DOCSLIB.ORG

Medications.Pdf

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Medications.Pdf Parkinson’s Disease Medications By David Houghton, MD, MPH, Howard Hurtig, MD, and Sharon Metz, RN, MPH, with guest authors Monique Giroux, MD, Giselle Petzinger, MD, Beth Fisher, PT, PhD, Lauren Hawthorne, BS, and Michael Jakowec, PhD 301277_NPF-Medications.indd 1 10/30/17 1:24 PM Parkinson’s Disease: Medications 301277_NPF-Medications.indd 2 10/30/17 1:24 PM Parkinson’s Disease: Medications Table of Contents Chapter 1 Introduction to Parkinson’s Disease..........................................................5 Chapter 2 Medications for Motor Symptoms ............................................................8 Chapter 3 Medications for Non-Motor Symptoms ................................................21 Chapter 4 Exercise Is Medicine ................................................................................... 46 Chapter 5 Integrative Medicine ................................................................................... 49 Chapter 6 Research and Future Developments ......................................................63 Summary of Tables Table 1 Symptoms in Parkinson’s Disease ............................................................6 Table 2 Medications for Motor Symptoms in PD ..................................................9 Table 3 Medications for Depression and Anxiety in PD ...................................25 Table 4 Medications for Dementia and Hallucinations in PD .........................32 Table 5 Medications for Gastrointestinal (GI) Symptoms and Drooling in PD ............................................................................................... 40 Appendix A Glossary ..........................................................................................................67 Appendix B Medical Alert Card .......................................................................................72 Appendix C Formula for Liquid Sinemet .......................................................................73 Appendix D Epworth Sleepiness Scale .........................................................................74 Appendix E Selected Readings........................................................................................75 About the Authors ............................................................................................................................76 Index ............................................................................................................................78 301277_NPF-Medications.indd 3 10/30/17 1:24 PM Parkinson’s Disease: Medications Introduction This book concentrates on the medications used in Parkinson’s disease (PD). Ideally, the treatment of PD would be symptomatic (control or reduction of symptoms), neuroprotective (halting or slowing of disease progression) and neuroregenerative (reversal of disease process). At present, proven therapies only help to relieve symptoms. More than a dozen different medications are now being used routinely to combat the motor symptoms of PD. Many others target the non-motor complications of PD. Considerable research remains dedicated to uncovering neuroprotective or neuroregenerative strategies, but to date, no such definitive therapies have been discovered. Throughout this manual, medications currently available for symptomatic treatment and future developments in the treatment of PD are discussed. 4 301277_NPF-Medications.indd 4 10/30/17 1:24 PM Parkinson’s Disease: Medications Chapter 1 Introduction to Parkinson’s Disease Classic Symptoms The primary symptoms of Parkinson’s disease (PD) were first described by James Parkinson in 1817 in his Essay on the Shaking Palsy. These include: • Tremor (usually most noticeable when the limb is at rest) • Bradykinesia (slowness of movement) • Rigidity (stiffness of movement) • Postural instability (imbalance when standing or walking) A PD diagnosis is based on evidence of at least two out of three specific signs and symptoms: tremor, slowed mobility (bradykinesia) and/or stiffness (rigidity). The occurrence of symptoms on only one side of the body is typical of the disease in its earliest stage. The diagnosis of Parkinson’s disease remains clinical; that is, there are no conventional or readily available laboratory tests or brain images that can “prove” PD, though dopamine transporter scanning may help with diagnostic puzzles (see discussion in Pathology section). Other characteristic features of PD include: • Micrographia (small handwriting) • Hypophonic dysarthria (soft, less understandable speech) • Stooped posture • Shuffling steps • Diminished facial expression • Infrequent eye blinking Early falling or postural instability, commonly seen later in classic PD, may suggest other parkinsonian syndromes such as: • Progressive supranuclear palsy (PSP) • Corticobasal degeneration (CBD) • Multiple system atrophy (MSA) • Dementia with Lewy bodies (DLB) As the above symptoms predominantly involve movement, they are called motor symptoms. Parkinson’s disease is not only a disorder of motor symptoms. It is now well known that non-motor symptoms also can be prominent and even disabling in PD. Non- motor symptoms include changes in mood, memory, blood pressure, bowel and bladder function, sleep, fatigue, weight and sensation (Table 1). Some symptoms have features of both (i.e., mixed motor and non-motor symptoms). 5 301277_NPF-Medications.indd 5 10/30/17 1:24 PM Parkinson’s Disease: Medications Table 1. Symptoms in Parkinson’s Disease MOTOR SYMPTOMS • Bradykinesia (slowness of movement) • Rigidity (stiffness of movement) • Tremor (involuntary shaking of the hands, feet, arms, legs, jaw or tongue; usually more prominent at rest) • Postural instability (tendency to fall, usually when pivoting) NON-MOTOR SYMPTOMS • Mood changes (depression, anxiety, irritability) • Cognitive changes (memory problems, personality changes, psychosis/hallucinations) • Orthostatic hypotension (lightheadedness and low blood pressure when standing) • Constipation and early satiety (a feeling of fullness after eating small amounts) • Hyperhidrosis (excessive sweating) • Seborrhea (oily skin) • Urinary urgency and incontinence • Sexual dysfunction • Loss of sense of smell • Sleep disorders • Insomnia, excessive daytime sleepiness (EDS), rapid eye movement behavioral disorder (RBD) or active dreaming, dream enactment, involuntary movements and vocalizations during sleep, restless leg syndrome (RLS)/periodic limb movement disorder (PLMD) • Fatigue • Sensory problems (pain, tightness, tingling, burning) MIXED MOTOR AND NON-MOTOR SYMPTOMS • Drooling due to slowed swallowing (sialorrhea) • Speech and swallowing problems 6 301277_NPF-Medications.indd 6 10/30/17 1:24 PM Parkinson’s Disease: Medications Much clinical research is being conducted to try to recognize early features of Parkinson’s disease. Motor symptoms typically begin on one side of the body, often as a rest tremor or a reduced ability to use the hand, arm or leg on the affected side. Prior to the appearance of the motor features of PD, individuals may also recognize that they have experienced constipation, vivid dreams, depression and/or diminished sense of smell for months or even years. These “pre-motor” symptoms may provide the opportunity for earliest recognition of the PD complex, with more clinical trials and earlier treatment strategies on the horizon. PATHOLOGY Parkinson’s disease is a result of the loss of specific types of brain cells (neurons) that produce a chemical called dopamine. The motor symptoms come from the slow and progressive degeneration and death of these neurons in an area of the brain called the substantia nigra, which is in the brain stem. One reason these brain cells begin to die may be due to genetic abnormalities. The earliest symptoms of PD usually don’t appear for several years after the onset of neurodegeneration because there is plenty of dopamine left in reserve to compensate for the declining supply. In other words, a person will lose at least 50% of the dopamine in his or her brain before noticing that something is wrong with his or her body. We now also know that the non- motor features of PD arise from the loss of neurons in areas of the brain outside of the substantia nigra and involve chemicals other than dopamine, particularly acetylcholine. In 2011, a computerized brain scan utilizing a radio-isotope that labels the molecule transporting dopamine into the cell (DaTscan) first became available in the United States. A DaTscan may be used to assist with the clinical diagnosis of PD and other parkinsonian syndromes when the patient’s presenting symptoms are not straightforward. TREATMENT It is important for persons with PD to realize that although the underlying disease progresses slowly, the clinical course over many years varies greatly with each