the LIBERTY corresponding item. The questionnaire was collected weekly study have been reported previously.7 and took approximately 10 min to complete at home. Due to the design of the questionnaire, patients who were not employed Migraine Physical Function Impact Diary or who were employed but with extensive ‘no-work status’ Additional endpoints including change from baseline in scores were not included in the analysis.
Recommended publications
  • TABLE 1 Studies of Antagonist Activity in Constitutively Active

    TABLE 1 Studies of Antagonist Activity in Constitutively Active

    TABLE 1 Studies of antagonist activity in constitutively active receptors systems shown to demonstrate inverse agonism for at least one ligand Targets are natural Gs and constitutively active mutants (CAM) of GPCRs. Of 380 antagonists, 85% of the ligands demonstrate inverse agonism. Receptor Neutral Antagonist Inverse Agonist Reference Human β2-adrenergic Dichloroisoproterenol, pindolol, labetolol, timolol, Chidiac et al., 1996; Azzi et alprenolol, propranolol, ICI 118,551, cyanopindolol al., 2001 Turkey erythrocyte β-adrenergic Propranolol, pindolol Gotze et al., 1994 Human β2-adrenergic (CAM) Propranolol Betaxolol, ICI 118,551, sotalol, timolol Samama et al., 1994; Stevens and Milligan, 1998 Human/guinea pig β1-adrenergic Atenolol, propranolol Mewes et al., 1993 Human β1-adrenergic Carvedilol CGP20712A, metoprolol, bisoprolol Engelhardt et al., 2001 Rat α2D-adrenergic Rauwolscine, yohimbine, WB 4101, idazoxan, Tian et al., 1994 phentolamine, Human α2A-adrenergic Napthazoline, Rauwolscine, idazoxan, altipamezole, levomedetomidine, Jansson et al., 1998; Pauwels MPV-2088 (–)RX811059, RX 831003 et al., 2002 Human α2C-adrenergic RX821002, yohimbine Cayla et al., 1999 Human α2D-adrenergic Prazosin McCune et al., 2000 Rat α2-adrenoceptor MK912 RX821002 Murrin et al., 2000 Porcine α2A adrenoceptor (CAM- Idazoxan Rauwolscine, yohimbine, RX821002, MK912, Wade et al., 2001 T373K) phentolamine Human α2A-adrenoceptor (CAM) Dexefaroxan, (+)RX811059, (–)RX811059, RS15385, yohimbine, Pauwels et al., 2000 atipamezole fluparoxan, WB 4101 Hamster α1B-adrenergic
  • Alpha^ and Beta^Blocking Agents: Pharmacology and Properties

    Alpha^ and Beta^Blocking Agents: Pharmacology and Properties

    CURRENT DRUG THERAPY DONALD G. VIDT, MD AND ALAN BAKST, PharmD, EDITORS Alpha^ and beta^blocking agents: pharmacology and properties PROFESSOR B.N.C. PRICHARD • Adrenergic receptors have been separated into alpha and beta groups, which have then been further subdivided. Agents have been developed that block each type of receptor with varying degrees of specificity between the sub-types, leading to differences in pharmacodynamic profile. A more recent innovation has been the development of multiple action beta-blocking drugs, ie, those not only blocking the beta receptors but also posessing a peripheral vasodilator effect that may be due to alpha blockade, beta-2 stimulation, or a vasodilator action independent of either alpha or beta receptors. • INDEX TERMS: ALPHA BLOCKERS; BETA BLOCKERS; HYPERTENSION • CLEVE CLIN ] MED 1991; 58:33 7-350 HE CONCEPT that binding of Rosenblueth suggested that a transmitter released at catecholamines to receptors leads to differ- sympathetic nerve endings produced either inhibitory ing responses was first described by Langley, or excitatory responses as a result of combination with who in 1905 noted that a cell may make sympathin I or sympathin E at the receptor.3 Tmotor or inhibitory substances or both, and that "the The current classification of alpha and beta respon- effect of a nerve impulse depends upon the proportion ses is based on the classic work of Ahlquist,4 who of the two kinds of receptive substance which is af- studied six sympathomimetic amines and found two fected by the impulse."1 In 1906, Dale reported that patterns of reactivity. One group of actions, mediated ergot blocked the excitatory but not the inhibitory ac- by what were termed "alpha receptors," were principally tions of adrenaline.2 In 1933, Cannon and excitatory.
  • Adrenoceptor Subtype 1Ian Marshall, Richard P

