Mechanism of Action of Anxiolytics (PDF)
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22 Psychiatric Medications for Monitoring in Primary Care
22 Psychiatric Medications for Monitoring in Primary Care Medication Warnings, Precautions, and Adverse Events Comments Class: SSRI Fluvoxamine Boxed Warnings: Suicidality Used much less than SSRIs in the group of eight Indications: Warnings and Precautions: Similar to other SSRIs medications for prescribing, probably because it has no Adult: OCD Adverse Events: Similar to other SSRIs FDA indication for MDD or any anxiety disorder. Still Child/Adolescent: OCD (10-17 years) somewhat popular as a medication for OCD. Uses: Anxiety, OCD Monitoring: Same as other SSRIs Citalopram Boxed Warning: Suicidality. Escitalopram, one of the SSRIs in the group of Indications: Warnings and Precautions: Similar to other SSRIs medications for prescribing, is an active metabolite of Adult: MDD Adverse Events: Similar to other SSRIs citalopram. Escitalopram reportedly has fewer AEs and Child/Adolescent: None less interaction with hepatic metabolic enzymes than Uses: Anxiety, MDD, OCD citalopram but is otherwise essentially identical. Citalopram offers no advantage other than price, as Monitoring: Same as other SSRIs escitalopram is branded until 2012. Paroxetine Boxed Warnings: Suicidality. Paroxetine used much less than the SSRIs for Indications: Warnings and Precautions: Similar to other SSRIs prescribing, probably because of its nonlinear kinetics. Adult: MDD, OCD, Panic Disorder, Generalized Anxiety Adverse Events: Similar to other SSRIs A study of children and adolescents showed doubling Disorder, Social Anxiety Disorder, Posttraumatic Stress Disorder the dose of paroxetine from 10 mg/day to 20 mg/day Child/Adolescent: None resulted in a 7-fold increase in blood levels (Findling et Uses: Anxiety, MDD, OCD al, 1999). Thus, once metabolic enzymes are saturated, paroxetine levels can increase dramatically with dose Monitoring: Same as other SSRIs increases and decrease dramatically with dose decreases, sometimes leading to adverse events. -
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development
Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives • Outline the Phase 1 studies conducted to characterize the Clinical Pharmacology of a drug; describe important design elements of and the information gained from these studies. • List the Clinical Pharmacology characteristics of an Ideal Drug • Describe how the Clinical Pharmacology information from Phase 1 can help design Phase 2/3 trials • Discuss the timing of Clinical Pharmacology studies during drug development, and provide examples of how the information generated could impact the overall clinical development plan and product labeling. Phase 1 of Drug Development CLINICAL DEVELOPMENT RESEARCH PRE POST AND CLINICAL APPROVAL 1 DISCOVERY DEVELOPMENT 2 3 PHASE e e e s s s a a a h h h P P P Clinical Pharmacology Studies Initial IND (first in human) NDA/BLA SUBMISSION Phase 1 – studies designed mainly to investigate the safety/tolerability (if possible, identify MTD), pharmacokinetics and pharmacodynamics of an investigational drug in humans Clinical Pharmacology • Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of the drug in humans – PK: what the body does to the drug (Absorption, Distribution, Metabolism, Excretion) – PD: what the drug does to the body • PK and PD profiles of the drug are influenced by physicochemical properties of the drug, product/formulation, administration route, patient’s intrinsic and extrinsic factors (e.g., organ dysfunction, diseases, concomitant medications, -
Benzodiazepine Anti-Anxiety Agents: Prevalence and Correlates of Use in a Southern Community
Benzodiazepine Anti-anxiety Agents: Prevalence and Correlates of Use in a Southern Community rn- rn Marvin Swartz, MD, Richard Landerman, PhD, Linda K George, PhD, Mary Lou Melville, MD, Dan Blazer, MD, PhD, and Karen Smith, PhD Introduction alence and patterns of benzodiazepine antianxiolytic drug use in the Piedmont re- Benzodiazepine anti-anxiety agents gion of North Carolina during 1982-83, uti- are the most widely prescribed psycho- lizing logistic regression analysis, which al- therapeutic drugs in the United States to- lows prediction of benzodiazepine use day.' First introduced in 1960, these drugs while introducing controls for potential rapidly achieved a lead position in the pre- confounding and mediating variables. scription drug market,2 stimulating public and professional debate over appropriate Method psychotropic drug use.3 Recent evidence, however, suggests that the prevalence and The present paper reports results patterns of psychotropic use, especially from Wave 1 of the Piedmont Health Sur- those of benzodiazepine anxiolytics, may vey, one site of the five-site National In- be changing and resulting in decreased stitute of Mental Health Epidemiologic use.4,5 The first detailed population survey Catchment Area program (NIMH- of psychotropic drug use, the National ECA).'1 The sampling frame for the Pied- Household Sample in 1970-71,6-9 found mont Health Survey (PHS) was a five- that 22 percent of American adults had county area in north central North used prescription psychotropic medica- Carolina, consisting of one urban county tion during the year 1969-70, with higher and four contiguous rural counties. The use among women and the elderly. -
