jacqueline rhoads, phd, acnp-bc, anp-c, gnp, ccrn phd...

NURSES’CLINICAL CONSULT

TO

PSYCHOPHARMACOLOGY

Jacqueline Rhoads, PhD, ACNP-BC, ANP-C, GNP, CCRN Patrick J. M. Murphy, PhD

This is the only advanced practice guide to provide an overview of the major DSM-IV-TR disorders across the lifespan and complete clinical guidelines for their psychopharmacologic management. It was compiled by expert practitioners in psychiatric care and designed for use by nurse practitioners and other primary caregivers in clinical practice.

The guide is organized in an easy-to-access format with disorders for which drugs can play a significant therapeutic role. The listing for each disorder includes clinical features and symptoms, as well as information about the most current and effective drugs for management. A clearly formatted table identifies the first and second lines of drug therapy along with adjunctive therapies for each disorder. Drugs are organized according to classification, and each listing provides the essential information needed to safely prescribe and monitor a patient’s response to a particular drug. This includes brand and generic names, drug class, customary dosage, side effects, drug interactions, pharmacokinetics, precautions, and management of special populations. Convenient, practical, and portable, this guide will be a welcome and frequently used resource.

KEY FEATURES : • Presents psychopharmacological treatment guidelines for major DSM-IV-

TR disorders and parameters for use of each drug • Prioritizes drugs according to their clinical efficacy• More than 110 drugs are presented in monographs format and include

brand and generic names, customary dosages, side effects, drug interactions, pharmacokinetics, precautions, and management of special populations

• Provides easy-to-read drug selection tables for quick clinical consultation • Includes prescribing considerations for patients with impairment of renal, hepatic,

and/or cardiac function

11 W. 42nd StreetNew York, NY 10036-8002www.springerpub.com 9 780826 105035

ISBN 978-0826105035 -5


TO

PSYCHOPH

ARMACOLOGY

Jacqueline Rhoads • Patrick J.M. MurphyRhoadsMurphy


TO

PSYCHOPHARMACOLOGY

NURSES’ CLINICAL CONSULT TO

Psychopharmacology

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Jacqueline Rhoads, PhD, ACNP-BC, ANP-C, GNP, CCRN, is Professor of Nursing at The University of Texas at Galveston Health Science Center School of Nursing, former Adjunct Professor at Tulane University School of Public Health in New Orleans, and former Adult Nurse Practitioner at Odyssey House Free Clinic in New Orleans and the U.S. Army-Reserve Command in Washington, DC. Dr. Rhoads has taught in nurse practitioner programs since 1994. She has been awarded major research funding for a variety of research projects, including $1.5M Tri-Service Department of Defense Combat Readiness Project, two HRSA grants ($1M CRNA Specialization Project and $600,000 CRNA and NP Distance Ed Program) and a $150,000 Role Delineation Study: Acute Care Nurse Practitioner grant from ANCC. She has been Primary Investigator for research on behalf of the March of Dimes, the United Way, the NONPF, and the military. She earned her PhD from the University of Texas, Austin, and has earned post-master’s degrees in Acute Care NP, Community Health Primary Care Adult NP, Gerontology NP, and Psych Mental Health NP. She is a Fellow in the American Academy of NPs and was awarded numerous commendations and medals for meritorious service in the U.S. Army Nurse Corps, including the Bronze Star, U.S. Army Meritorious Service Commendation, Army Commendation (11 times!), the Vietnam Service Medal, and numerous other academic and teaching awards, including Outstanding Faculty Award (undergraduate and graduate), STT Care Award, Outstanding Demonstration of Research and Practice Award, Teaching Excellence Award Nomination, Commander of Outstanding Reserve Unit Award and, lastly, Reserve Nurse of the Year (American Association of Military Surgeons of the United States, 1997 and 1998). Dr. Rhoads has authored three books for major nursing publishers, as well as numerous articles.

