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Evolve Student Resources for Haveles: Applied Pharmacology

for the Dental Hygienist, 6th Edition, offers the following:
Practice Quizzes
Approximately 350 questions are separated by chapter and provided
in an instant-feedback format that includes correct answers, rationales,
and page-number references to the location of that content within the
textbook.

Labeling Exercises
Selected illustrations from the book are reproduced with interactive drag-
and-drop labels for a fun and effective way to study.

Oral Pathology Exercises

Images included in the book’s full-color insert are reproduced in an
interactive activity that matches the image to its description.

Glossary Exercises
Flashcards are created from the key terms included within chapters and
the book’s glossary for an engaging study experience.

Drug Guides
Generic and trade name drugs are grouped and summarized by chapter
for a quick reference tool focusing on classification and use.
This page intentionally left blank
Elena Bablenis Haveles, BS Pharm, PharmD
Adjunct Associate Professor of Pharmacology
Gene W. Hirschfeld School of Dental Hygiene
College of Health Sciences
Old Dominion University
Norfolk, Virginia
3251 Riverport Lane
Maryland Heights, Missouri 63043

APPLIED PHARMACOLOGY FOR ISBN-13: 978-0-323-06558-0

THE DENTAL HYGIENIST

Copyright © 2011, 2007, 2000, 1995, 1989, 1982 by Mosby, Inc., an affiliate of Elsevier Inc.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means,
electronic or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights
Department: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail:
[email protected]. You may also complete your request on-line via the Elsevier website at http://
www.elsevier.com/permissions.

Notice

Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate.
Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the
manufacturer of each product to be administered, to verify the recommended dose or formula, the method
and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on
their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of
the law, neither the Publisher nor the Author assumes any liability for any injury and/or damage to persons
or property arising out of or related to any use of the material contained in this book.
The Publisher

Library of Congress Cataloging-in-Publication Data

Haveles, Elena B. (Bablenis)
Applied pharmacology for the dental hygienist / Elena Bablenis Haveles. — 6th ed.
    p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-323-06558-0 (pbk. : alk. paper) 1. Dental pharmacology. 2. Dental hygiene. I. Title.
[DNLM: 1. Pharmacology, Clinical. 2. Dental Hygienists. QV 50 H384a 2011]
RK701.R46 2011
617.6′01—dc22
2009043308

Vice President and Publisher: Linda Duncan

Executive Editor: John Dolan
Managing Editor: Kristin Hebberd
Publishing Services Manager: Catherine Jackson
Project Manager: David Stein
Designer: Teresa McBryan

Printed in the United States.

Last digit is print number: 9 8 7 6 5 4 3

Reviewers

Barbara Bennett, CDA, RDH, MS Deborah P. Milliken, DMD

Department Chair Supervising Dentist
Dental Hygiene and Dental Assisting Programs Professor, Dental Hygiene
Co-Division Director South Florida Community College
Health Programs Avon Park, Florida
Texas State Technical College
Harlingen, Texas Dr. Ron Swisher
Professor
Karen M. Bratus, DDS Department of Natural Sciences
Faculty Program in Health Sciences
Department of Dental Hygiene Oregon Institute of Technology
Baker College of Auburn Hills Klamath Falls, Oregon
Auburn Hills, Michigan

v
To my husband Paul and
sons Andrew and Harry
Preface

Knowledge of pharmacology is imperative to the success of a 2. Students should develop the ability to find the necessary
dental hygiene student. Applied Pharmacology for the Dental information about drugs with which they are not familiar.
Hygienist, Sixth Edition, is written with the specific needs of the The textbook encourages the use of the current reference
dental hygienist in mind to help ensure your success in this sources that will be available where dental hygienists
subject matter. practice.
Society is information-conscious, and it is expected that the 3. Students should develop the ability to apply that information
dental hygienist be knowledgeable about medications. Dental to their clinical dental patients within a reasonable time.
hygienists are called on to complete medication and health his-
tories, administer certain medications, provide counseling about
oral hygiene, and, in some states, prescribe medication and ORGANIZATION
provide counseling about medications.
The primary goal of this book remains to produce safe and The material has been organized to create a readable and clini-
effective dental practitioners and to offer them the tools that cally applicable resource in pharmacology that specifically
they need to continue to learn throughout their lifetimes. This addresses the needs of the dental hygiene student. The textbook
textbook provides the dental hygienist with the necessary knowl- is divided into four sections:
edge of pharmacology to assess for medical illness, adverse reac- PART ONE: General Principles of Pharmacology includes
tions, and drug interactions that may affect oral health care and general information about pharmacology, pharmacokinetics,
treatment. It is not intended that the dental hygienist take the drug action and handling, adverse reactions, prescription writing,
place of the dentist in providing the patient with information autonomic pharmacology, the role of the dental hygienist, and
about the various medications but that he or she will work with pharmacology in oral health care.
the dentist in providing appropriate patient care. PART TWO: Drugs Used in Dentistry includes the phar-
macology of nonopioid analgesics, opioid analgesics, antibiotics,
antifungals, antiviral drugs, local anesthetics, general anesthetics
INTENDED AUDIENCE with a special emphasis on nitrous oxide, and vitamins and
minerals. It also has chapters on the treatment of oral conditions
The primary intended audience of this specific textbook is the and dental hygiene–related disorders. Each chapter focuses on
dental hygiene student. However, practicing dental hygienists dental-related adverse effects, how the drug may affect oral
and dentists may find this book useful for a quick review of health care, and the specific dental hygiene considerations.
pharmacology, and the information may also benefit dental PART THREE: Drugs that May Alter Dental Treatment
students as a classroom text or resource. includes the more common disease states or medical conditions
that patients may present with, as well as how those medications
or the disease states themselves can affect oral health care. Each
IMPORTANCE TO THE PROFESSION chapter also focuses on dental-related adverse effects, how the
drug may affect oral health care, and specific dental hygiene
Continual learning after the completion of a formal education considerations.
is especially critical in the dynamic area of pharmacology. New PART FOUR: Special Situations includes significant infor-
drugs are constantly being discovered and synthesized. New mation on treating emergency situations, women who are preg-
effects of old drugs are identified. New diseases and drugs for nant or lactating, patients with substance abuse issues, and those
the treatment of those diseases are being studied. Today’s dental patients self-treating with herbal remedies or supplements. Each
hygiene student will need to be able to access new information chapter also focuses on dental-related adverse effects, how the
about new drugs in the future and intelligently communicate drug may affect oral health care, and specific dental hygiene
with others (professionals and patients) using the unique medical considerations.
and pharmacologic vocabularies. It is hoped that this textbook
will also help dental hygiene students to accomplish the follow-
ing goals: KEY FEATURES
1. Students should achieve an understanding of the need and
importance of obtaining and using appropriate reference This book includes many features and learning aids to assist the
material when needed. When confronted with a patient student studying pharmacology:
taking a new or unfamiliar drug, the professional will use the • Dental Focus: Although pharmacologic basics are covered
appropriate references to learn about the effects of the drug. overall and for specific types of drugs, interactions of clinical
Pharmacology is a field in which new information is con- interest in dentistry are incorporated throughout the book.
stantly becoming available. These sections offer explanations on why certain drugs are

vii
viii PREFACE

used or contraindicated in a dental treatment plan, providing • Dental Hygiene Considerations Boxes: Each chapter concludes
students with targeted information they will need for with a compilation of the most relevant dental-specific infor-
practice. mation, which is summarized in terms of how that chapter’s
• Consistent Presentation: Information about each drug varies, content specifically relates to the day-to-day practice of
but all drugs are presented using a similar format so that dental hygiene. These sections help explain to students the
sections can be easily identified. Each drug group is discussed need for an understanding of pharmacology and its impor-
and includes the group’s indications (for what purpose the tance in helping them achieve maximal oral health for their
drugs are used), pharmacokinetics (how the body handles the patients.
drugs), pharmacologic effects (what the drugs do), adverse • Writing Level: Certain content areas and tables throughout
reactions (bad things the drugs do), drug interactions (how the book have been simplified to better explain difficult con-
the drugs react with other drugs in the body), and the dosage cepts, such as receptors and metabolism. Pharmacology is a
of the drugs (how much is indicated). complex subject matter, and this book attempts to present
• Clinical Skills Assessment: Review questions are included at information in a way that helps ensure that students can fully
the end of each chapter, with answers available to instructors. comprehend the content and apply it to the practice of dental
These questions help students assess their knowledge and hygiene.
gauge comprehension of chapter material. • Art Program: Approximately one third of the images are new
• Key Terminology: Key terms are bolded throughout and to this edition, and many of those that appeared in the previ-
appear in color within chapter discussions; each term is ous edition have been updated and improved. The new
defined in a back-of-book glossary. The language of pharma- images are more targeted and visually appealing and help
cology is new to many dental hygiene students, and the support text discussions so that students can see key concepts
in-text highlights draw students’ attention to terms they may at work.
need to review. The glossary provides a centralized, quick, • Chapter Objectives: Each chapter begins with a list of learning
and handy reference. objectives that the student should master on completion. The
• Summary Tables and Boxes: Throughout, concepts are sum- objectives help students set goals for what they will accom-
marized in boxes and tables to accompany narrative discus- plish and also serve as checkpoints for comprehension and
sions, providing easy-to-read versions of text discussions that study tools in the preparation for examinations.
support visual learners and serve as useful tools for review • Textbook Design: A new design incorporates more graphics
and study. and a more modern look to help readers engage in the
• Note Boxes: Boxes are interspersed throughout text discus- content.
sions to briefly convey important concepts, indications, con-
traindications, memory tools, warnings, and more. They are
easy to see and provide quick statements or phrases that are ANCILLARIES
easy to remember.
• Reference Citations: Chapters contain bibliographical infor- A companion Evolve website has been created specifically for
mation as necessary, directing students to targeted sources of Applied Pharmacology for the Dental Hygienist and can be accessed
information where additional dental-related information can directly from http://evolve.elsevier.com/Haveles/pharmacology.
be located. The following resources are provided:
• Appendixes: Resources such as the top 200 drugs, What If …
scenarios that quickly outline situations in which relatively For the Instructor
quick assessments and decisions are required, and the calcula- • Test Bank: Approximately 900 objective-style questions—
tion of children’s dosages highlight additional information multiple-choice, true/false, matching, and short-answer—are
that proves useful in the clinical environment. provided, with accompanying rationales for correct answers
• Drug Index: A separate index covers the mention of all the and page-number references for remediation.
drugs discussed within the book, allowing readers to quickly • Image Collection: All the book’s images, organized by chapter
access targeted information about specific drugs or drug with correlating figure numbers to the textbook, are available
classes. for download into PowerPoint or other presentations and
materials.
• Animations: Three-dimensional narrated visualizations of
NEW TO THIS EDITION basic body system workings provide foundational anatomical
and physiological information to support pharmacologic
• Chapter on Hygiene-Related Oral Disorders: Oral hygiene is concepts.
highlighted, specifically in terms of the prevention of dental • PowerPoint Presentations: Lecture slides are included for each
caries, gingivitis, and hypersensitivity. Both pharmacologic chapter.
and nonpharmacologic therapies are discussed, and the role • Case Studies: Case presentations are followed by thought
of the dental hygienist in patient education is emphasized. questions that deal with drug indications, contraindications,
• Chapter on Natural/Herbal Products and Dietary Supplements: interactions, and more. Answers are provided.
Herbal medicine is explored, including its regulation, package • Chapter Features: A detailed chapter outline, listing of key
labeling, safety and potential drug interactions, manufactur- terms, chapter objectives, and Dental Hygiene Considerations
ing, and standardization. Several of the most common sup- are compiled for each chapter to support lesson planning.
plements are outlined, with specific information provided on • Color Pill Atlas: A labeled color image is provided for some
adverse effects and dental hygiene implications. of the most commonly prescribed medications.
 PREFACE ix

• Answers to Clinical Skills Assessments: Answers and rationales • Glossary Exercises: Crossword puzzles are created from
are provided for each end-of-chapter review question. the book’s glossary to help students master key
terminology.
For the Student • Drug Guides: The major groups and specific drugs covered
• Practice Quizzes: Approximately 575 questions are provided within each chapter are organized and summarized in terms
in an instant-feedback format to allow students to assess their of classification and mechanism of action for a quick study
understanding of content and prepare for examinations. tool.
Rationales and page-number references are provided for
remediation.
• Labeling Exercises: Drag-and-drop matching exercises are
created from many of the book’s illustrations to reinforce and
help students visualize concepts. Elena Bablenis Haveles
Acknowledgments

Thank you to my peers and administrators at the Gene W. Hirschfeld School of Dental
Hygiene, Old Dominion University, for their support.

To my children, Andrew and Harry, many thanks for allowing Mom to work on this book
when we would rather have done so many other things together.

To my husband, Paul, thank you for your guidance and support as I try to juggle this and
everything else in our lives. I love you.

