Reviews Insights Into Pathophysiology from Medication-Induced Tremor
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Optumrx Brand Pipeline Forecast
RxOutlook® 1st Quarter 2019 OptumRx brand pipeline forecast Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug 2019 Possible launch date Ophthalmological DS-300 DS-300 Eton undisclosed SC Filed NDA 2019 unknown N disease anti-sclerostin Evenity romosozumab Amgen Osteoporosis SC Filed NDA 2/2019 Y N monoclonal antibody tetrahydrofolate iclaprim iclaprim Motif Bio Bacterial infections IV Filed NDA 2/13/2019 Y Y dehydrogenase inhibitor tazarotene/ IDP-118 Valeant retinoid/ corticosteroid Psoriasis TOP Filed NDA 2/15/2019 N N halobetasol adenosine deaminase Mavenclad cladribine Merck/ Teva resistant Multiple sclerosis PO Filed NDA 2/15/2019 Y N deoxyadenosine analog Lotemax Gel loteprednol Valeant corticosteroid Ocular inflammation OP Filed NDA 2/25/2019 N N Nex Gen etabonate turoctocog alfa glyco-PEGylated factor NN-7088 Novo Nordisk Hemophilia IV/SC Filed BLA 2/27/2019 Y N pegol VIII derivative selective sphingosine-1 BAF-312 siponimod Novartis phosphate receptor Multiple sclerosis PO Filed NDA 3/1/2019 Y N agonist midazolam midazolam UCB benzodiazepine Seizures Intranasal Filed NDA 3/1/2019 N Y (USL-261) XeriSol glucagon Xeris glucagon analog Diabetes mellitus SC Filed NDA 3/1/2019 N N Glucagon optum.com/optumrx 1 RxOutlook® 1st Quarter 2019 Route of Regulatory Estimated Specialty Orphan Drug name Generic name Company Drug class Therapeutic use administration status release date drug drug dopamine receptor JZP-507 sodium oxybate Jazz Narcolepsy -
Theophylline Level
Lab Dept: Chemistry Test Name: THEOPHYLLINE LEVEL General Information Lab Order Codes: THEM Synonyms: Aminophylline, Theo-Dur, Slo-Bid CPT Codes: 80198 - Theophylline Test Includes: Theophylline concentration reported in mcg/mL. Logistics Test indications: Assessing and adjusting theophylline dosage for optimal therapeutic level. Assessing theophylline toxicity Theophylline is used to relax smooth muscles of the bronchial airways and pulmonary blood vessels to relieve and prevent symptoms of asthma and bronchospasm. Caffeine is a minor metabolite and is often seen in neonates taking theophylline. Peak levels are achieved in 30–90 minutes depending on the compound and type of preparation. Theophylline has a half-life of approximately 4 hours in children and adult smokers, and 8.7 hours in nonsmoking adults. Lab Testing Sections: Chemistry Referred to: Mayo Clinic Laboratories (MML Test: THEO) Phone Numbers: MIN Lab: 612-813-6280 STP Lab: 651-220-6550 Test Availability: Monday - Saturday Turnaround Time: 1 day Special Instructions: N/A Specimen Specimen Type: Blood Container: Preferred: Serum Gel (SST) Alternate: Red Top Draw Volume: 1.5 mL blood Processed Volume: 0.5 mL (Minimum: 0.25 mL) serum Collection: Routine blood collection Special Processing: Lab Staff: Centrifuge specimen within 2 hours of collection. Store and ship at refrigerated temperature. Patient Preparation: None Sample Rejection: Mislabeled or unlabeled specimen; gross hemolysis Interpretive Reference Range: Therapeutic: Bronchodilation: 8.0-20.0 mcg/mL Neonatal apnea (< or =4 weeks old): 6.0-13.0 mcg/mL Interpretation: Response to theophylline is directly proportional to the serum level. Patients usually receive the best response when the serum level is above 8.0 mcg/mL, with minimal toxicity experienced as long as the level is less than or equal to 20.0 mcg/mL Critical Values: >20.0 mcg/mL Limitations: Coadministration of cimetidine and erythromycin will significantly inhibit theophylline clearance, requiring dosagereduction. -
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. -
Atypical Antipsychotics TCO 02.2018
Therapeutic Class Overview Atypical Antipsychotics INTRODUCTION • Antipsychotic medications have been used for over 50 years to treat schizophrenia and a variety of other psychiatric disorders (Miyamato et al 2005). • Antipsychotic medications generally exert their effect in part by blocking dopamine (D)-2 receptors (Jibson et al 2017). • Antipsychotics are divided into 2 distinct classes based on their affinity for D2 and other neuroreceptors: typical antipsychotics, also called first-generation antipsychotics (FGAs), and atypical antipsychotics, also called second- generation antipsychotics (SGAs) (Miyamato et al 2005). • Atypical antipsychotics do not have a uniform pharmacology or mechanism of action; these differences likely account for the different safety and tolerability profiles of these agents (Clinical Pharmacology 2020, Jibson et al 2017). The atypical antipsychotics differ from the early antipsychotics in that they have affinity for the serotonin 5-HT2 receptor in addition to D2. Clozapine is an antagonist at all dopamine receptors (D1-5), with lower affinity for D1 and D2 receptors and high affinity for D4 receptors. Aripiprazole and brexpiprazole act as partial agonists at the D2 receptor, functioning as an ○ agonist when synaptic dopamine levels are low and as an antagonist when they are high. Cariprazine is a partial agonist at D2 and D3. Pimavanserin does not have dopamine blocking activity and is primarily an inverse agonist at 5-HT2A receptors. The remaining atypical antipsychotics share the similarity of D2 and 5-HT2A -
