Pharmacology in Rehabilitation 4th Edition docx

Potential Interactions between Physical Agents and Therapeutic Drugs
Listed here are some potential interactions between physical agents used in rehabilitation and various pharma-
cologic agents. It is impossible to list all the possible relationships between the vast array of therapeutic drugs
and the interventions used in physical therapy and occupational therapy. However, some of the more common
interactions are identified here.
Desired Drugs with Drugs with Other Drug-
Therapeutic Complementary/ Antagonistic Modality
Modality Effect Synergistic Effects Effects Interactions
Cryotherapy
Cold/ice packs
Ice massage
Cold bath
Vapocoolant sprays
Superficial and
deep heat
Local application
Hot packs
Paraffin
Infrared
Fluidotherapy
Diathermy
Ultrasound
Systemic heat
Large whirlpool
Hubbard tank
Ultraviolet radiation
Transcutaneous electrical
nerve stimulation (TENS)
Functional neuromuscular
electrical stimulation

Decreased pain, edema,
and inflammation
Muscle relaxation and
decreased spasticity
Decreased muscle/joint
pain and stiffness
Decreased muscle spasms
Increased blood flow
to improve tissue
healing
Decreased muscle/joint
stiffness in large areas
of the body
Increased wound healing
Management of skin disor-
ders (acne, rashes)
Decreased pain
Increased skeletal muscle
strength and endurance
Decreased spasticity and
muscle spasms
Anti-inflammatory steroids
(glucocorticoids); non-
steroidal anti-inflamma-
tory analgesics (aspirin
and similar NSAIDs)
Skeletal muscle relaxants
NSAIDs; opioid analgesics;
local anesthetics
Skeletal muscle relaxants

Peripheral vasodilators
Opioid and nonopioid anal-
gesics; skeletal muscle
relaxants
Various systemic and
topical antibiotics
Systemic and topical
antibiotics and anti-
inflammatory steroids
(glucocorticoids)
Opioid and nonopioid
analgesics
—
Skeletal muscle relaxants
Peripheral vasodilators
may exacerbate acute
local edema
Nonselective cholinergic ago-
nists may stimulate the
neuromuscular junction
—
Nonselective cholinergic ago-
nists may stimulate the
neuromuscular junction
Systemic vasoconstrictors
(e.g., alpha-1 agonists)
may decrease perfusion
of peripheral tissues
—
—

Many drugs may cause
hypersensitivity reactions
that result in skin rashes,
itching
Opioid antagonists
(naloxone)
Skeletal muscle relaxants
Nonselective cholinergic ago-
nists may stimulate the
neuromuscular junction
Some forms of cryotherapy
may produce local vaso-
constriction that temporarily
impedes diffusion of drugs
to the site of inflammation
—
—
—
—
Severe hypotension may occur
if systemic hot whirlpool is
administered to patients
taking peripheral vasodila-
tors and some antihyper-
tensive drugs (e.g., alpha-1
antagonists, nitrates, direct-
acting vasodilators, calcium
channel blockers)
Antibacterial drugs generally
increase cutaneous sensi-

tivity to ultraviolet light (i.e.,
photosensitivity)
Photosensitivity with antibac-
terial drugs
—
—
—
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Common Drug Suffixes
Medications that are chemically and functionally similar often have generic names that share a common ending
or suffix. Listed here are some drug classes that contain groups of drugs that share a common suffix. Please note
that some members of a drug class may have a suffix that is different from the one indicated; for instance, not all
benzodiazepines end with “-epam” or “-olam.”
Primary Indication or
Desired Effect (Chapter
Drug Class Suffix Common Examples in Parentheses)
Angiotensin-converting
enzyme (ACE) inhibitors
Azole antifungals
Barbiturates
Benzodiazepines
Beta blockers
Bisphosphonates
Bronchodilators (adrenergic)
Bronchodilators (xanthine derivatives)
Calcium channel blockers
(dihydropyridine group)
Cyclooxygenase type 2
(COX-2) inhibitors
Glucocorticoids

Histamine H
2
-receptor blockers
HIV protease inhibitors
HMG-CoA reductase inhibitors (statins)
Local anesthetics
Low molecular-weight heparins
Oral antidiabetics
(sulfonylurea group)
Penicillin antibiotics
Proton pump inhibitors
Tetracycline antibiotics
Various other antibacterials
*Some anabolic steroids also end with -olone, e.g., nandrolone, oxymetholone (Chapter 30).
†Some antibiotics ending with “-mycin” or “rubicin” are used as antineoplastics (Chapter 36).
-pril
-azole
-barbital
-epam or -olam
-olol
-dronate
-erol
-phylline
-ipine
-coxib
-sone or -olone
*
-idine
-avir
-statin

-caine
-parin
-amide
-cillin
-prazole
-cycline
-micin or -mycin
†
Captopril, enalapril
Fluconazole, miconazole
Phenobarbital, secobarbital
Diazepam, temazepam, alprazolam,
triazolam
Metoprolol, propranolol
Alendronate, pamidronate
Albuterol, pirbuterol
Theophylline, aminophylline
Nifedipine, nicardipine
Celecoxib
Cortisone, dexamethasone, prednis-
one, prednisolone, triamcinolone
Cimetidine, ranitidine
Ritonavir, saquinavir
Pravastatin, simvastatin
Lidocaine, bupivicaine
Dalteparin, enoxaparin
Chlorpropamide, tolbutamide
Penicillin, ampicillin, amoxicillin
Omeprazole, lansoprazole
Tetracycline, doxycycline

