iii

R e v i e w e r s

Susan Beggs, RN, MSNAssociate Professor, Nursing FacultyAustin Community CollegeAustin, Texas

MaryAnn Cosgarea, RN, BSN, BANurse Administrator, Practical NursingHealth Coordinator, Adult EducationPortage Lakes Career CenterW. Howard Nicol School of Practical NursingGreen, Ohio

Nancy T. Hatfield, RN, BSN, MADirector/Department ChairpersonHealth Occupations/Practical NursingAlbuquerque Public SchoolsCareer Enrichment CenterAlbuquerque, New Mexico

Debra Menshouse, RN, BSNNursing FacultyAshland Technical CollegeAshland, Kentucky

Esther Salinas, RN, MSN, MS EdAssociate Professor, NursingVocational Nursing and Registered Nursing DepartmentsDel Mar CollegeCorpus Christi, Texas

Julie A. Slack, RN, MSNNursing FacultyMohave Community CollegeColorado City, Arizona

Bonnie J. Smith, RN, BSNCoordinator, Practical Nurse ProgramSikeston Public Schools—Health OccupationsHayti, Missouri

Ginger White, RN, ADNInstructor, Vocational Nursing ProgramWharton County Junior CollegeWharton, Texas

iii

v

P r e f a c e

The seventh edition of Introductory ClinicalPharmacology reflects the ever-changing science ofpharmacology and the nurse’s responsibilities in admin-istering pharmacologic agents. All information has beenupdated and revised according to the latest availableinformation to prepare nurses to meet the challenges ofsafely administering medications. The text prepares thenurse to meet the challenges of the 21st century by pro-moting critical thinking and problem solving whenadministering medications.

PURPOSE●

This text is designed to provide students with a clear,concise introduction to pharmacology. The basic expla-nations presented in this text are not intended to suggestthat pharmacology is an easy subject. Drug therapy isone of the most important and complicated treatmentmodalities in modern health care. Because of its impor-tance and complexity and the frequent additions andchanges in the field of pharmacology, it is imperativethat health care professionals constantly review andupdate their knowledge.

CURRENT DRUG INFORMATION●

The student and practitioner should remember thatinformation about drugs, such as dosages and new forms,is constantly changing. Likewise, there may be new drugson the market that were not approved by the FederalDrug Administration (FDA) at the time of publication ofthis text. The reader may find that certain drugs or drugdosages available when this textbook was published mayno longer be available. For the most current drug infor-mation and dosages, the practitioner is advised to consultreferences such as the most current Physician’s DeskReference or Facts and Comparison and the packageinserts that accompany most drugs. If reliable referencesare not available, the hospital pharmacist or physicianshould be contacted for information concerning a specificdrug, including dosage, adverse reactions, contraindica-tions, precautions, interactions, or administration.

SPECIAL FEATURES●

A number of features have proven useful for students intheir study of basic pharmacology. The following fea-tures appear in the seventh edition:

• Key Terms—lists the important words defined inthe chapter

• Nursing Process—used as a framework in mostchapters for presenting care of the patient as itrelates to the drug and the drug regimen.Preadministration and Ongoing Assessments areincluded in the assessment phase of the nursingprocess. These assessments are divided in order tohighlight the important assessments to performbefore administering a specific drug and thoseimportant during the entire time the drug is beingadministering. In the implementation phase of thenursing process, most chapters contain sectionsPromoting an Optimal Response to Therapy andMonitoring and Managing Adverse Reactions.These sections provide invaluable informationneeded to ensure that the drug is properly admin-istered and nursing interventions to use when cer-tain adverse reactions occur.

• Nursing Alerts—short segments that identifyurgent nursing considerations in the managementof the patient receiving a specific drug or drug cat-egory

• Gerontologic Alerts—short segments to alert thenurse about specific problems for which the olderadult is at increased risk. As the number of theolder adults in our society increases, it becomesimperative that nurses recognize the necessity ofspecialized care.

• Contraindications, Precautions, and Inter-actions—of the most commonly used drugs in thecategory under discussion. While space preventsevery contraindication, precaution, and interac-tion to be listed, the more common ones areincluded in the text. Pregnancy categories areidentified for many drugs discussed within thechapter.

