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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.
20 PART ONE General Principles

Oxidative processes involving enzymes other than those of

the hepatic microsomal enzymes can take place. Some com- The liver acts as a small “factory”
pounds are oxidatively deaminated by enzymes located in the Dm Dm
liver, kidney, and nervous tissue. Other agents are detoxified by Dm
specific oxidative enzymes.
Normal
Hydrolysis. Some ester compounds are metabolized by hydro- Normal drug level
lysis. Hydrolytic enzymes, which are found in plasma and a
variety of tissues, break up esters and add water. The ester local D
A DD
anesthetics are inactivated by plasma cholinesterases.
Reduction. Many reduction reactions are mediated by the Dm Dm
enzymes found in the hepatic microsomes. Dm
Dm
Microsomal Enzymes. Phase I reactions are carried out by the Dm
microsomal or cytochrome P-450 enzymes, which are also
known as the mixed function oxidases in the liver. The concentra- Induction
(more Drug level lower
tion of these enzymes can be affected by drugs and environmen- enzymes) because enzymes
tal substances. Phase I metabolism may be affected by other
drugs that alter microsomal enzyme inhibition or induction.
Induction. The P-450 hepatic microsomal enzymes can be D
B
induced (the amount of enzyme increased) by some drugs and
by smoking tobacco. Because drugs that cause enzyme induction Dm
cause other drugs to be more quickly metabolized, the metabo-
lized drugs will have reduced pharmacologic effects. More recent Inhibition
(enzymes
evidence has discovered that the hepatic enzymes can be divided less
into many categories called isoenzymes. Examples of isoenzymes functional)
include cytochrome P-450 2D6 and 3A4. Table 2-1 lists samples
of drugs that are substrates of these enzymes and drugs that D D
D D Drug level higher
either induce or inhibit these isoenzymes. For example, pheno- C D because enzymes
barbital stimulates the production of microsomal enzymes that
normally metabolize the anticoagulant warfarin. Thus adminis- FIGURE 2-13
tering phenobarbital to a patient taking warfarin can decrease Alteration of drug metabolism induction and inhibition. Enzyme induction
warfarin’s anticoagulant response because the metabolism of the and inhibition alter the blood levels of drugs metabolized by the hepatic
anticoagulant is stimulated by phenobarbital (Figure 2-13). enzymes. A, Normal. The liver is metabolizing drugs at the normal rate
Some drugs, such as valproate and carbamazepine (anticon- producing the normal effects. B, Induction. With enzyme induction (stim-
vulsants), can also stimulate their own metabolism. The toler- ulation), increase in the enzymes causes the drug to be more quickly
metabolized, and blood level of the drug and its effect are decreased (assume
ance that patients develop to certain drugs can be explained, at
that metabolite is inactive). Induction = effect. C, Inhibition. With enzyme
least in part, by an increased ability to metabolize the drug inhibition, the metabolism of drugs is slower (weaker enzymes) and the
because of stimulation of microsomal enzymes. blood level of the drug that is metabolized is increased. Inhibition = effect.
Inhibition. Inhibition of the metabolism of certain drugs
may occur through several mechanisms. With inhibition, the
blood levels and action of the drugs metabolized by these
enzymes will be increased. Examples of drugs that inhibit the excretion is the most important. Extrarenal routes include the
metabolism of other drugs are erythromycin and cimetidine. lungs, bile, gastrointestinal tract, sweat, saliva, and milk. Drugs
Inhibiting the microsomal enzymes would result in an increase may be excreted unchanged or as metabolites.
in the effect of the drugs metabolized by the liver enzymes (see Kinetics. Kinetics is the mathematical representation of the
Table 2-1). way in which drugs are removed from the body. The most
Phase II. Phase II reactions involve conjugation with the common mechanism is first-order kinetics (see Figure 2-11).
following agents: glucuronic acid, sulfuric acid, acetic acid, or A few drugs, such as aspirin and alcohol, exhibit zero-order
an amino acid. The most common conjugation occurs with kinetics. With zero-order kinetics, the rate of metabolism
glucuronic acid. This conjugation is termed glucuronidation. remains constant over time, and the same amount of drug is
Glucuronic acid, which is a substance normally occurring in the metabolized per unit of time regardless of dose. Zero-order
body, may be transferred to a drug molecule that has an appro- kinetics occurs because the enzymes that metabolize these drugs
priate functional group to accept it. Functional groups that may can become saturated at usual therapeutic doses. If the dose of
be involved include ethers, alcohols, aromatic amines, and car- the drug is increased, the metabolism cannot increase above its
boxylic acid. This mechanism, either alone or in combination maximum rate. With small doses, drugs with zero-order kinetics
with a phase I reaction, allows the body to convert a lipid-soluble can metabolize the drug without buildup. With high doses, the
drug to a more polar compound. The enzymes that mediate the metabolism of the drug cannot increase and the duration of
conjugation are termed transferases. action of the drug can be greatly prolonged (Figure 2-14). Small
changes in the dose of these drugs may produce a large change
♦ EXCRETION in the serum concentration, leading to unexpected toxicity.
Although drugs may be excreted by any of several routes that Renal Route. Elimination of substances in the kidney can
have direct access to the external environment, renal (kidney) occur by the following three routes:
 Drug Action and Handling CHAPTER 2 21

TABLE 2-1 SELECTED CYP-450 ISOENZYMES SUBSTRATES, INHIBITORS, AND INDUCERS

Number Substrate Inhibitors Inducers

CYP 1A2 Antidepressants, tricyclic Fluoroquinolones Barbiturates
d-Warfarin Carbamazepine
Theophylline
CYP 2C8/9/10 Anticonvulsants Anticonvulsants Cimetidine
NSAIDs Antidepressants, SSRI Omeprazole
s-Warfarin
CYP 2C18/19 Antidepressants Antidepressants, SSRI Barbiturates
Naproxen Imidazoles Rifampin
Propranolol Omeprazole
Proton pump inhibitors
CYP 2D6 Antiarrhythmics Antidepressants, SSRI Not susceptible
Antidepressants Antipsychotics
Antipsychotics Cimetidine
Opioids
CYP 2E1 Alcohol Alcohol intoxication Alcohol, abuse (person sober)
CYP 3A3 Erythromycin Cimetidine
CYP 3A4 Antidepressants Antidepressants Anticonvulsants
Benzodiazepines Corticosteroids
Calcium channel blockers Grapefruit juice
Carbamazepine Imidazoles
HMG-CoA reductase Macrolides
inhibitors Omeprazole
Imidazoles
Macrolides
CYP 3A5 Lovastatin
Midazolam
Nifedipine

CYP, Cytochrome; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; NSAIDs, nonsteroidal antiinflammatory drugs; SSRI, selective serotonin reuptake inhibitor.

1. Glomerular filtration: Either the unchanged drug or its ● Alkaline urine: When the tubular urinary pH is more
metabolites are filtered through the glomeruli and concen- alkaline than the plasma, weak acids are excreted more
trated in the renal tubular fluid. This filtration process rapidly and weak bases are excreted more slowly.
depends on the amount of plasma protein binding and the ● Acid urine: When tubular urine is more acid, weak acids
glomerular filtration rate. Bound drugs cannot be filtered and are excreted more slowly and weak bases are excreted more
remain in the systemic circulation. Most drugs are managed rapidly.
by this mechanism. Extrarenal Routes. Certain drugs may be partially or com-
2. Active tubular secretion: Active secretion transports the drug pletely eliminated via routes other than the kidney by the lungs.
from the bloodstream across the renal tubular epithelial cells Gases used in general anesthesia are excreted across the lung
and into the renal tubular fluid. Glomerular filtration and tissue by a process of simple diffusion. Alcohol is also partially
active tubular secretion are relatively nonselective, and several excreted from the lungs. (One can smell alcohol on someone’s
compounds, both exogenous and endogenous (naturally breath if they have been drinking alcohol.) This fact is used
occurring), can compete for transport. when testing a driver’s breath for the presence of alcohol
3. Passive tubular diffusion: With most drugs, passive tubular (Breathalyzer).
diffusion (also termed passive reabsorption) plays a part in Biliary Excretion. Biliary excretion is the major route by
regulating the amount of drug in the tubular fluid. This which systemically absorbed drugs enter the gastrointestinal
process favors the reabsorption of nonionized, lipid-soluble tract and are eliminated in the feces. Drugs excreted in the bile
compounds. The more ionized, less lipid-soluble metabolites may also be reabsorbed from the intestines. Thus enterohepatic
have more difficulty penetrating the cell membranes of the circulation, discussed earlier, prolongs a drug’s action.
renal tubules and are likely to be retained in the tubular fluid Other. Two minor routes of elimination are in the milk and
and eliminated in the urine. This process is also influenced the sweat. The distribution of drugs in milk may be a potential
by the urinary pH, which affects the amount of ionized and source of undesirable effects for the nursing infant. Chapter 25
nonionized drug in the tubular fluid. By altering the pH of discusses dental drugs that can be given to nursing mothers.
the urine, drug excretion can be favored in cases of poisoning Saliva. Drugs can also be excreted into the saliva. After drugs
or can be inhibited when a prolongation of the drug effect is are excreted in the saliva, they are usually swallowed and their
desired. Weakly ionized acids or bases are excreted in the fate is the same as drugs ingested orally. The following drugs
following fashion: have been detected at significant levels in saliva after oral
22 PART ONE General Principles

