Table Of ContentR e v i e w e r s
Susan Beggs, RN, MSN Esther Salinas, RN, MSN, MS Ed
Associate Professor, Nursing Faculty Associate Professor, Nursing
Austin Community College Vocational Nursing and Registered Nursing Departments
Austin, Texas Del Mar College
Corpus Christi, Texas
MaryAnn Cosgarea, RN, BSN, BA
Nurse Administrator, Practical Nursing Julie A. Slack, RN, MSN
Health Coordinator, Adult Education Nursing Faculty
Portage Lakes Career Center Mohave Community College
W. Howard Nicol School of Practical Nursing Colorado City, Arizona
Green, Ohio
Bonnie J. Smith, RN, BSN
Nancy T. Hatfield, RN, BSN, MA Coordinator, Practical Nurse Program
Director/Department Chairperson Sikeston Public Schools—Health Occupations
Health Occupations/Practical Nursing Hayti, Missouri
Albuquerque Public Schools
Career Enrichment Center
Ginger White, RN, ADN
Albuquerque, New Mexico
Instructor, Vocational Nursing Program
Wharton County Junior College
Debra Menshouse, RN, BSN Wharton, Texas
Nursing Faculty
Ashland Technical College
Ashland, Kentucky
iiiiii
P r e f a c e
T
he seventh edition of Introductory Clinical SPECIAL FEATURES
(cid:2)
Pharmacology reflects the ever-changing science of
pharmacology and the nurse’s responsibilities in admin-
A number of features have proven useful for students in
istering pharmacologic agents. All information has been
their study of basic pharmacology. The following fea-
updated and revised according to the latest available
tures appear in the seventh edition:
information to prepare nurses to meet the challenges of
safely administering medications. The text prepares the • Key Terms—lists the important words defined in
nurse to meet the challenges of the 21st century by pro- the chapter
moting critical thinking and problem solving when • Nursing Process—used as a framework in most
administering medications. chapters for presenting care of the patient as it
relates to the drug and the drug regimen.
Preadministration and Ongoing Assessments are
PURPOSE included in the assessment phase of the nursing
(cid:2)
process. These assessments are divided in order to
highlight the important assessments to perform
This text is designed to provide students with a clear,
before administering a specific drug and those
concise introduction to pharmacology. The basic expla-
important during the entire time the drug is being
nations presented in this text are notintended to suggest
administering. In the implementation phase of the
that pharmacology is an easy subject. Drug therapy is
nursing process, most chapters contain sections
one of the most important and complicated treatment
Promoting an Optimal Response to Therapy and
modalities in modern health care. Because of its impor-
Monitoring and Managing Adverse Reactions.
tance and complexity and the frequent additions and
These sections provide invaluable information
changes in the field of pharmacology, it is imperative
needed to ensure that the drug is properly admin-
that health care professionals constantly review and
istered and nursing interventions to use when cer-
update their knowledge.
tain adverse reactions occur.
• Nursing Alerts—short segments that identify
urgent nursing considerations in the management
CURRENT DRUG INFORMATION
(cid:2) of the patient receiving a specific drug or drug cat-
egory
The student and practitioner should remember that • Gerontologic Alerts—short segments to alert the
information about drugs, such as dosages and new forms, nurse about specific problems for which the older
is constantly changing. Likewise, there may be new drugs adult is at increased risk. As the number of the
on the market that were not approved by the Federal older adults in our society increases, it becomes
Drug Administration (FDA) at the time of publication of imperative that nurses recognize the necessity of
this text. The reader may find that certain drugs or drug specialized care.
dosages available when this textbook was published may • Contraindications, Precautions, and Inter-
no longer be available. For the most current drug infor- actions—of the most commonly used drugs in the
mation and dosages, the practitioner is advised to consult category under discussion. While space prevents
references such as the most current Physician’s Desk every contraindication, precaution, and interac-
Reference or Facts and Comparison and the package tion to be listed, the more common ones are
inserts that accompany most drugs. If reliable references included in the text. Pregnancy categories are
are not available, the hospital pharmacist or physician identified for many drugs discussed within the
should be contacted for information concerning a specific chapter.