• Home Health Care Checklists—highlight spe-cific issues that the patient or family may

v

encounter while undergoing drug therapy in thehome setting. As more and more patients are caredfor outside the hospital, it becomes increasinglyimportant for the nurse to know what informationthe patient or family needs to obtain an optimalresponse the drug regimen.

• Patient and Family Teaching Checklists—highlight teaching points relating to specific phar-macologic techniques and most-know informationfor the patient undergoing drug therapy. Thisempowers the family to participate knowledgeablyand accurately in the patient’s drug regimen.

• Summary Drug Tables—contain commonlyused drugs representative of the class of drugs dis-cussed in the chapter. Important drug informationis provided, including the generic name, pronunci-ation guide for generic names, trade names,adverse reactions, and dosage ranges. In thesetables, generic names are followed by trade names;when a drug is available under several tradenames, several of the available trade names aregiven. The more common or serious adverse reac-tions associated with the drug are listed in thetable’s adverse reaction section. It should be notedthat any patient may exhibit adverse reactions notlisted in this text. Because of this possibility, thenurse, when administering any drug, should con-sider any sign or symptom as a possible adversereaction until the cause of the problem is deter-mined by the primary health care provider.

The adverse reactions are followed by the doseranges for the drug. In most cases, the adult doseranges are given in these tables because space doesnot permit the inclusion of all possible dosages forvarious types of disorders. Likewise, space limita-tion does not permit an inclusion of pediatric doseranges due to the complexity of determining thepediatric dose of many drugs. Many drugs given tochildren are determined on the basis of bodyweight or body surface area and have a variety ofdosage scheduling. When drugs are given to thepediatric patient, the practitioner is encouraged toconsult references that give complete and exten-sive pediatric dosages.

• Critical Thinking Exercises—realistic patientcare situations that help the student apply thematerial contained in the chapter by exploringoptions and making clinical judgments related tothe administration of drugs

• Abbreviations—important pharmacologic andgeneral medical abbreviations the nurse needs toknow when caring for the patient undergoingdrug therapy are spelled out in the back of thetext.

• Glossary—key terms and other drug-relatedterms are listed and defined in the back of the text

NEW FEATURES●

• Four-Color Illustrations—the text is beautifullyillustrated throughout with new four-color illus-trations. Each illustration highlights and explainsan important pharmacologic concept, technique,or idea.

• New Chapters—new chapters are included, suchas Chapter 33, Cholinesterase Inhibitors, andChapter 18, Nonsteroidal Anti-InflammatoryDrugs. Several of the chapters in previous editionshave been divided. For example, the chapter onantiviral and antifungal drugs was divided intotwo chapters: Chapter 14, Antiviral Drugs, andChapter 15, Antifungal Drugs.

• Drug Lists—replacing the chapter outline is a list-ing of the classifications and drugs discussed in thechapter. This new format allows the student toquickly identify the important drugs discussed inthe chapter.

• Herbal or Health Supplement Alerts—provideimportant information on common herbs and sup-plements not regulated under the auspices of theFederal Drug Administration. Appendix B gives alisting of select herbs with examples of their com-mon and scientific name(s). While not all of thecommon or scientific names are given, the morecommon names (both common and scientific) areincluded. With more and more individuals usingherbs as a part of their health care regimen, it iscritical that the nurse be aware of the more com-mon herbs currently in use. The nurse must con-sult appropriate sources when patients indicatethey are using herbs as part of their health careregimen.

• Review Questions—several questions, reviewingimportant information covered in the chapter, canbe found at the end of each chapter. The questionsare written in PN-NCLEX format and provide thestudent an opportunity to answer questions specif-ically about the drugs covered in the chapter. Spacedoes not permit more questions of this type, butprovides the student practice in answering ques-tions concerning medication therapy and adminis-tration of drugs.

• Medication Dosage Problems—Calculation ofmedication dosage is an important aspect of med-ication administration. Chapter 3 reviews themathematics involved in dosage calculation andformulas used in the calculate medicationdosages. To ensure the student’s understandingand application of this type of problem, two ormore medication dosage problems are included atthe end of most chapters dealing with specificmedications discussed in the chapter. This provides

vi Preface

the student an opportunity for immediate applica-tion in medication administration. As an addedbenefit, several current medication labels are usedthroughout the text to help the student learn toread these labels and solve medication dosageproblems using the information found on theselabels.