Patrick J. M. Murphy, PhD, is Assistant Professor at the Seattle University College of Nursing where he teaches Introduction to Pharmacology (BSN students), and Advanced Pharmacological Application in Primary Care and Psychopharmacology in Advanced Practice Nursing (MSN/NP students), among other courses. Dr. Murphy holds an MS and PhD in Pharmacology from the University of Michigan. He has served as the Scholar-in-Residence, Hope Heart Institute (Seattle, Washington) and as Visiting Scientist at Fred Hutchinson Cancer Research Center, also in Seattle. Previously, he served as a Research Fellow, University of Michigan Medical School, and Guest Lecturer, University of Michigan School of Nursing. He has published 22 peer-reviewed journal articles and multiple book chapters, as well as having presented 15 podium presentations and numerous invitational lectures. He is the Co- or the Primary Investigator on six funded research projects. Dr. Murphy is the recipient of multiple honors and awards, notably the Outstanding Teacher of the Year Award (2009 Seattle University), Outstanding Graduate Student Teaching Award (2001 University of Michigan Medical School), and a Horace H. Rackham Fellowship from the University of Michigan Graduate School. He is a member of the Phi Sigma Tau Academic Honorary Society and the Phi Eta Sigma Academic Honorary Society.

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NURSES’ CLINICAL CONSULT TO

Psychopharmacology

Jacqueline Rhoads, PhD, ACNP-BC,

ANP-C, GNP, CCRN

Patrick J. M. Murphy, PhD

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Copyright © 2012 Springer Publishing Company, LLC

All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Springer Publishing Company, LLC, or authorization through payment of the appropriate fees to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400, fax 978-646-8600, [email protected] or on the Web at www.copyright.com.

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ISBN: 978-0-8261-0503-5E-book ISBN: 978-0-8261-0504-2

12 13 14 15 / 5 4 3 2 1

The author and the publisher of this Work have made every effort to use sources believed to be reliable to provide information that is accurate and compatible with the standards generally accepted at the time of publication. Because medical science is continually advancing, our knowledge base continues to expand. Therefore, as new information becomes available, changes in procedures become necessary. We recommend that the reader always consult current research and specifi c institutional policies before performing any clinical procedure; to check the package insert especially for new and infrequently used drugs; and to consider drugs and dosages in light of the patient’s medical condition. The author and publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance on, the information contained in this book. The publisher has no responsibility for the persistence or accuracy of URLs for external or third-party Internet Web sites referred to in this publication and does not guarantee that any content on such Web sites is, or will remain, accurate or appropriate.

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Printed in the United States of America by Gasch Printing.

Rhoads, Jacqueline, 1948-

Nurses’ clinical consult to psychopharmacology / Jacqueline Rhoads,

Patrick J.M. Murphy.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-8261-0503-5 —ISBN 978-0-8261-0504-2 (e-book)

I. Murphy, Patrick J. M. II. Title.

[DNLM: 1. Mental Disorders—drug therapy. 2. Mental Disorders—nursing.

3. Psychotropic Drugs—pharmacology. 4. Psychotropic Drugs—therapeutic

use. WM 402]

616.89'18—dc23 2011036135

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I dedicate this book to all of the students to whom I have had the pleasure of teaching the art of nursing. With thanks for hours of enjoyment, years of inspiration, and a lifetime of admiration.

—Jackie Rhoads

To Dean Mary K. Walker and the students—past and future—of the Seattle University College of Nursing.

—Patrick Murphy

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Contents

Contributors ix

Reviewers xi

Preface xiii

Acknowledgments xv

Abbreviations xvii

1. The Relationship of Psychopharmacology to Neurotransmitters, Receptors, Signal Transduction, and Second Messengers 1

2. Clinical Neuroanatomy as It Relates to Pharmacology With Emphasis on Psychoactive Drugs 5

3. Principles of Pharmacokinetics and Pharmacodynamics in Psychopharmacology 11

4. Emergency Psychiatry 17

5. Treatment of Mood Disorders 27

6. Treatment of Psychotic Disorders 83

7. Treatment of Anxiety Disorders 149

8. Treatment of Childhood and Adolescent Disorders 245

9. Treatment of Substance-Related Disorders 283

10. Treatment of Eating Disorders 299

11. Treatment of Behavioral and Psychological Disorders in the Elderly 315

12. Treatment of Personality Disorders 329

13. Treatment of Sleep Disorders 405

14. Dissociative Disorders 429

References 467

Index 471

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Sandra S. Bauman, PhD, ARNP, LMHCNorth Miami Beach, FLChapter 6: Treatment of Psychotic Disorders

Deonne J. Brown-Benedict, DNP, ARNP, FNP-BCAssistant Professor, Family Nurse Practitioner Track Clinical Coordinator, Seattle