Streptomycin, gentamicin,
erythromycin
Antihypertensive (21), congestive
heart failure (24)
Fungal infections (35)
Sedative-hypnotic (6), antiseizure (9),
anesthetic (11)
Sedative-hypnotic (6), antianxiety (6),
antiseizure (9), anesthetic (11)
Antihypertensive (21), antianginal
(22), antiarrhythmic (23), conges-
tive heart failure (24)
Osteoporosis (31)
Bronchodilation (26)
Bronchodilation (26)
Antihypertensive (21),
antianginal (22)
Pain, inflammation (15)
Anti-inflammatory (16, 29), immuno-
suppressants (37)
Gastric ulcers (27)
HIV infection (34)
Hyperlipidemia (25)
Local anesthetic (12),
antiarrhythmics (23)
Anticoagulants (25)
Antidiabetic (type II diabetes melli-
tus) (32)
Bacterial infections (33)
Gastric ulcers (27)

Bacterial infections (33)
Bacterial infections (33)
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Pharmacology in
Rehabilitation
4th Edition
00Ciccone(p)-FM 2/6/07 4:25 PM Page i
Contemporary Perspectives in Rehabilitation
Steven L. Wolf, PT, PhD, FAPTA, Editor-in-Chief
Pharmacology in Rehabilitation, 4th Edition
Charles D. Ciccone, PT, PhD
Vestibular Rehabilitation, 3rd Edition
Susan J. Herdman, PT, PhD, FAPTA
Modalities for Therapeutic Intervention, 4th Edition
Susan L. Michlovitz, PT, PhD, CHT and Thomas P. Nolan, Jr., PT, MS, OCS
Fundamentals of Musculoskeletal Imaging, 2nd Edition
Lynn N. McKinnis, PT, OCS
Wound Healing: Alternatives in Management, 3rd Edition
Luther C. Kloth, PT, MS, CWS, FAPTA, and
Joseph M. McCulloch, PT, PhD, CWS, FAPTA
Evaluation and Treatment of the Shoulder:
An Integration of the Guide to Physical Therapist Practice
Brian J. Tovin, PT, MMSc, SCS, ATC, FAAOMPT and
Bruce H. Greenfield, PT, MMSc, OCS
Cardiopulmonary Rehabilitation: Basic Theory and Application, 3rd Edition
Frances J. Brannon, PhD, Margaret W. Foley, RN, MN,
Julie Ann Starr, PT, MS, CCS, and Lauren M. Saul, MSN, CCRN
For more information on each title in the Contemporary Perspectives in Rehabilitation
series, go to www.fadavis.com.
00Ciccone(p)-FM 2/2/07 6:59 PM Page ii

Pharmacology in
Rehabilitation
4th Edition
Charles D. Ciccone, PT, PhD
Professor
Department of Physical Therapy
School of Health Sciences
and Human Performance
Ithaca College
Ithaca, New York
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F. A. Davis Company
1915 Arch Street
Philadelphia, PA 19103
www.fadavis.com
Copyright © 2007 by F. A. Davis Company
Copyright © 1990 and 1996 by F. A. Davis Company. All rights reserved. This book is protected by
copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any from or by
any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission
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Printed in the United States of America
Last digit indicates print number: 10 9 8 7 6 5 4 3 2 1
Publisher: Margaret Biblis
Acquisitions Editor/Developmental Editor: Melissa Duffield
Manager Art and Design: Carolyn O’Brien
As new scientific information becomes available through basic and clinical research, recommended
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publication. The author, editors, and publisher are not responsible for errors or omissions or for
consequences from application of the book, and make no warranty, expressed or implied, in regard to the

contents of the book. Any practice described in this book should be applied by the reader in accordance
with professional standards of care used in regard to the unique circumstances that may apply in each
situation. The reader is advised always to check product information (package inserts) for changes and
new information regarding dose and contraindications before administering any drug. Caution is
especially urged when using new or infrequently ordered drugs.
Library of Congress Cataloging-in-Publication Data
Ciccone, Charles D., 1953–
Pharmacology in rehabilitation / Charles D. Ciccone. — 4th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN-13: 978-0-8036-1377-5
ISBN-10: 0-8036-1377-6
1. Pharmacology. 2. Medical rehabilitation. I. Title.
[DNLM: 1. Drug Therapy. 2. Pharmacokinetics. 3. Pharmacology. 4. Rehabilitation.
WB 330 C568p 2007]
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00Ciccone(p)-FM 2/2/07 6:59 PM Page iv
Dedicated to Penny, Kate, and Alex for providing con-
stant faith, support, and inspiration.
v
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There are very peculiar ways in which one can mark
time. We often do so by observing the rate at which
our siblings, children, or grandchildren grow, espe-
cially when we are not in daily contact, or by how we
inevitably underestimate the length of time transpired
since we last encountered an old friend. In this con-
text, it seems remarkable that over 13 years have tran-
spired since I first discussed with Chuck Ciccone the
prospects for a text on pharmacology for our Contem-
porary Perspectives in Rehabilitation. The realization
that the first edition of Pharmacology in Rehabilitation
appeared more than a decade ago is even more
astounding. The basis for the genesis of such a book
was founded on the belief that rehabilitation spe-
cialists received little formal training about drug
interactions and how any single pharmacological
agent could impact either treatment plans or out-
comes. Chuck took it upon himself to generate a text
that would address this educational and clinical short-
coming. The result is very clear. Pharmacology in Reha-
bilitation is the “gold standard” among all texts
addressing this content for nonphysician rehabilita-
tion specialists.
So why is it important to create a fourth edition
within one decade? Why is a more superficial com-
pendium of information about drugs and their actions
inadequate? The answer to these questions is directly
related to the rapidly emerging responsibilities incum-
bent upon rehabilitation specialists. During the past 5