    Adrenoceptor Subtype 1Ian Marshall, Richard P

    Brifish Journal of Pharmacology (I995) 115, 781 - 786 1995 Stockton Press All rights reserved 0007-1188/95 $12.00 X Noradrenaline contractions of human prostate mediated by aClA- (cxlc) adrenoceptor subtype 1Ian Marshall, Richard P. Burt & *Christopher R. Chapple Department of Pharmacology, University College London, Gower Street, London WC1E 6BT and *Department of Urology, The Royal Hallamshire Hospital, Glossop Road, Sheffield SlO 2JF 1 The subtype of a1-adrenoceptor mediating contractions of human prostate to noradrenaline was characterized by use of a range of competitive and non-competitive antagonists. 2 Contractions of the prostate to either noradrenaline (pD2 5.5), phenylephrine (pD2 5.1) or methoxamine (pD2 4.4) were unaltered by the presence of neuronal and extraneuronal uptake blockers. Noradrenaline was about 3 and 10 times more potent than phenylephrine and methoxamine respectively. Phenylephrine and methoxamine were partial agonists. 3 Pretreatment with the alkylating agent, chlorethylclonidine (10-4 M) shifted the noradrenaline concentration-contraction curve about 3 fold to the right and depressed the maximum response by 31%. This shift is 100 fold less than that previously shown to be produced by chlorethylclonidine under the same conditions on OlB-adrenoceptor-mediated contractions. 4 Cumulative concentration-contraction curves for noradrenaline were competitively antagonized by WB 4101 (pA2 9.0), 5-methyl-urapidil (pA2 8.6), phentolamine (pA2 7.6), benoxathian (pA2 8.5), spiperone (pA2 7.3), indoramin (pA2 8.2) and BMY 7378 (pA2 6.6). These values correlated best with published pKi values for their displacement of [3H]-prazosin binding on membranes expressing cloned oczc-adrenoceptors and poorly with values from cloned lb- and cld-adrenoceptors.
  • Drugs Affectin the Autonomic Nervous System

    Drugs Affectin the Autonomic Nervous System

    Fundamentals of Medical Pharmacology Paterson Public Schools Written by Néstor Collazo, Ph.D. Jonathan Hodges, M.D. Tatiana Mikhaelovsky, M.D. for Health and Related Professions (H.A.R.P.) Academy March 2007 Course Description This fourth year course is designed to give students in the Health and Related Professions (H.A.R.P.) Academy a general and coherent explanation of the science of pharmacology in terms of its basic concepts and principles. Students will learn the properties and interactions between chemical agents (drugs) and living organisms for the rational and safe use of drugs in the control, prevention, and therapy of human disease. The emphasis will be on the fundamental concepts as they apply to the actions of most prototype drugs. In order to exemplify important underlying principles, many of the agents in current use will be singled out for fuller discussion. The course will include the following topics: ¾ The History of Pharmacology ¾ Terminology Used in Pharmacology ¾ Drug Action on Living Organisms ¾ Principles of Pharmacokinetics ¾ Dose-Response Relationships ¾ Time-Response Relationships ¾ Human Variability: Factors that will modify effects of drugs on individuals ¾ Effects of Drugs Attributable to Varying Modes of Administration ¾ Drug Toxicity ¾ Pharmacologic Aspects of Drug Abuse and Drug Dependence Pre-requisites Students must have completed successfully the following courses: Biology, Chemistry, Anatomy and Physiology, Algebra I and II Credits: 5 credits Basic Principles of Drug Action Introduction to Pharmacology a. Basic Mechanisms of Drug Actions b. Dose-response relationships c. Drug absorption d. Biotransformation of Drugs e. Pharmacokinetics f. Factors Affecting Drug Distribution g. Drug Allergy and Pharmacogenetics h.
  • (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen Et Al