drug, including dosage, adverse reactions, contraindica- • Home Health Care Checklists—highlight spe-
tions, precautions, interactions, or administration. cific issues that the patient or family may
vv
vi Preface
encounter while undergoing drug therapy in the NEW FEATURES
(cid:2)
home setting. As more and more patients are cared
for outside the hospital, it becomes increasingly
important for the nurse to know what information • Four-Color Illustrations—the text is beautifully
the patient or family needs to obtain an optimal illustrated throughout with new four-color illus-
response the drug regimen. trations. Each illustration highlights and explains
• Patient and Family Teaching Checklists— an important pharmacologic concept, technique,
highlight teaching points relating to specific phar- or idea.
macologic techniques and most-know information • New Chapters—new chapters are included, such
for the patient undergoing drug therapy. This as Chapter 33, Cholinesterase Inhibitors, and
empowers the family to participate knowledgeably Chapter 18, Nonsteroidal Anti-Inflammatory
and accurately in the patient’s drug regimen. Drugs. Several of the chapters in previous editions
• Summary Drug Tables—contain commonly have been divided. For example, the chapter on
used drugs representative of the class of drugs dis- antiviral and antifungal drugs was divided into
cussed in the chapter. Important drug information two chapters: Chapter 14, Antiviral Drugs, and
is provided, including the generic name, pronunci- Chapter 15, Antifungal Drugs.
ation guide for generic names, trade names, • Drug Lists—replacing the chapter outline is a list-
adverse reactions, and dosage ranges. In these ing of the classifications and drugs discussed in the
tables, generic names are followed by trade names; chapter. This new format allows the student to
when a drug is available under several trade quickly identify the important drugs discussed in
names, several of the available trade names are the chapter.
given. The more common or serious adverse reac- • Herbal or Health Supplement Alerts—provide
tions associated with the drug are listed in the important information on common herbs and sup-
table’s adverse reaction section. It should be noted plements not regulated under the auspices of the
that any patient may exhibit adverse reactions not Federal Drug Administration. Appendix Bgives a
listed in this text. Because of this possibility, the listing of select herbs with examples of their com-
nurse, when administering any drug, should con- mon and scientific name(s). While not all of the
sider any sign or symptom as a possible adverse common or scientific names are given, the more
reaction until the cause of the problem is deter- common names (both common and scientific) are
mined by the primary health care provider. included. With more and more individuals using
The adverse reactions are followed by the dose herbs as a part of their health care regimen, it is
ranges for the drug. In most cases, the adult dose critical that the nurse be aware of the more com-
rangesare given in these tables because space does mon herbs currently in use. The nurse must con-
not permit the inclusion of all possible dosages for sult appropriate sources when patients indicate
various types of disorders. Likewise, space limita- they are using herbs as part of their health care
tion does not permit an inclusion of pediatric dose regimen.
ranges due to the complexity of determining the • Review Questions—several questions, reviewing
pediatric dose of many drugs. Many drugs given to important information covered in the chapter, can
children are determined on the basis of body be found at the end of each chapter. The questions
weight or body surface area and have a variety of are written in PN-NCLEX format and provide the
dosage scheduling. When drugs are given to the student an opportunity to answer questions specif-
pediatric patient, the practitioner is encouraged to ically about the drugs covered in the chapter. Space
consult references that give complete and exten- does not permit more questions of this type, but
sive pediatric dosages. provides the student practice in answering ques-
• Critical Thinking Exercises—realistic patient tions concerning medication therapy and adminis-
care situations that help the student apply the tration of drugs.
material contained in the chapter by exploring • Medication Dosage Problems—Calculation of
options and making clinical judgments related to medication dosage is an important aspect of med-
the administration of drugs ication administration. Chapter 3 reviews the
• Abbreviations—important pharmacologic and mathematics involved in dosage calculation and
general medical abbreviations the nurse needs to formulas used in the calculate medication
know when caring for the patient undergoing dosages. To ensure the student’s understanding
drug therapy are spelled out in the back of the and application of this type of problem, two or
text. more medication dosage problems are included at
• Glossary—key terms and other drug-related the end of most chapters dealing with specific
terms are listed and defined in the back of the text medications discussed in the chapter. This provides
Preface vii
the student an opportunity for immediate applica- Unit V has three chapters concerning drugs that
tion in medication administration. As an added affect the respiratory system. The first chapter in this
benefit, several current medication labels are used unit discusses antihistamines and decongestants, the
throughout the text to help the student learn to second chapter in the unit covers bronchodilators and
read these labels and solve medication dosage antiasthma drugs, and the last chapter of the unit deals
problems using the information found on these with antitussives, mucolytics, and expectorants.