• Drug and Health Care Information Sources onthe World Wide Web—The inside back coverprovides a listing of websites dealing with phar-macology and medication administration. The stu-dent can use these sites as valuable resources toidentify new drugs and important new informa-tion on current drugs.

ORGANIZATION●

The text contains 58 chapters, which are divided into 11units. Organization of the text in this manner allows thestudent to move about the text when these general areasare covered in the curriculum. While pharmacologicagents are presented in specific units, a disease may betreated with more than one type of drug, which mayrequire consulting one or more units.

Unit I presents a foundation for the study of phar-macology and covers general principles of pharmacol-ogy, the administration of drugs, a review of arithmeticand calculation of drug dosages, a discussion of thenursing process as applicable to pharmacology, and areview of the teaching learning process and generalareas of consideration when educating the patient andfamily.

Unit II contains 11 chapters that present the anti-infective drugs, grouped according to classification.These shorter chapters allow for more inclusive cover-age of the different types of anti-infectives and theappropriate nursing considerations for each classifica-tion.

Unit III includes four chapters covering the varioustypes of drugs used to manage pain: the nonnarcoticanalgesics (Salicylates, Nonsalicylates, and Nonste-roidal Anti-Inflammatory Drugs), the narcotic anal-gesics, and the narcotic antagonists.

Unit IV has been expanded to 15 chapters coveringthe many classifications of drugs that affect the nervoussystem and the neuromuscular system. These chaptersinclude the following types of drugs: drugs that affectthe musculoskeletal system, adrenergic drugs, adrener-gic blocking drugs, cholinergic drugs, cholinergic block-ing drugs, sedatives and hypnotics, central nervous sys-tem stimulants, anticonvulsants, antiparkinsonismdrugs, antianxiety drugs, antidepressant drugs, antipsy-chotic drugs, cholinesterase inhibitors, antiemetic andantivertigo drugs, and anesthetic drugs.

Unit V has three chapters concerning drugs thataffect the respiratory system. The first chapter in thisunit discusses antihistamines and decongestants, thesecond chapter in the unit covers bronchodilators andantiasthma drugs, and the last chapter of the unit dealswith antitussives, mucolytics, and expectorants.

Unit VI covers drugs that affect the cardiovascularsystem. This unit is divided into five chapters: car-diotonics and miscellaneous inotropic drugs, antiar-rhythmic drugs, antianginal and peripheral dilatingdrugs, antihypertensives, and antihyperlipidemics.

Unit VII consists of two chapters dealing with drugsthat affect the hematological system: anticoagulants andthrombolytic drugs, and agents used in the treatment ofanemia.

Unit VIII has been expanded to cover drugs thataffect both the gastrointestinal and urinary systems.The unit consists of three chapters: uretics, urinaryanti-infectives and miscellaneous urinary drugs, anddrugs that affect the gastrointestinal system.

Unit IX discusses drugs that affect the endocrinesystem and consists of five chapters: antidiabetic drugs,pituitary and andrenocortical hormones, thyroid andantithyroid drugs, male and female hormones, anddrugs acting on the uterus.

Unit X discusses drugs that affect the immune sys-tem. The unit consists of two chapters: immunologicagents and antineoplastic drugs.

Unit XI consists of three chapters that discussestypes of drugs not previously discussed or that are notmembers of a particular class or group. Chapters in thisunit include topical drugs used in the treatment of skindisorders, otic and ophthalmic preparations, and fluidsand electrolytes.

CHAPTER CONTENT●

Each chapter opens with learning objectives and a list-ing of key terms used and defined in the chapter. Lesscommonly used medical terms are also defined withinthe chapter and may be found in the Glossary. Chapters1 to 5 provide introductory information concerning gen-eral principals of pharmacology, medication administra-tion, a review of arithmetic and calculation of drugdosages, the nursing process, and patient and familyteaching. Each chapter ends with critical thinking ques-tions and several chapter review questions.