person. Effective management of PD symptoms requires an experienced and compassionate healthcare provider, the person with PD and his or her care partner to determine a treatment plan consisting of appropriate medications, regular exercise, a healthy diet, social engagement and cognitive activities, counseling and other therapies. As the disease progresses and problems accumulate, deep brain stimulation (DBS) surgery may be a reasonable therapeutic option for some individuals, although many people with PD do not qualify for DBS for a variety of reasons. However, the majority of people with PD can lead full and active lives with good symptom control for many years. 7 301277_NPF-Medications.indd 7 10/30/17 1:24 PM Parkinson’s Disease: Medications
Load more

Recommended publications
  • Citizen Cyborg.” Citizen a Groundbreaking Work of Social Commentary, Citizen Cyborg Artificial Intelligence, Nanotechnology, and Genetic Engineering —DR
    hughes (continued from front flap) $26.95 US ADVANCE PRAISE FOR ARTIFICIAL INTELLIGENCE NANOTECHNOLOGY GENETIC ENGINEERING MEDICAL ETHICS INVITRO FERTILIZATION STEM-CELL RESEARCH $37.95 CAN citizen LIFE EXTENSION GENETIC PATENTS HUMAN GENETIC ENGINEERING CLONING SEX SELECTION ASSISTED SUICIDE UNIVERSAL HEALTHCARE human genetic engineering, sex selection, drugs, and assisted In the next fifty years, life spans will extend well beyond a century. suicide—and concludes with a concrete political agenda for pro- cyborg Our senses and cognition will be enhanced. We will have greater technology progressives, including expanding and deepening control over our emotions and memory. Our bodies and brains “A challenging and provocative look at the intersection of human self-modification and human rights, reforming genetic patent laws, and providing SOCIETIES MUST RESPOND TO THE REDESIGNED HUMAN OF FUTURE WHY DEMOCRATIC will be surrounded by and merged with computer power. The limits political governance. Everyone wondering how society will be able to handle the coming citizen everyone with healthcare and a basic guaranteed income. of the human body will be transcended, as technologies such as possibilities of A.I. and genomics should read Citizen Cyborg.” citizen A groundbreaking work of social commentary, Citizen Cyborg artificial intelligence, nanotechnology, and genetic engineering —DR. GREGORY STOCK, author of Redesigning Humans illuminates the technologies that are pushing the boundaries of converge and accelerate. With them, we will redesign ourselves and humanness—and the debate that may determine the future of the our children into varieties of posthumanity. “A powerful indictment of the anti-rationalist attitudes that are dominating our national human race itself.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas Et Al
    US 20130253 056A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0253056A1 Nemas et al. (43) Pub. Date: Sep. 26, 2013 (54) CONTINUOUS ADMINISTRATION OF (60) Provisional application No. 61/179,511, filed on May LEVODOPA AND/OR DOPA 19, 2009. DECARBOXYLASE INHIBITORS AND COMPOSITIONS FOR SAME Publication Classification (71) Applicant: NEURODERM, LTD., Ness-Ziona (IL) (51) Int. Cl. A63L/216 (2006.01) (72) Inventors: Mara Nemas, Gedera (IL); Oron (52) U.S. Cl. Yacoby-Zeevi, Moshav Bitsaron (IL) CPC .................................... A6 IK3I/216 (2013.01) USPC .......................................................... 514/538 (73) Assignee: Neuroderm, Ltd., Ness-Ziona (IL) (57) ABSTRACT (21) Appl. No.: 13/796,232 Disclosed herein are for example, liquid aqueous composi (22) Filed: Mar 12, 2013 tions that include for example an ester or salt of levodopa, or an ester or salt of carbidopa, and methods for treating neuro Related U.S. Application Data logical or movement diseases or disorders such as restless leg (63) Continuation-in-part of application No. 12/961,534, syndrome, Parkinson's disease, secondary parkinsonism, filed on Dec. 7, 2010, which is a continuation of appli Huntington's disease, Parkinson's like syndrome, PSP. MSA, cation No. 12/836,130, filed on Jul. 14, 2010, now Pat. ALS, Shy-Drager syndrome, dystonia, and conditions result No. 7,863.336, which is a continuation of application ing from brain injury including carbon monoxide or manga No. 12/781,357, filed on May 17, 2010, now Pat. No. nese intoxication, using Substantially continuous administra 8,193,243. tion of levodopa and/or carbidopa or ester and/or salt thereof.