Study of Adulterants and Diluents in Some Seized Captagon-Type Stimulants
MedDocs Publishers ISSN: 2638-1370 Annals of Clinical Nutrition Open Access | Mini Review Study of Adulterants and Diluents in Some Seized Captagon-Type Stimulants Ali Zaid A Alshehri1,2*; Mohammed saeed Al Qahtani1,3; Mohammed Aedh Al Qahtani1,4; Abdulhadi M Faeq1,5; Jawad Aljohani1,6; Ammar AL-Farga7 1Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah, Saudi Arabia 2Poison Control and Medical Forensic Chemistry Center, Ministry of Health, Riyadh, Saudi Arabia 3Khammis Mushayte Maternity & Children Hospital, Ministry of Health, Saudi Arabia 4Ahad Rufidah General, Hospital, Aseer, Ministry of Health, Saudi Arabia 5Comprehensive Specialized Clinics of Security Forces in Jeddah, Ministry of Interior, Saudi Arabia 6Compliance Department, Yanbu Health Sector, Ministry of Health, Saudi Arabia 7Department of Biochemistry, Faculty of Science, University of Jeddah, Saudi Arabia *Corresponding Author(s): Ali Zaid A Alshehri Department of Medical Laboratory Technology, College of Applied Medical Sciences, University of Jeddah, Saudi Arabia Email: [email protected] Received: Apr 27, 2020 Accepted: Jun 05, 2020 Published Online: Jun 10, 2020 Journal: Annals of Clinical Nutrition Publisher: MedDocs Publishers LLC Online edition: http://meddocsonline.org/ Copyright: © Alshehri AZA (2020). This Article is distributed under the terms of Creative Commons Attribution 4.0 International License Introduction ATS are synthetic compounds belonging to the class of stimu- and heroin users combined [3,4]. Fenethylline, 7-(2-amethyl lants that excite the Central Nervous System (CNS) to produce phenyl-amino ethyl)-theophylline, is a theophylline derivative of adrenaline-like effects such as amphetamine, methamphet- amphetamine. It is a psychoactive drug which is similar to am- amine, fenethylline, methylphenidate and dextroamphetamine phetamine in many ways [5]. -
Low Continuation of Antipsychotic Therapy in Parkinson Disease – Intolerance, Ineffectiveness, Or Inertia? Thanh Phuong Pham Nguyen1,2,3,4*, Danielle S
Pham Nguyen et al. BMC Neurology (2021) 21:240 https://doi.org/10.1186/s12883-021-02265-x RESEARCH Open Access Low continuation of antipsychotic therapy in Parkinson disease – intolerance, ineffectiveness, or inertia? Thanh Phuong Pham Nguyen1,2,3,4*, Danielle S. Abraham1,2,3,4, Dylan Thibault1,2, Daniel Weintraub1,5 and Allison W. Willis1,2,3,4,6 Abstract Background: Antipsychotics are used in Parkinson disease (PD) to treat psychosis, mood, and behavioral disturbances. Commonly used antipsychotics differ substantially in their potential to worsen motor symptoms through dopaminergic receptor blockade. Recent real-world data on the use and continuation of antipsychotic therapy in PD are lacking. The objectives of this study are to (1) examine the continuation of overall and initial antipsychotic therapy in individuals with PD and (2) determine whether continuation varies by drug dopamine receptor blocking activity. Methods: We conducted a retrospective cohort study using U.S. commercially insured individuals in Optum 2001– 2019. Adults aged 40 years or older with PD initiating antipsychotic therapy, with continuous insurance coverage for at least 6 months following drug initiation, were included. Exposure to pimavanserin, quetiapine, clozapine, aripiprazole, risperidone, or olanzapine was identified based on pharmacy claims. Six-month continuation of overall and initial antipsychotic therapy was estimated by time to complete discontinuation or switching to a different antipsychotic. Cox proportional hazards models evaluated factors associated with discontinuation. Results: Overall, 38.6% of 3566 PD patients in our sample discontinued antipsychotic therapy after the first prescription, 61.4% continued with overall treatment within 6 months of initiation. Clozapine use was too rare to include in statistical analyses. -
Adenosine Strongly Potentiates Pressor Responses to Nicotine in Rats (Caffeine/Blood Pressure/Sympathetic Nervous System) REID W