EBH

x
How to Be Successful in Pharmacology

Before the lecture, read the syllabus outline for the subject to be might be encountered when treating a patient taking this medi-
covered during the class period. Become familiar with the vocab- cation? How can the chance that something untoward will
ulary. Guess what might be said about the various topics. Think happen be minimized?
of what has been said in pharmacology about the topic; look at Did you think of examples in “real life”? By thinking of real-
your pharmacology notes to see what you already know about life examples, readers can transform a topic into a picture in
the topic. Skim the textbook chapter(s) assigned to identify areas their brain. For example, the “fight or flight” response associated
to be covered. with the sympathetic nervous system can be visualized as a
Attend class, take notes in your syllabus, and ask yourself caveman, his eyes big and his heart pounding, being chased by
questions about what was said. Compare what was said with a hungry tiger.
what you previously thought about the topic.
Reread your lecture notes before the next class. Add and
complete things you remember from class. Ask fellow classmates USE OF OBJECTIVES TO FOCUS STUDYING
for clarification if you have questions. Reread notes from previ-
ous classes. Find out what the objectives are for your pharmacology class.
Read the textbook assignment. Note especially those areas These are some objectives that may give you an idea about the
discussed in class. Let the textbook assignment answer questions organization of the material.
you might have had in class. Answer general course objectives Goals for commonly prescribed dental drugs include the
in the front of your syllabus for the drug group covered. following:
Look up in a medical dictionary any words for which you • State the therapeutic use(s) for each drug group.
don’t know the meaning. Construct a vocabulary list for each • Discuss the mechanism of action of the drug, when
subject. Pay attention to the derivatives of the unknown medical applicable.
word—its stem, prefixes, and suffixes. • Explain the important pharmacokinetics for the drug group.
Use active learning when studying. Be able to determine what • List and describe the major pharmacologic effects associated
portion of your study time is spent in active learning. Use the with the drug group. State and discuss the important adverse
examples below to classify your study methods. reactions or side effects and their management or
• Active: Writing things down, making up flash cards, speaking minimization.
out loud, discussing the concepts with classmates, asking • Describe any contraindications/cautions to the use of the
each other questions, giving a lecture (to your parrot) without drug group.
notes, making a video or audio tape recording of your per- • Recognize clinically significant drug–drug, drug–disease, and
formances (for your own practice), or writing everything you drug–food interactions.
know about a drug on an empty blackboard. • Describe “patient instructions” for each drug group that
• Not active: Looking over notes, reading the book, listening could be prescribed.
in lecture, and reviewing your notes. Goals for agents patients may be taking that can alter dental
Did you answer the Clinical Skills Assessment questions? treatment:
These questions are included at the end of each chapter so the • Determine the “dental implications” of each drug group for
learner can check to see if he or she knows the answers to these the management of dental patients taking [drug group name].
questions. It is a review for your benefit. Answers are only avail- • Determine whether any dental drugs are likely to have drug
able through your instructor. interactions with these groups.
Did you think about what the information may mean to the • State change(s) in the treatment plans that would be required
dental hygienist? Trying to understand why things happen will for patients taking medications.
make learning more efficient and more fun, too. What problems

xi
This page intentionally left blank
Contents

PART ONE GENERAL PRINCIPLES

1 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription
Writing, 2
2 Drug Action and Handling, 12
3 Adverse Reactions, 28

PART TWO DRUGS USED IN DENTISTRY

4 Autonomic Drugs, 34
5 Nonopioid (Nonnarcotic) Analgesics, 49
6 Opioid (Narcotic) Analgesics and Antagonists, 65
7 Antiinfective Agents, 76
8 Antifungal and Antiviral Agents, 102
9 Local Anesthetics, 112
10 General Anesthetics, 127
11 Antianxiety Agents, 136
12 Vitamins and Minerals, 148
13 Oral Conditions and Their Treatment, 165
14 Hygiene-Related Oral Disorders, 174

PART THREE DRUGS THAT MAY ALTER DENTAL TREATMENT

15 Cardiovascular Drugs, 186
16 Anticonvulsants, 213
17 Psychotherapeutic Agents, 223
18 Autocoids and Antihistamines, 234
19 Adrenocorticosteroids, 241
20 Other Hormones, 249
21 Antineoplastic Drugs, 269
22 Respiratory and Gastrointestinal Drugs, 276

PART FOUR SPECIAL SITUATIONS

23 Emergency Drugs, 290
24 Pregnancy and Breast Feeding, 299
25 Drug Abuse, 308
26 Natural/Herbal Products and Dietary Supplements, 320

Appendix A Compilation of the Top 200 Generic and Branded Drugs of 2008 by
Total Prescriptions, 326
Appendix B Medical Acronyms, 331
Appendix C Medical Terminology, 334
Appendix D What if … , 336
Appendix E Oral Manifestations: Xerostomia and Taste Changes, 341
Appendix F Children’s Dose Calculations, 344

Glossary, 345
Drug Index, 355
Index, 367

xiii
This page intentionally left blank
 PART ONE

GENERAL PRINCIPLES

CHAPTER 1
Information, Sources, Regulatory Agencies, Drug
Legislation, and Prescription Writing, 2
CHAPTER 2
Drug Action and Handling, 12
CHAPTER 3
Adverse Reactions, 28

1
 Information, Sources,
1 Regulatory Agencies,
Drug Legislation, and
Prescription Writing
CHAPTER OUTLINE LEARNING OBJECTIVES
HISTORY 1. Discuss the history of pharmacology and its relationship to the oral health care
PHARMACOLOGY AND ORAL HEALTH CARE provider.
PROVIDERS 2. Define the ways in which drugs are named and the significance of each.
SOURCES OF INFORMATION 3. Describe the acts and agencies within the federal government designed to regulate
DRUG NAMES drugs.
Drug Substitution 4. Identify the four phases of clinical evaluation involved in drug approval and the five
Top 200 Drugs schedules of drugs.
FEDERAL REGULATIONS AND REGULATORY 5. Describe the elements of a drug prescription.
AGENCIES
Harrison Narcotic Act
Food and Drug Administration
Federal Trade Commission
Drug Enforcement Administration Pharmacology is derived from the Greek prefix pharmaco-, meaning “drug” or
Omnibus Budget Reconciliation Act “medicine,” and the Greek suffix -logy, meaning “study.” Therefore pharmacology
CLINICAL EVALUATION OF A NEW DRUG is the study of drugs. Dorland’s Illustrated Medical Dictionary defines the term drug
DRUG LEGISLATION as follows:
History
Any chemical compound used on or administered to humans or animals as an aid in
Scheduled Drugs
the diagnosis, treatment, or prevention of disease or other abnormal condition, for
PRESCRIPTION WRITING the relief of pain or suffering, or to control or improve any physiologic or pathologic
Measurement condition.
Prescriptions
Explanations Accompanying Prescriptions Others define a drug as any chemical substance that affects biologic systems.
These definitions, however, are not complete. For example, birth control pills are
indicated in the treatment of which disease? Is pregnancy a disease? Another
problem with the current definition of pharmacology is that there is a large group
of substances (drugs?) that are categorized as “dietary supplements.” These agents
include herbs, vitamins, minerals, and amino acids. Although these substances
may have pharmacologic effects on the body, by law they are not classified as drugs.
This classification avoids the Food and Drug Administration (FDA) approval for
efficacy and safety required for drugs.

HISTORY
In the beginning, plantsPharmacology had its beginning when human ancestors
found in the jungle noticed that ingesting certain plants altered body func-
were discovered to tions or awareness. The first pharmacologist was a person
produce beneficial who became more astute in observing and remembering
effects. which plant products produced predictable results. From
this humble beginning, a huge industrial and academic
community concerned with the study and development of drugs has evolved. Plants
from the rain forest and chemicals from tar have been searched for the presence of
drugs. The agents discovered and found to be useful are then prescribed and dis-

2
 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription Writing CHAPTER 1 3

pensed through the practice of medicine, dentistry, pharmacy, Specific topics to be covered in each discipline are deter-
and nursing. Health care providers who can write prescriptions mined by this process. In the best educational situation, the
include physicians (for humans), veterinarians (for animals), process would be patient specific and produce learning issues
dentists (for dental problems), and optometrists (for eye prob- and content that cross multiple disciplines. However, in the
lems). Physicians’ assistants, nurse practitioners, and pharma- meantime, educational experiences are still often organized in
cists can prescribe drugs under certain guidelines and in certain discipline-based units. This textbook is also arranged in this
states. manner.
Knowledge of pharmacology is imperative for the dental
professional to perform important functions such as the
PHARMACOLOGY AND ORAL HEALTH following:
CARE PROVIDERS • Obtaining a health history. To obtain a complete and useful
health history, a knowledge of commonly prescribed drugs is
The American Dental Association (ADA) and American Dental required. Patients with systemic diseases unrelated to their
Hygienists’ Association (ADHA) have been analyzing tasks that dental health are often taking medications prescribed by their
oral health care providers should be able to perform during the physician. An understanding of the actions, indications,
practice of their professions. In education, these activities are adverse reactions, and therapeutic uses of these drugs can
termed competencies. help determine potential effects on dental treatment. Com-
To perform each competency paring the medical conditions of the patient with the medica-
What knowledge is (meaning to do something), certain tions he or she is taking often raises questions in the interview.
needed to perform the facts or concepts (meaning something Examples of this would include patients taking calcium
functions of a dental
you know) must be accessed (find it) channel blockers for hypertension and the risk of xerostomia
professional?
by the dental professional. The facts or or patients taking an aspirin each day to prevent a heart
concepts needed include didactic information (something attack or stroke and the increased risk of gingival bleeding.
learned from a book) relative to the task being performed (a • Administering drugs in the office. Because both the dentist and
dental procedure). Decisions that surround performing the the dental hygienist administer certain drugs in the office,
competency rely on a body of information, termed the founda- knowledge of these agents is crucial. For example, the oral
tion knowledge. Each content area is then analyzed to determine health care provider commonly applies topical fluoride, and
what relationship exists among the course content, the compe- in some states, both the dentist and the dental hygienist
tencies, and the appropriate foundation knowledge. Examples administer local anesthetics and nitrous oxide. In-depth
of questions that would need to be answered to perform a certain knowledge of these agents is especially important because of
dental procedure (the foundation knowledge required to deter- their frequent use.
mine the pros and cons of performing a certain dental procedure • Handling emergency situations. The ability to recognize and
on a certain patient with certain diseases) could include the assist in dental emergencies requires knowledge of certain
questions shown in Table 1-1. drugs. The indications for these drugs and their adverse reac-
From the example in Table 1-1, it can be seen that the dental tions must be considered. For example, a patient having an
health care worker cannot practice by doing “something” to anaphylactic reaction must have epinephrine administered
“someone” with “some problem.” Thought, facts, reasoning, quickly.
and problem solving are involved in making decisions about • Planning appointments. Patients taking medication for sys-
each patient seen in the dental office. Dental professionals are temic diseases may require special handling in the dental
not robots; they use clinical judgment to make the best decisions office. For example, asthmatic patients should have afternoon
about each patient. appointments, whereas diabetic patients usually have fewer
Table 1-1 illustrates the relationship among the professional, problems with a morning appointment. Certain patients may
the task, and the foundation knowledge. Because the dental and need to take medication before their appointment. Patients
dental hygiene professions require knowledge and decision with rheumatic heart disease need to be premedicated with
making, the “explanation behind the task” is important. antibiotics before some of their dental or dental hygiene
appointments.
• Nonprescription medication. Often, nonprescription or over-
the-counter (OTC) products may be recommended for the
patient. The study of pharmacology will assist the oral health
TABLE 1-1 RELATIONSHIP AMONG TASKS care provider in an intelligent selection of an appropriate
PERFORMED IN PRACTICE AND INFORMATION OTC product.
LEARNED IN PHARMACOLOGY • Nutritional or herbal supplements. Many patients self-treat or
are prescribed nutritional or herbal supplements for any
Professional Competency (Ability) Foundation Knowledge number of disease states. Although the vast majority of these
Dental hygienist 1. Remove calculus Treatment modifications supplements do not carry FDA approval for treating disease
and plaque. based on existing states, patients still use them. These supplements are drugs
2. Administer local medical conditions or and can cause adverse effects and interact with different drugs.
anesthetics. current medications. • Discussing drugs. When drugs are discussed with either the
Dentist “Restore” a carious Same as above patient or another health professional, proper terminology is
lesion needed. Drugs prescribed by the dentist can cause adverse
effects in patients; patients often ask the oral health care
4 PART ONE General Principles

provider questions about their medications. Knowledge of provider of the patient’s care. The ability to refer to a drug’s
the terms used to describe adverse reactions can facilitate name(s) is complicated by the fact that all drugs have at least
discussions with the patient, dentist, or physician. For two names, and many have more.
example, the term allergy refers to an allergic response to a When a particular drug is being investigated by a company,
drug (e.g., hives from aspirin). Patients, however, often it is identified by its chemical name, which is determined by its
confuse the term allergy with the term side effects. Side effects chemical structure. If the structure is unknown at the time of
refer to predictable responses to drugs that act on nontarget investigation, a code name, usually a combination of letters and
organs (e.g., stomach upset). The correct knowledge of these numbers, is assigned to the product (e.g., RU-486). Often, the
terms can help clarify a patient’s symptoms. Understanding code name is used even when the chemical structure is identified
the difference between the two effects of aspirin aids in and named. It is much easier to speak and write the code name
determining whether a nonsteroidal antiinflammatory than the full name of the chemical structure.
drug (e.g., ibuprofen) can be used for dental discomfort in If a compound is found to be useful
a particular patient. When the health history is taken and the Each drug has only one and it is determined that the com-
generic name but may
drugs the patient is taking are listed, it is important that have several trade
pound will be marketed commercially,
treatment does not begin until the drugs are checked for any names. the pharmaceutical company discover-
problems relating to dentistry. ing the drug gives the drug a trade
• Life-long learning. Because it is impossible to remember name (e.g., Coke). This name, which is capitalized, is usually
everything learned about current drugs and because new chosen so that it can be easily remembered and promoted com-
drugs are always being discovered and marketed, appropriate mercially. This trade name, registered as a trademark under the
reference sources should be available and consulted. To be Federal Trademark Law, is the property of the registering
able to evaluate the information retrieved from reference company. The trade name is protected by the Federal Patent
sources, understanding of the terminology of pharmacology Law for 20 years from the earliest claimed filing date, plus patent
and its global organization is essential. term extensions. Although the brand name is technically the
name of the company marketing the product, it is often used
interchangeably with the trade name.
SOURCES OF INFORMATION Before any drug is marketed, it is given a generic name that
becomes the “official” name of the drug. For each drug, there is
There are many different medications available, and it is only one generic name (e.g., cola) selected by the United States
important for the dental hygienist to know where to look for Adopted Name Council, and the name is not capitalized. This
information about prescription medications, nonprescription council selects a generic name that hopefully does not conflict
medications, and herbal supplements. There are many sources, with other drug names. Recently, the names of several marketed
including reference texts, association journals, and the internet, drugs were changed because they were confused with the name
where pertinent drug information can be found. Table 1-2 of another drug that had already been marketed.
reviews the different sources of information. An example of the many names a product can have is provided
Each publication type may be judged on its lack of bias, its by lidocaine, a local anesthetic commonly used in dentistry.
publication date (when the current edition was released), its Figure 1-1 compares the generic and trade names of lidocaine.
readability (vocabulary, simplicity of explanations, and presence After the original manufacturer’s patents have expired, other
of visual aids), its degree of detail (all you want to know and companies can market the generic drug under a trade name of
much more, just the right amount of information, or not enough their choosing (e.g., Pepsi). When lidocaine first appeared on
to understand what is being said), and its price. the market, it was manufactured by Astra and was available only
Every dental office should have at least one reference book as Xylocaine, but when its patent expired, other companies
that lists the names of both prescription and OTC drugs. started making the drug, and each company gave it their own
Further, a standard pharmacology textbook would be helpful in brand name (e.g., Octocaine). When a patient states an allergy
understanding the reference books. Because of the release of new to Xylocaine, the oral health care provider must be aware that
drugs, a recent edition (not more than 1 to 2 years old) of a lidocaine is the generic name of this drug and that the patient
reference book is needed. Table 1-3 compares properties of dif- should not be given lidocaine under another trade name such
ferent reference sources. as Octocaine.
Although books serve as the usual source of information on Drugs prescribed by physicians cause a similar problem.
drugs, computer software and even Internet-based services are Patients often know these drugs by the trade name. If a patient
becoming more readily available. In addition, the practicing reports an allergic reaction to Amoxil (the trade name), the oral
pharmacist can be a source of information. It is particularly health care provider must be aware that this patient should not
important for the dental professional to establish a professional take other brands of amoxicillin (the generic name) or any other
relationship with a local pharmacist, who may assist him or her type of penicillin.
in understanding the possible effects of a new drug on a patient. This book uses generic names when discussing drugs
because there is only one generic name for each drug. Trade
names (also known as proprietary names) appear in parentheses
DRUG NAMES after the generic name. Most reference books include indexes
that allow a drug to be accessed using either the generic or trade
It is important for the dentist and the dental hygienist to under- name. Newer drugs are usually referred to by their trade names.
stand the ways in which a drug can be named because he or she Old and traditional drugs are often referred to by their generic
must be able to discuss drugs with both the patient and the names.
 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription Writing CHAPTER 1 5