    [Show full text]
  • Addictions and the Brain
    9/18/2012 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements • La Hacienda Treatment Center • American Society of Addiction Medicine • National Institute of Drug Abuse © 2012 La Hacienda Treatment Center. All rights reserved. 1 9/18/2012 Definition • A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability. DSM IV Criteria for dependency: At least 3 of the 7 below 1. Withdrawal 2. Tolerance 3. The substance is taken in larger amounts or over a longer period than was intended. 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use. 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. 6. Important social, occupational, or recreational activities are given up or reduced because of the substance use. 7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. © 2012 La Hacienda Treatment Center. All rights reserved. 2 9/18/2012 Dispute between behavior and disease Present understanding of the Hypothalamus location of the disease hypothesis. © 2012 La Hacienda Treatment Center. All rights reserved. 3 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 4 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 5 9/18/2012 Dispute regarding behavior versus disease © 2012 La Hacienda Treatment Center. All rights reserved. 6 9/18/2012 © 2012 La Hacienda Treatment Center.
    [Show full text]
  • The Postmortem Distribution of Vardenafil (Levitra | in an Aviation
    Journal of Analytical Toxicology, Vol. 31, July/August 2007 The Postmortem Distribution of Vardenafil (Levitra| in an Aviation Accident Victim with an Unusually High Blood Concentration* Robert D. Johnson ~, Russell J. Lewis, and Mike K. Angler Downloaded from https://academic.oup.com/jat/article/31/6/328/682815 by guest on 27 September 2021 Civil Aerospace Medical Institute, Federal Aviation Administration, Analytical Toxicology and Accident Research Laboratory, AAM-610, CAMI Building, 6500 S. MacArthur Blvd., Oklahoma City, Oklahoma 73169-6901 I Abstract phodiesterase type 5 enzyme (PDE5) found predominantly in the penile corpus cavernosum (2-7). Vardenafil (tevitra) is one of the most widely prescribed Vardenafil undergoes hepatic metabolism, producing the treatments for erectile dysfunction. This report presents a active desethyl metabolite M1. M1 contributes to the ob- rapid and reliable method for the identification and quantification served pharmacological effects provided by vardenafil, as M1 of vardenafil in postmortem fluids and tissues, applies this method exhibits approximately 30% of the potency of the parent to a postmortem case, and describes the distribution of vardenafil in various fluids and tissues.This procedure utilizes sildenafil-d8, drug (1). Under steady-state conditions, the plasma concen- which is structurally closely related to vardenafil, as an tration of M1 is approximately 26% of that seen for vardenafil internal standard for more accurate and reliable quantitation. (1). After oral administration of vardenafil, peak plasma con- The method incorporates solid-phaseextraction and liquid centrations are obtained within 30-60 min (1). Vardenafil chromatography-tandem mass spectrometry (MS) and and its active metabolite have a terminal half-life of approx- MS-MS-MS utilizing an atmospheric pressure chemical imately 4-5 h (1).
    [Show full text]
  • Parkinson Disease-Associated Cognitive Impairment
    PRIMER Parkinson disease-associated cognitive impairment Dag Aarsland 1,2 ✉ , Lucia Batzu 3, Glenda M. Halliday 4, Gert J. Geurtsen 5, Clive Ballard 6, K. Ray Chaudhuri 3 and Daniel Weintraub7,8 Abstract | Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment. Parkinson disease (PD) is the most common movement The full spectrum of cognitive impairment occurs in disorder and the second most common neurodegenera­ individuals with PD, from subjective cognitive decline tive disorder after Alzheimer disease (AD).