The remaining chapters discuss specific drug classifi-cations and contain a common format. In addition tothe learning objectives and key terms, the remainingchapters contain a table indicating the drug classifica-tions and drugs discussed in the chapter. The body ofeach chapter contains the actions, uses, adverse reac-tions, contraindications, precautions and interactions of

Preface vii

the class or type of drug being discussed, followed by asection devoted to the nursing process. These chaptersend with critical thinking questions, several chapterreview questions, and two or more medication dosageproblems. To promote easy retrieval of information,each area is identified by a large type heading.

• Actions—a basic explanation of how the drugaccomplishes its intended activity

• Uses—the more common uses of the drug class ortype are provided. No unlabeled or experimentaluses of drugs are given in the text (unless specifi-cally identified as an unlabeled use) because theseuses are not approved by the FDA. Studentsshould be reminded that, under certain circum-stances, some physicians may prescribe drugs for acondition not approved by the FDA or may pre-scribe an experimental drug.

When discussing the use of antibiotics, thistext does not list specific microorganisms.Microorganisms can become resistant to antibioticdrugs very rapidly. Because of this, the author feelsthat listing specific microorganisms or types ofinfections for an antibiotic may be misleading tothe user of the text. Instead, when antibiotics areneeded, the author recommends consulting cul-ture and sensitivity studies to indicate whichantibiotic has the most potential for controllingthe infection.

• Adverse Reactions—the most common adversedrug reactions are listed under this heading

• Contraindications—contraindications for admin-istration of the drug or drugs discussed in thechapter

• Precautions—precautions to take before, during,or after administration

• Interactions—more common interactions betweenthe drug(s) discussed in the chapter and otherdrugs

• Nursing Process—with a few exceptions, the nurs-ing process is used in every chapter of the test andgeared specifically to the administration of thedrugs discussed in the chapter. The assessmentphase is divided into two distinct parts to include apreadministration and ongoing assessment. Thisassists the reader in determining what assessmentsto perform before administration of specific drugs ofdrug categories and what important assessments toperform 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-noses checklist. Under “Implementation,” three sec-tions are included when applicable: “Promoting anOptimal Response to Therapy,” “Monitoring andManaging Adverse Reactions,” and “Educating thePatient and Family.”

• Critical Thinking Questions—each chapterincludes critical thinking questions that providethe student with the challenge of applying chaptercontent to specific clinical situations

• Review Questions—several PN-NCLEX reviewquestions are found at the end of each chapter

• Medication Dosage Problems—when applicable,the chapter contains real medication dosage pre-scriptions and the medication available for dis-pensing. The student solves medication dosageproblems using the information provided. Severalcurrent medication labels are used to help the stu-dent learn to read these labels and solve medica-tion dosage problems using the information foundon these labels.

APPENDICES●

Seven appendices containing important pharmacologicinformation are located at the back of the text.

Appendix A contains a MedWatch form, which isused by health care professionals for voluntary report-ing of adverse reactions and problems with the drugproduct. Is also contains advice about voluntary report-ing. This form is a part of the FDA medical productsreporting program.

Appendix B is a table of Select Herbs and NaturalProducts Used for Medicinal Purposes.

Appendix C contains a United States Pharmacopeia(USP) medication errors reporting program form,which is used by health care professionals for sharinginformation of medication errors to prevent them fromoccuring again. Also included is text explaining medica-tion error and the USP.

Appendix D provides metric–apothecary equivalentsand conversions. This guide covers liquid measurements;weights; Celsius and Fahrenheit temperatures; and a com-parative scale of measures, weights, and temperatures.

Appendix E contains two body surface area nomo-grams—one for infants and young children and one forolder children and adults.

Appendix F is a Vaccine Adverse Event ReportingForm.

Appendix G contains answers to the review anddosage calculation exercises appearing at the end of thechapters.

Appendix H lists examples of combination drugs.