Significant
drug remains
even after
5 half-lives

1 2 3 4 5
Large
dose
A

1 2 3 4 All gone after

Small 4 half-lives
dose
B

FIGURE 2-14
Zero-order kinetics. Large dose (A). Small dose (B). Disappearance of a drug whose metabolism is saturable: With small dose (B), the drug is metabolized
more quickly than when a large dose (A) is given. With large dose the metabolism cannot increase, so it takes a long time for the body to clear the drug.
The half-life varies with the dose of the drug.

ingestion: aspirin, phenytoin, ampicillin, diazepam, penicillin Although oral administration is considered the safest, least
VK, and phenobarbital. Present evidence suggests that most expensive, and most convenient route, the parenteral route has
drugs that are secreted in the salivary glands enter saliva by certain advantages. The injection results in fast absorption,
simple diffusion, and their passage depends mainly on the lipid which produces a rapid onset and a more predictable response
solubility of the drug. Thus a drug with high lipid solubility at than oral administration. The parenteral route is useful for
plasma and salivary pH will readily enter saliva from plasma. emergencies, unconsciousness, lack of cooperation, or nausea.
Drug levels in saliva have been studied to see if they can be Some drugs must be administered by injection to remain active.
used to monitor therapy with certain agents. For example, anti- The disadvantages of the parenteral route include the facts that
epileptic drug monitoring is essential for the rational treatment asepsis must be maintained to prevent infection, an intravas-
of epilepsy, and the measurement of these drugs in plasma is cular injection can occur by accident, administration by injec-
now routine. Assay of salivary concentrations of these drugs may tion is more painful, it is difficult to remove the drug, adverse
become a reliable method that is not invasive for predicting effects may be more pronounced, and self-medication is diffi-
plasma levels. More study is needed before salivary levels can cult. Parenteral therapy is also more dangerous and more expen-
replace measuring the blood levels of the drug. sive than oral medication. Figure 2-15 illustrates several common
Gingival Crevicular Fluid. Drugs may also be excreted in the forms of drug administration.
gingival crevicular fluid (GCF). Drugs excreted in the GCF
produce a higher level of drug in the gingival crevices, which can ♦ ORAL ROUTE
increase their usefulness in the treatment of periodontal disease. Oral—most common The oral route of administration is the
Some drugs, such as the tetracyclines, are concentrated in the and most popular route simplest way to introduce a drug into
GCF. This means that the drug level of tetracycline in the GCF of administration the body. It allows the use of many
will be several times (four or more times) higher than the blood different dose forms to obtain the
level. This property makes the systemic use of a drug more effec- desired results; tablets, capsules, and liquids are conveniently
tive within the gingival sulcus than one that is not concentrated. given. An advantage of this route is the large absorbing area
present in the small intestine. Oral administration produces a
slower onset of action than parenterally administered agents.
ROUTES OF ADMINISTRATION AND One disadvantage of this route is that stomach and intestinal
DOSE FORMS irritation may result in nausea and vomiting. Another disadvan-
tage is that certain drugs, such as insulin, are inactivated by
Routes of Administration gastrointestinal tract acidity or enzymes.
The route of administration of a drug When drugs are given orally, they are absorbed through the
Route—various ways a affects both the onset and duration of intestinal wall and then pass through the hepatic (liver) portal
drug can be
administered
response. Onset refers to the time it circulation, which can inactivate some drugs. This is termed the
takes for the drug to begin to have its first-pass effect because the drug passes through the liver first
effect. Duration is the length of a drug’s effect. The routes of before it circulates in the systemic circulation. During the drug’s
administration can be classified as enteral or parenteral. Drugs first pass through the liver, it is metabolized (amount metabo-
given by the enteral route are placed directly into the gastroin- lized varies) and the amount of drug available to produce a
testinal tract by oral or rectal administration. Parenteral admin- systemic effect is reduced. Drugs with a high first-pass effect
istration bypasses the gastrointestinal tract and includes various have a larger oral-to-parenteral dose ratio. This means that the
injection routes, inhalation, and topical administration. In prac- dose required for an equivalent effect orally is much greater than
tice, the term parenteral usually refers to an injection. the dose needed when used parenterally. Because morphine has
 Drug Action and Handling CHAPTER 2 23

a high first-pass effect, the oral dose needed to produce an most drugs are poorly and irregularly absorbed rectally, this
equivalent effect is much larger than its parenteral dose. route is not often used to achieve a systemic drug effect. In
Blood levels obtained after oral administration are less pre- addition, patient acceptance of this route is poor.
dictable than those obtained parenterally. The presence of food
in the stomach, the pathologic condition of the gastrointestinal ♦ INTRAVENOUS ROUTE
tract, the effects of gastric acidity, and passage through the Intravenous administration produces the most rapid drug
hepatic portal circulation can alter blood levels. Drug interac- response, with an almost immediate onset of action. Because the
tions can occur when two drugs are present in the stomach. The injection is made directly into the blood, the absorption phase
oral route necessitates greater patient cooperation. is bypassed. Another advantage of the intravenous route is that
it produces a more predictable response than oral administration
♦ RECTAL ROUTE because factors that affect drug absorption have been eliminated.
Drugs may be given rectally as suppositories, creams, or enemas. It is also the route of choice for an emergency situation. The
Rectal administration can be used if a patient is vomiting or disadvantages of administration include phlebitis caused by local
unconscious. This route may be used for either a local (e.g., irritation, drug irretrievability (cannot get it back), allergy, and
hemorrhoids) or a systemic (e.g., antiemetic) effect. Because side effects related to high plasma concentrations of the drug.

C
B

D E
FIGURE 2-15
Routes of drug administration. A, Oral route in the form of pills, tablets, capsules, or liquids. B, Topical route by applying on the surface of the mucosa
or skin. C, Transdermal route through a patch that continuously releases a controlled quantity of a medication through the skin. D, Inhalation route by
breathing in a gaseous substance. E, Sublingual route by placing medication under the tongue (absorption takes place through the oral mucosa).
Continued
 24 PART ONE General Principles

SUBCUTANEOUS INTRAMUSCULAR
45-degree angle 90-degree angle

Epidermis

INTRADERMAL Dermis
10- to 15-degree angle

Subcutaneous tissue

Muscle

10 degrees
F G
FIGURE 2-15, cont’d
F, Injection route. The type of drug determines how the injection is given: subcutaneous, directly under the skin; intramuscular, into a muscle; intradermal,
into the skin. G, Example of an intravenous push medication administration. (A, From Young AP, Proctor DB: Kinn’s the medical assistant: an applied
learning approach, ed 10, St. Louis, 2007, Saunders; B, from Daniel SJ, Harfst SA, Wilder RS: Mosby’s dental hygiene: concepts, cases, and competencies, ed
2, St. Louis, 2008, Mosby; C-F, from Chester GA: Modern medical assisting, Philadelphia, 1998, Saunders; G, from Clayton BD, Stock YN, Harroun RD:
Basic pharmacology for nurses, ed 14, St Louis, 2007, Mosby.)

♦ INTRAMUSCULAR ROUTE be absorbed through the mesenteric veins. This route of admin-
Absorption of drugs injected into the muscle occurs because of istration is also used for peritoneal dialysis. In this case, the
the high blood flow through skeletal muscles. Somewhat irritat- substances are passing from the body to the fluid. Large volumes
ing drugs may be tolerated if given by the intramuscular route. of fluids are slowly run into the peritoneal cavity. A waiting
This route may also be used for injection of suspensions to period of several hours allows the waste products from the body
provide a sustained effect. Injections are usually made in the to be exchanged with the fluid in the peritoneal cavity. The fluid
deltoid region or gluteal mass. is removed, and the body’s waste products are carried out in the
fluid. This process is used as a substitute for the failing kidney
♦ SUBCUTANEOUS ROUTE to manage patients with renal failure.
The subcutaneous route involves the injection of solutions or
suspensions of drugs into the subcutaneous areolar tissue to gain ♦ INHALATION ROUTE
access to the systemic circulation. If irritating solutions are Inhalation route—used The inhalation route may be used in
injected, sterile abscesses may result. Insulin is commonly for local or systemic the administration of the gaseous,
administered by this route. effects microcrystalline, liquid, or powdered
form of drugs. This route of adminis-
♦ INTRADERMAL ROUTE tration may be used for either local or systemic effects. An
Small amounts of drugs, such as local anesthetics, can be injected example of inhalers being used for their local effects are those
into the epidermis of the skin to provide local anesthesia. With used to treat asthma. After inhalation, the drug is deposited on
this type of injection, a small bump (bleb) rises as the liquid is the bronchiolar endothelium and exerts its action by producing
injected just under the skin. The tuberculosis skin test is per- bronchodilation or reducing inflammation. Inhalation of aero-
formed using the intradermal route. solized liquid in fine droplets also produces a local effect.
Today’s oral metered dose inhalers contain hydrofluorocarbons
♦ INTRATHECAL ROUTE that do not harm the ozone. These inhalers contain finely pow-
Intrathecal administration involves the injection of solutions dered drugs that are also inhaled into the lungs. One advantage
into the spinal subarachnoid space. This may be used for spinal of the use of the powdered form is that inhalation must con-
anesthesia or for the treatment of certain forms of meningitis. tinue until the visible powder is gone. General anesthetics in
the form of volatile liquids, such as isoflurane, or gases, such as
♦ INTRAPERITONEAL ROUTE nitrous oxide (N2O) and oxygen, are examples of the use of
The intraperitoneal route involves placing fluid into the perito- the inhalation route for systemic effects. This route of admin-
neal cavity, where exchange of substances can occur. A drug may istration is popular for the abuse of many drugs (smoked or
 Drug Action and Handling CHAPTER 2 25

even inhaled) because of the quick onset of action and the lack
of need for needles. Impenetrable membrane