    [Show full text]
  • Supplement Ii to the Japanese Pharmacopoeia Fifteenth Edition
    SUPPLEMENT II TO THE JAPANESE PHARMACOPOEIA FIFTEENTH EDITION Official From October 1, 2009 English Version THE MINISTRY OF HEALTH, LABOUR AND WELFARE Notice: This English Version of the Japanese Pharmacopoeia is published for the conven- ience of users unfamiliar with the Japanese language. When and if any discrepancy arises between the Japanese original and its English translation, the former is authentic. The Ministry of Health, Labour and Welfare Ministerial Notification No. 425 Pursuant to Paragraph 1, Article 41 of the Pharmaceutical Affairs Law (Law No. 145, 1960), we hereby revise a part of the Japanese Pharmacopoeia (Ministerial Notification No. 285, 2006) as follows*, and the revised Japanese Pharmacopoeia shall come into ef- fect on October 1, 2009. However, in the case of drugs which are listed in the Japanese Pharmacopoeia (hereinafter referred to as “previous Pharmacopoeia”) [limited to those listed in the Japanese Pharmacopoeia whose standards are changed in accordance with this notification (hereinafter referred to as “new Pharmacopoeia”)] and drugs which have been approved as of October 1, 2009 as prescribed under Paragraph 1, Article 14 of the same law [including drugs the Minister of Health, Labour and Welfare specifies (the Ministry of Health and Welfare Ministerial Notification No. 104, 1994) as those ex- empted from marketing approval pursuant to Paragraph 1, Article 14 of the Pharmaceu- tical Affairs Law (hereinafter referred to as “drugs exempted from approval”)], the Name and Standards established in the previous Pharmacopoeia (limited to part of the Name and Standards for the drugs concerned) may be accepted to conform to the Name and Standards established in the new Pharmacopoeia before and on March 31, 2011.
    [Show full text]
  • A Schematic Approach to Hypotonia in Infancy
    Leyenaar.qxd 8/26/2005 4:03 PM Page 397 NEUROLOGY SUBSPECIALTY ARTICLE A schematic approach to hypotonia in infancy JoAnna Leyenaar MD MPH, Peter Camfield MD FRCPC, Carol Camfield MD FRCPC J Leyenaar, P Camfield, C Camfield. A schematic approach Une démarche schématique envers l’hypotonie to hypotonia in infancy. Paediatr Child Health 2005; pendant la première enfance 10(7):397-400. L’hypotonie peut être le signe révélateur de nombreuses maladies Hypotonia may be the presenting sign for many systemic diseases and systémiques ou du système nerveux. Le présent article traite d’une diseases of the nervous system. The present paper discusses a rational, démarche diagnostique rationnelle, simple et précise envers l’hypotonie simple and accurate diagnostic approach to hypotonia in infancy, pendant la première enfance, illustrée par le cas d’une fillette de cinq mois illustrated by the case of a five-month-old infant girl recently referred récemment aiguillée vers le IWK Health Centre de Halifax, en Nouvelle- to the IWK Health Centre in Halifax, Nova Scotia. Key points in the Écosse. Les principaux points de l’anamnèse et de l’examen physique sont history and physical examination are outlined to allow a tailored exposés afin de permettre une exploration personnalisée de la patiente et investigation both for the patient and for other hypotonic infants. A des autres nourrissons hypotoniques. Un exposé sur une importante discussion of an important neuromuscular disease, diagnosed in the maladie neuromusculaire, diagnostiquée chez la patiente, conclut l’article. present patient, concludes the paper. Key Words: Hypotonia; Infant; Spinal muscular atrophy nfants with hypotonia pose challenges for clinicians respiratory syncytial virus-positive bronchiolitis.
    [Show full text]
  • Selegiline Orally Disintegrating Tablet in the Treatment of Parkinson's Disease
    DRUG PROFILE Selegiline orally disintegrating tablet in the treatment of Parkinson’s disease Anthony Clarke & Mono- and adjunctive therapy with the oral monoamine oxidase B inhibitor selegiline has Joseph Jankovic† been used to treat motor complications resulting from long-term treatment of Parkinson’s †Author for correspondence disease. However, oral selegiline undergoes extensive first-pass metabolism resulting in low Parkinson’s Disease Center and Movement Disorders bioavailability and production of amphetamine and other metabolites, as well as Clinic, Baylor College of compromised efficacy and tolerability. An orally disintegrating tablet of selegiline utilizing Medicine, Department of Zydis® technology undergoes markedly reduced presystemic metabolism, thus providing Neurology, The Smith Tower, Suite 1801 higher plasma concentrations and lower levels of amphetamine metabolites. As an adjunct 6550 Fannin, Houston, to levodopa, selegiline orally disintegrating tablet has been found to significantly reduce TX 77030, USA ‘off’ time, increase ‘on’ time, and improve motor function in Parkinson’s disease patients Tel.: +1 713 798 5998 Fax: +1 713 798 6808 experiencing ‘wearing off’ episodes. This article provides an overview of the Zydis [email protected] technology, the rationale for its application in delivering selegiline, and results from clinical trials of selegiline orally disintegrating tablet in patients with Parkinson’s disease. Although conventional oral administration is study was carried out in part to evaluate poten- the preferred and more convenient route of tially neuroprotective effects of selegiline in drug delivery, it has some disadvantages. Phar- patients with early PD. While results demon- macokinetic limitations to conventional oral strated that selegiline conferred some clinical administration can include poor absorption and benefit, they did not permit any conclusions enzymatic degradation of the drug within the regarding the medication’s neuroprotective effects gastrointestinal tract.