TEACHING/LEARNING PACKAGE●

• Student Study Guide—the Student Study Guide toAccompany Introductory Clinical Pharmacology,7th Edition, correlates with the textbook chapter

viii Preface

AQ1

by chapter. For each chapter in the textbook, theStudy Guide contains a corresponding chapter andincludes three or more of the following compo-nents: a crossword puzzle featuring importantterms of the chapter, multiple-choice questions,short-answer questions, word search puzzles, andcritical thinking exercises derived from the text-book. Multiple-choice question have been writtenusing the same format as currently used in theNCLEX-PN examinations. The Study Guide alsofeatures activities designed around specific drug-related websites. These activities promote use ofthe World Wide Web as an important learning toolin the study and practice of nursing pharmacology.

• Instructor’s Manual—the Instructor’s Manual toAccompany Introductory Clinical Pharmacology,7th Edition, contains a variety of testing items aswell as tips for classroom teaching. Multiple-choice questions and critical thinking exercises areprovided. Answers are given for the multiple-choice questions. No answers are supplied for thecritical thinking exercises, to encourage the stu-dents to use their creative abilities rather than beconfined to a predetermined answer. Alsoincluded is a computer disk contain PN-NCLEX-style test items in multiple-choice format.

ACKNOWLEDGMENTS●

I wish to thank everyone involved in the creation of this7th Edition of Introductory Clinical Pharmacology. Aspecial thanks to Lisa Stead, Acquisitions Editor, for herguidance and support during the preparation of themanuscript. My heartfelt gratitude goes to Joe Morita,Managing Editor, for his support and editorial assis-tance with manuscript preparation and development.His input was invaluable. A special thank-you to BrendaShaffer, RPh, for her assistance with the SummaryDrug Tables and to Tom Robinson for his assistance inobtaining drug labels. My gratitude to all those whoworked in any way in the design, production, andpreparation of this book: Debra Schiff, SeniorProduction Editor; Helen Ewan, Senior ProductionManager; and Brett MacNaughton, Art Director.

Although not a part of the professional developmentof this textbook, I wish to express my love and gratitudeto those who made my contribution to this book possi-ble, my family. Their unwavering support and encour-agement saw me through many difficult days, nights,and weekends of manuscript preparation.