University College of Nursing, Seattle, WAChapter 5: Treatment of Mood Disorders

Angela Chia-Chen Chen, PhD, RN, PMHNP-BC Assistant Professor, Arizona State University, College of Nursing & Healthcare

Innovation, Phoenix, AZ Chapter 6: Treatment of Psychotic Disorders

Karen Crowley, DNP, APRN-BC, WHNP, ANPChapter 10: Treatment of Eating Disorders

Deborah Gilbert-Palmer, EdD, FNP-BCAssociate Professor, Arkansas State UniversityChapter 11: Treatment of Behavioral and Psychological Disorders in the ElderlyChapter 13: Treatment of Sleep Disorders

Lori S. Irelan, FNP, APRN, MSNWilmington University, New Castle, DEChapter 8: Treatment of Childhood and Adolescent Disorders

Mitsi H. Lizer, PharmD, BCPP, CGPAssociate Professor Pharmacy Practice, Shenandoah University School of Pharmacy,

Winchester, VAChapter 4: Emergency Psychiatry

JoAnn Marrs, EdD, FNP-BCEast Tennessee State University, Johnson City, TNChapter 14: Treatment of Dissociative Disorders

Patrick J. M. Murphy, PhDAssistant Professor, Seattle College of Nursing, Seattle, WAChapter 3: Principles of Pharmacokinetics and Pharmacodynamics in Psychopharmacology

Stephanie Ann Plummer, DNP, APRN, PMHNP-BCAssistant Clinical Professor, UCLA School of Nursing, Fayetteville, AR;

Department of Psychiatry, VAMC—Jay CBOC, Jay, OklahomaChapter 1: The Relationship of Psychopharmacology to Neurotransmitters, Receptors, Signal Transduction,

and Second Messengers

Jacqueline Rhoads, PhD, ACNP-BC, ANP-C, GNP, CCRNProfessor of Nursing, University of Texas at Galveston Health Science Center School of

Nursing, Galveston, TXChapter 2: Clinical Neuroanatomy as It Relates to Pharmacology With Emphasis on Psychoactive Drugs

Contributors

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CONTRIBUTORSx

Ester Ruiz, PhD, RNProfessor Emeritus, Arizona State University, Tempe, AZ

Barbara Sartell, EdD, RN, CANPWilmington University, New Castle, DEChapter 7: Treatment of Anxiety Disorders

Antiqua Smart, BSN, MN, APRN, FNP-BC, CPESouthern University and A&M College, Baton Rouge, LAChapter 13: Treatment of Sleep Disorders

Sandra J. Wiggins Petersen, DNP, FNP, GNP-BCProgram Track Administrator, UTMB Masters in Nursing Leadership Program, UTMB

School of Nursing, Galveston, TXChapter 12: Treatment of Personality Disorders

Hsin-Yi (Jean) Tang, PhD, APRN-BC, PMHNP Assistant Professor, College of Nursing, Seattle University, Seattle, WAChapter 5: Treatment of Mood Disorders

Kristen M. Vandenberg, DNP, ARNP Nursing Faculty, University of North Florida Chapter 9: Treatment of Substance-Related Disorder

Lisa Waggoner, DNP, FNP-BCArkansas State University, State University, ARChapter 11: Treatment of Behavioral and Psychological Disorders in the Elderly

Veronica Wilbur, PhD, FNP-BC, CNEAssociate Professor, Wilmington University, New Castle, DEChapter 7: Treatment of Anxiety Disorder

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Melanie Blunk, DNP, Adult/Family PMHNP, APRNAdjunct Clinical Faculty, University of Missouri, Columbia, MO; Psychiatric Consultant,

Long Term Care Facilities and Personal Care Homes, Parkview Psychiatric Services, Bowling Green, KY

JoEllen Kubik, MSN, MA, ARNP/PMHNP-BC, LMHC Associate Professor of Nursing, Allen College, Waterloo, IA

Martha Kuhlmann, MSN, FNP, PMHCNSClinical Assistant Professor and Specialty Coordinator, Family Psychiatric Mental

Health Nurse Practitioner Program, UAMS College of Nursing, Little Rock, AR

Adrianne D. Linton, PhD, RNProfessor of Nursing (Tenured), Chair, Department of Family and Community