♦ TOPICAL ROUTE Drug reservoir

Topical routes consist of application to body surfaces. Topical
applications are administered to the skin, the oral mucosa, and Membrane
even sublingually (under the tongue). The inhalation route
could even be called topical. Drugs used topically may be
Adhesive
intended to produce either local or systemic effects.
Because most drugs do not penetrate intact skin, application
to the skin is generally used for local effects. Corticosteroids are Skin
applied to inflamed or irritated skin. Intravaginal creams or FIGURE 2-16
suppositories or solutions or suspensions instilled into the eye Layers of a transdermal patch.
or ear are other ways to administer topical agents to produce
local effects.
Rarely, systemic side effects (unintended) can occur from the circulation, providing the patient with injection-free local anes-
topical administration of drugs for their local effect. One thesia. An example of this type of anesthesia is the combination
example is the administration of topical corticosteroids over a of lidocaine and prilocaine (Oraqix).
large proportion of the body, resulting in symptoms of systemic Sublingual and Buccal Routes. Two
toxicity (Cushing’s syndrome). If an occlusive dressing (com- SL—“under the tongue” ways in which drugs can be applied
for systemic effects
mercial plastic wrap or a plastic suit) is used or if the surface is topically are sublingual (SL) and buccal
abraded, inflamed, or sloughing, the chance of side effects routes. The mucous membranes of the oral cavity provide a
increases dramatically. In the oral cavity, interruptions in the convenient absorbing surface for the systemic administration of
mucous membranes or mucosal inflammation increase the like- drugs, which can be placed under the tongue (sublingual) or on
lihood of a systemic effect. Local anesthetics sprayed into the other areas of the oral mucosa (buccal pouch). Absorption of
mouth may be adsorbed and produce a blood level equivalent many drugs into the systemic circulation occurs rapidly. An
to that produced by intravenous administration. example of this effect is the fast onset of action of nitroglycerin
Examples of drugs applied topically for a systemic effect sublingual tablets to treat acute anginal pain. Drugs that are
include transdermal patches and sublingual spray or tablet susceptible to degradation by the gastrointestinal tract and even
administration. Drugs that often produce allergic reactions by the liver, such as testosterone, are safely administered as
should not be administered topically because sensitization occurs sublingual tablets because they avoid both the first-pass effect
more readily than when used orally. and gastrointestinal acid and enzymes.
Subgingival Strips and Gels. A dental-specific topical applica-
tion involves the placement of drug-impregnated strips or gels ♦ OTHER ROUTES
subgingivally. Systemic effects are minimized because small Drugs, such as progestins (Norplant), can be implanted under
doses can be used when drugs are administered via this route. the skin to release a drug over a prolonged duration (5 years).
Doxycycline gel (Atridox) and a chlorhexidine-containing chip Pumps that deliver drugs intravenously can be implanted in the
(PerioChip) are examples of agents administered into the gingi- body. When insulin pumps are used, they can be programmed
val crevice. externally using a calculator-like keyboard.
Transdermal Patch. Transdermal drug delivery systems (drug
patches) are designed to provide continuous controlled release of Dose Forms
medication through a semipermeable membrane over a given Table 2-2 lists the usual dose forms. The most commonly used
period after application of drug to the intact skin. This eliminates dose forms in dentistry are the tablet and capsule given orally.
the need for repeated oral dosing. Examples of patches on the Liquid solutions or suspensions are often prescribed for children.
market include scopolamine (Transderm-Scop), nitroglycerin Sometimes drugs are given in solution or suspension when a
(Transderm-Nitro, Nitrodisc, Nitro-Dur), clonidine (Catapres- liquid form is desired. Liquid forms of a drug are often used for
TTS), estrogens (Estraderm, Climara), fentanyl (Duragesic), children. For injection, the drug may be in solution, such as a
and nicotine transdermal patches (NicoDerm, Nicobid). local anesthetic, or it may be in a suspension, such as procaine
Most patches consist of several layers. Beginning with the penicillin G, when a longer duration of action is desired. Mouth-
skin, the layers are as follows: adhesive (to stick to the skin), washes containing alcohol are also recommended by dental
membrane (to control the rate of drug release), drug reservoir health care workers. Elixirs (contain alcohol) and syrups (contain
(where the drug is stored), and a backing that is impenetrable sugar) are children’s dose forms.
to the drug (to keep the drug from evaporating into the air)
(Figure 2-16). Before use, the protective backing must be
removed. The most common problems with transdermal patches FACTORS THAT ALTER DRUG EFFECTS
are local irritation, erythema, and edema. These problems can
be minimized by rotating the location of the patch. Patches are When a drug is administered, the following factors may influ-
designed to be changed daily, every few days, or weekly, depend- ence or modify the drug’s effect:
ing on the drug. • Patient compliance: Through either lack of understanding or
Topical Anesthesia. Topical anesthetics are applied directly to lack of motivation, patients often take medication incorrectly
the mucous membranes and rapidly absorbed into the systemic or not at all. Sometimes this may result from faulty com-
26 PART ONE General Principles

TABLE 2-2 DOSAGE FORMS

Form Definition Example

Tablet Molded or compressed medicinal substance with inert binder included Acetaminophen tablet
to make a hard mass
Capsule Gelatin shell that disintegrates in water to administer solids or liquids Tetracycline capsule
Pill Globular or ovoid dose form made by incorporating medicinal agents Ferrous carbonate pill
with other binders to make a plastic mass; obsolete
Lozenge, troche Flavored dose form designed to be held in the mouth to dissolve or Cough drop
disintegrate slowly
Suppository Single-dose medication in waxy or fatty conical or ovoid shape that Glycerin suppository
liberates active ingredient after insertion into the rectum or vagina
for local or systemic effects
Solution One-phase system of two or more chemical components Saline water
Elixir Sweetened hydroalcoholic solution containing flavoring materials Acetaminophen and codeine elixir;
diphenhydramine
Syrup Nearly saturated aqueous solution of sugar Dextromethorphan syrup
Tincture Alcoholic or hydroalcoholic solution of drugs Iodine tincture
Spirit Solution of volatile substance in alcohol Aromatic ammonia spirit
Lotion Liquid suspension that can be protective Hand lotion
Emulsion Preparation of two immiscible liquids, usually water and oil, one Liquid petrolatum emulsion
dispersed as small globules in the other
Suspension Dispersion containing finely divided insoluble material suspended in Amoxicillin suspension
a liquid medium
Cream Emulsions that contain an oily and aqueous phase; external phase Hydrocortisone cream
aqueous
Ointment Semisolid preparation for external use that is a consistency that can Hydrocortisone ointment, A+D
be applied by rubbing; external phase oily ointment
Transdermal patch A permeable polymer membrane backed with a drug reservoir Nitroglycerin, scopolamine, fentanyl,
designed to provide controlled release of medication over a given nicotine
period after application to intact skin
Aerosol spray Solution of volatile liquids with a propellant that delivers drugs to Albuterol inhaler, foot spray
area
Intradermal implant Small pellets implanted under skin that allow drugs to be released Norplant
slowly
Micropump An implanted pump that delivers drug via a needle Insulin pump

munication, inadequate patient education, or the patient’s ance develops, a normal sensitivity to the drug’s effect may
health belief system. Thus poor patient compliance can be be restored by ceasing administration of the drug. Tachyphy-
an important factor in a therapeutic failure. laxis is the very rapid development of tolerance, often within
• Psychologic factors: The attitude of the prescriber and the hours.
dental staff can affect the efficacy of the drug prescribed. A • Pathologic state: Diseased patients may respond to the admin-
placebo is a dose form that looks like the active agent but istration of medication differently than other patients. For
contains no active ingredients (the “sugar pill”). The magni- example, patients with hyperthyroidism are extremely sensi-
tude of the placebo effect depends on the patient’s percep- tive to the toxic effects of epinephrine. Hepatic or renal
tion, and there is large individual variation. Health care disease influences the metabolism and excretion of drugs,
providers can maximize the drug’s effect to achieve an potentially leading to an increased duration of drug action.
improved therapeutic result by talking up the drug. This may With repeated doses in diseased patients, the serum level of
account for the popularity of herbs and plants. a drug may become toxic.
• Tolerance: A patient may exhibit tolerance to many drugs, • Time of administration: The time a drug is administered,
including the sedative-hypnotics and the opioids. Drug toler- especially in relation to meals, alters the response to that
ance is defined as the need for an increasingly larger dose of drug. Certain drugs with a sedative action are best adminis-
the drug to obtain the same effects as the original dose or the tered at bedtime to minimize the sedation experienced by the
decreased effect produced after repeated administration of a patient.
given dose of the drug. When a patient becomes tolerant to • Route of administration: The effect of the route of administra-
one drug, tolerance to other drugs with similar pharmaco- tion on the onset and duration of action of a drug was dis-
logic actions occurs. This is termed cross-tolerance. If toler- cussed previously.
 Drug Action and Handling CHAPTER 2 27