    (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen Et Al

    US009283192B2 (12) United States Patent (10) Patent No.: US 9,283,192 B2 Mullen et al. (45) Date of Patent: Mar. 15, 2016 (54) DELAYED PROLONGED DRUG DELIVERY 2009. O1553.58 A1 6/2009 Diaz et al. 2009,02976O1 A1 12/2009 Vergnault et al. 2010.0040557 A1 2/2010 Keet al. (75) Inventors: Alexander Mullen, Glasgow (GB); 2013, OO17262 A1 1/2013 Mullen et al. Howard Stevens, Glasgow (GB); Sarah 2013/0022676 A1 1/2013 Mullen et al. Eccleston, Scotstoun (GB) FOREIGN PATENT DOCUMENTS (73) Assignee: UNIVERSITY OF STRATHCLYDE, Glasgow (GB) EP O 546593 A1 6, 1993 EP 1064937 1, 2001 EP 1607 O92 A1 12/2005 (*) Notice: Subject to any disclaimer, the term of this EP 2098 250 A1 9, 2009 patent is extended or adjusted under 35 JP HO5-194188 A 8, 1993 U.S.C. 154(b) by 0 days. JP 2001-515854. A 9, 2001 JP 2001-322927 A 11, 2001 JP 2003-503340 A 1, 2003 (21) Appl. No.: 131582,926 JP 2004-300148 A 10, 2004 JP 2005-508326 A 3, 2005 (22) PCT Filed: Mar. 4, 2011 JP 2005-508327 A 3, 2005 JP 2005-508328 A 3, 2005 (86). PCT No.: PCT/GB2O11AOOO3O7 JP 2005-510477 A 4/2005 JP 2008-517970 A 5, 2008 JP 2009-514989 4/2009 S371 (c)(1), WO WO99,12524 A1 3, 1999 (2), (4) Date: Oct. 2, 2012 WO WOO1 OO181 A2 1, 2001 WO WOO3,O266.15 A2 4/2003 (87) PCT Pub. No.: WO2011/107750 WO WOO3,O26625 A1 4/2003 WO WO 03/026626 A2 4/2003 PCT Pub.
  • Systematic Evidence Review from the Blood Pressure Expert Panel, 2013

    Systematic Evidence Review from the Blood Pressure Expert Panel, 2013

    Managing Blood Pressure in Adults Systematic Evidence Review From the Blood Pressure Expert Panel, 2013 Contents Foreword ............................................................................................................................................ vi Blood Pressure Expert Panel ..............................................................................................................vii Section 1: Background and Description of the NHLBI Cardiovascular Risk Reduction Project ............ 1 A. Background .............................................................................................................................. 1 Section 2: Process and Methods Overview ......................................................................................... 3 A. Evidence-Based Approach ....................................................................................................... 3 i. Overview of the Evidence-Based Methodology ................................................................. 3 ii. System for Grading the Body of Evidence ......................................................................... 4 iii. Peer-Review Process ....................................................................................................... 5 B. Critical Question–Based Approach ........................................................................................... 5 i. How the Questions Were Selected ................................................................................... 5 ii. Rationale for the Questions
  • Association Between Stevens- Johnson Syndrome And

    Association Between Stevens- Johnson Syndrome And

    BRITISH MEDICAL JOURNAL VOLUME 282 2 MAY 1981 1433 urinary excretion rose to 2 17 1/24 h, with chloride 249 mmol/24 h and lymphocytic infiltration of the epidermis. Direct immunofluorescence tests potassium 178 mmol/24 h. Mean fall in body weight was 0-29 kg/day. The with labelled antihuman immunoglobulin A and G and C3 were negative. patient became oedema free over two weeks. Benoxaprofen was stopped on admission and the rash subsided over the Case 4-A 40-year-old man with severe ischaemic heart disease presented course of 14 days. Profuse desquamation occurred, particularly on the with congestive cardiac failure. Blood pressure was 170/90 mm Hg. palms of the hands. At no stage did the rash resemble a photoallergic or Piretanide was used in incremental doses up to 24 mg daily. On this dose phototoxic drug rash. urinary excretion was 1-0 1/24 h, with sodium 39 mmol/24 h, chloride 35 mmol/24 h, and potassium 35 mmol/24 h. Mean fall in body weight was 0-3 kg/day. As oedema persisted, 5 mg metolazone was added. Urinary Comment excretion rose to 2-48 1/24 h, with sodium 210 mmol/24 h, chloride 202 mmol/24 h, and potassium 73 mmol/24 h. Body weight fell by 0-6 kg/day. The Stevens-Johnson syndrome is a potentially lethal condition Oedema cleared over two weeks. Potassium supplements were necessary. that is often precipitated by drug treatment, sulphonamides being the drugs most commonly implicated.2 The association of this syndrome with treatment with benoxaprofen is important, especially Comment in view of the enthusiastic press reviews3 4 which greeted the launch of Adding relatively small doses of metolazone to high-dose "loop" the drug.
  • Prostate Gland Enlargement