Proc. Nadl. Acad. Sci. USA Vol. 81, pp. 5599-5603, September 1984 Neurobiology Adenosine strongly potentiates pressor responses to nicotine in rats (caffeine/blood pressure/sympathetic nervous system) REID W. VON BORSTEL, ANDREW A. RENSHAW, AND RICHARD J. WURTMAN Laboratory of Neuroendocrine Regulation, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, MA 02139 Communicated by Walle J. H. Nauta, May 14, 1984 ABSTRACT Intravenous infusion of subhypotensive doses epinephrine output during nerve stimulation is decreased (6). of adenosine strongly potentiates the pressor response of anes- Adenosine can be produced ubiquitously and is present in thetized rats to nicotine. A dose of nicotine (40 jpg/kg, i.v.), plasma and cerebrospinal fluid (7, 8); the nucleoside can which, given alone, elicits a peak increase in diastolic pressure therefore potentially act at a number of different loci, both of -15 mm Hg, increases pressure by -70 mm Hg when arte- central and peripheral, within the complex neural circuitry rial plasma adenosine levels have been increased to 2 puM from involved in the regulation of a single physiological function, a basal concentration of =1 puM. The pressor response to ciga- such as maintenance of blood pressure or heart rate. Neither rette smoke applied to the lungs is also strongly potentiated normal plasma adenosine levels nor the relative and absolute during infusion of adenosine. Slightly higher adenosine con- sensitivities of neural and cellular processes to adenosine centrations (-4 jaM) attenuate pressor responses to electrical have been well characterized in intact animals. The studies stimulation of preganglionic sympathetic nerves, or to injec- described below explore the effects of controlled measured tions of the a-adrenergic agonist phenylephrine, but continue alterations in arterial plasma adenosine concentrations on to potentiate pressor responses to nicotine. -
Narco-Terrorism Today: the Role of Fenethylline and Tramadol
Narco-terrorism today: the role of fenethylline and tramadol Introduction The relationship between psychoactive substances and violent crimes such as war acts and terrorism dates long back in history. Viking warriors famously fought in a trance-like state, probably as a result of taking agaric "magic" mushrooms and bog myrtle (McCarthy, 2016). More recently, under the German Nazis’ Third Reich, methamphetamine gained an extreme popularity, despite an official “drug-free” propaganda. Under the trademark Pervitin, it could be sold without prescription until 1939, and it was not regulated by the Reich Opium Law of 1941. Pervitin was commonly used in recreational and working settings, and, of course, the stimulant was shipped to German soldiers when the troops invaded France, allowing them to march sleepless for 36 to 50 hours (Ohler, 2016). On the other side, Benzedrine, a racemic mixture of amphetamine initially developed as a bronchodilator, was the stimulant of choice of the Allied forces during World War II (McCarthy, 2016). Vietnam War (1955-1975) is considered to be the first “pharmacological war” of modern history, so called due to an unprecedented high level of consumption of psychoactive substances by military personnel (Kamienski, 2016). In 1971, a report by the House Select Committee on Crime revealed that from 1966 to 1969, the US armed forces had used 225 million tablets of stimulants, mostly Dexedrine (dextroamphetamine), an amphetamine derivative that is nearly twice as strong as the Benzedrine used in the Second World War (Kamienski, 2016). The use of illicit drugs such as stimulants or painkillers by terrorists or insurgents while undertaking their terrorist activities has been hypothesized but still needs further documentation. -
Neuronal Adenosine A2A Receptors Signal Ergogenic Effects of Caffeine
www.nature.com/scientificreports OPEN Neuronal adenosine A2A receptors signal ergogenic efects of cafeine Aderbal S. Aguiar Jr1,2*, Ana Elisa Speck1,2, Paula M. Canas1 & Rodrigo A. Cunha1,3 Cafeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of cafeine, a nonselective antagonist of adenosine A1 and A2A receptors. We now investigated A2AR as a possible ergogenic mechanism through pharmacological and genetic inactivation. Forty-two adult females (20.0 ± 0.2 g) and 40 male mice (23.9 ± 0.4 g) from a global and forebrain A2AR knockout (KO) colony ran an incremental exercise test with indirect calorimetry (V̇O2 and RER). We administered cafeine (15 mg/kg, i.p., nonselective) and SCH 58261 (1 mg/kg, i.p., selective A2AR antagonist) 15 min before the open feld and exercise tests. We also evaluated