• Sex: The sex of the patient can alter a drug’s effect. Women CLINICAL SKILLS ASSESSMENT
may be more sensitive than men to certain drugs, perhaps
because of their smaller size or their hormones. Pregnancy 1. Define and differentiate between the potency and efficacy of a drug.
alters the effect of certain drugs. Women of child-bearing age 2. Describe the dose-response curve using the terms ED50 (effective
should avoid teratogenic drugs, and the oral health care pro- dose) and LD50 (lethal dose).
vider should determine whether the patient is pregnant
3. Define the term pharmacokinetics. Name the four categories
before administering any agent.
involved.
• Genetic variation: Many differences in patient response to
drugs have been associated with variations in ability to 4. Define the major routes of drug administration, including the
metabolize certain drugs. This difference may account for the following:
fact that certain populations have a higher incidence of a. Oral
adverse effects to some drugs—a genetic predisposition. b. Intravenous
• Drug interactions: A drug’s effect may be modified by previ- c. Inhalation
ous or concomitant administration of another drug. There d. Topical
are many mechanisms by which drug interactions may
modify a patient’s treatment. 5. State the dose forms most often used in dentistry.
• Age and weight: The dose of a drug administered to children 6. Explain the influence of pH on the dissociation characteristics of
should be reduced from the adult dose. Age or weight has weak acids and weak bases.
been suggested as a method of calculating a child’s dose. 7. Explain each of the steps involved in oral absorption, including the
Because of the great variability of weight in relation to age, following:
the child’s weight should be used to determine the child’s a. Disruption
dose. Because a child is not just a small adult, the manufac- b. Disintegration
turer’s recommendations for children’s dosing would be best.
c. Dispersion
Older adults may respond differently to drugs than younger
patients. Whether this is solely because of changes in renal d. Dissolution
or liver function or whether being elderly patients predisposes 8. Define the t 1 2 , or half-life, of a drug and state its significance.
this sensitivity is controversial. 9. Though an elderly patient appears healthy and weighs 110 pounds,
• Environment: The environment contains many substances what are your concerns regarding drug distribution?
that may affect the action of drugs. Smoking induces enzymes, 10. Define the following terms:
so higher doses of benzodiazepines are needed to produce the a. Agonist
same effect as compared to nonsmokers. Some chemical con-
taminants, such as pesticides or solvents, can have an effect b. Competitive antagonist
on a drug’s action. c. Physiologic antagonist
• Other: The action of drugs can be altered by the patient- d. Isomers
provider interaction. If the patient “believes” in the substance e. Chirals
or process (drug/herb//incantation) being used, the patient’s 11. What are the different ways that drugs can be metabolized?
opinion will enhance the drug’s effect. The attitude of both
12. State the major route of drug excretion.
the patient and the provider can alter the physiology of the
body. These actions may account for the positive effect of 13. Explain how metabolism can be altered by an effect on liver
many mental exercises (e.g., meditation). microsomal enzymes.

DENTAL HYGIENE CONSIDERATIONS Please visit http://evolve.elsevier.com/Haveles/pharmacology for review

questions and additional practice and reference materials.
1. Various factors can affect drug absorption. The dental hygienist
should be aware of them.
2. The most common factors affecting drug absorption include patient
compliance or adherence to medication therapy. Lack of health insur-
ance, misunderstanding of the reason for the medication, or a lack
of faith in the health care system can lead to noncompliance.
3. Patient age and pathologic state can affect drug metabolism. As a
result, lower doses and slower dose increases may be necessary. All
of this can be attained by knowing the patient’s age and during a
health history.
4. Lower protein stores can lead to less medication being stored in
protein, which puts the patient at risk for toxicity. This is most
common in elderly patients, who by virtue of their age have lower
protein stores.
5. The dental hygienist should also understand drug potency so that
the appropriate medication and dose are prescribed.
CHAPTER OUTLINE
3 Adverse Reactions
LEARNING OBJECTIVES
DEFINITION AND CLASSIFICATIONS 1. Define an adverse drug reaction and name five categories of reaction.
CLINICAL MANIFESTATIONS OF ADVERSE 2. Discuss the risk-to-benefit ratio of the use of a drug for therapeutic effect and its
REACTIONS potential adverse reactions.
Exaggerated Effect on Target Tissues 3. Explain how the toxic effects of drugs are evaluated.
Effect on Nontarget Tissues
Effect on Fetal Development (Teratogenic
Effect)
Local Effect
Drug Interactions Although drugs may act on biologic systems to accomplish a desired effect, they
Hypersensitivity (Allergic Reaction) lack absolute specificity in that they can act on many different organs or tissues.
Idiosyncrasy This lack of specificity is the reason for undesirable or adverse drug reactions.
Interference with Natural Defense No drug is free from producing some adverse effects in a certain number of
Mechanisms patients. It is estimated that between 5% and 10% of the patients hospitalized
TOXICOLOGIC EVALUATION OF DRUGS annually in the United States are admitted because of adverse reactions to drugs.
While hospitalized, 10% to 20% of patients experience adverse reactions caused
by drugs.
The dental health care worker is in a good position to observe any adverse reac-
tions or undesirable effects caused by drugs administered in the dental office.
Adverse reactions to drugs prescribed by the patient’s physician can be identified
in the health history. The dental health care worker should question the patient
about any potential oral manifestations of drugs. For example, if the patient is
taking phenytoin (Dilantin), questions about enlargement of the patient’s gums
should be explored. Because many drugs can produce xerostomia, complaints of
dry mouth should direct the dental health care worker to examine the patient’s
medications. Knowledge of the typical adverse drug reactions can help dental office
personnel identify, minimize, or prevent these types of reactions. Because of the
rapport between a patient and the dental health care worker, the patient will often
reveal important facts about the health history or ask questions concerning medica-
tions prescribed. The dental health care worker must know the terms used to
describe adverse reactions to discuss a drug’s undesirable effect accurately with
other health professionals. For example, allergy refers to a specific type of reaction
to a drug but does not include a complaint of excessive gas, or flatulence.

DEFINITIONS AND CLASSIFICATIONS

Unfortunately, every drug has more than one action. The clinically desirable
actions are termed therapeutic effects, and the undesirable reactions are termed
adverse effects. Dividing a drug’s effects into two categories is artificial because
it depends on the indication for which the drug is being used. For example, when
an antihistamine used to relieve hay fever causes drowsiness, the drowsiness can be
considered an adverse effect. However, if the antihistamine were being used to
induce sleep (over-the-counter [OTC] sleep aid), drowsiness would be considered
the therapeutic effect.
An adverse drug reaction is a response to a drug that is not desired, is potentially
harmful, and occurs at usual therapeutic doses. It may be an exaggeration of the
desired response, an expected but undesired response, an allergic reaction, a cyto-
toxic reaction, or an effect on the fetus. Often, adverse drug reactions are divided
into the following categories:

28
 Adverse Reactions CHAPTER 3 29

• Toxic reaction: A toxic reaction is an extension of the phar- types of adverse reactions and notes whether they are predictable
macologic effect resulting from a drug’s effect on the target or dose dependent.
organs. In this instance, the amount of the desired effect is
excessive.
• Side effect: A side effect is a dose-related reaction that is not CLINICAL MANIFESTATIONS OF
part of the desired therapeutic outcome. It occurs when a ADVERSE REACTIONS
drug acts on nontarget organs to produce undesirable effects.
The terms side effect and adverse reaction often are used inter- Before a drug is used, there must be an assessment of its risk
changeably. The upset stomach produced by ibuprofen is an against its benefits (risk-to-benefit ratio). This means that the
adverse reaction when ibuprofen is given to manage pain. beneficial effect of the drug must be weighed against its potential
• Idiosyncratic reaction: An idiosyncratic reaction is a geneti- for adverse reactions. For example, one would compare the
cally related abnormal drug response. Certain populations, drug’s therapeutic effect (e.g., controlling seizures) with its
because of their genetic constitution, are more susceptible to potential to cause an adverse reaction (e.g., birth defects). In a
certain adverse reactions to specific drugs. Eskimos metabo- real-life example, one should compare the therapeutic effect of
lize certain drugs faster than other populations; therefore a certain drugs to produce weight loss to their potential for the
larger dose of those drugs would be needed in that population serious adverse reactions of primary pulmonary hypertension
(e.g., isoniazid). (which is fatal in 50% of patients) or cardiac valvular damage.
• Drug allergy: A drug allergy is an immunologic response to a
drug resulting in a reaction such as a rash or anaphylaxis. Exaggerated Effect on Target Tissues
This response accounts for less than 5% of all adverse reac- An exaggerated effect on its target tissue or organ is considered
tions. Unlike other adverse reactions, allergic reactions are an extension of the therapeutic effect caused by the overreaction
neither predictable nor dose related. of a sensitive patient or by the use of a dose that is too large.
• Interference with natural defense mechanisms: Certain drugs, For example, a patient may experience exaggerated hypoglyce-
such as adrenocorticosteroids, can reduce the body’s ability mia when given a therapeutic dose of an oral hypoglycemic
to fight infection. Drugs that interfere with the body’s agent for the treatment of diabetes. The patient’s blood sugar
defenses cause a patient to get infections more easily and have may fall too low, either because of an unusual sensitivity to the
more trouble fighting them. drug or because the dose administered was too high for that
The importance of distinguishing between different types of patient. Occasionally, this type of adverse reaction may result
adverse effects can be seen using aspirin as an example. Aspirin from liver or kidney disease. Because the disease interferes with
can produce adverse reactions such as gastric upset or pain. At the drug’s metabolism or excretion, the drug’s action may be
higher doses, aspirin can predictably produce toxicity such as enhanced or prolonged.
tinnitus and hyperthermia (elevated temperature). Another type
of reaction to aspirin is allergic, often involving a rash or diffi- Effect on Nontarget Tissues
culty in breathing (asthma-like reaction). These differences are The effect on nontarget organs or tissues is caused by the non-
significant and become pertinent when discussing an adverse therapeutic action of the drug. These reactions can occur at usual
reaction with another health professional. Patients who experi- doses, but they appear more often at higher doses. For example,
ence allergic reactions to a medication should not receive that aspirin may produce gastric upset in usual therapeutic doses, but
medication or similar medications. Side effects such as gastroin- with higher doses salicylism, characterized by tinnitus, distur-
testinal upset, although bothersome, are not reasons to avoid bances in the acid-base balance, and confusion, can result. Toxic
prescribing a medication. It can be given. However, if the gas- reactions can affect many parts of the body. A reduction in the
trointestinal upset is too much for the patient, another drug dose of a drug usually reduces these adverse reactions.
should be considered. It is important to describe in the patient’s
chart the patient’s “problem” in enough detail so that side effects Effect on Fetal Development (Teratogenic Effect)
can be separated from allergic reactions. Figure 3-1 describes the The word teratogenic comes from the Greek prefix terato-,
meaning “monster,” and the suffix -genic, meaning “producing,”
or “producing a malformed fetus.” The relationship between
Adverse drugs and congenital abnormalities has been recognized since
reaction the middle of the twentieth century. In 1961, thalidomide, an
OTC drug marketed in Europe, was found to produce phoco-
melia (short arms and legs) in the exposed fetus. In some cases,
Side Toxic Allergic only one dose of this drug produced the effect. This incident
effect reaction reaction
reinforced the fact that more studies were needed to determine
• Predictable • Predictable • Not predictable the effect of drugs on pregnant women. For new drugs, there
• Dose-related • Dose-related • Not dose-related are many more studies on animals and their reproductive capac-
ity before the drugs are placed on the market. Although more
• Acts on • Acts on target information is now available about the safety of drugs in preg-
nontarget organs organs
• Extensions of
nant women, sufficient information is still lacking.
pharmacologic The Food and Drug Administration (FDA) has attempted to
effects address the concerns about the lack of adequate knowledge of
FIGURE 3-1 drugs by defining five FDA pregnancy categories: A, B, C, D,
Classification of common adverse reactions. and X, ranked from least risky to most risky. (See Table 25-2
Other documents randomly have
different content
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102 HANDBOOK FOR THE STUDY OF THE BIBLE were

already engaged in the religious worship. Saul had eighty-five priests
from Nobe killed at one time (I Kings xxii. 18). Even if indi viduals
here and there, following the custom of olden times, offered sacrifice
elsewhere in their capacity as heads of families or even as private
persons, this might be still tolerated as an ancient custom. Strict
centralization was possible, however, and its necessity appeared
more and more after the Temple was built, for the isolated
sanctuaries in the country had become for the most part the homes
of superstition, im morality and idolatry. In support of his theory,
Wellhausen relies: (1) upon the Book of Judges, in the greater part
of which (iii.-xvi.) there is no mention of a class of persons engaged
in religious observances; (2) upon the same book, which in an
appendix (xvii., xviii.) speaks of a priestly function in a way that does
not agree with the Pentateuch; (3) upon II Kings viii. 18, where we
read that David's sons were priests, which, according to the
Pentateuch, they could not have been permitted to be. In reply it
may be stated ( 1 ) that other passages of the Old Testa ment,
belonging to a later period, also contain no mention of a priestly
class, because there is no reason why such mention should be made
in them. For instance, in the first and second sections of the Psalms
the words priest and Levite do not once occur ; and yet, according
to modern critics, the whole psalter belongs to the period after the
Captivity, and Wellhausen even regards it as doubtful whether any
psalms of an earlier date exist. Is it possible to argue from the
silence of these two sections that there was no legally established
priesthood even after the Captiv ity? No! Therefore it is not
permissible to prove from the above-men tioned chapters in the
Book of Judges that in the time of the Judges the official priesthood
organized by Moses did not exist. (2) That even in that remote
period the tribe of Levi was officially connected with public worship
appears as a recognized fact in Judges xvii. and xviii. — the very
chapters upon which Wellhausen relies. Michas, an Ephraimite,
caused a costly metal statue of Yahweh to be made, and appointed
one of his own sons to be priest of this statue and of the little
temple erected to contain it. That this was an abuse, aris ing
probably out of superstition, is suggested by the words, "In those
days there was no king in Israel, but every one did that which
seemed right to himself." Then a Levite named Jonathan came into
the dis trict from Bethlehem.1 Michas persuaded him to remain with
him as 1 As Bethlehem was not a Levite town, it has been
suggested, as this place is mentioned as Jonathan's home, that he
belonged to the tribe of Juda, and that, in the time of the Judges,
the word Levite did not mean a man belonging to the tribe of Levi,
but one of the wandering people, who, being descended from
Egyptian priests, practiced all manner of arts (fortune-telling, etc.),
like our modern gypsies. Their ancestors are supposed to have left
Egypt with Moses, and in course of time they succeeded in securing
plenty of money on the ground of their priestly powers. The text of
the Book of Judges, however, contains a clear sattement that
Jonathan was descended from Moses, and consequently from Levi,
Jacob's son. "Jonathan, the son of Gerson, the son of Moses" (xviii.
30). His residence in Bethlehem had nothing to do with
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HOLY PEKSONS 103 priest, in place of his son, in return for

payment, food and clothing, and the Levite consented. Michas felt
quite happy at having " a priest of the race of the Levites " with him.
Afterwards men belonging to the tribe of Dan, in the course of their
wanderings to their new settlement, came to Michas, and violently
deprived him of his statue and all con nected with it, including the
Levite, and erected a sanctuary for them selves in their new home
farther north. Thenceforth the Levite was their priest. That the tribe
of Levi " was completely destroyed at the first attempt to conquer
Chanaan " (Volck, p. 44) cannot be inferred from Genesis xlix. 5-7,
as the tribe of Simeon, mentioned in the same verses, continued to
exist. (3) While the sons of David are called Kohanim in II Kings viii.,
this word cannot here bear its ordinary meaning of " priest." In
verses 16-18 the men are named who held posts of honor at court;
Joab was commander of the army, Josaphat was recorder, Sadok
and Achiinelech were priests, Saraias was the scribe, Banaias was
set over the body guard and " David's sons were Kohanim." As the
priests are mentioned in verse 17, the word Kohanim must receive
another interpretation. The Septuagint renders it av\apxai. Probably
the king's sons held some high offices about the court, that we no
longer know. The word is generally translated " princes." By
designating the king's sons Kohanim, as if they were priests, the
writer suggests that they lived with the king as his confidants in the
same way as the priests dwelt with God in the sanctuary. The king
represents God's majesty. (Cf. I Chron. xviii. 17, where David's sons
are called the first at the king's hand. APPENDIX THE SYNEDRIUM
AND THE JEWISH SECTS The Synedrium or Sanhedrin, the Council
of the Jews, was, during the closing period of the Jews' existence as
a State, the chief religious and political body, hav ing authority to
decide on the most important matters in the national life, and
claiming also the right to pronounce sentences of life and death. Our
Saviour and the Apostles, Saint Stephen also and Saint Paul, were all
brought before this tribunal, which was formed on the lines laid
down by Moses (Ex. xviii. 25; Num. xi. 16) of seventy of the chief
priests, elders and doctors of the law, and met under the presidency
of the high priest, generally in one of the side buildings of the
Temple, but occasionally in the high priest's house. Jewish Sects 1.
Mention is often made in the New Testament of Scribes, doctors and
teachers of the law (ypa^arels, vo/MKot, vopodiSdcrKaXoi) ; these
perhis descent; possibly his mother came thence, as in xvii. 7 we
read that he was " of Bethlehem Juda (rrUTT nnSEto) of the kindred
thereof, and he was a Levite and dwelt there '
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104 HANDBOOK FOE THE STUDY OF THE BIBLE sons were