    [Show full text]
  • Serotonin 2A Activation and a Novel Therapeutic Drug
    Psychopharmacology (2018) 235:3083–3091 https://doi.org/10.1007/s00213-018-5042-1 THEORETICAL AND METHODOLOGICAL PERSPECTIVE The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug Baland Jalal1 Received: 23 April 2018 /Accepted: 17 September 2018 /Published online: 5 October 2018 # The Author(s) 2018 Abstract Sleep paralysis is a state of involuntary immobility occurring at sleep onset or offset, often accompanied by uncanny Bghost-like^ hallucinations and extreme fear reactions. I provide here a neuropharmacological account for these hallucinatory experiences by evoking the role of the serotonin 2A receptor (5-HT2AR). Research has shown that 5-HT2AR activation can induce visual hallucinations, Bmystical^ subjective states, and out-of-body experiences (OBEs), and modulate fear circuits. Hallucinatory experiences triggered by serotonin—serotonergic (Bpseudo^) hallucinations, induced by hallucinogenic drugs—tend to be Bdream-like^ with the experiencer having insight (Bmeta-awareness^) that he is hallucinating, unlike dopaminergic (Bpsychotic^ and Blife-like^) hallucinations where such insight is lost. Indeed, hallucinatory experiences during sleep paralysis have the classic features of serotonergic hallucinations, and are strikingly similar to perceptual and subjective states induced by hallucinogenic drugs (e.g., lysergic acid diethylamide [LSD] and psilocybin), i.e., they entail visual hallucinations, mystical experiences, OBEs, and extreme fear reactions. I propose a possible mechanism whereby serotonin could be functionally implicated in generating sleep paralysis hallucinations and fear reactions through 5-HT2AR activity. Moreover, I speculate on the role of 5-HT2C receptors vis-à-vis anxiety and panic during sleep paralysis, and the orbitofrontal cortex—rich with 5-HT2A receptors—in influencing visual pathways during sleep paralysis, and, in effect, hallucinations.
    [Show full text]
  • “STOP” and “GO” Pathways for the Treatment of Alcohol Use Disorders
    UCSF UC San Francisco Previously Published Works Title Targeting the intracellular signaling "STOP" and "GO" pathways for the treatment of alcohol use disorders. Permalink https://escholarship.org/uc/item/6hd3x2cv Journal Psychopharmacology, 235(6) ISSN 0033-3158 Authors Ron, Dorit Berger, Anthony Publication Date 2018-06-01 DOI 10.1007/s00213-018-4882-z Peer reviewed eScholarship.org Powered by the California Digital Library University of California Psychopharmacology (2018) 235:1727–1743 https://doi.org/10.1007/s00213-018-4882-z REVIEW Targeting the intracellular signaling “STOP” and “GO” pathways for the treatment of alcohol use disorders Dorit Ron1 & Anthony Berger1 Received: 18 January 2018 /Accepted: 12 March 2018 /Published online: 14 April 2018 # The Author(s) 2018 Abstract In recent years, research has identified the molecular and neural substrates underlying the transition of moderate “social” con- sumption of alcohol to the characteristic alcohol use disorder (AUD) phenotypes including excessive and compulsive alcohol use which we define in the review as the GO signaling pathways. In addition, growing evidence points to the existence of molecular mechanisms that keep alcohol consumption in check and that confer resilience for the development of AUD which we define herein as the STOP signaling pathways. In this review, we focus on examples of the GO and the STOP intracellular signaling pathways and discuss our current knowledge of how manipulations of these pathways may be used for the treatment of AUD. Keywords Alcohol . Addiction . Signaling . Translation . Medication Development . Fyn . mTOR . BDNF . GDNF Introduction medications such as naltrexone, acamprosate, and disulfiram not only are beneficial but also suffer from efficacy and com- Alcohol use disorder (AUD) is a serious worldwide health prob- pliance issues (Wackernah et al.