TABLE 1-2 SELECTED DRUG INFORMATION REFERENCES

Reference Brief Description

American Health-Systems Detailed reference source that provides an unbiased guide to all aspects of a drug’s properties. It is updated
Formulary Service yearly, and quarterly supplements are provided. The detail in this book is especially valuable when a specific
drug fact is needed. CD-ROM available.
United States Pharmacopeia- Volume 1: Drug Information for the Health Care Provider provides the health professional with necessary
Drug Information (USP DI) information regarding basic pharmacology and pharmacokinetics, dosing, adverse reactions, and drug
interactions. Volume 2: Advice for the Patient is written for the patient and includes appropriate information
on pharmacology, pharmacokinetics, dosing, adverse reactions, and drug interactions. The USP DI is published
annually with quarterly updates via CD-ROM. Monthly updates are available for those with the online USP DI.
Drug Facts and Comparisons Contains the most complete listing of currently available drugs, including prescription and OTC medications and
is arranged by pharmacologic class. It is available in a loose-leaf binder (updated monthly), annual hardback
book, online, or as CD-ROM.
Physicians’ Desk Reference (PDR) Most common reference book in the dental office because of its historically inexpensive price. New drugs
are added annually, and, often, older drugs are removed from the book to make space for newer drugs.
Information provided comes directly from the manufacturer’s package insert. The manufacturers are listed
alphabetically, and drugs are listed alphabetically within each manufacturer’s section. CD-ROM is available.
Handbook of Nonprescription Published every 3 years by the American Pharmaceutical Association. This textbook provides the reader with
Drugs: An Interactive detailed information about all classes of nonprescription drugs available in the United States. It also reviews
Approach to Self-Care (OTC the pathophysiology of different disease states and their treatments. There are several chapters that pertain to
Handbook) oral health care, and one chapter devoted to nicotine-related products.
PDR for Nonprescription Drugs, This reference book provides information on OTC drugs, supplements, and herbs and is organized alphabetically
Supplements, and Herbs by manufacturers or product name. It also provides complete descriptions of commonly used OTC
medications; useful, at-a-glance information such as ingredients, indications, and interactions on hundreds of
drugs; administration and dosage recommended for symptomatic relief; and color photographs of OTC drugs
for quick identification.
PDR for Herbal Medicines The fourth edition of this book provides health care professionals with an updated reference so they can better
advise patients who ask about specific herbal remedies. The information presented in this reference book
provides the latest scientific data in the most comprehensive herbal reference compiled, including Commission
E indications, which is the closest thing to an approved usage guide in the world of herbal medicines. Key
monographs have been updated to include recent scientific findings on efficacy, safety, and potential
interactions; clinical trials (including abstracts); case reports; and meta-analysis results. There are also updated
sections on enhanced patient management techniques and nutritional supplements.
Natural Products: A Case-Based Written by Karen Shapiro and published by the American Pharmaceutical Association, this reference book
Approach for Health Care offers practitioners guidelines for integrating natural products—including vitamins, soy and whey protein
Professionals supplements, fish oils, dong quai, evening primrose oil, pygeum, stinging nettle, etc—into their treatment plan
for a variety of common conditions and goals. The most common conditions discussed include dementia,
osteoarthritis, menopause, depression, erectile dysfunction, diabetes, cold and flu, weight loss, and
performance enhancement. This book is intended for classroom use.
Merck Manual for Medical Published every 5 to 6 years by Merck Research Labs, this reference book provides the reader with general
Information information on disease states and drug therapy. Online version and CD-ROM available.
Drug Interaction Facts Published yearly with monthly updates, this book provides information on reported drug interactions and rates
clinical significance of those interactions. Online version and CD-ROM available.
Mosby’s Dental Drug Reference Provides access to information on drugs commonly taken by patients. Drugs are presented alphabetically by
generic name and include indications, contraindications, dental considerations, and pharmacologic
classification. An alphabetic cross-index offers access to both brand and generic name drugs. Fact tables are
located on the inside covers and in the appendixes. Images of pathologic conditions, a color pill atlas, and
patient education sheets are available on a CD ROM and/or a companion website. Updated every 2 years.
Lexi-Comp’s Drug Information Contains concise lists of drug attributes and sections relevant to dentistry for each drug. The book is written
Handbook for Dentistry by dentists and covers over 7600 drugs and herbal products. Each monograph contains up to 32 fields of
information, including dosage, local anesthetic/vasoconstrictor precautions, drug interactions, and effects on
dental treatment.
Goodman and Gilman’s The This pharmacology textbook, published every 5 years, is the standard pharmacology textbook for pharmacy and
Pharmacologic Basis of medicine. It provides the reader with in-depth information regarding the chemistry, mechanism of action,
Therapeutics pharmacologic effects, pharmacokinetics, adverse reactions, and therapeutic uses of drugs. Also available on
CD-ROM.
6 PART ONE General Principles

TABLE 1-3 COMPARISONS AMONG REFERENCE SOURCES

Reference* Organization Bias Price Update Frequency Comments

DDR Alphabetic by generic drug name N $ Every 2 years Dental implications, brief
LCD Alphabetic by generic drug name N $$ 1/year; CD = 4/year Dental implications, brief
PDR Alphabetic by manufacturer’s Y $$ 1/year; 4/year; CD = 4/year Package insert, not often updated, contains
name; within that list, selected drugs
alphabetic by trade name
F&C By therapeutic class N $$$$ 1/year; 12/year (paper); Has many tables; includes most prescriptions
CD = 4/year and OTC drugs
AHFS Alphabetic by pharmacologic class N $$$ 1/year; CD = 4/year Detailed coverage; useful to answer specific
questions
USP DI Alphabetic by pharmacologic class N $$$ 1/year; 12/year; CD = 4/year Extensive list of properties of drugs

N, No; Y, yes; OTC, over the counter; $, least expensive; $$, moderately expensive; $$$, expensive; $$$$, most expensive.
*DDR, Mosby’s Dental Drug Reference (Mosby); LCD, Lexi-Comp’s Drug Information Handbook for Dentistry (Lexi-Comp); PDR, Physicians’ Desk Reference (Thomson Reuters);
F & C, Drug Facts and Comparisons (Wolters Kluwer); AHFS, AHFS Drug Information (American Society of Health-System Pharmacists); USP DI, United States Pharmacopeia-
Drug Information (Thomson Reuters).

Drugs can be judged “similar” in several ways. When two

generic
• Only one name formulations of a drug meet the chemical and physical standards
• First letter lowercase established by the regulatory agencies, they are termed chemically
lidocaine
equivalent. If the two formulations produce similar concentra-
tions of the drug in the blood and tissues, they are termed
biologically equivalent. If they prove to have an equal therapeutic
effect in a clinical trial, they are termed therapeutically equivalent.
A preparation can be chemically equivalent yet not biologically
trade name
• More than one name or therapeutically equivalent. These products are said to differ
• First letter capitalized in their bioavailability. Before generic drugs are marketed, they
Xylocaine
Octocaine
must be shown to be biologically equivalent, which would make
them therapeutically equivalent.
FIGURE 1-1
A comparison between the trade and generic drug names of lidocaine. Top 200 Drugs
Appendix A lists the 200 drugs most often prescribed in 2008
and their pharmacologic group. In the right column of the
A problem occurs in naming multiple-entity drugs, which appendix the rank order appears. This number represents the
are drugs with several ingredients. These drugs are difficult to position that the drug appears in the top 200. The rank of 1 is
discuss by their generic names because they contain several the most often prescribed drug for that year. Both generic and
ingredients. trade names appear on the list, depending on how the prescrip-
tion is written. The oral health care provider must become
Drug Substitution familiar with these names because patients may know the names
In the discussion of generic and trade of the drugs they are taking but not know how the names are
For dental drugs, names, the question of generic equiva- spelled. By referring to the list of the top 200 drugs, the oral
generic substitution
lence and substitution arises. Are the health care provider can check the patient’s medications and
provides equivalent
therapeutic results at a various different generic products spell them accurately so that they can be accessed in reference
cost savings. equivalent? After 17 years, the patent sources. This textbook discusses most of the agents included in
of the original drug expires, and other this list.
companies can market the same compound under a generic
name. In 1984, Congress passed the Drug Price Competition
and Patent Term Restoration Act, which allowed generic drugs FEDERAL REGULATIONS AND
to receive expedited approval. The FDA still requires that the REGULATORY AGENCIES
active ingredient of the generic product enter the bloodstream
at the same rate as the trade name product. The variation allowed Many agencies are involved in regulating the production, mar-
for the generic name product is the same as for the reformula- keting, advertising, labeling, and prescribing of drugs.
tions of the brand name product. For the few drugs that are
difficult to formulate and have narrow therapeutic indexes, no Harrison Narcotic Act
differences exist between the trade name product and the generic In 1914 the Harrison Narcotic Act established regulations gov-
product; therefore generic substitution drugs give equivalent erning the use of opium, opiates, and cocaine. Marijuana laws
therapeutic results and provide a cost savings to the patient. were added in 1937. Before this law, mixtures sold OTC could
 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription Writing CHAPTER 1 7

NDA Postmarketing
Preclinical Clinical review surveillance

Synthesize Phase 1
or
discover Phase 2 Report
adverse
Phase 3 reactions

FIGURE 1-2
Development of a new drug. IND, Investigational new drug; NDA,
Animal studies Surveys new drug application.
toxicity & kinetics

Teratogenicity Phase 4

IND NDA NDA

submitted submitted approved

contain opium and cocaine. These mixtures were promoted to CLINICAL EVALUATION OF A NEW DRUG
be effective for many “problems.”
If a discovered or synthesized compound becomes a marketed
Food and Drug Administration drug, it must pass through many steps before it is approved
The FDA of the Department of Health and Human Services (Figure 1-2). Animal studies begin by measuring both the acute
(DHHS) grants approval so that drugs can be marketed in the and chronic toxicity. The median lethal dose is determined for
United States. Before a drug can be approved by the FDA, it several species of animals. Long-term animal studies continue,
must be determined to be both safe and effective. The FDA including a search for teratogenic effects. Toxicity and pharma-
requires physical and chemical standards for specific products cokinetic properties are also noted. An investigational new drug
and quality control in drug manufacturing plants. It determines application (INDA) must be filled before any clinical trials can
what drugs may be sold by prescription and OTC and regulates be performed. Human studies of drugs involve the following
the labeling and advertising of prescription drugs. Because the four phases:
FDA is often more stringent than regulatory bodies in other • Phase 1: Small and then increasing doses are administered to
countries, drugs are often marketed in Europe and South a limited number of healthy human volunteers, primarily to
America before they are available in the United States. determine safety. This phase determines the biologic effects,
metabolism, safe dose range in humans, and toxic effects of
Federal Trade Commission the drug.
The Federal Trade Commission (FTC) regulates the trade prac- • Phase 2: Larger groups of humans are given the drug and any
tices of drug companies and prohibits the false advertising of adverse reactions are reported to the FDA. The main purpose
foods, nonprescription (OTC) drugs, and cosmetics. of phase 2 is to test effectiveness.
• Phase 3: More clinical evaluation takes place involving a large
Drug Enforcement Administration number of patients who have the condition for which the
The Drug Enforcement Administration (DEA) of the Depart- drug is indicated. During this phase, both safety and efficacy
ment of Justice administers the Controlled Substances Act of must be demonstrated. Dosage is also determined during this
1970. This federal agency regulates the manufacture and distri- phase.
bution of substances that have a potential for abuse, including • Phase 4: This phase involves postmarketing surveillance. The
opioids (narcotics), stimulants, and sedatives. toxicity of the drug that occurs in patients taking the drug
after it is released is recorded. Several drugs in recent years
Omnibus Budget Reconciliation Act have been removed from the market only after phase 4 has
The newest federal regulation concerning drugs is the Omnibus shown serious toxicity.
Budget Reconciliation Act (OBRA) of 1990. It mandates that,
beginning January 1, 1993, pharmacists must provide patient
counseling and a prospective drug utilization review (DUR) for DRUG LEGISLATION
Medicaid patients. Although this federal law covers only Med-
icaid patients, State Boards of Pharmacy are interpreting this law History
to apply to all patients. Dental patients who have their prescrip- The Food and Drug Act of 1906 was the first federal law to
tions filled at a pharmacy should receive counseling from the regulate interstate commerce in drugs. The Harrison Narcotic
pharmacist about their prescriptions. Act of 1914 and its amendments provided federal control over
8 PART ONE General Principles

narcotic drugs and required registration of all practitioners pre- • Any prescription for a controlled substance requires a DEA
scribing narcotics. number.
The Food and Drug Act was rewritten and became the Food, • All Schedule II through IV drugs require a prescription.
Drug and Cosmetic Act of 1938. This law and its subsequent • Any prescription for Schedule II drugs must be written in
amendments prohibit interstate commerce of drugs that have pen or indelible ink or typed. A designee of the dentist, such
not been shown to be safe and effective. The Durham- as the dental hygienist, may write the prescription, but the
Humphrey Law of 1952 is a particularly important amendment prescriber must personally sign the prescription in ink and is
to the Food, Drug and Cosmetic Act because it requires that responsible for what any designee has written.
certain types of drugs be sold by prescription only. This law • Schedule II prescriptions cannot be telephoned to the phar-
requires that these drugs be labeled as follows: “Caution: Federal macist (except at the discretion of the pharmacist for an
law prohibits dispensing without prescription.” This law also emergency supply to be followed by a written prescription
prohibits the refilling of a prescription unless directions to the within 72 hours).
contrary are indicated on the prescription. The Drug Amend- • Because Schedule II prescriptions cannot be refilled, the
ments of 1962 (Kefauver-Harris Bill) made major changes in patient must obtain a new written prescription to obtain
the Food, Drug and Cosmetic Act. Under these amendments, more medication.
manufacturers were required to demonstrate the effectiveness of • Certain states require the use of “triplicate” or “duplicate”
drugs, to follow strict rules in testing, and to submit to the FDA prescription blanks for Schedule II drugs. These blanks, pro-
any reports of adverse effects from drugs already on the market. vided by the state, are requested by the dentist. After a pre-
Manufacturers were also required to list drug ingredients by scription is written, the dentist keeps one copy and gives two
generic name in labeling and advertising and to state adverse copies to the patient. The patient presents these two copies
effects, contraindications, and efficacy of a drug. to the pharmacist, who must file one copy and send the other
The Drug Abuse Control Amendments of 1965 required to the State Board of Pharmacy. These consecutively num-
accounting for drugs with a potential for abuse such as barbi- bered blank prescription pads provide additional control for
turates and amphetamines. Schedule II drugs.
The Controlled Substance Act of 1970 replaced the Harrison • Prescriptions for Schedule III and IV drugs may be tele-
Narcotic Act and the Drug Abuse Control Amendments to the phoned to the pharmacist and may be refilled no more than
Food, Drug and Cosmetic Act. The Controlled Substances Act five times in 6 months, if so noted on the prescription.
is extremely important because it sets current requirements
for writing prescriptions for drugs often prescribed in dental
practice. PRESCRIPTION WRITING
Scheduled Drugs Dental practitioners need to become familiar with the basics of
Federal law divides controlled substances into five schedules prescription writing for the following reasons:
according to their abuse potential (Table 1-4). The rules for • If prescriptions are written correctly, it will save the time of
prescribing these agents, whether prescriptions can be tele- the office personnel, dentist, and pharmacist who must call
phoned to the pharmacist, and whether refills are allowed differ to clarify prescriptions.
depending on the drug’s schedule. New drug entities are evalu- • Prescriptions written carefully are less likely to result in
ated and added to the appropriate schedule. Drugs on the mistakes.
market may be moved from one schedule to another if changes • With extra effort when unusual prescriptions are written, the
in abuse patterns are discovered. dentist can save the patient’s and pharmacist’s time. For
The current requirements for prescribing controlled drugs example, if the unusual is explained on the prescription,
(Controlled Substance Act of 1970) are as follows: problems will be minimized. Sometimes it may be expedient

TABLE 1-4 SCHEDULES OF CONTROLLED SUBSTANCES

Schedule Abuse Potential Examples Handling

I Highest Heroin, LSD, marijuana, hallucinogens No accepted medical use; experimental use, only in
research
II High Oxycodone, morphine, amphetamine, Written prescription with provider’s signature only;
secobarbital no refills
III Moderate Codeine mixtures (Tylenol #3), Prescriptions may be telephoned; no more than five
hydrocodone mixtures (Vicodin) prescriptions in 6 months
IV Less Diazepam (Valium), dextropropoxyphene Prescriptions may be telephoned; no more than five
forms (Darvon) prescriptions in 6 months
V Least Some codeine-containing cough syrups Can be bought OTC in some states

LSD, Lysergic acid diethylamide; OTC, over the counter.