not connected with the Temple worship in these capacities, but
belonged for the most part to the sect of the Pharisees, the
upholders of the claims and doctrines of orthodox Judaism. Their
name comes from parasch, to separate, and means " those set
apart," those who by their piety and wisdom are conspicuous above
the mass of the people. Their reputation was so great that even the
priests, who formed the hereditary aristocracy of the nation, found it
expedient to join this sect, in order to retain their prestige, and the
Council or Synedrium consisted chiefly of Pharisees. They seem to
have originated before the time of the Machabees, as they were
already strong and influential under Jonathan Machabaeus in 144
B.C. (Jos., Ant., XIII, v. 9). Besides the Holy Scrip tures they
reverenced a particular tradition, which they ascribed to Moses, as
the source of the Law; this developed later into the Talmud. The sect
was at first worthy of high esteem, but it gradually degenerated, and
at the time of our Lord the Pharisees appear as sanctimonious per
sons, full of uncharitableness, pride and avarice. There were,
however, noble exceptions, e.g. Nicodemus (John iii.) and Gamaliel
(Acts v. 34). Inasmuch as they were the expounders and teachers of
the Law, they re ceived the honorable title of Rabbi = master ( ^3"\
from 3*1 , much, great = magister ) . At the time of Christ there
were two famous teachers with a numer ous following, — Shammai
and Hillel. The former represented the strict est school of thought,
especially with regard to divorce; the latter ad hered to milder
doctrines and practice. 2. In direct contrast to the stern Judaism of
the Pharisees were the easy-going views of the party of the
Sadducees, which had penetrated into Palestine from the west after
the Grseco-Persian wars. It is impos sible not to recognize a
connection between the Sadducees and the Epi curean philosophy.
In origin and name this sect is generally derived from a certain
Sadok, a disciple of Antigonus of Socho ( died 264 B. c. ) . According
to another account they called themselves Zaddikim — honest
people. It is, however, most probable that they declared themselves
to be Sadokides, i. e. members of the high priest's party, for, from
the time of David, the high priesthood remained hereditary in the
family of Saclok. They accepted Holy Scripture, at least the
Pentateuch, but no tradi tions. They believed in God, but not in
angels ; declared the soul to be material and mortal, and
consequently rejected the doctrines of the resurrection of the body
and of future rewards or punishments; more over they denied the
action of Divine Providence. This sect consisted chiefly of rich and
powerful persons, for which reason it became influen tial in the
Synedrium, and secured the high priesthood (Acts xxiii. 6, etc.), but
it never won much esteem among the nation as a whole (Jos. Fl.,
Bell Jud., II, viii. 14; Ant., XVIII, i. 2). 3. The Essenes are not
mentioned in the Bible, but Josephus and Philo describe them as
ascetics, who apparently had added to Judaism the tenets of
heathen and especially of the Pythagorean philosophy. Various
explanations are given of their name; it may be derived from an
Aramaic word chase, pious, pi. chasen, chasajja. They formed a kind
of religious order governed by definite rules and divided into four
classes. They conceived of the Deity as the purest light, and the sun
they re garded as His symbol. They honored Moses and his law ;
believed in the
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HOLY PERSONS 105 immortality of the soul; observed the

Sabbath very strictly but re jected the Jewish sacrificial worship.
Their morality was based on love of God and man, and on self-
control. For love of God they sought to lead pure lives and always to
speak the truth ; their love of man showed itself in good will,
charitable deeds and community of property. They exercised self-
control by despising wealth, honors and pleasures, and many
refrained from marriage. They lived partly in settlements of their
own near the Dead Sea, partly in the midst of other Jews in towns
and villages, supporting themselves by the work of their hands or by
agri culture. Their number did not exceed four thousand. 4. A fourth,
and probably not numerous sect, was that of the Herodians, who are
mentioned a few times in the New Testament. They were adherents
of the Herodian royal family, and were therefore inclined to favor the
Romans, and were hostile to the Jewish religion.
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THIBD SECTION SACEED EITUAL I. SACRIFICES 18. WHAT

COULD BE OFFERED AS a rule it was required of an Israelite coming
to the Temple, that he should not appear empty handed. The gifts
which might be offered up in honor of God were partly animal, partly
vegetable, and also salt. Only clean, domestic animals could be
sacrificed, viz. (1) oxen (bullocks, cows and calves); (2) rams,
sheep, lambs, goats and kids; (3) doves (turtledoves and young
pigeons = bene jona). The latter were sometimes offered by the
poor, who could not afford to give more costly creatures, but
sometimes they served for the less important sacrifices.1 The
animals for sacrifice had to be with out blemish; they might not be
mutilated or deformed, blind, or affected with sores or wounds; they
must not walk crooked, etc. (Lev. xxii. 19-25). Moreover, they must
have reached a certain age; the young must be at least eight days
old; sheep and goats were generally sacrificed when a year old, and
bullocks when three years old. The following vegetable products
might be offered : (a) grain, including ears of grain, flour, bread and
cakes variously prepared; (&) garden produce, fruit, especially
grapes, wine and olive oil; (c) incense. Salt was used at all sacrifices
both bloody and unbloody. The incense and even the blood were
salted. 1 Leviticus xii. 6: A woman after childbirth had to offer a
lamb and a pigeon, or, in case of poverty, two pigeons. Leviticus xv.
14 and 29: Certain defilements required to be cleansed by the
sacrifice of pigeons. Numbers vi. 10: A Nazarite who had broken his
vow had to sacrifice two pigeons.
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SACRED RITUAL 107 The chief sacrifices always consisted

of animals. A man doing sacri fice may give what he possesses. The
Israelites were originally a pas toral people. (Gen. xlvi. 34: "We are
shepherds . . . both we and our fathers.") It was only later that they
practiced agriculture also, and hence the sacrifice of animals was
always the most important, especially as the sense of guilt finds its
serious expression in shedding the blood of the sacrifice. This is
implied also by God's satisfaction at Abel's sacri fice, whose faith is
extolled in Heb. xi. 4. Abel in spirit beheld the future Redeemer, but
Cain did not recognize Him. Honey and leaven were expressly
forbidden.1 19. EITUAL OP SACRIFICE Animal sacrifices were
performed in the following way: The animal was brought into the
court of the Tabernacle or Temple, for it was forbidden, under pain
of death, to offer sacrifices else where. It was tied up to a ring
fastened in the earth, and the person offering it laid his hands on its
head. (This was omitted in the case of the Paschal lamb, and of
pigeons.) The meaning of this ceremony was that the sin of the
offerer passed over to the victim, who was to die in place of the
sinful man.2 Accord ing to the Rabbis (Otho, Lex Rabbin.}, a
confession of sin accom panied the laying on of hands, the words
being as follows : " I have sinned, have acted amiss, have been
rebellious, especially have I committed3 . . . But I return to Thee full
of repentance. May this [i. e. the offering of the victim] be my
expiation! " Cf. Numbers v. 6, 7. 1 Leviticus ii. 11 : " Neither shall
any leaven or honey be burnt in the sacrifice to the Lord." The
reason is probably that honey by its sweet ness symbolized sinful
sensual enjoyments, and leaven as the means of fermentation
typified that inherited element in human nature which al ways keeps
it in a state of wild passion, viz. sensual concupiscence, which
originated in sin and leads to sin. Sin, and all connected with it, had
to be excluded from the altar of sacrifice, which was undefiled, a
place dedicated to God, raised above the sin-stained earth. 2
Leviticus i. 4 : " He shall put his hand upon the head of the victim,
and it shall be acceptable and help to its expiation." 8 The
confession of sins answers a need of human nature and has at all
times appeared as accompanying true penance. Adam had to
acknowl edge his guilt and did so, but Cain refused (Gen. iii. 11, iv.
9). David says of himself, " Because I was silent my pain consumed
me." He rightly perceived that sacrifice alone was not enough. Si
voluisses sacrificium, dedissem utique (Ps. 1. 18). Happily for him
God sent tho prophet Nathan, before whom he acknowledged his
guilt (II Kings xii.
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108 HANDBOOK FOR THE STUDY OF THE BIBLE Thus