years, the advent of clinical doctoral programs in
physical and occupational therapy has heralded a rapid
transformation in these educational arenas. Several
attributes now take on a meaning that previously
might have been underappreciated. First, the label of
“doctor” implies an expectation on the part of the con-
sumer that the practitioner is the penultimate expert
on providing an analysis and treatment plan for
improving upon the pathology of any system’s move-
ment, whether muscle, joint, pulmonary, etc. Second,
given the status associated with the professional label,
there is an associated obligation on the part of the
practitioner to address all aspects of the patients’ signs
and symptoms. This obligation requires that the clini-
cian differentiate patient responses to treatment from
patient responses to pharmacy. As one physical thera-
pist so astutely told me, her recognition that a patient
was not responding to pain medication taken well
above the specified dosage, in the absence of any evi-
dence for malingering behavior, resulted in the subse-
quent detection and successful removal of a renal
tumor. Third, as practitioners, the DPT or DOT now
assumes a greater responsibility for keeping a contem-
porary knowledge base about the interface between
treatment plan and concurrent synergies or exacerba-
tions that might result from single or multiple med-
ications taken by the patient.
This collection of attributes can be best appreci-
ated if the student is first informed and the clinician is
educated about the most recent medications, their

pharmokinetics, and the interactions they have with
patients with specific diagnoses. Since the drug indus-
try is arguably one of the most dynamic corporate
structures in the world, changes in pharmacy occur at
an alarmingly fast rate, one that will increase even
more dramatically as transplants and the sequelae
resulting from genetic engineering (as two examples)
take on greater roles in medicine. Such rapid changes,
then, call for contemporary and comprehensive
updates in available information. Such updates must
be presented in a manner that is compelling, yet easy
to understand.
Inclusive in this perception is the absolute
requirement that the student or clinician be able
to relate to the text meaningfully. Toward this impor-
tant goal, the 4th edition of Pharmacology in Rehabilita-
tion is designed to address rehabilitation relevance
in every clinical chapter as well as to present impor-
tant case histories to reinforce this relevance. New
materials on agents used in or even as complemen-
tary and alternative medicines have been added.
Moreover, we have made efforts to add to the appeal
of the book through the addition of colorization,
use of double columns, and encasing the text within
a newly designed hard cover. These changes are in
contradistinction to one standard that remains
immutable—Dr. Ciccone’s remarkable gift for tak-
ing complex material and making it easy to under-
stand.
vii

Foreword
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For those clinicians who have in their possession
early editions of this book, I invite you to compare
your copy to the 4th edition as validation for the asser-
tions made in this Foreword. We have not compro-
mised the comprehensive nature of this volume in
favor of a “simpler” approach to understanding
pharmacology. We believe that the topic, by its very
nature and from the implications inherent in its
knowledge base, requires a comprehensive, yet user-
friendly, delivery. This belief system remains unhin-
dered in this latest edition; yet the problem-solving
and evidence-based nature of the content is preserved
and enhanced.
The thought of having a reference text for reha-
bilitation specialists was considered by us to be a
unique concept 13 years ago. Today, many doctoral
programs include pharmacology as a separate course or
as an important component in teaching the rationale
for treatment approaches and their assessment. There
is much gratification to be gained from recognizing
this transformation and in knowing that the content of
this book contributes to the evolving maturation of our
educational programs and our clinical services.
Steven L. Wolf, PT, PhD, FAPTA
Series Editor
viii Foreword
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In one sense, pharmacology can be considered a “good

news, bad news” scenario. The good news is that
exciting and innovative changes in drug therapy con-
tinue to occur at lightning speed. The bad news is that
it is often difficult for health care practitioners to stay
abreast of this rapidly changing field. Oftentimes,
drug therapies that were considered state-of-the-art
only a few years ago are now outdated and replaced by
more contemporary treatments.
Hence, the fourth edition of this text has been
revised extensively to reflect the science and practice
of pharmacology, with particular emphasis on how
drug therapy impacts patients receiving physical reha-
bilitation. Efforts were made to use the peer-reviewed
literature to obtain the most recent information on
pharmacotherapeutics. This information has become
incredibly accessible because of computerized data-
bases such as PubMed and resources such as the FDA
website. The volume of this information, however, is
so extensive that I was often astounded by the number
of articles on a given topic. It was certainly a challenge
to condense this information into a meaningful format
for busy students and clinicians. Nonetheless, I believe
this edition is successful in presenting the most recent
and pertinent details of pharmacotherapeutics and
that it underscores the relevance of this topic to phys-
ical therapy and occupational therapy.
As in previous editions, basic pharmacology con-
cepts are addressed in the first section (Chapters 1
through 4), with subsequent chapters dealing with
drug applications in specific diseases and pathological