 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription Writing CHAPTER 1 9

to call the prescription to the pharmacy so that the unusual

use can be explained and a reference given. ♦ HOUSEHOLD MEASURES
Although clinicians will direct the pharmacist to dispense a
Measurement liquid preparation in milliliters, it is generally converted by the
pharmacist into a convenient household unit of measurement
♦ METRIC SYSTEM to be included in the directions to the patient. Liquids are con-
The metric system is In pharmacy, the primary measuring verted into teaspoonfuls (tsp or t; 1 tsp equals 5 ml) and table-
based on multiples system is the metric system. Scientific spoonfuls (tbsp or T; 1 tbsp equals 15 ml). This is because the
of 10. calculations use a base of 10. Conse- average American does not use the metric system of measure-
quently, the metric system, which is ment in daily life. The pharmacist will give a calibrated oral
based on 10, is the language of scientific measurement. Only syringe or dropper for infants and younger children. Most liquid
metric units should be used in prescription writing. dose forms come with calibrated dosing cups for both adults and
The basic metric unit for the measurement of weight is the children. Household utensils should not be used. The dosing
kilogram (kg). The basic metric unit for volume is the liter (L). cups are available in 2.5-, 5-, and 10-ml volumes with milliliters
One milliliter (ml), one one-thousandth of a liter, is exactly 1 marked along the length.
cubic centimeter (cc). Because the various units of the metric
system are based on multiples of 10, several prefixes can apply Prescriptions
to units of both weight and volume (Table 1-5).
Solid drugs are dispensed by weight (milligrams [mg]) and ♦ FORMAT
liquid drugs by volume (milliliters [ml]). It is rarely necessary to The parts of the prescription are divided into three sections.
use units other than the milligram or the milliliter in prescrip- They are the heading, body, and closing (Figure 1-3).
tion writing; occasionally, grams (gm) or micrograms (µg) are Heading. The heading of the prescription contains the fol-
used. In addition to the milliliter, the liter is also used to measure lowing information:
volume. • Name, address, and telephone number of the prescriber
(printed on the prescription blank)
• Name, address, age, and telephone number of the patient
(written)
• Date of prescription (not a legal prescription unless filled in
TABLE 1-5 COMMON ABBREVIATIONS with date); often missing
Abbreviations English The name, address, and telephone number of the prescriber
are important when the pharmacist must contact the prescrib-
a or ā before ing clinician for verification or questions. The date is particu-
ac before meals larly important because it allows the pharmacist to intercept
bid twice a day prescriptions that may not have been filled at the time of
c with writing. For example, a prescription for an antibiotic written 3
cap capsule months before being presented to the pharmacist might be used
for a different reason than the dentist originally intended. Like-
d day
wise, a prescription for a pain medication that is even a few
disp dispense days old requires the pharmacist to question the patient as to
gm gram why the prescription is being filled so long after it was written.
gr grain The age of the patient enables the pharmacist to check for the
gtt drop proper dose.
Body. The body of the prescription contains the following
h hour
information:
hs at bedtime • The Rx symbol
p after • Name and dose size or concentration (liquids) of the drug
pc after meals • Amount to be dispensed
PO by mouth • Directions to the patient
prn as required, if needed
The first entry after the Rx symbol is the name of the drug
being prescribed. This is followed by the size (milligrams) of the
q every tablet or capsule desired. In the case of liquids, the name of the
qid 4 times a day drug is followed by its concentration (milligrams per milliliter
s without [mg/ml]). The second entry is the quantity to be dispensed, that
sig write (label) is, the number of capsules or tablets or milliliters of liquid. In
ss one-half the case of tablets and capsules, the word “Dispense” is often
replaced with #, the symbol for a number. When writing
stat immediately (now) prescriptions for opioids or other controlled substances, the
tab tablet prescriber should add in parentheses the number of tablets or
tid 3 times a day capsules written out in Roman numerals or in longhand after
ud as directed the Arabic number of tablets or capsules. This reduces the pos-
sibility of an intended 8 becoming an 18 or 80 at the discretion
10 PART ONE General Principles

Mary Smith, DDS

1234 Main St.
Kansas City, MO 64111
(816) 555-1234

Heading
Name Date

Address Age

FIGURE 1-3
A typical prescription form. Drug Name # mg table

Disp: # Body

Sig: 1-2 tabs q 4-6 h prn pain

Substitution
Closing
permitted Signature
not permitted DEA #
Refill 0 1 2 3

BOX 1-1 COMMON METRIC PREFIXES Acme Pharmacy 555-1234

Weight 1234 Main St. Anywhere, KS 66666
1 kilogram (kg) = 1000 grams (g or gm)
1 gram (g) = 10 decigrams (dg) Rx 12345 Dr. Knowpaign
1 gram = 100 centigrams (cg) Doe, John
1 gram = 1000 milligrams (mg) Take one tablet every four to six hours
1 gram = 1,000,000 micrograms (µg or mcg) if needed for pain.
Acetaminophen/codeine 300 mg/30 mg
Volume Rugby #12 No refills 6-1-09 brc
1 liter (L) = 10 deciliters (dl)
1 liter = 100 centiliters (cl) FIGURE 1-4
1 liter = 1000 milliliters (ml) Sample of a typical prescription label.
1 liter = 1,000,000 microliters (µl)

of an enterprising patient. Directions to the patient are preceded After the body of the prescription, space is provided for the
by the abbreviation “Sig:” (Latin for signa, “write”). The direc- prescriber’s signature. Certain states have more than one place
tions to the patient must be completely clear and explicit and to sign. Certain institutions also provide a space on which to
should include the amount of medication and the time, fre- print the prescriber’s name. This is not necessary for dentists
quency, and route of administration. The pharmacist will tran- with their own prescription blanks. If there are several dentists
scribe any Latin abbreviations (Box 1-1) into English on the in one office, the names of all the dentists in the practice should
label when the prescription is filled. The use of ud (“as directed”) be included on the prescription blanks. Then the individual
does not provide the proper information on the label for the dentist should check a box or circle his or her name so the
patient. Often with ud prescriptions, the patient does not pharmacist will know who signed the prescription.
remember how to take the medicine. To clarify for the patient In addition, the law requires that all prescriptions must be
without adequate written instructions, the pharmacist must labeled with the name of the medication and its strength. Figure
contact the prescriber for clarification (this wastes dentist, phar- 1-4 is a sample prescription label. This allows easy identification
macist, and patient time). After a few months, the patient will by other practitioners or quick identification in emergency situ-
forget the quick instructions given verbally in the dental office ations. One should note that the name, address, and telephone
after a dental appointment. Even prescriptions for chlorhexidine number of the pharmacy; the patient’s and dentist’s names; the
should be specific for amount, time, other activities to perform, directions for use; the name and strength of the medication; and
and when water can be used. the original date and the date filled (refilled) are required. The
Closing. The closing of the prescription contains the quantity of medication dispensed (number of tablets) and the
following: number of refills remaining may be noted as well. If a generic
• Prescriber’s signature drug is prescribed, then the generic name of the drug and the
• DEA number, if required manufacturer is required on the label. If the trade drug is used,
• Refill instructions only the trade name is required on the label.
 Information, Sources, Regulatory Agencies, Drug Legislation, and Prescription Writing CHAPTER 1 11

In most states, before a dentist can legally write a prescription DENTAL HYGIENE CONSIDERATIONS
for a patient, the following two criteria must be met:
• Patient of record: The person for whom the prescription is 1. The dental hygienist should understand the importance of obtaining
being written is a patient of record (no next-door neighbors a patient health/medication history.
or relatives, unless they are also patients of record). 2. The dental hygienist should have an in-depth understanding of phar-
• Dental condition: The condition for which the prescription macology because many dental hygienists are now licensed to
is being prescribed is a dental-related condition (no birth administer local anesthetics and nitrous oxide.
control pills or thyroid replacement drugs). 3. The dental hygienist should be able to explain to the patient how to
Abbreviations. A few abbreviation forms are used in prescrip- take a prescription or nonprescription medicine.
tion writing to save time. The abbreviations also make alteration 4. The dental hygienist should discuss the name of the drug prescribed,
of a prescription by the patient more difficult. In some cases what it is used to treat or prevent, the dose, the amount prescribed,
they are necessary to get all the required information into the and how often it should be taken.
space on the prescription form. Some abbreviations that may be 5. The dental hygienist should also tell the patient what to do if the
useful are shown in Table 1-5. If abbreviations are used on a patient feels that he/she is experiencing a side effect or allergic
prescription, they should be clearly written. For example, the reaction.
three abbreviations qd (every day), qod (every other day), and 6. The dental hygienist should have the patient repeat back what is told
qid (four times a day) can look quite similar, and choosing the to him/her. This should help determine if there are any knowledge
wrong one could be disastrous. gaps.
7. The dental hygienist should answer any questions that the patient
Explanations Accompanying Prescriptions may have.
The dental health care worker should be able to answer the
patient’s questions about the prescription and should make sure
that the patient knows how to take the medication prescribed
(how long and when), what precautions to observe (drug inter- CLINICAL SKILLS ASSESSMENT
actions, possible side effects, driving limitations), and the reason
for taking the medication. Information about the consequences 1. Define the term pharmacology.
of noncompliance should be included. By informing the patient 2. Explain why the oral health care provider should have a knowledge
about the medication, the likelihood that the patient will comply of pharmacology.
with the prescription instructions increases. The dental office 3. Explain the importance of conducting health/medication histories.
should either keep a copy of each prescription written in the 4. Why should a dental practice keep more than one type of reference
patient’s record or record the medication, dose, and number book?
prescribed. A patient should never get home and not know
which drug is the antibiotic (for infection) and which is the 5. Discuss the most important features of a good reference book.
analgesic (for pain). Side effects, such as drowsiness (for Sched- 6. Define and give an example of the following terms:
ule II drugs) or stomach upset, should be noted on the label. a. Chemical name
Some drug abusers (“shoppers”) search for dental offices that b. Trade name
might provide them with prescriptions for controlled substances c. Brand name
or prescription blanks that they can use to forge their own pre-
d. Generic name
scriptions. Every dental office should keep prescription blanks
in a secure place. The prescriber’s DEA number should not be 7. Explain why a list of the most current drugs should be available in
printed on the prescription blanks but should be written in only every dental office.
when needed.* The dental health care worker should watch to 8. Name three federal regulatory agencies and state the major
see that prescription blanks are not scattered around the office. responsibility of each.
If the dentist practices in a state that requires “triplicate” or 9. Explain the various stages of testing through which a drug must pass
“duplicate” prescription blanks for Schedule II prescriptions, before it is marketed for the general public.
then those pads must be stored under lock and key to prevent 10. List the information required in a prescription.
them from being stolen. 11. Explain two precautions that should be taken in the dental office to
discourage drug abusers.
12. List the components of the Controlled Substance Act.

*Because of the use of DEA numbers to file insurance claims, there may
come a time when including the DEA number on the prescription blank Please visit http://evolve.elsevier.com/Haveles/pharmacology for review
becomes commonplace. questions and additional practice and reference materials.
 2 Drug Action and Handling

CHAPTER OUTLINE LEARNING OBJECTIVES

CHARACTERIZATION OF DRUG ACTION 1. Differentiate dose, potency, and efficacy in the context of the actions of drugs.
Log Dose Effect Curve 2. Explain the pharmacologic effect of a drug.
Potency 3. Discuss the major steps of pharmacokinetics: absorption, distribution, metabolism,
Efficacy and excretion.
Chemical Signaling among Cells
4. Summarize the various routes of drug administration.
MECHANISM OF ACTION OF DRUGS
Nerve Transmission
5. Provide example of factors that may alter the effect of a drug.
Receptors
PHARMACOKINETICS
Passage across Body Membranes
Absorption To discuss the drugs used in dentistry or those that patients may be taking when
Distribution they come to the dental office, the dental health care worker must be familiar with
Half-Life some basic principles of pharmacology. This chapter discusses the action of drugs
Blood-Brain Barrier in the body and methods of drug administration. Chapter 3 considers the problems
Redistribution or adverse reactions these drugs can cause. By understanding how drugs work, what
Metabolism (Biotransformation) effects they can have, and what problems they can cause, the dental health care
ROUTES OF ADMINISTRATION AND DOSE worker can better communicate with the patient and other health care providers
FORMS about medications the patient may be taking or may need to have prescribed for
Routes of Administration dental treatment.
Dose Forms Drugs are broadly defined as chemical substances used for the diagnosis, preven-
FACTORS THAT ALTER DRUG EFFECTS tion, or treatment of disease or for the prevention of pregnancy. Most drugs are
differentiated from inert chemicals and chemicals necessary for the maintenance
of life processes (e.g., vitamins) by their ability to act selectively in biologic systems
to accomplish a desired effect. Historically, drugs were discovered by randomly
searching for active components among plants, animals, minerals, and the soil.
Today, organic synthetic chemistry researchers are primarily responsible for devel-
oping new drugs. Parent compounds that exhibit known pharmacologic activity
are chemically modified to produce congeners or analogs: agents of a similar chemi-
cal structure with a similar pharmacologic effect. This technique of modifying a
chemical molecule to provide more useful therapeutic agents has evolved from
studies of the relationship between the chemical structure and the biologic activity
called structure-activity relationship (SAR).