laden with the sin of the offerer, the victim was slain on the north
side of the altar, generally by the person who offered it, but it might
be done by the priest (II Chron. xxix. 24). The priest caught the
blood in a vessel, and, according to the kind of sacrifice intended, he
sprinkled some of it either on the side of the altar, or on the horns,
or on the altar of incense, or even towards the Kapporeth in the Holy
of Holies. The rest of the blood was poured out on the ground near
the altar of holocausts (Lev. iv. 7). Then the victim was skinned and
cut to pieces. Either all the flesh was laid upon the altar and burnt,
or only some of the fat was consumed by the altar fire, and the rest
of the flesh was cooked and eaten by the priests, or used by the
offerer of the sacrifice for a sacrificial feast, or burnt outside the city
or encampment. When pigeons were offered, the priest killed them
by breaking their necks, not by cutting off the heads (Lev. i. 15; v.
8).1 Apparently a cut was then made in one place, and the blood
was allowed to drip on the side of the altar. The wings were slightly
torn and then the birds were thrown into the fire on the altar.
Vegetable offerings were seldom made alone, but generally in
conjunction with bloody sacrifices. The procedure was as follows: (1)
If the sacrifice belonged to the class of burnt offerings, the priest
took only a small portion of the flour, cakes, etc., and burnt it with
incense on the altar. The rest belonged to the priest, but had to be
eaten unleavened in the Court, after being prepared for food. If the
offerer were him self a priest, the whole was burnt. If the sacrifice
was a peace offering, one cake out of all that were brought was
taken for the Lord and given to the priest; the rest was used by the
offerer for a sacrificial feast. 13). The Baptism of John was
connected with confession of sins (Matt. iii. 6). It cannot, however,
be maintained that under the old dispensa tion a special confession
of sins was a conditio sine qua non of forgive ness. Special
confession was ordained first by Christ (John xx. 23). 1 The Hebrew
pyD means to break off; Septuagint, airoKvL^iv ; Vul gate,
retorquere ad collum, ad pennulas. It seems that the neck was not
wrung, but violently bent backwards, so that the throat was
separated inside from the body, remaining united to it only by the
skin.
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SACRED RITUAL 109 20. VARIETIES OF SACRIFICES

According to the objects brought as offerings, sacrifices were divided
into (1) bloody, or slain offerings, and (2) unbloody, or meat and
drink offerings. According to the reasons for offering the sacrifices
they were distinguished as (1) holocausts, or burnt offerings; (2)
peace offerings; (3) sin offerings; (4) trespass offerings. There can
be no doubt that the offerings have a symbolic meaning. In the New
Testament we have but one sacrifice, which, however, contains all
the various sacrifices of the Old Testament, and they were merely
foreshadowings of it. The holy Sacrifice of the Mass is a holocaust,
— the whole victim, the Lamb, who hung in burning agony on the
Cross, is offered up ; it is a peace offering — • a sacrificial feast
takes place, at which Christians appear as God's guests; it is a sin
offering, for our sins constrain us to offer this holy sacrifice in order
to appease the wrath of God; it is a trespass offering, — making
reparation for the wrong done to God, and obtaining reconciliation
with one's neighbor, hence the kiss of peace. It is at the same time a
bloody and an unbloody sacrifice. (a) Bloody Sacrifices 21.
HOLOCAUSTS, OR BURNT OFFERINGS (Leviticus i. 3-17, vi. 8-13) 1.
Name. The Hebrew name for this kind of sacrifice is old = that which
rises, i. e. that which rises to heaven from the altar as a fragrance
pleasing to God. Still more expressive are the Greek names,
oXotcavrcofjia or oXo/caur&xrts, selected by the Septuagint with
reference to the Hebrew word Jcalil,1 or okoKdva-Tov, which Philo
uses. All these signify that the whole victim was burnt. The Vulgate
has adopted the word holocaustum from the Greek. The words "
burnt offering " are less expressive. 2. Ritual. Only male animals
could be used for these sacri fices; in fact, in all animal sacrifices
males are preferred, as being larger and stronger. Every kind of
animal that could be sacrificed at all might be offered. The victims
were brought 1 Deuteronomy xiii. 17, xxxiii. 10; I Kings vii. 9; Ps. li.
22.
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110 HANDBOOK FOE THE STUDY OP THE BIBLE in, hands

were laid upon them, and they were slain, as in all sacrifices. The
blood was sprinkled round about the altar. The skins belonged to the
priest, who did not as a rule take them off himself, this being done
by the offerer. The animal was cut to pieces, its entrails taken out
and purified, and then the whole was burnt together on the altar of
holocausts in the Court. Only the sinew of the thigh (the so-called
sciatic nerve) was removed. The reason for this is stated in Genesis
xxxii. 32, "therefore the children of Israel unto this day eat not the
sinew that shrank in Jacob's thigh, because He [God] touched the
sinew of his thigh and it shrank." Just as men are not accustomed to
eat flesh without bread and drink, so with every holocaust was
connected an unbloody addition, a meat and drink offering. The
materials and quan tities of these offerings varied in accordance with
the animal sacrificed. There was no unbloody sacrifice connected
with an offering of doves. The holocaust was the most usual form of
sacrifice. Twice daily, morning and evening, a lamb was sacrificed in
accordance with the law; and in addition similar offerings were
prescribed on various occasions, such as the purification of women
after childbirth, of those who had re covered from leprosy, etc.
There were also voluntary holocausts (Ps. 1. 20), and these might
be offered even by Gentiles. According to Philo, the Emperor
Augustus had a bull and two lambs offered for himself daily as
holocausts in the Temple at Jerusalem. 22. PEACE OFFERINGS (Lev.
iii. 1-17, vii. 11-21, vii. 28-36) 1. The second kind of bloody sacrifice
is known by various names; the commonest is schelem, or sebach
sclielamim = peace offering x = elpqmtcTJ sc. Ovcria (Sept.); the
others are sebach hatto da = thank or praise offering, sebach neder
= votive offering, sebach nedaba = freewill offering. We may
assume that "peace offering" is a general name, and that the 1 The
name seems to have been chosen by way of contrast to the sin and
trespass offerings, which presupposed a sort of separation between
God and man, whereas this sacrifice has a more cheerful character,
and man appears as God's guest at the sacrificial meals.
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SACRED RITUAL 111 three other expressions designate

particular kinds of peace offerings. 2. Every animal regarded as fit
for sacrifice could be used as a peace offering; it was not necessary
that it should be a male, and for freewill offerings of this kind
animals might be taken that had some imperfection in them. 3. The
ritual began like that of the holocaust. The blood was sprinkled all
round the altar, but from this point the pro cedure differed. Only
four, or, in the case of sheep, five parts of the victim were placed on
the altar, viz. : (1) the fatty tissues enclosing the entrails; (2) the fat
on the entrails; (3) the two kidneys; (4) the liver, and (in sheep) (5)
the fat tail ('alja). The breast (chase) and the right leg (sclwq) 1
were separated from the rest of the flesh, and laid by the priest on
the hands of the man offering the sacrifice. Then the priest laid his
own hands under those of the offerer, and made a movement
forwards (towards the altar and the sanctuary) and back again, —
this ceremony was called " waving " (tenupha), — then another
movement from below upwards, and then down again, which was
called "heaving" (teruma). After this the pieces of fat were burnt on
the altar, and a sacrificial meal followed. The breast (wave offering)
and the leg (heave offering) 2 were eaten by the priests, and their
wives and children could share the food. The people who offered the
sacrifice consumed the rest on the holy spot, being in a condition of
legal purity. If the sacrifice was a thank offering, the meal was
bound to take place on the day that the victim was killed; if it was a
free-will or a votive offering, the flesh remaining over from that day
might be consumed on the following morning, but whatever was still
1 The right hind leg must be meant, for scfioq means runner, and is
used of the thigh of a man's legj below the loins. The Septuagint
read ing is jSpaxt'wj' and the Vulgate armus = shoulder. Cf. Knobel
on Leviti cus vii. 32, 33; Scholz, Altertumer, II, 175. 2 Chase
hattenupha, schoq hatteruma. It seems that sometimes only the
breast was " waved " and only the leg " heaved," but sometimes the
two movements were connected. Exodus xxix. 26, 27 : " take the
breast . . . and elevating it thou shalt sanctify it to the Lord . . . and
thou shalt sanctify both the consecrated breast and the shoulder."
The cere mony signified that the portions of the victim should be
devoted to the sanctuary and lifted up to the altar.
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112 HANDBOOK FOR THE STUDY OF THE BIBLE left had to

be burnt.1 An unbloody offering always accom panied sacrifices of
this kind also. 23. SIN OFFERINGS (Leviticus iv. 1, etc., vi. 24-30) 1.
The third kind of sacrifice bears the same name as the Bm =
c7iattath, and the very name shows that in this case the victim was
offered as an atonement for definite transgressions. These were not,
however, intentional, as every intentional vio lation of the law was
punishable with death; but they were rather unintentional faults and
certain conditions of uncleanness, which had some resemblance to
or connection with sin, such as leprosy, issue of blood. Moreover, at
certain times it was required that sin offerings should be made on
behalf of the whole people, for it was taken for granted that many
un noticed violations of the law must have occurred. Before our
Lord's coming there was no certain outward means of get ting rid of
sin, for the so-called " sacraments of the Old Covenant " (cir
cumcision, consecration of priests and Levites, the Paschal lamb and
the various sacrifices and purifications) could not of themselves
remove sin; they secured only righteousness in the eyes of the law.
Hence Saint Paul calls them ( Gal. iv. 9 ) " weak and needy
elements." The means of removing sin were the inward acts of faith
in a future Redeemer (Heb. xi. ) which found expression in prayer
and in sacrifice, accompanied with an acknowledgment of guilt. Cf.
p. 107. 2. The occasions when a sin offering had to be made, can be
divided into (a) permanent occasions recurring at certain fixed times,
and (&) unforeseen occasions. a. The fixed times when sin offerings
had to be made were (a) the Pasch, (6) Pentecost, (c) feast of
Tabernacles, (d) Day of Atonement, (e) the New Year's festival, (/)
the New Moons, i. e. the first day of each month. At each of these
seasons a sin offering was made for the whole people, the victim
being always a he-goat. 2 The Agape of the early Christians had
probably no connection with these sacrificial feasts of the Old
Testament, but was an imitation of the Paschal supper, eaten by our
Lord and His Apostles before the institu tion of the holy Eucharist.
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SACRED RITUAL 113 b. The unforeseen occasions were