labels. Unit VI covers drugs that affect the cardiovascular
• Drug and Health Care Information Sources on system. This unit is divided into five chapters: car-
the World Wide Web—The inside back cover diotonics and miscellaneous inotropic drugs, antiar-
provides a listing of websites dealing with phar- rhythmic drugs, antianginal and peripheral dilating
macology and medication administration. The stu- drugs, antihypertensives, and antihyperlipidemics.
dent can use these sites as valuable resources to Unit VII consists of two chapters dealing with drugs
identify new drugs and important new informa- that affect the hematological system: anticoagulants and
tion on current drugs. thrombolytic drugs, and agents used in the treatment of
anemia.
Unit VIII has been expanded to cover drugs that
affect both the gastrointestinal and urinary systems.
ORGANIZATION
(cid:2) The unit consists of three chapters: uretics, urinary
anti-infectives and miscellaneous urinary drugs, and
The text contains 58 chapters, which are divided into 11 drugs that affect the gastrointestinal system.
units. Organization of the text in this manner allows the Unit IX discusses drugs that affect the endocrine
student to move about the text when these general areas system and consists of five chapters: antidiabetic drugs,
are covered in the curriculum. While pharmacologic pituitary and andrenocortical hormones, thyroid and
agents are presented in specific units, a disease may be antithyroid drugs, male and female hormones, and
treated with more than one type of drug, which may drugs acting on the uterus.
require consulting one or more units. Unit X discusses drugs that affect the immune sys-
Unit I presents a foundation for the study of phar- tem. The unit consists of two chapters: immunologic
macology and covers general principles of pharmacol- agents and antineoplastic drugs.
ogy, the administration of drugs, a review of arithmetic Unit XI consists of three chapters that discusses
and calculation of drug dosages, a discussion of the types of drugs not previously discussed or that are not
nursing process as applicable to pharmacology, and a members of a particular class or group. Chapters in this
review of the teaching learning process and general unit include topical drugs used in the treatment of skin
areas of consideration when educating the patient and disorders, otic and ophthalmic preparations, and fluids
family. and electrolytes.
Unit II contains 11 chapters that present the anti-
infective drugs, grouped according to classification.
These shorter chapters allow for more inclusive cover-
CHAPTER CONTENT
age of the different types of anti-infectives and the (cid:2)
appropriate nursing considerations for each classifica-
tion. Each chapter opens with learning objectives and a list-
Unit III includes four chapters covering the various ing of key terms used and defined in the chapter. Less
types of drugs used to manage pain: the nonnarcotic commonly used medical terms are also defined within
analgesics (Salicylates, Nonsalicylates, and Nonste- the chapter and may be found in the Glossary. Chapters
roidal Anti-Inflammatory Drugs), the narcotic anal- 1 to 5 provide introductory information concerning gen-
gesics, and the narcotic antagonists. eral principals of pharmacology, medication administra-
Unit IV has been expanded to 15 chapters covering tion, a review of arithmetic and calculation of drug
the many classifications of drugs that affect the nervous dosages, the nursing process, and patient and family
system and the neuromuscular system. These chapters teaching. Each chapter ends with critical thinking ques-
include the following types of drugs: drugs that affect tions and several chapter review questions.
the musculoskeletal system, adrenergic drugs, adrener- The remaining chapters discuss specific drug classifi-
gic blocking drugs, cholinergic drugs, cholinergic block- cations and contain a common format. In addition to
ing drugs, sedatives and hypnotics, central nervous sys- the learning objectives and key terms, the remaining
tem stimulants, anticonvulsants, antiparkinsonism chapters contain a table indicating the drug classifica-
drugs, antianxiety drugs, antidepressant drugs, antipsy- tions and drugs discussed in the chapter. The body of
chotic drugs, cholinesterase inhibitors, antiemetic and each chapter contains the actions, uses, adverse reac-
antivertigo drugs, and anesthetic drugs. tions, contraindications, precautions and interactions of
viii Preface
the class or type of drug being discussed, followed by a • Critical Thinking Questions—each chapter
section devoted to the nursing process. These chapters includes critical thinking questions that provide
end with critical thinking questions, several chapter the student with the challenge of applying chapter
review questions, and two or more medication dosage content to specific clinical situations
problems. To promote easy retrieval of information, • Review Questions—several PN-NCLEX review
each area is identified by a large type heading. questions are found at the end of each chapter
• Medication Dosage Problems—when applicable,
• Actions—a basic explanation of how the drug the chapter contains real medication dosage pre-
accomplishes its intended activity scriptions and the medication available for dis-
• Uses—the more common uses of the drug class or pensing. The student solves medication dosage
type are provided. No unlabeled or experimental problems using the information provided. Several
uses of drugs are given in the text (unless specifi- current medication labels are used to help the stu-
cally identified as an unlabeled use) because these dent learn to read these labels and solve medica-
uses are not approved by the FDA. Students tion dosage problems using the information found AQ1
should be reminded that, under certain circum- on these labels.