CHARACTERIZATION OF DRUG ACTION

Dose-response curve, potency, and efficacy are terms used to measure drug response
or action.
Log Dose Effect Curve
When a drug exerts an effect on biologic systems, the effect can be related
quantitatively to the dose of the drug given. If the dose of the drug is plotted
against the intensity of the effect, a curve will result (Figure 2-1). If this curve
is replotted using the log of the dose (log dose) versus the response, another
curve is produced from which the potency and efficacy of a drug’s action may
be determined (Figure 2-2).

12
 Drug Action and Handling CHAPTER 2 13
100 More Less
potent potent
Intensity of response
(% of maximum)
Drug A Drug B

Intensity of response
More Less

Dose
Log dose
FIGURE 2-1
Dose effect curve. The x-axis (horizontal) is an increasing dose of the drug, FIGURE 2-3
and the y-axis (vertical) is an increasing effect of the drug. Potency of agent. The arrow is shaded proportional to increasing potency.
(Dark shading, very potent; light shading, low potency.)

100%
Drug A Drug B
(morphine) (meperidine)
% Maximum response

Intensity of response
(% of maximum)
50%

Higher POTENCY Lower

50% 10 100 1000

% Effective dose Log dose
FIGURE 2-2 FIGURE 2-4
Log dose effect curve. As the dose is increased (going to the right on the Comparison of log dose effect curves for morphine and meperidine.
x-axis), the effect (the y-axis) is zero at first, then there is a small effect, and
finally the effect quickly increases. Around the dose where the line is increas-
ing sharply is the therapeutic range of the compound. Finally, the curve because I just drank beer,” the statement is false. The absolute
plateaus (flattens out). This is the maximum response a drug can exhibit.
potency of a drug is immaterial as long as an appropriate dose
is administered. Both meperidine and morphine have the ability
to treat severe pain, but approximately 100 mg of meperidine
Potency would be required to produce the same action as 10 mg of
The potency of a drug is a function of morphine. Thus the absolute potency of oral morphine is 10
Potency—related to the the amount of drug required to produce times that of oral meperidine, or meperidine is one-tenth as
amount of drug needed
an effect. The potency of a drug is potent as morphine, even though both agents can relieve intense
to produce an effect
shown by the location of that drug’s pain (equal efficacy, as explained next). In Figure 2-4, the curve
curve along the log-dose axis (x-axis). for drug B (meperidine) is to the right of the curve for drug A
The curves in Figure 2-3 illustrate two drugs with different (morphine) because the dose of meperidine needed to produce
potencies. The potency of drug A is greater because the dose pain relief is larger (10 times larger) than that for morphine. The
required to produce its effect is smaller. The potency of B is less potency of different drugs that elicit similar effects can be com-
than A because B requires a larger dose to produce its effect. pared by observing the dose that produces 50% (drop a vertical
As an example of different potencies, three alcoholic bever- line down from the center of the curve) of the total, or maximum,
ages are compared: bourbon, beer, and wine cooler (or spritzer). effect.
One ounce of bourbon contains the same amount of alcohol as
one beer (12 oz) or as one wine cooler or spritzer (16 oz [depends Efficacy
on dilution]). All of these drinks could equally inebriate an Efficacy is the maximum intensity of
individual (produce adverse reactions). To produce a similarly Efficacy—related to the effect or response that can be produced
maximal effect of a
drunk individual, the same amount of alcohol would have to be drug, regardless of dose
by a drug. Administering more drug
ingested. However, this amount would be contained in a differ- will not increase the efficacy of the
ent volume of fluid, depending on its concentration (or drug but can often increase the probability of an adverse reac-
potency).* Therefore, when someone says “I’m not drunk tion. The efficacy of a drug increases as the height of the curve
increases (Figure 2-5). The efficacy of the drugs whose curves
*Ignoring the effect on the stomach of different nonalcoholic fluids or food are illustrated in Figure 2-5 are shown by the height of the curve
ingested. when it plateaus (levels out horizontally). It is shaded from least
14 PART ONE General Principles

(light) to most (dark) potent. The efficacy of any drug is a major neurotransmitters are released and quickly travel across the
descriptive characteristic indicating its action. For example, the synapse to the receptor (Figure 2-6). There are at least 50 differ-
efficacy of drug B (meperidine) and drug A (morphine) is about ent agents that transmit messages. Examples of neurotransmitters
the same because both drugs relieve severe pain. include acetylcholine, norepinephrine/epinephrine, dopamine,
If one “drink” of both bourbon (1 oz) and beer (12 oz) were serotonin, γ-aminobutyric acid (GABA), and histamine.
ingested, they could produce equal “silliness” in an individual. If
very large doses of either agent were ingested, unconsciousness ♦ LOCAL
could be produced. Both are equally efficacious, but they differ in Some organs secrete chemicals that work near them. These
their potency. The efficacy and the potency of a drug are unrelated. chemicals are not released into the systemic circulation. Prosta-
Because death is the endpoint when measuring the lethal glandins and histamine are examples. For example, a person
dose, the median lethal dose (LD50) is the dose when one-half wears a nickel-containing watch and a red spot appears on the
of the subjects die. For obvious reasons, the LD50 is only deter- skin beneath the watch. This localized allergic reaction is caused
mined in animals. by release of inflammation-producing substances, such as hista-
mine, at that point on the skin. Because the reaction is localized,
Chemical Signaling Among Cells the patient’s nose does not begin to run. Prostaglandins contract
For the autonomic nervous system to function, messages from the uterine muscles and become important as a baby is born.
the brain must be transmitted to many parts of the body com- When prostaglandins are released in the uterus, they produce
manding the parts to “do something” (e.g., enlarge pupil or menstrual “cramps,” and when released in the stomach, they
sweat). Complex mechanisms for transmitting these messages protect its lining.
allow for amplification or damping of the effect, depending on
a multitude of factors. The complexity allows for very fine ♦ HORMONES
tuning of the body’s functions. Neurotransmitters are chemicals Hormones are secreted to produce effects throughout the body.
responsible for transporting a wide variety of messages across the Examples include insulin, thyroid hormone, and adrenocortico-
synapse (space between nerve and receptor). Chemical signaling steroids. These reactions are usually slower than the ones associ-
involves release of neurotransmitters, local substances, and ated with the neurotransmitters.
hormone secretion.
♦ NEUROTRANSMITTERS
MECHANISM OF ACTION OF DRUGS
The messengers that move the electrical impulses from a nerve
are transmitted across the synapse via neurotransmitters. The After drugs have been distributed to their site of action, they
elicit a pharmacologic effect. The pharmacologic effect occurs
More because of a modulation in the function of an organism. Drugs
Most do not impart a new function to the organism; they merely
Intensity of response

efficacious
produce either the same action as an endogenous agent or block
the action of an endogenous agent. This signaling mechanism
Less has two functions: amplification of the signal and flexible regula-
tion. The presence of very fine controls to modulate the body’s
Less
function allows the regulation of certain reactions, slowing or
efficacious speeding them.

Log dose Nerve Transmission

FIGURE 2-5 Within a nerve, the transmission of impulses travels along the
Efficacy of agent. nerve, producing a nerve action potential. The action potential
e
e

b ra n
b r an

me m
l me m

I ns i d e c e l l
Outside cel

FIGURE 2-6
For the neurotransmitter (or drug acting like a
neurotransmitter) to complete the message, it
must get inside the cell. After the drug binds with Drug or Enters
its receptor, the reaction often opens a channel neurotransmitter Tunnel opens cell
so that the message can get inside the cell. binds here
 Drug Action and Handling CHAPTER 2 15

To
CNS

Synapse

Neuro-
transmitter
released Receptor

Neurotransmitter
crosses synapse

Enzyme Enzyme
activated

FIGURE 2-7
The neurotransmitter is transmitting the message (like electricity) across the synapse (space where nerve is absent). The neurotransmitter then interacts
with the receptor (shaped to fit together), which then may signal an enzyme to be synthesized or activated.

is triggered by the neurotransmitter released at the previous Receptor

synapse. Drugs that interfere with this process, such as local
anesthetics (see Chapter 10), block messages from being sent.
The processes involved in the drug’s effect begin the drug-
receptor interaction. The receptors, macromolecular chemical
structures, interact with both endogenous substances and drugs.
This drug-receptor interaction results in a conformational Drug
(shape) change, which may allow the drug inside the cell to
produce its effect or may cause the release of a second messenger, A B C
which then produces the effect. Many of the effects involve FIGURE 2-8
altering enzyme-regulated reactions or regulatory processes for A, Drugs act by forming a chemical bond with specific receptor sites, similar
protein synthesis after a series of reactions, similar to a chain to a lock and key. B, The better the “fit,” the better the response. Drugs
with complete attachment and response are called agonists. C, Drugs that
reaction. These steps in the process of communicating are briefly
attach but do not elicit a response are called antagonists. (From Clayton
discussed. BD, Stock YN, Harroun RD: Basic pharmacology for nurses, ed 14, St Louis,
Receptors 2007, Mosby.)

Once a drug passes through the biologic membrane, it is carried

to many different areas of the body, or site of action, to exert its to produce a pharmacologic response. Drugs with a stronger
therapeutic effect or adverse effect. For the drug to exert its affinity for receptor sites are more potent than drugs with weaker
effects, it must bind with the receptor site on the cell membrane. affinities for the same site.
Drug receptors appear to consist of many large molecules that
exist either on the cell membrane or within the cell itself (Figure ♦ AGONISTS AND ANTAGONISTS
2-7). More than one receptor type or identical receptors can be When a drug combines with a receptor, it alters the function of
found at the site of action. Usually, a specific drug will bind with the organism. It may produce enhancement or inhibition of the
a specific receptor in a lock-and-key fashion. Many drug-receptor function. Drugs that combine with the receptor may be classi-
interactions consist of weak chemical bonds, and the energy fied as either agonists or antagonists (Figure 2-9).
formed during this interaction is very low. As a result, the bonds Agonist. An agonist is a drug that (1) has affinity for a recep-
can be formed and broken easily. Once a bond is broken, another tor, (2) combines with the receptor, and (3) produces an effect.
drug molecule immediately binds to the receptor. Naturally occurring neurotransmitters are agonists.
Different drugs often compete for the same receptor sites. Antagonist. An antagonist counteracts the action of the
The drug with the stronger affinity for the receptor will bind to agonist. The following are three different types of antagonists:
more receptors than the drug with the weaker affinity (Figure • A competitive antagonist is a drug that (1) has affinity for a
2-8). More of the drug with the weaker affinity will be required receptor, (2) combines with the receptor, and (3) produces
16 PART ONE General Principles

Effect
Passage Across Body Membranes
More
The amount of drug passing through a cell membrane and the
rate at which a drug moves are important in describing the time
course of action and the variation in individual response to a
drug. Before a drug is absorbed, transported, distributed to body
tissues, metabolized, and subsequently eliminated from the
body, it must pass through various membranes such as cellular
membranes, blood capillary membranes, and intracellular mem-
Less branes. Although these membranes have variable functions, they
share certain physicochemical characteristics that influence the
passage of drugs across their borders.
Lower Higher These membranes are composed of lipids (fats), proteins, and
Drug
dose dose carbohydrates. The membrane lipids make the membrane rela-
Agonist
tively impermeable to ions and polar molecules. Membrane
Noncompetitive antagonist proteins make up the structural components of the membrane
Partial agonist and help move the molecules across the membrane during the
Competitive antagonist transport process. Membrane carbohydrates are combined with
FIGURE 2-9 either proteins or lipids. The lipid molecules orient themselves
Agonists and antagonists and their interactions. so that they form a fluid bimolecular leaflet structure with the
hydrophobic (lipophilic) ends of the molecules shielded from the
surrounding aqueous environment and the hydrophilic ends in
no effect. This causes a shift to the right in the dose-response contact with the water. The various proteins are embedded in and
curve (see Figure 2-9). The antagonist competes with the layered onto this fluid lipid bilayer, forming a mosaic. Studies of
agonist for the receptor, and the outcome depends on the the ability of substances to penetrate this membrane have indi-
relative affinity and concentrations of each agent. If the con- cated the presence of a system of pores or holes through which
centration of the agonist is increased, the competitive antago- lower-molecular-weight and smaller size chemicals can pass.
nism can be overcome and vice versa. The physicochemical properties of drugs that influence the
• Noncompetitive antagonists bind to a receptor site that is dif- passage of drugs across biologic membranes are lipid solubility,
ferent from the binding site for the agonist. This reduces the degree of ionization, and molecular size and shape. The mecha-
maximal response of the agonist (see Figure 2-9). nisms of drug transfer across biologic membranes are passive
• A physiologic antagonist has affinity for a different receptor transfer and specialized transport.
site than the agonist. This decreases the maximal response of
the agonist by producing an opposite effect via different ♦ PASSIVE TRANSFER
receptors. Lipid-soluble substances move across the lipoprotein membrane
Transport carriers are systems that are available for moving by a passive transfer process called simple diffusion. This type
neurotransmitters or drugs into the cell. In the process of making of transfer is directly proportional to the concentration gradient
a neurotransmitter, the precursors (chemical to make a neu- (difference) of the drug across the membrane and the degree of
rotransmitter) must be taken into the cell by an active transport lipid solubility. For example, a highly lipid-soluble compound
pump (requires adenosine triphosphatase [ATPase]). For will attain a higher concentration at the membrane site and will
example, the precursor for norepinephrine is tyramine, so it readily diffuse across the membrane into an area of lower con-
must be pumped into the cell. After the neurotransmitter is centration (Figure 2-10). A water-soluble agent will have diffi-
synthesized, it is placed in little “suitcases” called granules. These culty passing through a membrane.
go to the membranes and await the signal to “dump” their Water-soluble molecules small enough to pass through the
contents into the synapse. After the neurotransmitter is released, membrane pores may be carried through the pores by the bulk
there are three paths that it can take. It can be broken down by flow of water. This process of filtration through single-cell mem-
enzymes designed to terminate the neurotransmitter’s effect, it branes may occur with drugs having molecular weights of 200
can migrate to the receptor and interact to produce an effect, or or less. However, drugs with molecular weights of 60,000 can
it can be taken up by the presynaptic nerve ending (reuptake). “filter” through capillary membranes.
Reuptake is an easy way (requires little energy) to recover the
neurotransmitter for future use because it is as easy as vacuuming ♦ SPECIALIZED TRANSPORT
up dirt. Certain substances are transported across cell membranes by
processes that are more complex than simple diffusion or filtra-
tion. These processes include the following:
PHARMACOKINETICS • Active transport is a process by which a substance is trans-
ported against a concentration gradient or electrochemical
Pharmacokinetics is the study of how a drug enters the body, gradient. This action is blocked by metabolic inhibitors.
circulates within the body, is changed by the body, and leaves Active transport is believed to be mediated by transport “car-
the body. Factors that influence the movement of a drug are riers” that furnish energy for the transportation of the drug.
divided into four major steps: absorption, distribution, metabo- • Facilitated diffusion does not move against a concentration
lism, and excretion (ADME). gradient. This phenomenon involves the transport of some
 Drug Action and Handling CHAPTER 2 17