    Prostate Gland Enlargement

    Prostate Gland Enlargement The prostate gland commonly becomes larger in older men. This is called Benign Prostatic Hyperplasia. It can cause problems with passing urine. Symptoms are often mild. Without treatment, symptoms do not always get worse, and may even improve over time. If symptoms become troublesome or distressing they can often be improved by medicines or surgery. This leaflet only deals with benign (non-cancerous) enlargement of the prostate. Cancer of the prostate is a separate condition and is dealt with in another leaflet. What is the prostate gland? The prostate gland (just called 'prostate' from now on) is only found in men. It lies just beneath the bladder (see diagram). It is normally about the size of a chestnut. The urethra (the tube which passes urine from the bladder) runs through the middle of the prostate. The prostate helps to make semen, but most semen is made by the seminal vesicle (another gland nearby). The prostate gets bigger ('enlarges') gradually after the age of about 50. By the age of 70, about 8 in 10 men have an enlarged prostate. So, in later life it is as normal for your prostate to enlarge as it is to have grey hair. What are the symptoms of prostate enlargement? About 1 in 3 men aged over 50 have some symptoms due to an enlarged prostate. As the prostate enlarges it may cause narrowing of the first part of the urethra. This may partially obstruct the flow of urine from the bladder. This can lead to 'obstructive' symptoms such as: • Poor stream.
  • Indoramin in the Treatment of Hypertension

    Indoramin in the Treatment of Hypertension

    SA MEDICAL JOURNAL VOLUME 63 26 FEBRUARY 1983 307 Indoramin in the treatment of hypertension A mini-review and update J. L. ARCHIBALD, P. TURNER prevent this reflex response; the mode of action of indoramin Summary reflects this approach.2 In the synthesis of indoramin,3 features of two types of mole­ The origins, pr-eclinical development a'nd clinical cule were combined. A series ofso-called bis-indoles4 had shown pharmacology of a new antihypertensive agent, good antihypertensive activity in which a-blockade was believed indoramin (Baratol; Wyeth), are briefly reviewed. ro have played an important part. Replacement of one indolyl­ Indoramin is a competitive postsynaptic a-adreno­ ethyl moiety of the bis-indole by a benzamido group gave ri e ro ceptor antagonist with a myocardial membrane­ indoramin, in which a resemblance to procainamide had been stabilizing component of action. These features are incorporated.; The extent to which an a-blocking action (as in believed to be responsible for its antihypertensive the bis-indole) and membrane-stabilizing action (as in procam­ efficacy. They may also explain the absence of prob­ amide) had been combined in the new molecule can perhaps be lems common to older a-blockers such as reflex judged from the following section. tachycardia and postural hypotension. Clinical ev~­ luation of a new agent such as indoramin in the management of hypertension is discussed in terms Preclinical development of efficacy, dosage regimen, tolerance, adverse effects, interactions, withdrawal syndrome, and Indoramin lowered blood pressure effectively in all species stu­ long-term influence on the complications of high 6 died.
  • Insights from Studies of the Renal Regulation of Arterial Blood Pressure