conditions. Chapters that deal with specific diseases
begin with background information on each system or
disorder, followed by detailed descriptions of the
physiologic and pharmacologic actions of these drugs,
their primary beneficial and adverse effect, and how
drug therapy can impact physical rehabilitation. A new
chapter on complementary and alternative medica-
tions (Chapter 38) has been added to this edition. This
chapter complements the other chapters that deal with
more traditional and conventional medications. This
edition also has a new “look,” with many features
added to help students and clinicians access this infor-
mation more easily.
Once again, I am pleased to present students and
clinicians with a resource that might ultimately
improve their ability to provide therapeutic interven-
tions. Pharmacology continues to expand both in
terms of the number of medications available to our
patients, and in our understanding of how drugs can
be used most effectively as part of a comprehensive
health care regimen. It is essential that we understand
the beneficial and adverse affects of medications com-
monly taken by our patients, and consider how we can
capitalize on the beneficial effects while dealing with
drug side effects. I hope this book will continue to
serve as a primary resource on this topic, and that
readers find this fourth edition interesting and useful.
Charles D. Ciccone
ix
Preface

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This page has been left intentionally blank.
This edition is the culmination of the invaluable assis-
tance and input from some very talented people. In
particular, I want to thank Barbara MacDermott
Costa, Linda D. Crane, John F. Decker, Mark Greve,
Sandra B. Levine, Donald L. Merrill, Grace Minerbo,
Peter Panus, and Jeffrey Rothman. I am deeply
indebted to these individuals for their suggestions on
previous editions. Without their help, it is unlikely
that the fourth edition of this text would have ever
become a reality.
I would also like to thank Bonnie DeSombre,
Fred Estabrook, and Cheryl Tarbell for their help in
preparing various tables and figures appearing in this
text.
Finally, Steve Wolf, editor of the CPR series, has
been a strong and consistent advocate for this book,
and I thank him for his steadfast support and encour-
agement over the years. I also want to thank the staff at
F. A. Davis Company for their help and proficiency in
developing this text. In particular, Margaret Biblis and
Melissa Duffield were instrumental in developing the
fourth edition of this text, and for implementing most
of the obvious changes in the design and presentation
of this material. I cannot thank them enough for all
their insight and expertise, and I am sure their efforts
will be appreciated by everyone who uses this text.
xi

Acknowledgments
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This page has been left intentionally blank.
Susan Sullivan Glenney, PT, MS
Former Assistant Professor
Department of Physical Therapy
University of Hartford
West Hartford, Connecticut
Gary Gorniak, PT, PhD
Director and Associate Professor
Physical Therapy Program
University of St. Augustine for Health Sciences
St. Augustine, Florida
Ellen Wruble Hakim, PT, DScPT, MS, CWS
Assistant Professor
Department of Physical Therapy and Rehabilitation
Science
University of Maryland School of Medicine
Baltimore, Maryland
Steven Raymond Tippett, PT, PhD, SCS, ATC
Associate Professor
Department of Physical Therapy and Health Science
Bradley University
Peoria, Illinois
xiii
Reviewer List
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Section 1. General Principles of
Pharmacology, 1
Chapter 1. Basic Principles of
Pharmacology, 3
Drug Nomenclature, 4
Substitution of Generic Drugs for Brand-Name
Products, 5
What Constitutes a Drug: Development and
Approval of Therapeutic Agents, 5
Drug Approval Process, 5
Prescription Versus Over-the-Counter
Medication, 7
Controlled Substances, 8
Basic Concepts in Drug Therapy, 8
Dose-Response Curves and Maximal Efficacy, 8
Potency, 9
Elements of Drug Safety, 10
Quantal Dose-Response Curves and the Median
Effective Dose, 10
Median Toxic Dose, 10
Therapeutic Index, 11
Chapter 2. Pharmacokinetics I:
Drug Administration, Absorption,
and Distribution, 13
Routes of Administration, 13
Enteral, 13
Parenteral, 15
Transdermal, 17
Drug Absorption and Distribution:
Bioavailability, 17

Membrane Structure and Function, 17
Movement Across Membrane Barriers, 18
Active Transport, 20
Distribution of Drugs Within the Body, 21
Factors Affecting Distribution, 21
Volume of Distribution, 21
Drug Storage, 22
Storage Sites, 22
Adverse Consequences of Drug Storage, 23
Newer Techniques for Drug Delivery, 23
Controlled-Release Preparations, 23
Implanted Drug Delivery Systems, 23
Targeting Drug Delivery to Specific Cells and
Tissues, 24
Chapter 3. Pharmacokinetics II: Drug
Elimination, 29
Biotransformation, 29
Cellular Mechanisms of Drug Biotransformation, 29
Organs Responsible for Drug Biotransformation, 31
Enzyme Induction, 31
Drug Excretion, 31
Drug Elimination Rates, 32
Clearance, 33
Half-Life, 33
Dosing Schedules and Plasma Concentration, 34
Variations in Drug Response and Metabolism, 34
Chapter 4. Drug Receptors, 41
Receptors Located on the Cell’s Surface, 41
Surface Receptors Linked Directly to Ion Channels, 41
Surface Receptors Linked Directly to Enzymes, 42

Surface Receptors Linked to Regulatory (G) Proteins:
Role of the Second Messenger, 42
Intracellular Receptors, 44
Drug-Receptor Interactions, 44
Functional Aspects of Drug-Receptor
Interactions, 45
Drug Selectivity and Receptor Subtypes, 45
Dose-Response, 46
Classification of Drugs: Agonist Versus Antagonist, 46
Competitive Versus Noncompetitive Antagonists, 46
Partial Agonists, 47
Mixed Agonist–Antagonists and Inverse Agonists, 48
xv
Contents
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Receptor Regulation, 48
Receptor Desensitization and Down-Regulation, 48
Receptor Supersensitivity, 49
Nonreceptor Drug Mechanisms, 50
Section 2. Pharmacology of the
Central Nervous System, 53
Chapter 5. General Principles of
Central Nervous System
Pharmacology, 55
CNS Organization, 55
Cerebrum, 55
Basal Ganglia, 55
Diencephalon, 56
Mesencephalon and Brainstem, 56
Cerebellum, 56