stances, some physicians may prescribe drugs for a
condition not approved by the FDA or may pre-
scribe an experimental drug. APPENDICES
(cid:2)
When discussing the use of antibiotics, this
text does not list specific microorganisms.
Seven appendices containing important pharmacologic
Microorganisms can become resistant to antibiotic
information are located at the back of the text.
drugs very rapidly. Because of this, the author feels
Appendix A contains a MedWatch form, which is
that listing specific microorganisms or types of
used by health care professionals for voluntary report-
infections for an antibiotic may be misleading to
ing of adverse reactions and problems with the drug
the user of the text. Instead, when antibiotics are
product. Is also contains advice about voluntary report-
needed, the author recommends consulting cul-
ing. This form is a part of the FDA medical products
ture and sensitivity studies to indicate which
reporting program.
antibiotic has the most potential for controlling
Appendix B is a table of Select Herbs and Natural
the infection.
Products Used for Medicinal Purposes.
• Adverse Reactions—the most common adverse
Appendix Ccontains a United States Pharmacopeia
drug reactions are listed under this heading
(USP) medication errors reporting program form,
• Contraindications—contraindications for admin-
which is used by health care professionals for sharing
istration of the drug or drugs discussed in the
information of medication errors to prevent them from
chapter
occuring again. Also included is text explaining medica-
• Precautions—precautions to take before, during,
tion error and the USP.
or after administration
Appendix D provides metric–apothecary equivalents
• Interactions—more common interactions between
and conversions. This guide covers liquid measurements;
the drug(s) discussed in the chapter and other
weights; Celsius and Fahrenheit temperatures; and a com-
drugs
parative scale of measures, weights, and temperatures.
• Nursing Process—with a few exceptions, the nurs-
Appendix E contains two body surface area nomo-
ing process is used in every chapter of the test and
grams—one for infants and young children and one for
geared specifically to the administration of the
older children and adults.
drugs discussed in the chapter. The assessment
Appendix F is a Vaccine Adverse Event Reporting
phase is divided into two distinct parts to include a
Form.
preadministration and ongoing assessment. This
Appendix G contains answers to the review and
assists the reader in determining what assessments
dosage calculation exercises appearing at the end of the
to perform before administration of specific drugs of
chapters.
drug categories and what important assessments to
Appendix Hlists examples of combination drugs.
perform during the entire time the drug is adminis-
tered. Nursing diagnoses related to the administra-
tion of the drug are highlighted in a nursing diag-
TEACHING/LEARNING PACKAGE
noses checklist. Under “Implementation,” three sec- (cid:2)
tions are included when applicable: “Promoting an
Optimal Response to Therapy,” “Monitoring and • Student Study Guide—the Student Study Guide to
Managing Adverse Reactions,” and “Educating the Accompany Introductory Clinical Pharmacology,
Patient and Family.” 7th Edition, correlates with the textbook chapter
Preface ix
by chapter. For each chapter in the textbook, the ACKNOWLEDGMENTS
(cid:2)
Study Guidecontains a corresponding chapter and
includes three or more of the following compo-
I wish to thank everyone involved in the creation of this
nents: a crossword puzzle featuring important
7th Edition of Introductory Clinical Pharmacology. A
terms of the chapter, multiple-choice questions,
special thanks to Lisa Stead, Acquisitions Editor, for her
short-answer questions, word search puzzles, and
guidance and support during the preparation of the
critical thinking exercises derived from the text-
manuscript. My heartfelt gratitude goes to Joe Morita,
book. Multiple-choice question have been written
Managing Editor, for his support and editorial assis-
using the same format as currently used in the
tance with manuscript preparation and development.