    Insights from Studies of the Renal Regulation of Arterial Blood Pressure

    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector REVIEW published: 29 July 2016 doi: 10.3389/fphys.2016.00320 How Do Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of Arterial Blood Pressure Holly Digne-Malcolm 1, Matthew C. Frise 2 and Keith L. Dorrington 2, 3* 1 Medical Sciences Division, University of Oxford, Oxford, UK, 2 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK, 3 Nuffield Department of Anaesthetics, John Radcliffe Hospital, Oxford, UK Though antihypertensive drugs have been in use for many decades, the mechanisms by which they act chronically to reduce blood pressure remain unclear. Over long periods, mean arterial blood pressure must match the perfusion pressure necessary for the kidney to achieve its role in eliminating the daily intake of salt and water. It follows that the kidney is the most likely target for the action of most effective antihypertensive agents used chronically in clinical practice today. Here we review the Edited by: long-term renal actions of antihypertensive agents in human studies and find three Alexander Staruschenko, Medical College of Wisconsin, USA different mechanisms of action for the drugs investigated. (i) Selective vasodilatation of Reviewed by: the renal afferent arteriole (prazosin, indoramin, clonidine, moxonidine, α-methyldopa, ++ Roger Evans, some Ca -channel blockers, angiotensin-receptor blockers, atenolol, metoprolol, Monash University, Australia bisoprolol, labetolol, hydrochlorothiazide, and furosemide). (ii) Inhibition of tubular solute Zhen Wang, University of Mississippi Medical reabsorption (propranolol, nadolol, oxprenolol, and indapamide). (iii) A combination of Center, USA these first two mechanisms (amlodipine, nifedipine and ACE-inhibitors).
  • New Hypnotic and Anxiolytic Resources

    New Hypnotic and Anxiolytic Resources

    NORTHERN IRELAND MEDICINES MANAGEMENT January 2021 Volume 12, Issue 1 Health and Social Care Board NEWSLETTER In This Issue Advise Patients on Risk of Addiction with Opioid Medicines NEW Resources New Hypnotic and Anxiolytic Resources ! Correction: NI Formulary Lower Urinary Tract Symptoms in men Managed Entry Decisions and potential duplication of therapy Advise Patients on Risk of Addiction with Opioid Medicines Following a review of risks of dependence and addiction associated with prolonged use of opioids for non-cancer pain, the MHRA now advises all healthcare professionals to: Discuss with patients that prolonged use of opioids may lead to drug dependence and addiction, even at therapeutic doses – warnings have been added to the labels (packaging) of UK opioid medicines Before starting treatment, agree with the patient a treatment strategy and plan for end of treatment Explain the risks of tolerance and potentially fatal unintentional overdose, and counsel patients and caregivers on signs and symptoms of opioid overdose to be aware of Provide regular monitoring and support especially to individuals at increased risk, such as those with current or past history of substance use disorder (including alcohol misuse) or mental health disorder At the end of treatment, taper dosage slowly to reduce the risk of withdrawal effects associated with sudden cessation of opioids; tapering from a high dose may take weeks or months Consider the possibility of hyperalgesia if a patient on long-term therapy presents with increased sensitivity to pain Consult the latest advice and warnings for opioids during pregnancy Report suspected dependence or addiction to any medicine, including to an opioid, via the Yellow Card scheme.
  • Indoramin Pregnancy in the Treatment Hypertension

    Indoramin Pregnancy in the Treatment Hypertension

    458 SAMJ VOL 78 20 OCT 1990 Indoramin in the treatment of pregnancy hypertension A placebo-controlled trial comparing the efficacy ofindoramin with alpha-methyldopa J. ANTHONY, A. E. REES, D. A. DAVEY Summary controlled clinical trial was carried out to compare the effects of indoramin with those of an established antihypertensive A placebo-controlled trial was used to assess the anti­ drug, alpha-methyldopa, and those of a placebo. hypertensive efficacy of indoramin in the management of pregnancy hypertension. Sixty patients were recruited into the study and only 17 attained satisfactory blood pressure control. In the doses of drugs administered indoramin was Patients and methods not shown to be more effective than alpha-methyldopa. Black and coloured patients between 28 weeks' and 36 weeks' S Atr Med J 1990; 78: 458-461. gestation attending the Pregnancy Hypertension Clinic at Groote Schuur Hospital were recruited into the study after informed consent about the nature and purpose of the trial The use of antihypertensive agents in pregnancy hypertension had been obtained. All patients were admitted for preliminary is controversial, since treatment is primarily directed to the assessment and were only entered into the trial if their mean control of one of the manifestations and not to the disease 24-hour diastolic blood pressure after admission was in the itself. Severe hypertension, however, may be a risk to the range 100 - 120 mmHg with or without proteinuria. mother and necessitate treatment. When hypertension is severe Patients were allocated to one of three treatment groups and thl' '"etus is immature it may be possible to 'buy time' with (indoramin, methyldopa or placebo) using.