Limbic System, 57
Spinal Cord, 57
The Blood-Brain Barrier, 57
CNS Neurotransmitters, 57
Acetylcholine, 58
Monoamines, 59
Amino Acids, 59
Peptides, 59
Other Transmitters, 59
CNS Drugs: General Mechanisms, 60
Chapter 6. Sedative-Hypnotic and
Antianxiety Agents, 65
Sedative-Hypnotic Agents, 65
Benzodiazepines, 65
Nonbenzodiazepines, 68
Pharmacokinetics, 69
Problems and Adverse Effects, 69
Residual Effects, 69
Tolerance and Physical Dependence, 69
Other Side Effects, 70
Antianxiety Drugs, 70
Benzodiazepines, 70
Buspirone, 71
Use of Antidepressants in Anxiety, 72
Other Antianxiety Drugs, 72
Problems and Adverse Effects, 72
Special Consideration of Sedative-Hypnotic and
Antianxiety Agents in Rehabilitation, 73
Case Study
Sedative-Hypnotic Drugs, 74

Chapter 7: Drugs Used to Treat
Affective Disorders: Depression and
Bipolar Syndrome, 77
Depression, 77
Clinical Picture, 77
Pathophysiology of Depression, 78
Antidepressant Drugs, 79
Use of Antidepressants in Chronic Pain, 86
Treatment of Bipolar Disorder: Antimanic
Drugs, 86
Bipolar Disorder, 86
Lithium, 86
Other Drugs Used in Bipolar Disorder, 87
Special Concerns in Rehabilitation
Patients, 88
Case Study
Antidepressant Drugs, 89
Chapter 8. Antipsychotic Drugs, 93
Schizophrenia, 93
Neurotransmitter Changes in Schizophrenia, 94
Antipsychotic Mechanism of Action, 94
Antipsychotic Medications, 95
Traditional Antipsychotics, 95
Atypical Antipsychotics, 95
Pharmacokinetics, 96
Other Uses of Antipsychotics, 98
Problems and Adverse Effects, 98
Extrapyramidal Symptoms, 98
Nonmotor Effects, 100
Sedation, 100

Anticholinergic Effects, 100
Other Side Effects, 100
Special Concerns in Rehabilitation
Patients, 101
Case Study
Antipsychotic Drugs, 101
xvi Contents
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Chapter 9. Antiepileptic Drugs, 105
Classification of Epileptic Seizures, 105
Rationale for Drug Treatment, 107
Drugs Used to Treat Epilepsy, 107
Barbiturates, 107
Benzodiazepines, 107
Hydantoins, 108
Iminostilbenes, 109
Succinimides, 109
Valproic Acid, 109
Newer “Second-Generation” Agents, 110
Selection of a Specific Antiepileptic
Agent, 111
Single-Drug Therapy Versus Drug
Combinations in Epilepsy, 113
Pharmacokinetics, 113
Special Precautions During Pregnancy, 113
Treatment of Status Epilepticus, 113
Withdrawal of Antiseizure Medications, 114
Special Concerns in Rehabilitation
Patients, 114
Case Study

Antiepileptic Drugs, 115
Chapter 10. Pharmacological
Management of Parkinson
Disease, 119
Pathophysiology of Parkinson Disease, 119
Etiology of Parkinson Disease: Genetic and
Environmental Factors, 120
Therapeutic Agents in Parkinsonism, 121
Levodopa, 122
Other Drugs Used to Treat Parkinson
Disease, 126
Clinical Course of Parkinson Disease: When to
Use Specific Drugs, 129
Neurosurgical Interventions in Parkinson
Disease, 129
Special Considerations for Rehabilitation, 130
Case Study
Anti-Parkinson Drugs, 131
Chapter 11. General Anesthetics, 135
General Anesthesia: Requirements, 135
Stages of General Anesthesia, 135
General Anesthetics: Classification and Use
According to Route of Administration, 136
General Anesthetics: Specific Agents, 136
Inhalation Anesthetics, 136
Intravenous Anesthetics, 136
Pharmacokinetics, 139
Mechanisms of Action, 139
Adjuvants in General Anesthesia, 141
Preoperative Medications, 141

Neuromuscular Blockers, 141
Special Concerns in Rehabilitation, 145
Case Study
General Anesthetics, 145
Chapter 12. Local Anesthetics, 149
Types of Local Anesthetics, 149
Pharmacokinetics, 150
Clinical Use of Local Anesthetics, 150
Mechanism of Action, 154
Differential Nerve Block, 155
Systemic Effects of Local Anesthetics, 156
Significance in Rehabilitation, 157
Case Study
Local Anesthetics, 157
Section 3. Drugs Affecting Skeletal
Muscle, 161
Chapter 13. Skeletal Muscle
Relaxants, 163
Increased Muscle Tone: Spasticity Versus Muscle
Spasms, 163
Specific Agents Used to Produce Skeletal
Muscle Relaxation, 164
Agents Used to Treat Muscle Spasms, 164
Diazepam, 164
Polysynaptic Inhibitors, 165
Contents xvii
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Agents Used to Treat Spasticity, 166
Baclofen, 167
Intrathecal Baclofen, 168