NCLEX-PN examinations. The Study Guide also
His input was invaluable. A special thank-you to Brenda
features activities designed around specific drug-
Shaffer, RPh, for her assistance with the Summary
related websites. These activities promote use of
Drug Tables and to Tom Robinson for his assistance in
the World Wide Web as an important learning tool
obtaining drug labels. My gratitude to all those who
in the study and practice of nursing pharmacology.
worked in any way in the design, production, and
• Instructor’s Manual—the Instructor’s Manual to
preparation of this book: Debra Schiff, Senior
Accompany Introductory Clinical Pharmacology,
Production Editor; Helen Ewan, Senior Production
7th Edition, contains a variety of testing items as
Manager; and Brett MacNaughton, Art Director.
well as tips for classroom teaching. Multiple-
Although not a part of the professional development
choice questions and critical thinking exercises are
of this textbook, I wish to express my love and gratitude
provided. Answers are given for the multiple-
to those who made my contribution to this book possi-
choice questions. No answers are supplied for the
ble, my family. Their unwavering support and encour-
critical thinking exercises, to encourage the stu-
agement saw me through many difficult days, nights,
dents to use their creative abilities rather than be
and weekends of manuscript preparation.
confined to a predetermined answer. Also
included is a computer disk contain PN-NCLEX-
style test items in multiple-choice format. Sally Roach, MSN, RN, CHN
C o n t e n t s
UNIT I FOUNDATIONS OF CLINICAL UNIT IV DRUGS THAT AFFECT
PHARMACOLOGY 1 THE NEUROMUSCULAR
SYSTEM 185
1 General Principles of Pharmacology 1
2 The Administration of Drugs 15 21 Drugs That Affect the Musculoskeletal
System 185
3 Review of Arithmetic and Calculation of
Drug Dosages 29 22 Adrenergic Drugs 199
4 The Nursing Process 46 23 Adrenergic Blocking Drugs 210
5 Patient and Family Teaching 52 24 Cholinergic Drugs 221
25 Cholinergic Blocking Drugs 229
26 Sedatives and Hypnotics 230
27 Central Nervous System Stimulants 246
UNIT II ANTI-INFECTIVES 59 28 Anticonvulsants 253
29 Antiparkinsonism Drugs 264
6 Sulfonamides 59
30 Antianxiety Drugs 274
7 Penicillins 65
31 Antidepressant Drugs 281
8 Cephalosporins and Related
Antibiotics 75 32 Antipsychotic Drugs 294
9 Tetracyclines, Macrolides, and 33 Cholinesterase Inhibitors 304
Lincosamides 83 34 Antiemetic and Antivertigo Drugs 310
10 Fluroquinolones and Aminoglycosides 91 35 Anesthetic Drugs 317
11 Miscellaneous Anti-infectives 100
12 Antitubercular Drugs 108 UNIT V DRUGS THAT AFFECT THE
13 Leprostatic Drugs 116 RESPIRATORY SYSTEM 325
14 Antiviral Drugs 119
36 Antihistamines and Decongestants 325
15 Antifungal Drugs 129
37 Bronchodilators and Antiasthma Drugs 333
16 Antiparasitic Drugs 138
38 Antitussives, Mucolytics, Expectorants 350
UNIT VI DRUGS THAT AFFECT
UNIT III DRUGS USED TO MANAGE THE CARDIOVASCULAR
PAIN 150 SYSTEM 357
17 Nonnarcotic Analgesics: Salicylates and 39 Cardiotonics and Miscellaneous Inotropic
Nonsalicylates 150 Drugs 357
18 Nonnarcotic Analgesics: Nonsteroidal 40 Antiarrhythmic Drugs 367
Anti-inflammatory Drugs 159 41 Antianginal and Peripheral Dilating Drugs 380
19 Narcotic Analgesics 167 42 Antihypertensives 393
20 Narcotic Antagonists 180 43 Antihyperlipidemic Drugs 407
xi
xii Contents
UNIT VII DRUGS THAT AFFECT UNIT X DRUGS THAT AFFECT
THE HEMATOLOGICAL THE IMMUNE SYSTEM 567
SYSTEM 417
54 Immunologic Agents 567
44 Anticoagulant and Thrombolytic 55 Antineoplastic Drugs 583
Drugs 417
45 Agents Used in the Treatment
of Anemia 433 UNIT XI DRUGS THAT AFFECT
OTHER BODY SYSTEMS 603
56 Topical Drugs Used in the Treatment of Skin
Disorders 603
UNIT VIII DRUGS THAT AFFECT
57 Otic and Ophthalmic Preparations 616
THE GASTROINTESTINAL
AND URINARY SYSTEMS 443 58 Fluids and Electrolytes 633
46 Diuretics 443 Abbreviations 647
47 Urinary Anti-infectives and Miscellaneous Glossary 651