Health Systems, University of Texas Health Science Center at San Antonio, Graduate School of Biomedical Sciences, San Antonio, TX

Cynthia Luther, DSN, GNP-BC, FNP-BCAssistant Professor of Nursing, Director, Mississippi Educational Consortium

for Specialized Advanced Practice Nursing (MECSAPN); Director, Gerontological and Psychiatric Mental Health Nurse Practitioner Tracks, University of Mississippi Medical Center School of Nursing, Jackson, MS

Evelyn Parrish, PhD, APRNProfessor of Nursing, Eastern Kentucky University, Richmond, KY

Reviewers

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Preface

The main intent in writing this clinical reference was to present to both primary care providers and psychiatric/mental health specialists a wide-ranging guide to psychopharmacology in relation to its application in practice. It is hoped that the contents of this text will offer providers and nurses in advanced practice the basic concepts and in-depth prescribing guidelines that are necessary for the clinical management of those patients with mental health disorders. Compiled by expert practitioners in psychiatric care, this work provides an overview of the management of the major Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (American Psychiatric Association, 2000), disorders across the lifespan, and complete clinical guidelines for their psychopharmaco-logic management for use by nurse practitioners and others caring for patients in clinical practice. Not every mental health disorder is listed. The disorders chosen are those where drugs can play a signifi cant therapeutic role in altering the course or progression of the disease.

We have constructed each chapter in a bullet format for quick reference using a structured approach. The book is organized into two major sections: The fi rst is the overview of the principles of clinical psychopharmacology; the second is the treatment section, where the major disorders that benefi t from drug inter-vention are used to organize and present drugs that are appropriate to prescribe for their management.

In the treatment section, handy psychopharmacology drug selection tables present fi rst- and second-line drug therapies, along with adjunctive therapy, that can be benefi cial to support optimal functioning of the individual with a mental health disorder. Drugs are then presented in monograph format, organized according to the drug classifi cations in the tables. More than 90 drugs are clearly presented.

It is important to note that, in the drug tables, the order in which drugs are listed within the classifi cation is signifi cant and will help guide drug choice for specifi c disorders. Note, too, that not every drug within a classifi cation is included for all disorders; rather, only drugs that have been shown to have clinical effi cacy are listed in a priority fashion, again to help guide the drug choice by the prescriber.

Essential drug information that is needed to safely prescribe and monitor the patient’s response to those drugs includes drug names (generic and brand names), drug class, usual and customary dosage, administration of the drug, availability (e.g., tablet, injection, intravenous, capsule), side effects, drug interaction, pharmacokinetics, precautions, patient and family education, and special populations. The special populations section includes management of pregnant, breastfeeding, elderly, child, and adolescent populations, and patients with impaired renal, hepatic, or cardiac function.

Pharmacology knowledge and applied clinical practices are constantly evolving owing to new research and applied science that expand our diagnostic capabilities and treatments. Therefore, it must be emphasized that practitioners carry an important responsibility to ensure that the selected treatment refl ects current research and is appropriate according to manufacturer drug information and that dosages, routes of administration, side effects/precautions, drug interactions, and use in special populations have been taken into consideration and are accurate and appropriate for each patient. The practitioner is ultimately responsible to know each patient’s history, to conduct a thorough physical

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PREFACExiv

examination, and to consult appropriate diagnostic test results to ascertain the best possible pharmacotherapeutic actions for optimal patient outcomes and appropriate safety procedures.

The contributors to this text have worked hard to present current and applicable content that is of therapeutic value in the understanding of specifi c mental health disorders. We are very grateful to the contributors of this text for their hard work and focused support.

Jackie RhoadsPatrick Murphy

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Acknowledgments

The publication of this book would not have been possible without the gener-ous help and support of many people. The contributors were among the most accomplished advanced practice nurses in the discipline of nursing. They were selected because each is recognized to be among the most accomplished in their fi elds. They provided up-to-date information on their topics, discussing both personal and best-practice principles.

A special thank you also goes to Dr. Patrick Murphy for critiquing chapters in the book for specifi c pharmacological content and providing many benefi cial suggestions. The textbook was greatly enhanced by his focused and timely input.

Last and most important, I would like to acknowledge the support of Margaret Zuccarini, Publisher, Nursing, at Springer Publishing Company. Her ongoing support and encouragement made this work possible during a time in my life when I didn’t think I could possibly pursue this endeavor.