Dantrolene Sodium, 169
Diazepam, 170
Gabapentin, 170
Tizanidine, 171
Use of Botulinum Toxin as a Muscle Relaxant, 171
Pharmacokinetics, 174
Special Concerns in Rehabilitation Patients, 174
Case Study
Muscle Relaxants, 175
Section 4. Drugs Used to Treat
Pain and Inflammation, 181
Chapter 14. Opioid Analgesics, 183
Source of Opioid Analgesics, 183
Endogenous Opioid Peptides and Opioid
Receptors, 184
Endogenous Opioids, 184
Opioid Receptors, 184
Classification of Specific Agents, 185
Pharmacokinetics, 187
Mechanism of Action, 188
Effect of Opioids on the CNS, 188
Effect of Opioids on CNS Synapses, 188
Peripheral Effects of Opioids, 190
Clinical Applications, 190
Treatment of Pain, 190
Use of Opioids in Patient-Controlled Analgesia, 191
Other Opioid Uses, 191
Problems and Adverse Effects, 192
Concepts of Addiction, Tolerance, and Physical
Dependence, 192

Tolerance, 192
Physical Dependence, 193
Tolerance and Dependence During Therapeutic Opioid
Use, 193
Pharmacological Treatment of Opioid Addiction, 193
Special Concerns in Rehabilitation
Patients, 194
Case Study
Opioid Analgesics, 195
Chapter 15. Nonsteroidal
Anti-Inflammatory Drugs, 199
Aspirin and Other NSAIDs: General Aspects, 199
Prostaglandins, Thromboxanes, and
Leukotrienes, 200
Eicosanoid Biosynthesis, 200
Role of Eicosanoids in Health and Disease, 201
Mechanism of NSAID Action: Inhibition
of Prostaglandin and Thromboxane
Synthesis, 202
Aspirin: Prototypical NSAID, 203
Clinical Applications of Aspirinlike Drugs, 203
Treatment of Pain and Inflammation, 203
Treatment of Fever, 204
Treatment of Vascular Disorders, 204
Prevention of Cancer, 204
Problems and Adverse Effects of Aspirinlike
Drugs, 204
Gastrointestinal Problems, 204
Other Side Effects, 205
Comparison of Aspirin with Other NSAIDs, 206

COX-2 Selective Drugs, 209
COX-2 Drugs and the Risk of Heart Attack and
Stroke, 210
Acetaminophen, 210
Pharmacokinetics of NSAIDs and
Acetaminophen, 211
Special Concerns in Rehabilitation Patients, 212
Case Study
Nonsteroidal Anti-Inflammatory Drugs, 212
Chapter 16. Pharmacologic
Management of Rheumatoid Arthritis
and Osteoarthritis, 217
Rheumatoid Arthritis, 217
Immune Basis for Rheumatoid Arthritis, 218
Overview of Drug Therapy in Rheumatoid
Arthritis, 219
Nonsteroidal Anti-Inflammatory Drugs, 219
Glucocorticoids, 221
Disease-Modifying Antirheumatic Drugs, 222
DMARD Combinations Used in Rheumatoid
Arthritis, 228
Dietary Implications for Rheumatoid Arthritis, 229
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Osteoarthritis, 229
Acetaminophen and NSAIDs, 230
Viscosupplementation, 230
Glucosamine and Chondroitin Sulfate, 230
Special Concerns for Antiarthritic Drug Therapy
in Rehabilitation Patients, 231

Case Study
Rheumatoid Arthritis, 232
Chapter 17. Patient-Controlled
Analgesia, 237
Pharmacokinetic Basis for PCA, 237
PCA Dosing Strategies and Parameters, 238
Loading Dose, 238
Demand Dose, 238
Lockout Interval, 238
1- and 4-Hour Limits, 238
Background Infusion Rate, 239
Successful Versus Total Demands, 239
Types of Analgesics Used for PCA, 239
Administration Routes During PCA, 240
Intravenous PCA, 240
Epidural PCA, 241
Transdermal PCA, 241
Regional PCA, 242
PCA Pumps, 242
Comparison of PCA to Traditional Methods of
Analgesic Administration, 243
Problems and Side Effects of PCA, 245
Pharmacologic Side Effects, 245
Problems with PCA Delivery, 245
Special Concerns for PCA in Rehabilitation
Patients, 246
Case Study
Patient-Controlled Analgesia, 247
Section 5. Autonomic and
Cardiovascular Pharmacology, 251

Chapter 18. Introduction to
Autonomic Pharmacology, 253
Anatomy of the Autonomic Nervous System:
Sympathetic and Parasympathetic Divisions, 253
Preganglionic and Postganglionic Neurons, 253
Sympathetic Organization, 254
Parasympathetic Organization, 254
Functional Aspects of the Sympathetic and Parasympa-
thetic Divisions, 254
Function of the Adrenal Medulla, 255
Autonomic Integration and Control, 256
Autonomic Neurotransmitters, 257
Acetylcholine and Norepinephrine, 257
Other Autonomic Neurotransmitters, 257
Autonomic Receptors, 258
Cholinergic Receptors, 258
Adrenergic Receptors, 259
Pharmacologic Significance of Autonomic
Receptors, 261
Chapter 19. Cholinergic Drugs, 263
Cholinergic Receptors, 263
Cholinergic Stimulants, 264
Direct-Acting Cholinergic Stimulants, 264
Indirect-Acting Cholinergic Stimulants, 264
Clinical Applications of Cholinergic Stimulants, 266
Adverse Effects of Cholinergic Stimulants, 267
Anticholinergic Drugs, 268
Source and Mechanism of Action of Antimuscarinic
Anticholinergic Drugs, 268
Clinical Applications of Antimuscarinic Drugs, 268