the estrous cycle and infrared temperature immediately at the end of the exercise test. Cafeine and SCH 58621 were psychostimulant. Moreover, Cafeine and SCH 58621 were ergogenic, that is, they increased V̇O2max, running power, and critical power, showing that A2AR antagonism is ergogenic. Furthermore, the ergogenic efects of cafeine were abrogated in global and forebrain A2AR KO mice, showing that the antagonism of A2AR in forebrain neurons is responsible for the ergogenic action of cafeine. Furthermore, cafeine modifed the exercising metabolism in an A2AR-dependent manner, and A2AR was paramount for exercise thermoregulation. Te natural plant alkaloid cafeine (1,3,7-trimethylxantine) is one of the most common ergogenic substances for physical activity practitioners and athletes 1–10. -
IRIS Università Degli Studi Di Ferrara
Università degli Studi di Ferrara DOTTORATO DI RICERCA IN "Farmacologia e Oncologia Molecolare" CICLO XXVI COORDINATORE Prof. Antonio Cuneo ADENOSINE RECEPTORS IN HEALTH AND DISEASE Settore Scientifico Disciplinare BIO/14 Dottorando Tutore Dott.ssa Angela Stefanelli Dott.ssa Stefania Gessi Anni 2011/2013 TABLE OF CONTENTS Pag Abstract 1 Adenosine receptors (ARs) in health and disease 3 Adenosine 4 GPCRs 6 Adenosine Receptors 8 A1 Adenosine Receptor 10 A2A Adenosine Receptor 15 A2B Adenosine Receptor 21 A3 Adenosine Receptor 25 Conclusion 32 References 34 Downregulation of A1 and A2B ARs in human trisomy 21 50 mesenchymal cells from first-trimester chorionic villi Introduction 51 Angiogenesis 51 Adenosine and angiogenesis in pregnancy 52 Aim of the thesis 55 Materials and methods 56 Results 61 Discussion 64 Figures Legend 67 Figures 69 References 78 A1 and A3 ARs inhibit LPS-induced hypoxia-inducible factor-1 85 accumulation in murine astrocytes Introduction 86 Astrocyte 87 Hypoxia-inducible factor 91 HIF-Regulated genes: Neuroprotection or Inflammation 95 Effect of adenosine in astrocytes 96 Possible role of HIF, Astrocyte and Adenosine in neuroprotection 99 Aim of the thesis 100 Materials and methods 101 Results 105 Discussion 110 Figures Legend 113 I Figures 118 References 132 Curriculum vitae 145 List of Publications 146 Meetings 148 Acknowledgements 149 II Abstract Adenosine (Ado) is an endogenous nucleoside released from almost all cell types. It exerts neuroprotective and anti-inflammatory functions by acting through four receptor subtypes A1, A2A, A2B and A3 (ARs). These receptors differ in their affinity for Ado, in the type of G protein that they recruit and finally in the downstream signalling that are activated in target cells. -
The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. -
Pimavanserin: a Potentially Safer Alternative to Clozapine for Refractory Hallucinations and Delusions
From the Editor Pimavanserin: A potentially safer alternative to clozapine for refractory hallucinations and delusions Up to 30% of patients with schizo- established a nonprofit foundation Henry A. Nasrallah, MD we called CURESZ (Comprehensive Editor-in-Chief phrenia do not respond to dopamine antagonists, which include all first- and Understanding via Research and Education in Schizophrenia), and assem- second-generation antipsychotics. bled a panel of 80 clozapine experts They are labeled as “treatment-resis- across the country to provide access to tant” if they have a partial response, clozapine for the hundreds of thousands Our clinical team or “treatment-refractory” if their hal- of individuals with refractory psychosis who never received a trial of clozapine made a serendipitous lucinations and/or delusions do not from their psychiatrists or psychiatric discovery about the improve at all despite multiple trials nurse practitioners. (Visit CURESZ.org efficacy of pimavanserin of antipsychotics. for details.) Bethany was very lucky to respond in patients with That’s why clozapine is considered and recover completely, because only schizophrenia who a “lifesaver” for such patients, a last- 40% of patients with refractory psycho- failed to respond to resort medication that unshackles sis respond to clozapine. She does not patients with refractory psychotic mind having her blood drawn every clozapine therapy symptoms from the tyranny of audi- week to measure her white blood cell tory and/or visual hallucinations and count for early detection of potentially the reality distortion of fixed false fatal agranulocytosis. Many refrac- beliefs such as paranoid delusions. tory, often homeless patients with Many long-suffering patients with chronic schizophrenia refuse to have refractory psychosis recover and return weekly phlebotomy and therefore are to their baseline, thanks to clozapine.