Jackie Rhoads

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Abbreviations

ABA applied behavior analysis

ACE angiotension-converting enzyme

AD Alzheimer’s disease

ADHD attention-defi cit hyperactivity disorder

AIDS acquired immunodefi ciency syndrome

ALT alanine aminotransferase

AMI acute myocardial infarction

ANA antinuclear antibody

ANC absolute neutrophil count

ANS autonomic nervous system

ASA acetylsalicylic acid

ASAP as soon as possible

ASD acute stress disorder

AST aspartate aminotransferase

BDNF brain-derived neurotropic factor

bid two times a day

BMI body mass index

BP blood pressure

BPH benign prostatic hyperplasia

BUN blood urea nitrogen

BZD benzodiazepine

Ca2+ calcium

cAMP cyclic adenosine monophosphate

CBC complete blood count

CBT cognitive–behavioral therapy

CHF congestive heart failure

CK creatine kinase

CMI clomipramine

CNS central nervous system

COPD chronic obstructive pulmonary disease

CrCl creatinine clearence

CSF cerebrospinal fl uid

CSID critical incident stress debriefi ng

CT computed tomography

CV cardiovascular

CYP cytochrome P450

DBT dialectical behavior therapy

DDI drug–drug interaction

DEA Drug Enforcement Administration

ECG electrocardiogram

ECT electroconvulsive therapy

EEG electroencephalogram

EENT eye, ear, nose, and throat

EKG electrocardiogram

EPS extrapyramidal symptoms

ER extended release

ESRD end-stage renal disease

ETT endotracheal tube

exam examination

FDA Food and Drug Administration

FGAs fi rst-generation antipsychotics

GABA gamma-amino butyric acid

GAD general anxiety disorder

GGT gamma-glutamyl transpeptidase

GI gastrointestinal

GPCRs G protein-coupled receptors

GU genitourinary

H histamine

HD heart disease

HHS Health and Human Services

HLA human leukocyte antigen

HR heart rate

HTN hypertension

IM intramuscular

IO intraosseous

IOP intraocular pressure

IP3 triphosphate

IR immediate release

IV intravenous

LFT liver function test

MAOI monoamine oxidase inhibitor

MDD major depressive disorder

MFO mixed-function oxidases

MI myocardial infarction

MRI magnetic resonance imaging

NaSSA noradrenergic and specifi c serotonergic

antidepressants

NDRI norepinephrine and dopamine reuptake

inhibitor

NE norepinephrine

NMDA N-methyl-d-aspartate

NMS neuroleptic malignant syndrome

NOS not otherwise specifi ed

NREM nonrapid eye movement

NRT nicotine replacement therapy

AB

BR

EV

IAT

ION

S

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AB

BR

EV

IAT

ION

Sxviii ABBREVIATIONS

NSAID nonsteroidal anti-infl ammatory

drugs

OCD obsessive–compulsive disorder

ODD oppositional defi ant disorder

ODT orally disintegrating tablet

OTC over the counter

OTP opioid treatment programs

PD panic disorder

PKU phenylketonuria

PMDD premenstrual dysphoric disorder

PNS peripheral nervous system

PO orally

PSNS parasympathetic nervous system

PTSD posttraumatic stress disorder

RBC red blood cell

RDA recommended dietary allowances

REM rapid eye movement

RPR rapid plasma reagin

SAMHSA Substance Abuse and Mental Health

Services Administration

SARI serotonin antagonist and reuptake

inhibitor

SC subcutaneous

SIADH syndrome of inappropriate anti

diuretic hormone

SNRI serotonin and norepinephrine

reuptake inhibitor

SNS sympathetic nervous system

SSNRI selective serotonin norepinephrine

reuptake inhibitor

SSRI selective serotonin reuptake inhibitor

TCA tricyclic antidepressant

TD tardive dyskinesia

tid three times a day

TZD thiazolidinediones

UA uric acid

UCD urea cycle disorder

UTI urinary tract infection

WBC white blood cell

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1The Relationship of Psychopharmacology to Neurotransmitters, Receptors, Signal

Transduction, and Second Messengers

The last 20 years have afforded scientists with a greater understanding of the brain. Extreme changes in psychopharmacology have produced newer medicines with fewer side effects and greater benefi ts than ever before. These changes translate into improved wellness for patients with mental health disorders.