High Lipid Low ionized form (B), which can more easily penetrate tissues. Con-
concentration membrane concentration versely, if the pH of the site falls, the hydrogen ion concentration
will rise. This results in an increase in the ionized form (BH+),
D A which cannot easily penetrate tissues. In summary, weak acids
D D are better absorbed when the pH is less than the pKa, whereas
D
D weak bases are better absorbed when the pH is greater than
the pKa.
B This dissociation also explains the fact that in the presence
of infection the acidity of the tissue increases (and the pH
D
decreases) and the effect of local anesthetics decreases. In the
D
D
presence of infection, the [H+] increases because of accumulating
waste products in the infected area. The increase in [H+]
D
(decrease in pH) leads to an increase in ionization and a decrease
in penetration of the membrane. This reduced penetration
reduces the clinical effect of the local anesthetic.
FIGURE 2-10 ♦ ORAL ABSORPTION
Passage of drug and metabolite through membranes. A, Lipid soluble,
nonionized: drug easily passes through the cell membrane from area of high The dose form of a drug is an important factor influencing
to low drug concentration. B, Water soluble, ionized: drug cannot pass absorption of drugs administered via the oral route. Unless the
through the cell membrane. D, Drug. drug is administered as a solution, the absorption of the drug in
the gastrointestinal tract involves a release from a dose form such
as a tablet or capsule. This release requires the following steps
substances, such as glucose, into cells. It has been suggested before absorption can take place:
that the process of pinocytosis may explain the passage of • Disruption: The initial disruption of a tablet coating or
macromolecular substances into the cells. capsule shell is necessary.
• Disintegration: The tablet or capsule contents must disinte-
Absorption grate (break apart).
Absorption is the process by which drug molecules are trans- • Dispersion: The concentrated drug particles must be dis-
ferred from the site of administration to the circulating persed (spread) throughout the stomach or intestines.
blood. This process requires the drug to pass through biologic • Dissolution: The drug must be dissolved (in solution) in the
membranes. gastrointestinal fluid.
The following factors influence the rate of absorption of A drug in solution skips these four steps, so it usually has a
a drug: quicker onset of action.
• The physicochemical factors discussed previously.
• The site of absorption, which is determined by the route of ♦ ABSORPTION FROM INJECTION SITE
administration. For example, one advantage of the oral route Absorption of a drug from the site of injection depends on the
is the large absorbing area presented by the intestinal mucosa. solubility of the drug and the blood flow at that site. For
• The drug’s solubility. Drugs in solution are more rapidly example, drugs with low water solubility, such as some penicillin
absorbed than insoluble drugs. salts, are absorbed very slowly after intramuscular injection.
Absorption at injection sites is also affected by the dose form.
♦ EFFECT OF IONIZATION Drugs in suspension are absorbed much more slowly than those
Drugs that are weak electrolytes dissociate in solution and equili- in solution. Certain insulin preparations are formulated in sus-
brate into a nonionized form and an ionized form. The nonion- pension form to decrease their absorption rate and prolong their
ized, or uncharged, portion acts like a nonpolar, lipid-soluble action. Drugs that are least soluble will have the longest dura-
compound that readily crosses body membranes (see Figure tion of action.
2-10). The ionized portion will traverse these membranes with
greater difficulty because it is less lipid soluble. Distribution
The pH of the tissues at the site of administration and the
dissociation characteristics (pKa) of the drug will determine the ♦ BASIC PRINCIPLES
amount of drug present in the ionized and nonionized state. All drugs occur in two forms in the blood: bound to plasma
The proportion in each state will determine the ease with which proteins and the free drug. The free drug is the form that exerts
the drug will penetrate the tissues. the pharmacologic effect. The bound drug is a reservoir (place
Weak Acids. When the pH at the site of absorption increases, to store) for the drug. The proportion of drug in each form
the hydrogen ion concentration simply falls. This results in an depends on the properties of that specific drug (percent protein
increase in the ionized form (A−), which cannot easily penetrate bound). Within each compartment (e.g., blood, brain), the drug
tissues. is split between the bound drug and the free drug. Only the free
Conversely, if the pH of the site falls, the hydrogen ion drug can pass across cell membranes.
concentration will rise. This results in an increase in the un- For a drug to exert its activity, it must be made available at
ionized form (HA), which can more easily penetrate tissues. its site of action in the body. The mechanism by which this is
Weak Bases. If the pH of the site rises, the hydrogen ion accomplished is distribution, which is the passage of drugs into
concentration will fall. This results in an increase in the un- various body fluid compartments such as plasma, interstitial
18 PART ONE General Principles

#1 #2

t½ t½

100%  1 50%  ½ 25%  ¼

remains remains
#3 t½

“essentially” gone

#4 #5

t½ t½

12.5%  ¼8 6.25%  ¼16 3.13%  ¼32

remains remains remains

FIGURE 2-11
First-order kinetics. Half-life constant throughout usual doses. Half of the dose of the drug in the body is removed with each half-life. #1, #2 … #5,
Number of half-lives that have passed.

fluids, and intracellular fluids. The manner in which a drug is level (Figure 2-11). When the half-life of a drug is short, it is
distributed in the body will determine how rapidly it produces quickly removed from the body and its duration of action is
the desired response; the duration of that response; and in some short. When the half-life of a drug is long, it is slowly removed
cases, whether a response will be elicited at all. from the body and its duration of action is long.
Drug distribution occurs when a drug moves to various sites Figure 2-11 shows the percent of a drug remaining after each
in the body, including its site of action in specific tissues. of four and five half-lives. Because only 3% to 6% remains after
However, drugs are also distributed to areas where no action is four or five half-lives, respectively, we can say that the drug is
desired (nonspecific tissues). Some drugs, because of their char- essentially gone. Conversely, it takes about four or five half-lives
acteristics, are poorly distributed to certain regions of the body. of repeated dosing for a drug’s level to build up to a steady state
Other drugs are distributed to their site of action and then (level amount) in the body. If the half-life of a drug is 1 hour,
redistributed to another tissue site. The distribution of a drug then in 4 or 5 hours the drug would be mostly gone from the
is determined by several factors such as the size of the organ, the body. In 4 hours, 94% of the drug would be gone. However, if
blood flow to the organ, the solubility of the drug, the plasma the half-life of a drug is 60 hours, then it would take 240 (10
protein-binding capacity, and the presence of certain barriers days) to 300 hours (12 days) for that drug to be eliminated from
(blood-brain barrier, placenta). the body. Even after discontinuing a drug with a long half-life,
its effect can take several days to dissipate, depending on its
♦ DISTRIBUTION BY PLASMA half-life.
After a drug is absorbed from its site of administration, it is
distributed to its site of action by the blood plasma. Therefore Blood-Brain Barrier
the biologic activity of a drug is related to the concentration of The tissue sites of distribution should be considered before
the free, or unbound, drug in the plasma. Drugs are bound administration. For example, for drugs to penetrate the central
reversibly to plasma proteins such as albumin and globulin. The nervous system (CNS), they must cross the blood-brain barrier.
drug that is bound to the protein does not contribute to the The passage of a drug across this barrier is related to the drug’s
intensity of the drug action because only the unbound form is lipid solubility and degree of ionization. The endothelium of
biologically active. The bound drug is considered a storage site. this barrier contains a cell layer and a basement membrane. The
If one drug is highly bound, another administered drug that is welding of the endothelial cells together prevents the formation
highly bound may displace the first drug from its plasma pro- of clefts, gaps, or pores that might allow the penetration of
tein-binding sites, increasing the effect of the first drug. This is certain drugs. To diffuse transcellularly, the drug must penetrate
one mechanism of drug interaction. the epithelial and basement membrane cells. Thiopental, a
highly lipid-soluble, nonionized drug, easily penetrates the
Half-Life blood-brain barrier to gain access to the cerebrospinal fluid and
The half-life (t 12 ) of a drug is the amount of time that passes induce sleep within seconds after intravenous administration. In
for the concentration of a drug to fall to one-half of its blood contrast, a highly ionized compound such as hexamethonium
 Drug Action and Handling CHAPTER 2 19

would not be likely to cross this barrier and therefore would 1. D Dim
produce few if any effects on the brain. Active metabolized Inactive
drug metabolite
♦ PLACENTA
2 . Dp D
The passage of drugs across the placenta involves simple diffu- metabolized
Prodrug, Active
sion in accordance with their degree of lipid solubility. Although not active drug
the placenta may act as a selective barrier against a few drugs,
most drugs pass easily across the placental barrier. Lipid-soluble 3. D Dam
drugs penetrate this membrane most easily. Therefore when Active metabolized Active
agents are administered to the mother, they are concomitantly drug metabolite
administered to the fetus. The term barrier is a misnomer. FIGURE 2-12
Metabolism mechanisms.
♦ ENTEROHEPATIC CIRCULATION
Drugs are typically absorbed via the intestines, are distributed
through the serum, pass to specific and nonspecific sites of common type of reaction in drug biotransformation. Agents
action, come to the liver, and are metabolized before being that interfere with the metabolism of certain drugs will
excreted via the kidneys. When a drug undergoes enterohepatic increase the blood level of the drugs whose metabolism is
circulation, the process varies. The steps are the same until the inhibited. An example of this is doxycycline. Doxycycline
drug is metabolized. At that point, the metabolite is secreted via itself is the active compound and is metabolized by the liver
the bile into the intestine. The metabolite is broken down by into a metabolite without activity.
enzymes and releases the drug. The drug is then absorbed again, • Inactive to active: An inactive parent drug may be trans-
and the process continues. After being taken up by the liver the formed into an active compound. The inactive compound is
second time, these drugs are again secreted into the bile. This then termed a prodrug. Interference with the metabolism of
circular pattern continues with some drug escaping with each this drug will delay its onset of action because it will be harder
passing. This process prolongs the effect of a drug. If enterohe- for the active compound to be formed. For example, acyclo-
patic circulation is blocked, the level of the drug in the serum vir is an antiviral agent. To be effective, it must be taken into
will fall. the cell and converted to its active metabolite.
• Active to active: An active parent drug may be converted to a
Redistribution second active compound, which is then converted to an inac-
Redistribution of a drug is the movement of a drug from the tive product. The total effect of such a drug would be the
site of action to nonspecific sites of action. A drug’s duration of addition of the effect of the parent drug plus the effect of the
action can be affected by redistribution of the drug from one active drug metabolite. When an active metabolite is formed,
organ to another. If redistribution occurs between specific sites the action of the drug is prolonged. For example, diazepam
and nonspecific sites, a drug’s action will be terminated. For (Valium), an active antianxiety agent, is metabolized into its
example, thiopental produces sleep within seconds, but the active metabolite, desmethyldiazepam. Diazepam’s action is
effect is terminated within a few minutes. This is because the prolonged because of its own effect combined with that of
drug is first distributed to the CNS (sleep), subsequently redis- its active metabolite.
tributed through the plasma to the muscle (action terminated), Although the rates and pathways of drug metabolism vary
and finally reaches the fat depots of the body (no action still). among species, most studies indicate that drug biotransforma-
tion in laboratory animals is similar to that in humans. Many
Metabolism (Biotransformation) synthetic mechanisms of drug metabolism occur in the body to
Metabolism, which is also known as form metabolites.
Drug metabolism biotransformation, is the body’s way of
produces compounds changing a drug so that it can be more ♦ FIRST-PASS EFFECT
that are more polar
(ionized) and more
easily excreted by the kidneys. Many Metabolism of drugs may be divided into two general types:
easily excreted. drugs undergo metabolic transforma- phase I and phase II. If a drug has no functional groups with
tion or change, most commonly in the which to combine, then the drug must undergo a phase I
liver. The metabolite (metabolic product) formed is usually reaction.
more polar (ionized) and less lipid soluble than its parent com- Phase I. In phase I reactions, lipid molecules are metabolized
pound. This means that renal tubular reabsorption of the metab- by the three processes of oxidation, reduction, and hydrolysis.
olite will be reduced because reabsorption favors lipid-soluble Oxidation. When a drug is administered that does not possess
compounds. Metabolites are also less likely to bind to plasma or an appropriate functional group suitable for combining with
tissue proteins and less likely to be stored in fat tissue. Decreased body acids (conjugation), the body has more difficulty detoxify-
renal tubular reabsorption, decreased binding to the plasma or ing that drug. An enzyme system responsible for the oxidative
tissue proteins, and decreased fat storage cause the metabolite metabolism of many drugs is located in the liver. The enzymes
to be excreted more easily. Drug metabolism is an enzyme- are located in the endoplasmic reticulum and are termed micro-
dependent process that has developed through evolution. somal enzymes because they are found in the microsomal fraction
Drugs can be metabolized in one of three of the following as prepared from liver homogenates. A variety of oxidative reac-
different means (Figure 2-12): tions, such as hydroxylation or the incorporation of oxygen into
• Active to inactive: By metabolism, an inactive compound may the substrate molecule, occur in these hepatic microsomal
be formed from an active parent drug. This is the most enzymes.
Other documents randomly have
different content
for usually he was the most reticent of men in relation to his own
exploits. The night was pretty dark, there was no moon, and our fire
of dry knots blazed up beautifully every time the two Indians, whom
we had appointed to this special duty, threw a fresh armful on. The
flames cast their weird and fanciful shadows on the side of the
mountain, and contrasted curiously with the inky blackness all
around below us, while far above could be seen the dim outline of
"Old Baldy's" scarred and weather-beaten crest—crag piled upon
crag, until they seemed to touch the starlit sky.
For an hour or two the conversation was confined to the probabilities
of gold being found in paying quantities in the mountains and
gulches of the range; and when the interest on that subject flagged,
Maxwell having made a casual remark in relation to some peak near
by, just discernible in the darkness, and connecting the locality with
some trouble he had had ten or a dozen years before with the
Indians, his reminiscences opened Kit Carson's mouth, and he said
he remembered one of the "worst difficults" a man ever got into; so
he made a fresh corn-shuck cigarette and told us the following about
Pawnee Rock, which he said had been written up years ago, and
that he had a paper containing it (which he afterward gave me), and
which, with what Kit related orally that night, is here presented:
"It was old Jim Gibson—poor fellow, he went under in a fight with
the Utes over twenty years ago, and his bones are bleaching
somewhere in the dark cañons of the range, or on the slopes of the
Spanish Peaks. He used to tell of a scrimmage he and another fellow
had on the Arkansas with the Kiowas, in 1836.
"Jim and his partner, Bill something-or-other,—I disremember his
name now,—had been trapping up in the Powder river country
during the winter, with unusual good luck. The beaver was mighty
thick in the whole Yellowstone region in them days, and Jim and Bill
got an early start on their journey for the River[2] that spring. You
see they expected to sell their truck in Weston, Mo., which was the
principal trading-point on the River then. They walked the whole
distance—over fifteen hundred miles—driving three good mules
before them, on which their plunder was packed, and they got along
well enough until they struck the Arkansas river at Pawnee Rock.
Here they met a war party of about sixty Kiowas, who treed them on
the Rock. Jim and Bill were notoriously brave, and both dead shots.