DESCRIPTION CLINICAL PHARMACOLOGY Mechanism Of
NDA 20-844/ Topamav Sprinkle Capsules Approved Labeling Text Version: 10/26/98 DESCRIPTION Topiramate is a sulfamate-substituted monosaccharide that is intended for use as an antiepileptic drug. TOPAMAX@ (topiramate capsules) Sprinkle Capsules are available as I5 mg, 25 mg and 50mg sprinkle capsules for oral administration as whole capsules or for opening and sprinkling onto soft food. Topiramate is a white crystalline powder with a bitter taste. Topiramate is most soluble in alkaline solutions containing sodium hydroxide or sodium phosphate and hawng a pH of 9 to IO. It is freely soluble in acetone, chloroform, dimethylsulfoxide, and ethanol. The solubility in water is 9.8 mg/mL. Its saturated solution has a pH of 6.3. Topiramate has the molecular formula C,,H,,NO,S and a molecular weight of 339.37. Topiramate is designated chemically as 2,3:4,5-Di-O-isopropylidene-~- D-fructopyranose sulfamate and has the following structural formula: H3C CH3 TOPAMAX” (topiramate capsules) Sprinkle Capsules contain topiramate coated beads in a hard gelatin capsule. The inactive ingredients are: sugar spheres (sucrose and starch), povidone, cellulose acetate, gelatin, silicone dioxide, sodium lauryl sulfate, titanium dioxide, and black pharmaceutical ink. CLINICAL PHARMACOLOGY Mechanism of Action: The precise mechanism by which topiramate exerts its antiseizure effect is unknown; however, electrophysiological and biochemical studies of the effects of topiramate on cultured neurons have revealed three properties that may contribute to topiramate’s antiepileptic efficacy. First, action potentials elicited repetitively by a sustained depolarization of the neurons are blocked by topiramate in a time-dependent manner, suggestive of a state-dependent sodium channel blocking action. -
Moving Beyond Single Gene-Drug Pairs in Clinical Pharmacogenomics Testing
Moving Beyond Single Gene-Drug Pairs in Clinical Pharmacogenomics Testing Yuan Ji, PhD, DABCP, FACMG Gwendolyn McMillin, PhD, DABCC Learning Objectives • Describe the strengths and limitations of pharmacogenomic testing. • List examples of single gene-drug associations with the strongest levels of evidence for clinical implementation. • Discuss cautions when considering the use of multi-gene drug associations to inform drug therapy decisions. 2 Disclosure • None 3 Outline • Singe gene-drug based pharmacogenomics (PGx) testing – An introduction – Evidence and examples – Considerations for developing and evaluating clinical PGx laboratory developed tests (LDTs) • Multi-gene PGx panels – Evidence and examples – PROs and CONs for utilizing PGx panels – Considerations for successful PGx implementation 4 Single Gene-Drug Based PGx Testing Yuan Ji, PhD, DABCP, FACMG Medical Director of Genomics and Genetics; PGx, ARUP Laboratories Associate Professor (Clinical) of Pathology, University of Utah Medications: Myths and Facts • are~30% peoplenot take“one at least-size one medication fits all” within a 30-day period • Most medications cause adverse drug events (ADEs) • Some medications like antibiotics may do more harm than good • CDC statistics: – ~ 200,000 ADEs-related ER visits in pediatric population (17 years or younger) – ~ 450,000 ADEs-related ER visits in older adults (65 years or older) – Medications, e.g., anticoagulant warfarin • Many ADEs are preventable by closely supervising of dosing, blood tests (therapeutic drug monitoring, TDM), -
(Orion) 5 Mg Tablets Buspirone (Orion) 10 Mg Tablets
NEW ZEALAND DATA SHEET 1. PRODUCT NAME Buspirone (Orion) 5 mg tablets Buspirone (Orion) 10 mg tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 5 mg buspirone hydrochloride. Each tablet contains 10 mg buspirone hydrochloride. Excipient with known effect: 5 mg tablet: Each tablet contains 59.5 mg lactose (as monohydrate) 10 mg tablet: Each tablet contains 118.9 mg lactose (as monohydrate). For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Tablet. 5 mg tablet: White or almost white, oval tablets debossed with ‘ORN 30’ on one side and a score on the other side. The tablet can be divided into equal doses. 10 mg tablet: White or almost white, oval tablets debossed with ‘ORN 31’ on one side and a score on the other side. The tablet can be divided into equal doses. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Buspirone hydrochloride is indicated for the management of anxiety with or without accompanying depression in adults. Buspirone hydrochloride is indicated for the management of anxiety disorders or the short- term relief of symptoms of anxiety with or without accompanying depression. 4.2 Posology and method of administration The usual starting dose is 5 mg given three times daily. This may be titrated according to the needs of the patient and the daily dose increased by 5 mg increments every two or three days depending upon the therapeutic response to a maximum daily dose of 60 mg. After dosage titration the usual daily dose will be 20 to 30 mg per day in divided doses. -