This chapter presents:A basic outline of the currently understood pro- ■

cesses by which the brain communicatesInformation to support an improved under- ■

standing of the inner brain mechanisms from synaptic and cellular viewpoints in regard to psychopharmacologyThe signaling pathways associated with the six ■

neurotransmitters most commonly altered in modern psychopharmacological therapyA strong scientifi c background on which to base ■

psychopharmacological prescribing practices

NEUROTRANSMITTERSThese are the molecules that mediate intracellular signaling of the brain.

Neurotransmitters are chemicals that communi- ■

cate their messages to the interior of the neurons:Through their release from the presynaptic ■

terminalBy diffusing across the synaptic cleft ■

To further bind to receptors in the postsynap- ■

tic membraneThere are more than several dozen known or ■

suspected neurotransmitters in the brain.Theoretically there may be several hundred ■

neurotransmitters based on the amount of genetic materials in the neurons.Neurotransmitters are endogenous mole- ■

cules; examples include various peptides and hormones (Table 1.1).Psychoactive drugs act by increasing, decreas- ■

ing, or otherwise modulating the actions of neu-rotransmitters at their receptor sites.Ligand ■ is a generic term referring to either endog-enous or exogenous receptor binding partner pro-teins to which neurotransmitters bind, resulting in changes to downstream cellular processes.Six neurotransmitter systems are the major tar- ■

gets for psychotropic drugs:Serotonergic neurons ■ (neurotransmitter = serotonin) originating primarily in the raphe nuclei of the reticular formation extending from the medulla to the midbrainNoradrenergic neurons ■ (neurotransmitter = nor-epinephrine) originating in the locus coeruleus

Dopaminergic neurons ■ (neurotransmitter = dopamine) originating primarily in the ven-tral tegmental areaMuscarinic cholinergic neurons ■ (neu-rotransmitter = acetylcholine), one of the principal neurotransmitters in the ANSGlutamatergic neurons ■ (neurotransmitter = glutamate), an amino acid transmitter syn-thesized by the brain from glucose and other nutrients for motor activityGABAergic neurons ■ (neurotransmitter = GABA), an inhibitory amino acid neurotrans-mitter, which is synthesized from glutamate in the brain and decreases activity in nerve cells

These six neurotransmitters are relatively low- ■

molecular-weight amines or amino acids.Multiple neurons that release more than one ■

neurotransmitter may converge at a single synapse.Co-transmission involves a monoamine coupled ■

with a neuropeptide.This natural combination of multiple signal- ■

ing molecules at the synapse is the basis for the modern treatment rationale of prescrib-ing drugs affecting multiple neuronal signal-ing pathways.

Table 1.1 Major Neurotransmitters in the CNSNEUROTRANSMITTER EFFECTS

Acetylcholine (ACh) Cognition, learning, memory,

alertness, muscle contraction

Dopamine Pleasure, pain, movement

control, emotional response

GABA Psychomotor agitation/

retardation, stress, anxiety

Glutamate Memory, energy

Norepinephrine Arousal, dreaming, depressed

mood, suicide, apathy,

psychomotor agitation/

retardation, constricts blood

vessels, increases heart rate

and blood pressure, affects

attention and the sleep/wake

cycle

Serotonin Mood control, temperature

regulation, impulsiveness,

aggression, cognitive

problems, depressed mood,

suicide, apathy, psychomotor

agitation/retardation

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CHAPTER 1: RELATIONSHIP OF PSYCHOPHARMACOLOGY 2

SIX NEUROTRANSMITTERS MOST COMMONLY AFFECTED BY PSYCHOPHARMACOLOGY

TREATMENT REGIMENS*Communication within the brain happens in three ways: anterograde, retrograde, or nonsynaptic. Chemical neurotransmission is the foundation of psychopharmacology.

