Post on 20-May-2020
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
NURSES’CLINICAL CONSULT
TO
PSYCHOPH
ARMACOLOGY
Jacqueline Rhoads • Patrick J.M. MurphyRhoadsMurphy
NURSES’CLINICAL CONSULT
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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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
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CHAPTER 1: RELATIONSHIP OF PSYCHOPHARMACOLOGY 3
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
TYPE DISTRIBUTION EFFECTS
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
TYPE DISTRIBUTION EFFECTS
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
TYPE DISTRIBUTION EFFECTS
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
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CHAPTER 1: RELATIONSHIP OF PSYCHOPHARMACOLOGY 4
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
2G-protein linked cAMP or IP
3
beta1
G-protein linked cAMP or IP3
Epinephrine alpha1, alpha
2G-protein linked cAMP or IP
3
beta1, beta
2G-protein linked cAMP or IP
3
Serotonin 5HT1A, 5HT1B, 5HT1D,
5HT1E, 5HT1F
G-protein linked cAMP or IP3
5HT2, 5HT2A, 5HT2B,
5HT2C
G-protein linked cAMP or IP3
5HT3 Ion channel linked Calcium5HT4 G-protein linked cAMP or IP
3
5HT5A G-protein linked cAMP or IP3
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