Calcium Channel Blockers in Mental Health and Neuro Sciences
Article NIMHANS Journal Editorial : Calcium Channel Blockers in Mental Health and Neuro Sciences Volume: 15 Issue: 01 January 1997 Page: 3-5 S M Channabasavanna, - Vice-Chancellor, NIMHANS, (Deemed University), Bangalore Calcium is a familiar ion; first year medical students learn of its physiological importance in a host of situations, such as in nutrition, in enzymatic reactions, in muscle contraction, and in the structure of bone. Calcium has long been known to also play an important role in the physiology of the nervous system, for example, it is well recognised that calcium is a co-factor in several enzymatic processes in the central nervous system (CNS), that release of neurotransmitters from synaptic vesicles is calcium-dependent, that the stability of the neuronal membrane is partly regulated by calcium, that calcium is involved in neurotoxic processes etc. [1]. Several cognitive functions have been associated with calcium mechanisms. For example, the involvement of calcium is learning and memory processes is widely documented [2], [3]; most of the work to-date concerns calcium influx through receptors for excitatory amino acids [4]; compounds that block inonotropic glutamate receptors and inhibit calcium inflow, such as MK 801, are reported to impair memory [5], [6]. Voltage-dependent calcium channels, of which the best characterized are those that contain dihydropyridine binding sites, form a second mechanism controlling calcium inflow into the cells [7]. In recent years, these calcium channels in the neuron have assumed substantial importance; treatments affecting these channels have been shown to affect a number of functions related to the CNS. For example, repeated electroconvulsive shocks upregulate voltage dependent calcium channels, which effect appears to increase sensitivity to pain, enhance responsiveness to dopaminergic agonists etc [8], [9], [10]. -
Cathinone-Derived Psychostimulants Steven J
Review Cite This: ACS Chem. Neurosci. XXXX, XXX, XXX−XXX pubs.acs.org/chemneuro DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants Steven J. Simmons,*,† Jonna M. Leyrer-Jackson,‡ Chicora F. Oliver,† Callum Hicks,† John W. Muschamp,† Scott M. Rawls,† and M. Foster Olive‡ † Center for Substance Abuse Research (CSAR), Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19140, United States ‡ Department of Psychology, Arizona State University, Tempe, Arizona 85281, United States ABSTRACT: Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These “synthetic cathinones” include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. -
Immediately Dangerous to Life Or Health (IDLH) Value Profile: Butane
Butane CAS® No. 106-97-8 DEPARTMENT OF HEALTH AND HUMAN SERVICES Center for Disease Control and Prevention National Institute of Occupational Safety and Health This page intentionally left blank. Immediately Dangerous to Life or Health (IDLH) Value Profile Butane [CAS® No. 106-97-8] H3C CH3 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health This document is in the public domain and may be freely copied or reprinted. Disclaimer Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations to websites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these websites. Ordering Information To receive this document or information about other occupational safety and health topics, contact NIOSH: Telephone: 1-800-CDC-INFO (1-800-232-4636) TTY: 1-888-232-6348 E-mail: [email protected] or visit the NIOSH ebsite at: www.cdc.gov/niosh For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. Suggested Citation NIOSH [2016]. Immediately dangerous to life or health (IDLH) value profile: butane. By Dotson GS, Maier A, Parker A, Haber L. Cincinnati, OH: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupa- tional Safety and Health, DHHS (NIOSH) Publication 2016-174. DHHS (NIOSH) Publication No. 2016-174 September 2016 ii IDLH Value Profile for Butane Foreword Chemicals are a ubiquitous component of the modern workplace. -
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss
Supplemental Material can be found at: /content/suppl/2020/12/18/73.1.202.DC1.html 1521-0081/73/1/202–277$35.00 https://doi.org/10.1124/pharmrev.120.000056 PHARMACOLOGICAL REVIEWS Pharmacol Rev 73:202–277, January 2021 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: MICHAEL NADER Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss Antonio Inserra, Danilo De Gregorio, and Gabriella Gobbi Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada Abstract ...................................................................................205 Significance Statement. ..................................................................205 I. Introduction . ..............................................................................205 A. Review Outline ........................................................................205 B. Psychiatric Disorders and the Need for Novel Pharmacotherapies .......................206 C. Psychedelic Compounds as Novel Therapeutics in Psychiatry: Overview and Comparison with Current Available Treatments . .....................................206 D. Classical or Serotonergic Psychedelics versus Nonclassical Psychedelics: Definition ......208 Downloaded from E. Dissociative Anesthetics................................................................209 F. Empathogens-Entactogens . ............................................................209 -
Multiple Drug Resistance: a Fast-Growing Threat
Review Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2019.21.003572 Multiple Drug Resistance: A Fast-Growing Threat Eremwanarue Aibuedefe Osagie1,2* and Shittu Hakeem Olalekan1 1Department of Plant Biology and Biotechnology, University of Benin, Nigeria 2Lahor Research Laboratories and Diagnostics Centre, Nigeria *Corresponding author: Eremwanarue Aibuedefe Osagie, Department of Plant Biology and Biotechnology, University of Benin, Nigeria ARTICLE INFO Abstract Received: September 03, 2019 The spread of antibiotic resistant bacteria is a growing problem and a public health Published: September 10, 2019 issue. Over the years, various genetic mechanisms concerned with antibiotic resistance have been identified to be natural and acquired resistance. The natural resistance Citation: Eremwanarue Aibuedefe Osag- ie, Shittu Hakeem Olalekan. Multiple Geneticinvolved Elements mutation [MGEs] via target such modification,as plasmid, transposon reduced permeability, and integrons efflux genetic system elements and Drug Resistance: A Fast-Growing Threat. on the other hand, acquired resistance via horizontal gene tranfer include Moblie Biomed J Sci & Tech Res 21(2)-2019. Integrons are widely distributed, especially in Gram-negative bacteria; they are carried BJSTR. MS.ID.003572. bythat Mobile can acquire, Genetic exchange, Elements and such express as plasmids, genes embeddedand transposons, within whichGene Cassettespromote [GC].their spread within bacterial communities and have been studied mainly in the clinical setting Keywords: Antibiotics; Multiple Drug for their involvement in antibiotic resistance, their role in the environment is now an Resistant Bacteria; Mobile Genetic increasing focus of attention. The aim of this review is to educate the populise about Element; Integrons Plasmid the mechanisms of multiple drug resistance bacteria isolates and the danger ahead if appropriate regulations are not put in place especially in developing country like Nigeria. -
Anxiolytic-Like Activity of SB-205384 in the Elevated Plus Maze Test in Mice
Psicothema 2006. Vol. 18, nº 1, pp. 100-104 ISSN 0214 - 9915 CODEN PSOTEG www.psicothema.com Copyright © 2006 Psicothema Anxiolytic-like activity of SB-205384 in the elevated plus maze test in mice José Francisco Navarro, Estrella Burón and Mercedes Martín-López Universidad de Málaga Recent studies point to a major role for α2-containing GABA-A receptors in modulating anxiety. Ho- wever, the possible implication of GABA-A receptors containing the α3 subunit on anxiety is less known. The aim of this study was to examine the effects of SB-205384 (0.5-4 mg/kg, ip), an α3 su- bunit positive modulator of GABA-A receptor, on anxiety tested in the elevated plus-maze in male mi- ce, using classical and ethological parameters. Mice treated with SB-205384 showed an increase in the frequency of entries and the time spent in open arms, as well as a reduction in the time spent in closed arms, as compared with the control group. A notable increase of «head-dipping» unprotected and a re- duction of «stretched-attend posture» protected was also evident. These findings indicate that SB- 205384 exhibits an anxiolytic-like profile in the elevated plus-maze test, suggesting that GABA-A re- ceptors which contain the α3 subunit might be involved in regulation anxiety. Actividad ansiolítica del SB-205384 en el laberinto elevado en cruz en ratones. Recientes investiga- ciones indican que los receptores GABA-A que contienen subunidades α2 desempeñan un importan- te papel en la modulación de la ansiedad. Sin embargo, la posible implicación de los receptores GA- BA-A que contienen la subunidad α3 es menos conocida.