[2] In the old days, among the plainsmen and

mountaineers, whenever "the River" was alluded to it
was understood to mean the Missouri.

"Before they reached the Rock, to which they were driven, they
killed ten of the Kiowas, and had not received a scratch. They had
plenty of powder and a pouchful of bullets each. They also had a
couple of jack-rabbits for food in case of a siege, and the
perpendicular walls of the Rock made them a natural fortification—
an almost impregnable one.
"They succeeded in securely picketing their animals on the west side
of the Rock, where they could protect them by their unerring rifles
——but the story of the fight must be told in Jim's own way; he was
a pretty well educated fellow, and had been to college, I believe, in
his younger days,—lost the gal he was going to marry, or had some
bad luck or other, and took to the prairies when he was about
twenty. I will try to tell it as near as he did as possible:
"After the durned red cusses had treed us, they picked up their dead
and packed them to their camp at the mouth of the creek a little
piece off. In a few moments back they all came, mounted, with all
their fixings and war-paint on. Then they commenced to circle
around us, coming closer, Indian fashion, every time, till they got
within easy rifle range, when they slung themselves on the fore
sides of their ponies, and in that position opened on us. Their arrows
fell like a hail-storm around us for a few minutes, but as good luck
would have it, none of them struck. I was afraid that first of all, they
would attempt to kill our mules; but I suppose they thought they
had the dead wood on us, and the mules would come mighty handy
for their own use after our scalps were dangling at their belts. But
we were taking in all the chances. Bill kept his eyes skinned, and
whenever he saw a stray leg or head he drew a bead on it, and
thug! over tumbled its owner every time, with a yell of rage.
"Whenever they attempted to carry off their dead, that was the
moment we took the advantage, and we poured it into them as soon
as they rallied for that purpose, with telling effect. We wasted no
shots; we had now only about forty bullets between us, and the
miserable cusses seemed thick as ever.
"The sun was nearly down by this time, and at dark they did not
seem anxious to renew the fight that night, but I could see their
mounted patrols at a respectable distance on every side, watching to
prevent our escape. I took advantage of the darkness to go down
and get a few buffalo-chips to cook our supper, for we were mighty
hungry, and to change the animals to where they could get a little
more grass,—though for that matter it was nearly up to a man's
head all over the bottom.
"I got back to our camp on top without any trouble, when we made
a little fire and cooked a rabbit. We had to go without water, and so
did the animals; though we did not mind the want of it so much
ourselves, we pitied the mules, which had had none since we broke
camp in the morning. It was of no use to worry about it, though; the
nearest water was in the spring at the Indian camp, and it would be
certain death to attempt to get there.
"I was afraid the red devils would fire the prairie in the morning and
endeavor to smoke or burn us out. The grass was just in a condition
to make a lively blaze, and we might escape the flames,—and we
might not.
"We watched with eager eyes for the first gray streaks of dawn that
would usher in another day—perhaps the last for us.
"The next morning's sun had scarcely peeped above the horizon,
when, with an infernal yell, the Indians broke for the Rock, and we
knew some new project had entered their heads.
"The wind was springing up pretty fresh, and nature seemed to
conspire with the red devils if they really meant to burn us out,—and
I had no doubt now from their movements that that was what they
intended. The darned cusses kept at such a respectful distance from
our rifles that it chafed us to know that we could not stop the
infernal throats of some of them with our bullets; but we had to
choke our rage and watch events closely.
"I took occasion during the lull in hostilities to crawl down to where
the mules were and shift them to the east side of the Rock, where
the wall was the highest, so that the flames and smoke might
possibly pass by them without so much danger as on the exposed
other side.
"I succeeded in doing this, and also in tearing away the grass for
several yards around the animals, and was just starting back when
Bill called out, '—— 'em, they've fired the prairie!'
"I reached the top of the Rock in a moment, and took in at a glance
what was coming. The spectacle for a short interval was
indescribably grand. The sun was shining with all the powers of its
rays on the huge clouds of smoke as they rolled down from the
north, tinting them with a glorious crimson. I had barely time to get
under shelter of a projecting point of the Rock when the wind and
smoke swept down to the ground, and instantly we were enveloped
in the darkness of midnight. We could not discern a single object,
neither Indians, horses, the prairie, nor sun—and what a terrible
wind! I have never experienced its equal in violence since. We stood
breathless, and clinging to the projection of our little mass of rock
did not realize that the fire was so near until we were struck in the
face by the burning buffalo-chips that were carried toward us with
the rapidity of the wind. I was really scared; it seemed as if we must
suffocate. But we were saved miraculously. The sheet of flame
passed us twenty yards away, as the wind fortunately shifted the
moment the fire reached the Rock. Yet the darkness was so perfect
we did not see the flame; we only knew that we were safe, as the
clear sky greeted us "behind the dense cloud of smoke.
"Two of the Indians and their horses were caught in their own trap,
and perished miserably. They had attempted to reach the east side
of the Rock where the mules were, either to cut them loose or crawl
up on us while bewildered in the smoke, if we escaped death. But
they had proceeded only a few rods on their little expedition when
the terrible darkness of the smoke-cloud overtook them.
"All the game on the prairie which the fire swept over was killed too.
Only a few buffaloes were visible in that region before the fire, but
even they were killed. The path of this horrible passage of flames, as
we learned afterward, was marked all along with the crisped and
blackened carcasses of wolves, coyotes, turkeys, grouse, and every
variety of small birds. Indeed, it seemed as if no living thing it met
had escaped its fury.
"The fire assumed such gigantic proportions and moved with such
rapidity before the terrible wind, that even the Arkansas river did not
check its path for a moment, and we watched it carried across as
readily as if the river had not been in the way. This fearful prairie-fire
traveled at the rate of eight miles in fifteen minutes, and was
probably the most violent in its features that ever visited that
country. It was the most sublime picture I ever looked upon, and for
a moment it made us forget our perilous position.
"My first thought, after the danger had passed, was of the poor
mules. I crawled down to where they were, and found them badly
singed but not seriously hurt. I thought, 'So far so good;' our mules
and traps were all right, so we took courage and began to think we
should get out of the nasty scrape in some way or other.
"In the meantime the Indians, with the exception of four or five left
to guard the Rock so we could not escape, had gone back to their
camp on the creek, and were evidently concocting some new
scheme to capture or kill us.
"We waited patiently two or three hours for the development of
events, snatching a little sleep by turns, until the sun was about four
hours high, when the Indians commenced their infernal howling
again, and we knew they had hit upon something; so we were on
the alert in a moment to discover it, and euchre them if possible.
"The devils this time had tied all their horses together, covered them
with branches of trees that they had cut on the creek, packed all the
lodgeskins on these, and then, driving the living breastworks before
them toward us, themselves followed close behind on foot. They
kept moving slowly but surely in the direction of the Rock, and
matters began to look serious for us once more.
"Bill put his hand in mine now, and said, 'Jim, now by —— we got to
fight; we hain't done nothin' yit; this means business.'
"I said, 'You're right, Bill, old fellow; but they can't get us alive. Our
plan is to kill their ponies and make the cusses halt.'
"As I spoke, Bill—who was one of the best shots on the Plains—kind
o' threw his eye carelessly along the bar'l of his rifle, and one of the
ponies tumbled over on the blackened sod. One of the Indians ran
out to cut him loose, as I expected, and I took him clean off his feet
without a groan. Quicker than it takes me to tell it, we had stretched
out twelve of them on the prairie, and we made it so hot for them
that they got out of range, and were apparently holding a council of
war.
"We kept watching the devils' movements, for we knew they would
soon be up to some confounded trick. The others did not make their
appearance immediately from behind their living breastworks, so we
fired two shots apiece into the horses, killing three of them and
throwing the whole outfit into confusion.
"We soon stopped their little plan, and they had now only the dead
bodies of the ponies we had killed, to protect them, for the others
had broken loose and stampeded off to camp. It was getting pretty
hot for Mr. Indian now, who was on foot and in easy range of our
rifles. We cleaned out one or two more while they were gradually
pulling themselves out of range, when of course we had to stop
firing. The Indians started off to their camp again, and during the lull
in hostilities we took an account of stock. We found we had used up
all our ammunition except three or four loads, and despair seemed
to hover over us once more.
"In a few moments we were surprised to see one of the warriors
come out alone from camp, and tearing off a piece of his white
blanket, he boldly walked toward the Rock. Coming up within
hearing, he asked if we would have a talk with him. We told him yes,
but did not look for any good results from it. We could not expect
anything less than torture if we allowed ourselves to be taken alive,
so we determined not to be caught in any trap. We knew we had
done them too much damage to expect any mercy, so we prepared
to die in the fight, if we must die.
"We beckoned the young buck nearer and listened to what he had to
say. He said they were part of White Buffalo's band of Kiowas; that
the war chief who was here with them was O-ton-son-e-var ('a herd
of buffaloes'), and that he wanted us to come to the camp; that we
were 'heap brave'; we should be kindly treated, and that the tribe
would adopt us. They were on their way to the Sioux country north
of the Platte; that they were going there to steal horses from the
Sioux. They expected a fight, and wanted us to help them.
 O-TON-SON-E-VAR.

"Bill and myself knew the darned Indians too well to swallow their
chaff, so we told them that we could not think of accepting their
terms; that we were on our way to the Missouri, and meant to get
there or die in the attempt; that we did not fear them,—the white
man's God would take care of us; and that if that was all they had to
talk about, he could go back and tell his party they could begin the
fight again as soon as they pleased.
"He started back, and before he had reached the creek they came
out and met him, had a confab, and then began the attack on us at
once. We made each of our four loads tell, and then stood at bay,
almost helpless and defenseless: we were at the mercy of the
savages, and they understood our situation as quickly as ourselves.
"We were now thrown upon our last resource—the boy's-play of
throwing stones. As long as we could find detached pieces of rock
they did not dare to make an assault, and while we were still
wondering what next, the white flag appeared again and demanded
another talk. We knew that now we had to come to terms, and make
up our minds to accept anything that savored of reason and our
lives, trusting to the future to escape if they kept us as prisoners.
"'The Kiowas are not prisoners, and they know brave men,' said the
Indian; 'we will not kill you, though the prairie-grass is red with the
blood of our warriors that have died by your hands. We will give you
a chance for your lives, and let you prove that the Great Spirit of the
white man is powerful, and can save you. Behold,' said the Indian,
pointing with an arrow to a solitary cottonwood on the banks of the
Arkansas, a mile or more away, 'you must go there, and one of you
shall run the knife-gauntlet from that tree two hundred steps of the
chief out toward the prairie. If the one who runs escapes, both are
free, for the Great Spirit has willed it. O-ton-son-e-var has said it,
and the words of the Kiowa are true.'
"'When must the trial take place?' said I.
"'When the sun begins to shine upon the western edge of the Rock,'
replied the Indian.
"'Say to your chief we accept the challenge and will be ready,' said
Bill, motioning the young warrior away. 'I am sure I can win,' said
he, 'and can save both our lives. O-ton-son-e-var will keep his word
—I know him.'
"'Bill,' said I, 'I shall run that race, not you;' and taking him by the
hand I told him that if he saw I was going to fail, to watch his
chance, and in the excitement of the moment mount one of their
horses and fly toward Bent's Fort; he could escape—he was young;
it made no difference with me—my life was not worth much, but he
had all before him.
"'No,' replied Bill, 'my heart is set on this; I traveled the same race
once before when the Apaches got me, and their knives never struck
me once. I ask this favor as my life, for I have a presentiment that it
is only I can win. I know how to get every advantage of them. So
say no more.'
"The sun had scarcely gilded that portion of the dark line of the Rock
that juts out boldly toward the western horizon, before all the
warriors, with O-ton-son-e-var at their head, marched silently toward
the tree and beckoned us to come.

PACER'S SON—CHIEF OF ALL THE APACHES.

"Quickly we were on the prairie beside them, when they opened a

space, and we walked in their center without exchanging a word.
There were only thirty left of that band of sixty proud warriors who
had commenced the attack on us the day before, and I could see by
the scowls with which they regarded us, and by the convulsive
clutching at their knives by the younger ones, that it was only the
presence and power of O-ton-son-e-var which prevented them from
taking summary vengeance upon us.
"As soon as we reached the tree, O-ton-son-e-var paced the two
hundred steps, and arranged his warriors on either side, who in a
moment stripped themselves to the waist, and each seizing his long
scalping-knife, and bracing himself, held it high over his head, so as
to strike a blow that would carry it to the hilt at once.
"The question of who should be their victim was settled immediately,
for as I stepped forward to face that narrow passage of probable
death, the chief signaled me back with an impulsive gesture not to
be misunderstood, and pointing to Bill, told him to prepare himself
for the bloody trial.
"I attempted to protest, and was urging my most earnest words,
when O-ton-son-e-var said he had decided, and 'the young man
must run,' adding that 'even a drop of blood from any one of the
knives meant death to both.'
"Each savage stood firm, with his glittering blade reflecting the rays
of the evening sun, and on each hard cold face a determination to
have the heart's blood of their victim.
"The case seemed almost hopeless—it was truly a race for life; and
as Bill prepared himself I wished ourselves back on the Rock, with
only as many good bullets as the number of red devils who stood
before us, the very impersonation of all the hatred of the detestable
red man.
"How well I remember the coolness and confidence of Bill! He could
not have been more calm if he had been stripping for a foot-race for
fun. He had perfect faith in the result, and when O-ton-son-e-var
motioned to commence the fearful trial, Bill spoke to me, but I could
not answer—my grief was too great.
"He stripped to his drawers, and standing there awaiting the signal,
naked from the belt up, he was the picture of the noblest manhood I
ever saw. He tightened his belt, and stood for a few seconds
looking, with compressed lips, down the double row of savages, as
they stood, face to face, gloating on their victim. It seemed like an
age to me, and when the signal came I was forced by an irresistible
power to look upon the scene.
"At the instant Bill darted like a flash of lightning from the foot of the
tree; on rushed the devils with their gleaming blades, yelling, and
crowding one another, and cutting at poor Bill with all the rage of
their revengeful nature. But he evaded all their horrible efforts—now
tossing a savage here and another there, now almost creeping like a
snake at their feet, then like a wildcat he would jump through the
line, dashing the knives out of their hands, till at last, with a single
spring, he passed almost twenty feet beyond the mark where the
chief stood.
"We were saved, and when the disappointed savages were crowding
around him I rushed in and threw myself in his arms. The chief
motioned the impatient warriors away, and with sullen footsteps
followed them.
"In a few moments we slowly retraced our way to the Rock, where,
taking our mules, we pushed on in the direction of the Missouri. We
camped on the bank of the Arkansas that night, only a few miles
from the terrible Rock; and while we were resting around our little
fire of buffalo-chips, and our animals were quietly nibbling the dried
grass at our feet, we could still hear the Kiowas chanting the death-
song as they buried their lost warriors under the blackened sod of
the prairie."
 SHERIDAN'S ROOST.