Side Effects of Anticholinergic Drugs, 271
Chapter 20. Adrenergic Drugs, 273
Adrenergic Receptor Subclassifications, 273
Adrenergic Agonists, 274
Alpha Agonists, 275
Beta Agonists, 276
Drugs with Mixed Alpha- and Beta-Agonist
Activity, 278
Adrenergic Antagonists, 279
Alpha Antagonists, 279
Beta Antagonists, 281
Other Drugs That Inhibit Adrenergic Neurons, 284
Chapter 21. Antihypertensive
Drugs, 287
Normal Control of Blood Pressure, 288
Pathogenesis of Hypertension, 288
Essential Versus Secondary Hypertension, 288
Possible Mechanisms in Essential Hypertension, 288
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Drug Therapy, 289
Diuretics, 290
Mechanism of Action and Rationale for Use, 290
Classification of Diuretics, 291
Adverse Effects of Diuretics, 292
Sympatholytic Drugs, 292
Beta Blockers, 292
Alpha Blockers, 293
Presynaptic Adrenergic Inhibitors, 294
Centrally Acting Agents, 295

Ganglionic Blockers, 295
Vasodilators, 296
Mechanism of Action and Rationale for Use, 296
Specific Agents, 296
Adverse Effects, 297
Inhibition of the Renin-Angiotensin
System, 297
Mechanism of Action and Rationale for
Use, 297
Specific Agents, 298
Adverse Effects, 298
Calcium Channel Blockers, 299
Specific Agents, 299
Adverse Effects, 299
Stepped-Care Approach to Hypertension, 300
Nonpharmacologic Treatment of
Hypertension, 300
Special Concerns in Rehabilitation
Patients, 301
Case Study
Hypertension, 301
Chapter 22. Treatment of Angina
Pectoris, 307
Drugs Used to Treat Angina Pectoris, 308
Organic Nitrates, 308
Mechanism of Action and Rationale for Use, 308
Specific Agents, 309
Adverse Side Effects of Nitrates, 310
Beta-Adrenergic Blockers, 310
Mechanism of Action and Rationale for Use, 310

Specific Agents, 310
Adverse Side Effects, 311
Calcium Channel Blockers, 311
Mechanism of Action and Rationale for Use, 311
Specific Agents, 311
Adverse Side Effects, 312
Use of Anticoagulants in Angina Pectoris, 312
Treatment of Specific Types of Angina
Pectoris, 313
Stable Angina, 314
Variant Angina (Prinzmetal Ischemia), 314
Unstable Angina, 315
Nonpharmacologic Management of Angina
Pectoris, 315
Special Concerns in Rehabilitation Patients, 316
Case Study
Antianginal Drugs, 316
Chapter 23. Treatment of Cardiac
Arrhythmias, 321
Cardiac Electrophysiology, 321
Cardiac Action Potentials, 321
Normal Cardiac Rhythm, 322
Normal Conduction of the Cardiac Action
Potential, 322
Mechanisms of Cardiac Arrhythmias, 323
Types of Arrhythmias, 324
Classification of Antiarrhythmic Drugs, 324
Class I: Sodium Channel Blockers, 324
Class II: Beta Blockers, 326
Class III. Drugs That Prolong Repolarization, 326

Class IV: Calcium Channel Blockers, 327
Other Drugs Used to Treat Arrhythmias, 327
Nonpharmacologic Treatment of
Arrhythmias, 327
Special Concerns in Rehabilitation Patients, 328
Case Study
Antiarrhythmic Drugs, 328
Chapter 24. Treatment of Congestive
Heart Failure, 331
Pathophysiology of Congestive Heart Failure, 331
Vicious Cycle of Heart Failure, 331
Congestion in Left and Right Heart Failure, 333
Pharmacotherapy, 334
Drugs That Increase Myocardial Contraction
Force (Positive Inotropic Agents), 334
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Digitalis, 334
Other Positive Inotropic Agents, 338
Agents That Decrease Cardiac Workload, 339
Drugs Affecting the Renin-Angiotensin System, 339
Beta Blockers, 340
Diuretics, 341
Vasodilators, 342
Summary of Drug Therapy, 342
Special Concerns in Rehabilitation Patients, 343
Case Study
Congestive Heart Failure, 343
Chapter 25. Treatment of Coagulation
Disorders and Hyperlipidemia, 347

Normal Mechanism of Blood Coagulation, 347
Clot Formation, 348
Clot Breakdown, 349
Drugs Used to Treat Overactive Clotting, 349
Anticoagulants, 349
Antithrombotic Drugs, 352
Thrombolytic Drugs, 354
Treatment of Clotting Deficiencies, 356
Hemophilia, 356
Deficiencies of Vitamin K-Dependent Clotting
Factors, 357
Antifibrinolytics, 357
Agents Used to Treat Hyperlipidemia, 357
HMG-CoA Reductase Inhibitors (Statins), 358
Fibric Acids, 359
Other Lipid-Lowering Agents, 360
Adverse Effects of Antihyperlipidemia Agents, 360
Special Concerns in Rehabilitation
Patients, 361
Case Study
Clotting Disorders, 362
Section 6. Respiratory and
Gastrointestinal Pharmacology,
367
Chapter 26. Respiratory Drugs, 369
Drugs Used to Treat Respiratory Tract Irritation
and Control Respiratory Secretions, 369
Antitussives, 369
Decongestants, 370
Antihistamines, 370