Urinary Drugs 456
Appendices:
48 Drugs That Affect the Gastrointestinal
A: MedWatch 657
System 466
B: Select Herbs and Natural Products Used for
Medicinal Purposes 659
C: USP Medication Errors Reporting
Program 662
UNIT IX DRUGS THAT AFFECT
THE ENDOCRINE D: Metric—Apothecary Equivalents and
SYSTEM 487 Conversions 664
E: Body Surface Area Nomograms 667
49 Antidiabetic Drugs 487
F: Vaccine Adverse Event Reporting
50 Pituitary and Adrenocortical System 669
Hormones 510
G: Multiple Choice Answers 671
51 Thyroid and Antithyroid Drugs 530
H: Combination Drugs 679
52 Male and Female Hormones 538
53 Drugs Acting on the Uterus 559 Index 685
UNIT I • Foundations of Clinical Pharmacology
1
c h a p t e r
General Principles of Pharmacology
Key Terms Chapter Objectives
additive drug reaction macromolecule On completion of this chapter, the student will:
adverse reaction nonprescription drugs (cid:2) Define pharmacology.
agonist pharmaceutic (cid:2) Discuss drug development in the United States.
allergic reaction pharmacodynamics (cid:2) Identify the different names assigned to drugs.
anaphylactic shock pharmacogenetic (cid:2) Distinguish between prescription drugs, nonprescription drugs, and
angioedema disorder controlled substances.
antagonist pharmacokinetics (cid:2) Discuss the laws governing the manufacture, distribution, and sale of
antibodies pharmacology drugs.
antigen physical dependency (cid:2) Discuss the various types of drug reactions produced in the body.
biotransformation polypharmacy (cid:2) Identify factors that influence drug action.
botanical medicine prescription drugs (cid:2) Define drug tolerance, cumulative drug effect, and drug idiosyncrasy.
controlled substances psychological (cid:2) Discuss the types of drug interactions that may be seen with drug
cumulative drug effect dependency administration.
drug idiosyncrasy receptor (cid:2) Discuss the nursing implications associated with drug actions, interac-
drug tolerance synergism tions, and effects.
half-life teratogen (cid:2) Discuss the use of botanical medicines.
hypersensitivity toxic
P
harmacologyis the study of drugs and their action on phase (Fig. 1-1). During the pre-FDA phase, a manufac-
living organisms. A sound knowledge of basic pharmaco- turer discovers a drug that looks promising. In vitro test-
logic principles is essential if the nurse is to safely admin- ing (testing in an artificial environment, such as a test
ister medications and to monitor patients who receive tube) using animal and human cells is done. This testing
these medications. This chapter gives a basic overview of is followed by studies in live animals. The manufacturer
pharmacologic principles that the nurse must understand then makes application to the FDA for Investigational
when administering medications. The chapter also dis- New Drug (IND) status.
cusses drug development, federal legislation affecting the With IND status, clinical testing of the new drug
dispensing and use of drugs, and the use of botanical begins. Clinical testing involves three phases, with each
medicines as they relate to pharmacology. phase involving a larger number of people. All effects,
both pharmacologic and biologic, are noted. Phase I lasts
4 to 6 weeks and involves 20 to 100 individuals who are
DRUG DEVELOPMENT
(cid:2) either “normal” volunteers or individuals in the intended
treatment population. If Phase I studies are successful,
Drug development is a long and arduous process, taking the testing moves to Phase II, and if those results are pos-
anywhere from 7 to 12 years, and sometimes even itive, to Phase III. Each successive phase has a larger sub-
longer. The United States Food and Drug ject population. Phase III studies offer additional infor-
Administration (FDA) has the responsibility of approv- mation on dosing and safety. The three phases last any-
ing new drugs and monitoring drugs currently in use for where from 2 to 10 years, with the average being 5 years.