GENERAL P. H. SHERIDAN.

Less than a third of a century ago the western half of southern

Kansas and the whole region beyond, including the historical
Washita, where General Custer defeated the famous chief of the
Cheyennes, Black Kettle, was the habitat of our noblest indigenous
bird, the wild turkey. The dense woods bordering all the streams
were full of them, for the wild turkey makes his haunts in the timber.
Having visited that once favorite winter rendezvous of the
Cheyennes and Kiowas during the early spring, and stood again on
the ground where Sheridan and Custer in their celebrated campaign
of 1868-9 so effectually subdued the Indians that the Western
frontier has ever since been exempt from their bloody raids, the
recollection of many exciting wild-turkey hunts by the two
incomparable soldiers came vividly to my mind. I remember
distinctly, as if it were but a week since, how during that winter
campaign of nearly thirty years ago the troops sent into the field
against the allied hostile tribes subsisted for days on wild turkey—
luckily for them, too, as they were almost without a ration, and
would have suffered in a greater degree than they did but for the
presence of great flocks of the delicious birds.
In addition to the stern necessity of securing them, shooting them
under the brilliant mid-continent full moon that nowhere else shines
more intensely, afforded an immense amount of sport to both
officers and enlisted men, divesting their weary march through that
then desolate region of its terrible monotony. General Sheridan was
a crack shot, recognized as an expert in pheasant-hunting when a
young lieutenant in the wilds of Oregon, long before the Civil War,
and where large game roamed in immense numbers through the
vast forests. Then the height of the embryo great General's ambition
was that he might attain the rank of Major before he died!
There is a large body of timber on the North Fork of the Canadian
river in the Indian Territory, about sixty miles directly south of the
Kansas line, known as "Sheridan's Roost"—so marked on the maps.
It was there that General Sheridan with Custer bagged an almost
incredible number of wild turkeys while camping on the now historic
spot.
It was on the afternoon of one of the last days in the month of
December, 1868, when the tired command found itself encamped
very near an immense turkey roost. Both Sheridan and Custer, as
soon as they had dismounted from their horses, made the fortuitous
discovery and grasped the important situation: an abundance of
food for the half-starved troopers and a relief to the ennui and
tiresome routine of the monotonous march through the seemingly
interminable sand-dunes so frequent in that region.
In order that the necessities of the command and the anticipated
sport might not be thwarted by a general firing of the rank and file
under the excitement natural to the average soldier, Sheridan
immediately issued an order that no one—officer, enlisted man, or
civilian—should leave camp without his permission. He was well
aware of the fact that if any prowling around was allowed, the now
absent birds would not return to their accustomed resting-place
when night came on.
The whole command was restless, anxious and impatient for hours,
waiting for the seemingly tardy sun to set. At last, after two hours of
suspense, the fading rays began to gild the summits of the low
range of hills west of the camp. Then, just as the twilight curve
reached the horizon, the General, with Custer and several other
officers whom he had chosen as companions, left their camp-fire of
blazing logs and sauntered slowly into the thick woods where it had
been discovered early in the afternoon that the coveted birds were
in the habit of congregating to roost.
Arriving at the very center of the vast sleeping-place, at the
suggestion of General Custer each gentleman took a position on the
ground, separated from each other some distance, to watch from
their individual vantage-point until the moment should come for the
birds to seek their accustomed resting-place.
They did not have to wait long. Before it had grown fairly dark, two
or three flocks containing at least two hundred of the bronzed
beauties came walking stealthily down the sheltered ravines leading
out into the broad bottom where the great trees stood in aggregated
clumps, under whose shadows General Sheridan had first observed
the unmistakable signs of a vast roost. At the head of each flock, as
it unsuspiciously advanced, strutted a magnificent male bird in all
the arrogance of his leadership, and on whose bronzed plumage the
soft full moon which had just risen, glinted like a calcium light as its
golden rays sifted through the interstices of the bare limbs of the
winter-garbed forest.
When the leader had arrived at the spot where his charge had been
accustomed to roost, he suddenly halted, glanced all around him for
a few seconds, then seemingly satisfied that everything was right,
he gave the signal—a sharp, quick, shrill whistle. At that instant
every bird with one accord and a tremendous fluttering of wings,
raised itself and alighted in the loftiest branches of the tallest trees.
In a few moments more, many more flocks arrived and went
through exactly the same evolutions as the first two, when, having
settled themselves for an undisturbed slumber, General Sheridan
gave the word for the slaughter to begin. Each officer then began to
shoot on his own account, and the turkeys fell like the leaves in
October. The stupid birds not killed at the first fusillade did not seem
to have sense enough to get out of harm's way: they flew from tree
to tree at every shot, persistently remaining in the immediate vicinity
of their roost with all the characteristic idiocy of a sage-hen, which,
according to my observation, has less sense than any other bird that
flies.
It was soon time that all honest men whether "in camp or court"
were in bed, but the two famous generals and their companions, so
exciting was the rare sport, did not leave until the moon was far
down the western horizon.
They then returned to the friendly fires near their tents and counted
the number of birds which had fallen under the accurate aim of
those engaged. It was discovered they had bagged nearly a hundred
of the magnificent bronzed creatures, of which Sheridan had killed
the lion's share.
From that midnight incident in the beginning of that eventful winter
on the Great Plains, "Sheridan's Roost" received its name; the spot
became classic, and will go down to the generations yet unborn with
its suggestive title.
Although the majority of the birds stuck to the vicinity of their roost,
yet continually slaughtered by the unerring rifles of the officers,
appearing to be too senseless to avert their doom by flying off,
some, however, did go recklessly into the very camp of the troopers.
The picket-line had long since been stretched, and preparations for
the men's evening meal, scanty as it was to be, were fairly under
way. But the cooks, expecting that some of the birds would,
frightened as they evidently were by the deadly shots of the officers,
fly into camp in their bewilderment, were a little slow and
perfunctory, anticipating that the bill of fare, that night at least,
would vary materially from the customary horse-meat and hardtack.
Sure enough, several large flocks "rounded up" in full view of the
command just as the firing commenced. It was a curious as well as
a remarkable scene to watch the evident surprise and discomfiture
of the birds to discover the whole ground usurped by the soldiers;
they were bewildered beyond the power of description. They stood
still for a few moments seemingly paralyzed, but as other flocks
began to enter the camp, all in the quickest imaginable time flew
into the tallest trees. At this juncture every soldier was seized with a
desire to shoot, and a fusillade began right there, resulting in
tumbling off the huge limbs fifty or more of the crazed birds. Of
course, the remainder were driven away from their roost, until the
very air was black with the alarmed and bewildered turkeys.
As the dark night came on, not knowing where to go, and failing to
seek another quiet roosting-place, back they all came, but in
increased numbers, evidently determined to roost there or nowhere.
The air was filled and the ground covered with wild turkeys. They
were dazed at the turn affairs had taken, and great flocks ran,
bewildered, right among the soldiers and wagons of the supply train.
Then was a scene enacted such as perhaps was never before
witnessed, nor has it since, in all probability. All the dogs in the
command—and there was every breed and every size in the camp,
for the average American soldier loves a dog and keeps as many as
he can—joined in the pandemonium that ensued in the chase after
the frightened birds, accompanied by a fusillade which in point of
rapidity and volume of noise would have done credit to a corps in a
general engagement.
Some casualties occurred, of course, but no lives were lost save that
of a horse, under the following circumstances: One of the troopers
of the Nineteenth Kansas Cavalry, who was in the act of leading his
animal to the picket-line at the height of the chase, was somewhat
astonished to find that his faithful beast failed to respond to the
tugging at his halter-strap as he endeavored to bring him to the
stretched rope, and looking around to discover the cause, the
excited trooper saw the unfortunate animal on the ground, dead,
having been instantly killed by an erratic ball!
There was great feasting in the command that night. Never did
turkey taste so delicious as did the magnificent birds served in every
conceivable style at that late meal in camp on the classic Washita, to
the half-famished soldiers of the famous Seventh Cavalry and the
gallant boys of the Kansas regiment.
 THE PASSING OF THE BUFFALO.

To the old trapper and hunter of the palmy days of '68 and '70, I
dedicate this chapter. That time is now faded into the past, and so
far faded, indeed, that the present generation knows not its
sympathy nor its sentiment.
The buffalo—as my thoughts turn to the past, the memory of their
"age" (if I may so call it) crowds upon me. I remember when the
eye could not measure their numbers. I saw a herd delay a railroad
train from 9 o'clock in the morning until 5 o'clock in the afternoon.
Countless millions, divided by its leaders and captains like an
immense army! How many millions there were, none could guess.
On each side of us, and as far as we could see—our vision was
limited only by the extended horizon of the flat prairie—the whole
vast area was black with the surging mass of affrighted animals, as
they rushed onward to the south in a mad stampede.
At another time Gens. Sheridan, Custer, Sully, and myself rode
through another and larger one, for three consecutive days. This
was in the fall of 1868. It seems almost impossible to those who
have seen them, as numerous apparently as the sands of the
seashore, feeding on the illimitable natural pasturage of the Great
Plains, that the buffalo should have become practically extinct. When
I look back only twenty-five years and recall the fact that they
swarmed in countless numbers even then as far east as Fort Harker,
only 200 miles west from the Missouri river, I ask myself, "Have they
all disappeared?" And yet, such is the fact. Two causes can be
assigned for this great hecatomb: First, the demand for their hides,
which brought about a great invasion of hunters into this region; and
second, the crowds of thoughtless tourists who crossed the
continent for the mere novelty and pleasure of the trip. This latter
class heartlessly killed for the excitement of the new experience as
they rode along in the cars at a low rate of speed, often never
touching a particle of the flesh of their victims, or possessing
themselves of a single robe.
The former, numbering hundreds of old frontiersmen, all expert
shots, with thousands of novices, the pioneer settlers on the public
domain, day after day for years made it a lucrative business to kill
for the robes alone, a market for which had suddenly sprung up all
over the country.
The beginning of the end was marked by the completion of the
Kansas Pacific across the Plains to the foot-hills of the Rockies in
1868, this being the western limit of the buffalo range.
In 1872 a writer in "The Buffalo Land" said:
"Probably the most cruel of all bison-shooting pastime is
that of firing from the cars. During certain periods in the
spring and fall, when the large herds are crossing the
Kansas Pacific Railroad, the trains run for a hundred miles
or more among countless thousands of the shaggy
monarchs of the Plains. The bison has a strange and
entirely unaccountable instinct or habit which leads it to
attempt crossing in front of any moving object near it. It
frequently happened, in the time of the old stages, that the
driver had to rein up his horses until the herd which he had
started had crossed the road ahead of him. To accomplish
this feat, if the object of their fright was moving rapidly, the
animals would often run for miles.
"When the iron horse comes rushing into their solitudes,
and snorting out his fierce alarms, the herds, though
perhaps half a mile from his path, will lift their heads and
gaze intently for a few minutes toward the object thus
approaching them with a roar which causes the earth to
tremble, and enveloped in a white cloud that streams
further and higher than the dust of the old stage-coach
ever did; and then, having determined its course, instead of
fleeing back to the distant valleys, away they go, charging
over the ridge across which the iron rails lie, apparently
determined to cross in front of the locomotive at all
hazards. The rate per mile of the passenger trains is slow
upon the Plains, and hence it often happens that the cars
and buffaloes will be side by side for a mile or two, the
brutes abandoning the effort to cross only when their foe
has emerged entirely ahead. During these races the car
windows are opened, and numerous breech-loaders fling
hundreds of bullets among the densely crowded and fast-
flying masses. Many of the poor animals fall, and more go
off to die in the ravines. The train speeds on, and the act is
repeated every few miles until Buffalo Land is passed."
Almost with prophetic eye he continued:

"Let this slaughter continue for ten years, and the bison of
the American continent will become extinct. The number of
valuable robes and pounds of meat which would thus be
lost to us and posterity, will run too far into the millions to
be easily calculated. All over the Plains, lying in disgusting
masses of putrefaction along valley and hill, are strewn
immense carcasses of wantonly slain buffalo. They line the
Kansas Pacific road for two hundred miles."

A great herd of buffaloes on the Plains in the early days, when one
could approach near enough without disturbing it to quietly watch its
organization, and the apparent discipline which its leaders seemed to
exact, was a very curious sight. Among the striking features of the
spectacle was the apparently uniform manner in which the immense
mass of shaggy animals moved; there was constancy of action
indicating a degree of intelligence to be found only in the most
intelligent of the brute creation. Frequently the larger herd was
broken up into many smaller ones, that traveled relatively close
together, each led by an independent master. Perhaps only a few
rods marked the dividing-line between them, but it was always
unmistakably plain, and each moved synchronously in the direction
in which all were going.
The leadership of the herd was attained only by hard struggles for
the place; once reached, however, the victor was immediately
recognized, and kept his authority until some new aspirant overcame
him, or he became superannuated and was driven out of the herd to
meet his inevitable fate, a prey to those ghouls of the desert, the
gray wolves.
In the event of a stampede, every animal of the separate yet
consolidated herds rushed off together, as if all had gone mad at
once; for the buffalo, like the Texas steer, mule, or domestic horse,
stampedes on the slightest provocation—frequently without any
assignable cause. Sometimes the simplest affair will start the whole
herd: a prairie-dog barking at the entrance of his burrow, a shadow
of one of themselves or that of a passing cloud, is sufficient to make
them run for miles as if a real and dangerous enemy were at their
heels.
Stampedes were a great source of profit to the Indians of the Plains.
The Comanches were particularly expert and daring in this kind of
robbery. They even trained their horses to run from one point to
another, in expectation of the coming of the wagon trains on the
trail. When a camp was made that was nearly in range, they turned
their trained animals loose, which at once flew across the prairie,
passing through the herd and penetrating the very corrals of their
victims. All of the picketed horses and mules would endeavor to
follow these decoys, and were invariably led right into the haunts of
the Indians, who easily secured them. Young horses and mules were
easily frightened; and in the confusion which generally ensued, great
injury was frequently done to the runaways themselves.
At times when the herd was very large, the horses scattered over
the prairie and were irrevocably lost; and such as did not become
wild fell a prey to the wolves. That fate was very frequently the lot
of stampeded horses bred in the States, they not having been
trained by a prairie life to care for themselves. Instead of stopping
and bravely fighting off the bloodthirsty beasts, they would run.
Then the whole pack were sure to leave the bolder animals and
make for the runaways, which they seldom failed to overtake and
dispatch.
Like an army, a herd of buffaloes put out vedettes to give the alarm
in case anything beyond the ordinary occurred. These sentinels were
always to be seen in groups of four, five, or even six, at some
distance from the main body. When they saw something
approaching that the herd should beware of or get away from, they
started on the run directly for the center of the great mass of their
peacefully grazing congeners. Meanwhile, the young bulls were on
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