    [Show full text]
  • Patient Information Leaflet
    Package leaflet : Information for the User anti-arrhythmic medicines, used to treat an uneven heart beat, as these medicines may interact with Zofran & affect the rhythm of the ® heart Zofran Zydis 4mg beta-blocker medicines used to treat certain heart or eye problems, anxiety or prevent migraines, as these medicines may interact with oral lyophilisate Zofran and affect the rhythm of the heart tramadol, a pain killer, as Zofran may reduce the effect of tramadol ondansetron medicines that affect the heart (such as haloperidol or methadone) cancer medicines (especially anthracyclines) as these may interact Read all of this leaflet carefully before you start taking this with Zofran to cause heart arrhythmias medicine because it contains important information for you. medicines used to treat depression and/or anxiety: Keep this leaflet. You may need to read it again. • SSRIs (selective serotonin reuptake inhibitors) including If you have any further questions about your illness or your fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, medicine, ask your doctor, nurse or pharmacist. escitalopram This medicine has been prescribed for you only. Do not pass it on • SNRIs (serotonin noradrenaline reuptake inhibitors) including to others. It may harm them, even if their signs of illness are the venlafaxine, duloxetine same as yours. If you are not sure if any of the above applies to you, talk to your doctor, If you get any side effects, talk to your doctor, nurse or pharmacist. nurse or pharmacist before having Zofran Zydis. This includes any possible side effects not listed in this leaflet. Pregnancy, breast-feeding and fertility What is in this leaflet: 1.
    [Show full text]
  • Pyridostigmine in the Treatment of Postural
    Pyridostigmine in the Treatment of Postural Orthostatic Tachycardia: A Single-Center Experience KHALIL KANJWAL, M.D.,* BEVERLY KARABIN, PH.D.,* MUJEEB SHEIKH, M.D.,* LAWRENCE ELMER, M.D., PH.D.,† YOUSUF KANJWAL, M.D.,* BILAL SAEED, M.D.,* and BLAIR P. GRUBB, M.D.* From the *Electrophysiology Section, Division of Cardiology, Department of Medicine, The University of Toledo, Toledo, Ohio; and †Department of Neurology, The University of Toledo College of Medicine, Health Science Campus, Toledo, Ohio Background: The long-term efficacy of pyridostigmine, a reversible acetyl cholinesterase inhibitor, in the treatment of postural orthostatic tachycardia syndrome (POTS) patients remains unclear. We report our retrospective, single-center, long-term experience regarding the efficacy and adverse effect profile of pyridostigmine in the treatment of POTS patients. Methods: This retrospective study included an extensive review of electronic charts and data collection in regards to patient demographics, orthostatic parameters, side-effect profile, subjective response to therapy, as well as laboratory studies recorded at each follow-up visit to our institution’s Syncope and Autonomic Disorders Center. The response to pyridostigmine therapy was considered successful if patient had both symptom relief in addition to an objective response in orthostatic hemodynamic parameters (heart rate [HR] and blood pressure). Three hundred patients with POTS were screened for evaluation in this study. Of these 300, 203 patients with POTS who received pyridostigmine therapy were reviewed. Of these 203 patients, 168 were able to tolerate the medication after careful dose titration. The mean follow- up duration in this group of patients was 12 ± 3 (9–15) months. Pyridostigmine improved symptoms of orthostatic intolerance in 88 of 203 (43%) of total patients or 88 of 172 (51%) who were able to tolerate the drug.
    [Show full text]