much more numerous. As chief of them may be mentioned: (a) the
purification of a woman after childbirth; (&) the purification of a
leper or of one suffering from any discharge; (c) the purification of a
woman with an issue of blood. In these cases doves were gen erally
offered, (d) If the high priest accidentally violated any precept in the
law, he sacrificed a young bullock, free from all blemish, (e) If the
whole community had transgressed in the same way, the same
offering had to be made. (/) In such case the head of a tribe or
family offered a he-goat, (g) Any indi vidual Israelite atoned for such
a transgression by offering a she-goat. 3. With regard to the ritual
observed, sin offerings were divided into two classes, interior and
exterior. The former were sacrifices in which the blood of the victim
was carried inside the Temple or Tabernacle. The latter were
sacrifices in which the blood only was taken to the altar of
holocausts. The flesh of the victims in the former class of sin
offerings was burnt outside the city or the camp. The flesh of the
victims in the second class was eaten by the priests, with the
exception of the pieces of fat, which were burnt on the altar. Interior
sin offer ings were the more important; such was, for instance, the
sacrifice on the great Day of Atonement.1 24. TRESPASS OFFERINGS
(Leviticus v. 15, etc.; Vulgate, also vi. 2, etc.) 1. The Hebrew name
for this kind of offering is 'ascliam = guilt. The ritual for it was the
same as that for the sin offering, and therefore many archaeologists
identify the two, and regard 'ascliam only as a particular kind of
chattaih. Those who 1 Cf. on this subject Heb. xiii. 10-15, which is
explained as follows: It was certainly no mere accident that Christ
was crucified outside the city. He died as a sin offering. The Jews
were forbidden to eat the flesh of the more important sin offerings;
it had to be burnt outside the city. Therefore the author of this
epistle calls upon the Jewish Christians thus : " Let us go forth to
him without the camp, bearing his reproach " — let us separate
ourselves from the Jews, let us share in His sacrifice, even if those
who believe not despise.
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114 HANDBOOK FOE THE STUDY OF THE BIBLE identify

them reckon only three bloody sacrifices. There are,, however.,
differences in the cause for these sacrifices and in their object, (a)
The trespass offering was always made for an individual, whilst the
sin offering might also be on behalf of the whole people, (b) The
chief difference lies in the fact that a trespass offering was always
connected with some in jury committed to the rights of God Himself
or of a man's neighbors; whereas, no such thing was presupposed in
the case of a sin offering. The damage done had to be made good, a
fifth of the value being paid in addition, and a sacrifice offered. 2. In
the Law of Moses several cases are mentioned in which a trespass
offering was required. The chief are: (a) If a man keep back or
diminish the duties payable to the priests. (b) If he deny the receipt
of a deposit, or that he has found or damaged anything, (c) If he
unintentionally violate the law to the detriment of his neighbor, and
later recognize his fault. In every case, as with the sin offerings, it is
assumed that the fault proceeded, not from malice, but from
inattention and carelessness. 3. The victim was a ram, sometimes a
lamb. 4. Ritual. The blood was sprinkled on the altar of holo causts;
the fat was burnt on the altar and the rest of the flesh was eaten by
the priests within the sacred precincts. Thus the ritual is the same as
that of the exterior sin offerings. The rationalistic theory of sacrifice
denies the Mosaic origin of the various kinds of offering and seeks to
explain the bloody sacrifice by the act of killing. " At all times people
have shrunk from attacking nature. One of the most grievous attacks
possible is killing, i. e. suppressing, de stroying the life of an animal
created by God. As, however, men desired to slaughter animals, and
were obliged to do so, they tried to calm their fears at least by
restoring to God, i. e. by sacrificing, the blood, in which is the life. As
often as they prepared flesh food they gave a befitting share to the
Deity. If the feast was particularly solemn^ or if many were invited
to share it, the Deity received a whole animal. In this way arose first
the kind of sacrifice called later peace offerings, but originally
referred to as victims or offerings (I Kings iii. 14) and subsequently
the holocausts (Deut. xii. 11) developed. In very early times
sacrifices of atonement (sin and trespass offerings) were unknown.
They arose first out of the consciousness of guilt felt by the people
in exile — hence they are mentioned for the first time in the Priests'
Code."
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SACRED BITUAL 115 All these are arbitrary assumptions.

The act of slaughtering was not accompanied by sacrifice (Gen. xviii.
7).1 The so-called " Priests' Code " dates, as we have shown on p.
46, etc., not from the time of the Captivity, but from a far earlier
period. And quite apart from these considerations, the custom of
offering human sacrifices, once prevailing over the whole world, is
opposed to this theory. Human sacrifices point to a primeval
consciousness of guilt felt by the whole human race, and they
certainly belonged to the earliest period, since they were of universal
occurrence. On the subject of consuming blood, see page 131, Laws
concerning Food. 25. SPECIAL KINDS OF BLOODY SACRIFICES The
Sacrifice of the Red Cow (Num. xix.) This peculiar sacrifice was not
made either in the Tabernacle or in the Temple, but outside the
camp or town. A young full-grown cow, red in color and without
blemish,, that had never carried the yoke, was chosen and given
over to the priest. He had to lead her outside the camp or town, in
later times always to the Mount of Olives, and kill her there. Then
dipping his finger in her blood, he sprinkled it seven times towards
the Tabernacle or Temple. Then the cow's body was laid on a pile of
wood, which was set on fire, cedar wood hyssop and scarlet wood
being laid upon it. The cow had to be reduced to ashes, which were
sifted and then used in the preparation of water for purification. If
any one had incurred one of the legal defilements, he had to be
separated from the people, and could only be purified again after
the lapse of a definite time ; the puri fication consisted of being
sprinkled with water containing some of the red cow's ashes. Not
only persons, but vessels, houses and tents, were sprinkled with this
water and restored to their normal condition,2 if they had become
legally unclean 3 (cf. Heb. ix. 13). 1 Abraham caused beasts to be
slain as soon as the three strangers arrived. 2 A bunch of hyssop,
fastened by a red thread to a stick of cedar wood, was used for
sprinkling persons or things. 3 The red cow seems to represent the
people of Israel, that through their repeated unfaithfulness (red
symbolizes guilt) had deserved death, i. e. destruction, but through
faith in the future Messias and by doing penance might hope for
salvation.
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116 HANDBOOK FOR THE STUDY OF THE BIBLE Sacrifice

for Lepers (Leviticus xiv.) When a leper recovered from his disease,
he had to show himself to a priest, and if the latter judged him to be
cured, he had to bring two living birds, which must be "clean," not
birds of prey that eat carrion, and also a bunch of hyssop. One of
the birds was killed over living water (i. e. water from a spring or a
river) in such a way that its blood dripped into the water, into which
the bunch of hyssop was dipped, and the healed leper sprinkled
seven times. The other bird was dipped in the same water and then
allowed to fly away; this symbolized the recovery of health. Then the
man who was healed washed his clothes, cut his hair and bathed his
body, and thenceforth he was clean, and might come into the camp
or city, though he must not occupy his tent or house for another
week. On the eighth day he had to bring a threefold sacrifice,1 and
was then on a level with all the other Israelites. The significance of
the ceremony concerning the two birds was prob ably this: The leper
was to acknowledge that as a sinner he had de served death, which
is " the wages of sin," but he was preserved through the offering of
living creatures, which the justice of God accepted as types of a
better sacrifice. The Nazirite Sacrifice (Num. vi. 1-21) Every Israelite
coulo^by a vow, consecrate himself exclusively to God, either for a
definite period or for life. Persons bound by such a vow were called
Nazirites, i. e. set apart (YU from *ITJ, 1 Namely, a trespass offering
(a ram and one log of oil), a sin offering (a female lamb) and a burnt
offering (a ram and three issaron of fine flour ) . In case of poverty
two pigeons might be used for the burnt and sin offerings, and only
one issaron of flour was required, but no reduc tion could be made
in the trespass offering, which was required because the leper,
during his illness, had been unable to render any service in the
sanctuary or to his neighbors; a sin offering was necessary, because
he had been prevented from keeping the law in every point, and a
burnt offering was his homage paid to God.
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