Anterograde neurotransmission: ■

Most predominant means of excitation-cou- ■

pling and synapses.Occurs in one direction (i.e., presynaptic to ■

postsynaptic), from the cell body, down the axon, to the synaptic cleft.Involves stimulation of a presynaptic neuron ■

causing electrical impulses to be sent to its axon terminal (may be regarded as “classic” neurotransmission).Electrical impulses are converted into chemi- ■

cal messengers, known as neurotransmitters.Chemical messengers (neurotransmitters) ■

are released to stimulate the receptors of the postsynaptic neuron.Communication ■ within a neuron is mediated by electrical conduction of an action poten-tial from the cell body down the axon of the neuron where it ends at the synaptic cleft.Communication ■ between neurons is chemical and mediated by one of several neurotrans-mitters described earlier.Excitation–secretion coupling is the process ■

by which an electrochemical signal in the fi rst (i.e., presynaptic) neuron is converted from a chemical impulse into the release of a chemical signal at the synapse.Electrical impulses result from the open- ■

ing of ion channels in the neuronal cell mem-brane along the axon, causing a change in net charge of the neuron. The difference in charge between the inside of the cell and the outside of the cell is referred to as an action potential.

Voltage-sensitive sodium channels −Voltage-sensitive potassium channels −

This all happens very quickly once the elec- ■

trical impulse enters the presynaptic neuron.Occurs predominately in one direction (from ■

the cell body, down the axon, to the synaptic cleft).

Retrograde neurotransmission: ■

Postsynaptic neurons can talk back directly ■

and indirectly.Indirectly through a long neuronal feed- −back loopDirectly through retrograde neurotrans- −mission from postsynaptic to presynaptic

Examples of retrograde neurotransmitters ■

synthesized in the postsynaptic neuron, released, and diffused into the presynaptic neuron are:

Endocannabinoids (endogenous compou nds −similar to marijuana, also known as cannabis)Nitric oxide −

Nonsynaptic neurotransmission: ■

No neurotransmission across a synaptic cleft ■

Chemical messengers sent by one neuron dif- ■

fuse to compatible receptor sites distant to the synapse

RECEPTORSThese are proteins to which neurotransmitters bind, resulting in changes to downstream cellular processes.

Found within plasma membranes and cyto- ■

plasm of a cellAffected by psychoactive drugs ■

Located on cell membranes of neurons ■

Receptors Specifi c to PsychopharmacologyPsychotropic medications are developed to target these various receptor sites.

*Currently prescribed psychotropic medications are deve-

loped to target these neurotransmitter signaling pathways.

Serotonin

RECEPTOR

TYPE DISTRIBUTION EFFECTS

5HT1,

5HT1A, 1B,

1D, 1E, 1F

Brain, blood

vessels,

intestinal

nerves

Inhibitory: neuronal

inhibition, cerebral

vasoconstriction

Behavioral effects:

addiction, aggression,

anxiety, appetite,

impulsivity, learning,

memory, mood, sexual

behavior, sleep

5HT2, 2A,

2B, 2C

Brain, blood

vessels, heart,

lungs, smooth

muscle control,

GI system,

blood vessels,

platelets

Excitatory:

neuronal excitation,

vasoconstriction

Behavioral effects:

addiction, anxiety,

appetite, mood, sexual

behavior, sleep

5HT3 Limbic system,

CNS, PNS, GI

system

Excitatory: nausea

Behavioral effects:

addiction, anxiety,

learning, memory

5HT4 CNS, smooth

muscle, GI

system

Excitatory: neuronal

excitation, GI

Behavioral effects:

anxiety, appetite,

learning, memory, mood

5HT5, 5A,

6, 7

Brain Inhibitory: may be

linked to BDNF

Behavioral effects: sleep

5HT6 CNS Excitatory: may be

linked to BDNF

Behavioral effects:

anxiety, cognition,

learning, memory, mood

5HT7 CNS, blood

vessels GI

system

Excitatory: may be

linked to BDNF

Behavioral effects:

anxiety, memory,

sleep, mood



GABA: ■ Binds to GABAA and GABA

B receptors

Glutamate: Binds to AMPA, kainate, and NMDA receptors

SIGNAL TRANSDUCTIONIt is the movement of signals from the outside of a cell to the inside.