Mucolytics and Expectorants, 373
Drugs Used to Maintain Airway Patency in
Obstructive Pulmonary Disease, 373
Beta-Adrenergic Agonists, 373
Xanthine Derivatives, 376
Anticholinergic Drugs, 377
Glucocorticoids, 378
Cromones, 379
Leukotriene Inhibitors, 380
Treatment of Bronchial Asthma, 380
Pathophysiology of Bronchial Asthma, 380
Long-Term Management of Asthma, 381
Treatment of Reversible Bronchospasm in
COPD, 382
Treatment of Respiratory Problems in Cystic
Fibrosis, 382
Special Concerns in Rehabilitation Patients, 383
Case Study
Respiratory Drugs, 384
Chapter 27. Gastrointestinal
Drugs, 389
Drugs Used to Control Gastric Acidity and
Secretion, 389
Antacids, 389
H
2
Receptor Blockers, 390
Proton Pump Inhibitors, 391
Treatment of H. Pylori Infection in Gastric Ulcer
Disease, 392

Other Agents Used to Control and Treat Gastric
Ulcers, 393
Antidiarrheal Agents, 393
Opioid Derivatives, 394
Adsorbents, 395
Bismuth Salicylate, 395
Miscellaneous Agents Used to Treat Diarrhea, 395
Laxatives and Cathartics, 395
Rationale for Use, 395
Specific Agents and Mechanism of Action, 396
Adverse Effects, 397
Miscellaneous Gastrointestinal Drugs 397
Digestants, 397
Emetics, 397
Antiemetics, 397
Cholelitholytic Agents, 397
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Special Concerns in Rehabilitation Patients, 398
Case Study
Gastrointestinal Drugs, 398
Section 7. Endocrine
Pharmacology, 401
Chapter 28. Introduction to Endocrine
Pharmacology, 403
Primary Endocrine Glands and Their Hormones,
403
Hypothalamus and Pituitary Gland, 403
Thyroid Gland, 405
Parathyroid Gland, 406

Pancreas, 406
Adrenal Gland, 406
Gonads, 407
Endocrine Physiology and Pharmacology, 407
Hormone Chemistry, 407
Synthesis and Release of Hormones, 407
Feedback Control Mechanisms in Endocrine
Function, 408
Hormone Transport, 408
Hormone Effects on the Target Cell, 409
Clinical Use of Endocrine Drugs, 411
Chapter 29. Adrenocorticosteroids,
415
Steroid Synthesis, 415
Glucocorticoids, 417
Role of Glucocorticoids in Normal Function, 417
Mechanism of Action of Glucocorticoids, 417
Physiologic Effects of Glucocorticoids, 418
Therapeutic Glucocorticoid Agents, 421
Clinical Uses of Glucocorticoids, 421
Glucocorticoid Use in Endocrine Conditions, 421
Use in Nonendocrine Conditions, 421
Adverse Effects of Glucocorticoids, 423
Adrenocortical Suppression, 423
Drug-Induced Cushing Syndrome, 423
Breakdown of Supporting Tissues, 425
Other Adverse Effects, 425
Drugs That Inhibit Adrenocortical Hormone
Biosynthesis, 426
Mineralocorticoids, 426

Regulation of Mineralocorticoid Secretion, 426
Mechanism of Action and Physiologic Effects of
Mineralocorticoids, 426
Therapeutic Use of Mineralocorticoid Drugs, 428
Adverse Effects of Mineralocorticoid Agonists, 428
Mineralocorticoid Antagonists, 428
Special Concerns of Adrenal Steroid Use in
Rehabilitation Patients, 429
Case Study
Adrenocorticosteroids, 430
Chapter 30. Male and Female
Hormones, 435
Androgens, 435
Source and Regulation of Androgen Synthesis, 435
Physiologic Effects of Androgens, 437
Pharmacologic Use of Androgens, 437
Clinical Use of Androgens, 437
Specific Agents, 438
Adverse Effects of Clinical Androgen Use, 439
Antiandrogens, 440
Androgen Abuse, 440
Nature of Androgen Abuse, 440
Effects of Androgens on Athletic Performance, 442
Adverse Effects of Androgen Abuse, 442
Estrogen and Progesterone, 443
Effects of Estrogen and Progesterone on Sexual
Maturation, 443
Regulation and Effects of Hormonal Synthesis During
the Menstrual Cycle, 443
Female Hormones in Pregnancy and Parturition, 445

Pharmacologic Use of Estrogen and
Progesterone, 445
Conditions Treated with Estrogen and Progesterone, 445
Specific Agents, 446
Adverse Effects of Estrogen and Progesterone, 447
Selective Estrogen Receptor Modulators, 448
Antiestrogens, 449
Antiprogestins, 449
Hormonal Contraceptives, 450
Types of Contraceptive Preparations, 450
Mechanism of Contraceptive Action, 452
Adverse Effects of Hormonal Contraceptives, 452
Case Study
Male and Female Hormones, 453
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