adverse or toxic reactions. The development of a new A New Drug Application (NDA) is submitted after
drug is divided into the pre-FDA phase and the FDA the investigation of the drug in Phases I, II, and III is
1
2 UNIT I (cid:2) Foundations of Clinical Pharmacology
Orphan Drug Program
Pre-FDA Phases FDA Phases
The Orphan Drug Act of 1983 was passed to encourage
the development and marketing of products used to treat
Drug designed by
rare diseases. The act defines a “rare disease” as a condi-
molecular modeling FDA submission
or discovered tion affecting fewer than 200,000 individuals in the
Investigational
in extract United States. The National Organization of Rare
New Drug
Application (IND) Disorders reports that there are more than 6000 rare dis-
orders that affect approximately 25 million individuals.
FDA submission Examples of rare disorders include Tourette’s syndrome,
New drug molecule
synthesized or Clinical Trials ovarian cancer, acquired immunodeficiency syndrome
produced Phases I-III (AIDS), Huntington’s disease, and certain forms of
leukemia.
FDA submission The act provides for incentives, such as research
New Drug grants, protocol assistance by the FDA, and special tax
In vitro testing
Application (NDA) credits, to encourage manufacturers to develop orphan
drugs. If the drug is approved, the manufacturer has
7 years of exclusive marketing rights. More than 100
FDA approval
Live animal testing new drugs have received FDA approval since the law
Phase IV marketing
and was passed. Examples of orphan drugs include thalido-
safety and efficacy Post marketing
mide for leprosy, triptorelin pamoate for ovarian cancer,
studies surveillance
tetrabenazine for Huntington’s disease, and zidovudine
for AIDS.
Ongoing safety
and efficacy studies Accelerated Programs
Accelerated approval of drugs is offered by the FDA as a
FIGURE1-1. Phases of drug development. Adapted from (1997, Spring)
PharmPhax,3 (2), 2. means to make promising products for life-threatening
diseases available on the market, based on preliminary
evidence before formal demonstration of patient benefit.
complete and the drug is found to be safe and effective.
With the NDA, the manufacturer submits all data col-
lected concerning the drug during the clinical trials. A DISPLAY 1-1 (cid:2) How to Report Adverse Reactions
panel of experts, including pharmacologists, chemists,
physicians, and other professionals, reviews the appli- A drug must be used and studied for many years before all of the
cation and makes a recommendation to the FDA. The adverse reactions are identified. To help in identifying adverse reac-
FDA then either approves or disapproves the drug for tions the nurse must be aware of reporting mechanisms. The FDA
established a reporting program called MedWatch by which nurses or
use. This process of review takes approximately 2 years.
other health care professionals can report observations of serious
After FDA approval, continued surveillance is done to
adverse drug effects by using a standard form (see Appendix A). The
ensure safety. FDA protects the identity of those who voluntarily report adverse
Postmarketing surveillance occurs after the manufac- reactions. This form also is used to report an undesirable experience
turer places the drug on the market. During this sur- associated with the use of medical products (eg, latex gloves, pace-
makers, infusion pumps, anaphylaxis, blood, blood components, etc.).
veillance, an ongoing review of the drug occurs with
It is important to submit reports, even if there is uncertainty about
particular attention given to adverse reactions. Health
the cause-effect relationship.
care professionals are encouraged to help with this sur- Nurses play an important role in monitoring for adverse reactions. The
veillance by reporting adverse effects of drugs to the FDA considers serious adverse reactions those that may result in
FDA by using MedWatch (see Display 1-1). death, life-threatening illness, hospitalization, or disability or those
that may require medical or surgical intervention.
Adverse drug reactions may be reported to the FDA by completing the
MedWatch form and sending it to:
SPECIAL FDA PROGRAMS MedWatch
(cid:2) 5600 Fishers Lane
Rockville, MD 20852-9787
Although it takes considerable time for most drugs to get Reports may be faxed to the following number:
1-800-FDA-0178
FDA approval, the FDA has special programs to meet dif-
Forms are available online and can be downloaded, completed, and
ferent needs. Examples of these special programs include
returned via mail, fax, or electronic mail. See the following website:
the orphan drug program, accelerated programs for www.fda.gov/medwatch/index.html
urgent needs, and compassionate use programs.
Description:concise introduction to pharmacology. The basic expla- nations presented in this
text are not intended to suggest that pharmacology is an easy subject.