Signal ■ → receptor → change in cell functionPlays a very specifi c role through messaging ■

and activation of an inactive moleculeStarts a reaction that cascades through ■

chemical neurotransmission via numerous molecules

Long-term effects of late gene products and −many more messages

Serotonin: ■ Binds to 5HT1A, 5HT1B, 5HT1D, 5HT1E, 5HT1F, 5HT2, 5HT2A, 5HT2B, 5HT2C, 5HT3, 5HT4, and 5HT5A receptors

Norepinephrine: ■ Binds to alpha1 and alpha

2,

beta1, beta

2, and beta

3 receptors

Norepinephrine

RECEPTOR


Alpha1

Brain, heart,

smooth muscle

Excitatory:

vasoconstriction,

smooth muscle

contraction

Alpha2

Presynaptic

neurons in brain,

pancreas, smooth

muscle

Inhibitory:

vasoconstriction,

GI relaxation

presynaptically

Beta1

Heart, brain Excitatory:

increased heart

rate

Beta2

Lungs, brain,

skeletal muscle

Excitatory:

bronchial

relaxation,

vasodilation,

smooth muscle

relaxation

Beta3

Adipose tissue Excitatory:

stimulation of

effector cells

Dopamine

RECEPTOR


D1 Brain, smooth

muscle

Excitatory:

possible role in

schizophrenia and

Parkinson’s

D2 Brain,

cardiovascular

system,

presynaptic

nerve terminals

Inhibitory:

possible role in

schizophrenia

D3 Brain,

cardiovascular

system,

presynaptic

nerve terminals

Inhibitory:

possible role in

schizophrenia

D4 Brain,

cardiovascular

system,

presynaptic

nerve terminals

Inhibitory:

possible role in

schizophrenia

D5 Brain, smooth

muscle

Excitatory:

possible role in

schizophrenia and

Parkinson’s

Acetylcholine: ■ Binds to nicotinic (N) and mus-carinic (M) receptors

Acetlycholine

RECEPTOR


M1 Ganglia,

secretory glands

Excitatory: CNS

excitation, gastric

acid secretion

M2 Heart, nerves,

smooth

muscle

Inhibitory:

cardiac inhibition,

neural

inhibition

M3 Glands, smooth

muscle,

endothelium,

secretory glands

Excitatory:

smooth muscle

contraction,

vasodilation

M4 CNS, PNS,

smooth muscle,

secretory glands

Inhibitory

M5 CNS Inhibitory

NM

Skeletal

muscle,

neuromuscular

junction

Excitatory:

neuromuscular

transmission

NN

Postganglionic

cell body

dendrites

Excitatory:

ganglionic

transmission

Glutamate

RECEPTOR TYPE DISTRIBUTION EFFECTS

AMPA CNS Excitatory

Kainate CNS Excitatory

NMDA CNS Excitatory

GABA

RECEPTOR TYPE DISTRIBUTION EFFECTS

GABAA

CNS Inhibitory

GABAB

ANS Excitatory

Dopamine: ■ Binds to D1, D2, D3, D4, and D5 receptors



Can occur over the time course of minutes, −hours, days, or weeksEffects may be temporary or permanent −

Signal transduction translates into the follow- ■

ing diverse biological responses:Gene expression ■

Synaptogenesis ■

SECOND MESSENGERSThese are synthesized and activated by enzymes, and help mediate intracellular signaling in response to a ligand binding to its receptor.

Relay and amplify signals received by receptors ■

such as cAMP, IP3, and Ca2+.

ENDOGENOUS NEUROTRANSMITTERSSee Table 1.2. ■

Table 1.2 Endogenous Neurotransmitters

NEUROTRANSMITTER RECEPTOR SIGNAL TRANSDUCTIONSECOND

MESSENGER

Acetylcholine Muscarinic G-protein linked cAMP or IP3

Nicotinic Ion channel linked Calcium

Dopamine D1, D2, D3, D4, D5 G-protein linked cAMP or IP3

alpha1, beta

2G-protein linked cAMP or IP

3

GABA GABAA

Ion channel linked and

ligand-gated ion channels

Calcium

GABAB

G-protein linked cAMP or IP3

Glutamate AMPA, Kainate, and

NMDA

Ion channel linked Calcium

Metabotropic G-protein linked cAMP or IP3

Norepinephrine alpha1, alpha


3

beta1


Epinephrine alpha1, alpha


3

beta1, beta


3

Serotonin 5HT1A, 5HT1B, 5HT1D,

5HT1E, 5HT1F


5HT2, 5HT2A, 5HT2B,

5HT2C


5HT3 Ion channel linked Calcium5HT4 G-protein linked cAMP or IP

3

5HT5A G-protein linked cAMP or IP3


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