Sally Roach, MSN, RN, CHN

Preface ix

xi

C o n t e n t s

UNIT I FOUNDATIONS OF CLINICALPHARMACOLOGY 1

1 General Principles of Pharmacology 1

2 The Administration of Drugs 15

3 Review of Arithmetic and Calculation of Drug Dosages 29

4 The Nursing Process 46

5 Patient and Family Teaching 52

UNIT II ANTI-INFECTIVES 59

6 Sulfonamides 59

7 Penicillins 65

8 Cephalosporins and Related Antibiotics 75

9 Tetracyclines, Macrolides, and Lincosamides 83

10 Fluroquinolones and Aminoglycosides 91

11 Miscellaneous Anti-infectives 100

12 Antitubercular Drugs 108

13 Leprostatic Drugs 116

14 Antiviral Drugs 119

15 Antifungal Drugs 129

16 Antiparasitic Drugs 138

UNIT III DRUGS USED TO MANAGE PAIN 150

17 Nonnarcotic Analgesics: Salicylates andNonsalicylates 150

18 Nonnarcotic Analgesics: Nonsteroidal Anti-inflammatory Drugs 159

19 Narcotic Analgesics 167

20 Narcotic Antagonists 180

UNIT IV DRUGS THAT AFFECT THE NEUROMUSCULARSYSTEM 185

21 Drugs That Affect the Musculoskeletal System 185

22 Adrenergic Drugs 199

23 Adrenergic Blocking Drugs 210

24 Cholinergic Drugs 221

25 Cholinergic Blocking Drugs 229

26 Sedatives and Hypnotics 230

27 Central Nervous System Stimulants 246

28 Anticonvulsants 253

29 Antiparkinsonism Drugs 264

30 Antianxiety Drugs 274

31 Antidepressant Drugs 281

32 Antipsychotic Drugs 294

33 Cholinesterase Inhibitors 304

34 Antiemetic and Antivertigo Drugs 310

35 Anesthetic Drugs 317

UNIT V DRUGS THAT AFFECT THERESPIRATORY SYSTEM 325

36 Antihistamines and Decongestants 325

37 Bronchodilators and Antiasthma Drugs 333

38 Antitussives, Mucolytics, Expectorants 350

UNIT VI DRUGS THAT AFFECTTHE CARDIOVASCULAR SYSTEM 357

39 Cardiotonics and Miscellaneous Inotropic Drugs 357

40 Antiarrhythmic Drugs 367

41 Antianginal and Peripheral Dilating Drugs 380

42 Antihypertensives 393

43 Antihyperlipidemic Drugs 407

UNIT VII DRUGS THAT AFFECT THE HEMATOLOGICAL SYSTEM 417

44 Anticoagulant and Thrombolytic Drugs 417

45 Agents Used in the Treatment of Anemia 433

UNIT VIII DRUGS THAT AFFECT THE GASTROINTESTINAL AND URINARY SYSTEMS 443

46 Diuretics 443

47 Urinary Anti-infectives and MiscellaneousUrinary Drugs 456

48 Drugs That Affect the Gastrointestinal System 466

UNIT IX DRUGS THAT AFFECT THE ENDOCRINE SYSTEM 487

49 Antidiabetic Drugs 487

50 Pituitary and Adrenocortical Hormones 510

51 Thyroid and Antithyroid Drugs 530

52 Male and Female Hormones 538

53 Drugs Acting on the Uterus 559

UNIT X DRUGS THAT AFFECT THE IMMUNE SYSTEM 567

54 Immunologic Agents 567

55 Antineoplastic Drugs 583

UNIT XI DRUGS THAT AFFECT OTHER BODY SYSTEMS 603

56 Topical Drugs Used in the Treatment of SkinDisorders 603

57 Otic and Ophthalmic Preparations 616

58 Fluids and Electrolytes 633

Abbreviations 647

Glossary 651

Appendices:

A: MedWatch 657

B: Select Herbs and Natural Products Used forMedicinal Purposes 659

C: USP Medication Errors Reporting Program 662

D: Metric—Apothecary Equivalents andConversions 664

E: Body Surface Area Nomograms 667

F: Vaccine Adverse Event Reporting System 669

G: Multiple Choice Answers 671

H: Combination Drugs 679

Index 685

xii Contents

1

General Principles of Pharmacology

1c h a p t e r

additive drug reactionadverse reactionagonistallergic reactionanaphylactic shockangioedemaantagonistantibodiesantigenbiotransformationbotanical medicinecontrolled substancescumulative drug effectdrug idiosyncrasydrug tolerancehalf-lifehypersensitivity

macromoleculenonprescription drugspharmaceutic pharmacodynamicspharmacogenetic

disorderpharmacokinetics pharmacologyphysical dependencypolypharmacyprescription drugspsychological

dependencyreceptorsynergismteratogentoxic

Key Terms Chapter Objectives

On completion of this chapter, the student will:

● Define pharmacology.● Discuss drug development in the United States.● Identify the different names assigned to drugs.● Distinguish between prescription drugs, nonprescription drugs, and

controlled substances.● Discuss the laws governing the manufacture, distribution, and sale of

drugs.● Discuss the various types of drug reactions produced in the body.● Identify factors that influence drug action.● Define drug tolerance, cumulative drug effect, and drug idiosyncrasy.● Discuss the types of drug interactions that may be seen with drug

administration.● Discuss the nursing implications associated with drug actions, interac-

tions, and effects.● Discuss the use of botanical medicines.

phase (Fig. 1-1). During the pre-FDA phase, a manufac-turer discovers a drug that looks promising. In vitro test-ing (testing in an artificial environment, such as a testtube) using animal and human cells is done. This testingis followed by studies in live animals. The manufacturerthen makes application to the FDA for InvestigationalNew Drug (IND) status.

With IND status, clinical testing of the new drugbegins. Clinical testing involves three phases, with eachphase involving a larger number of people. All effects,both pharmacologic and biologic, are noted. Phase I lasts4 to 6 weeks and involves 20 to 100 individuals who areeither “normal” volunteers or individuals in the intendedtreatment population. If Phase I studies are successful,the testing moves to Phase II, and if those results are pos-itive, to Phase III. Each successive phase has a larger sub-ject population. Phase III studies offer additional infor-mation on dosing and safety. The three phases last any-where from 2 to 10 years, with the average being 5 years.

A New Drug Application (NDA) is submitted afterthe investigation of the drug in Phases I, II, and III is

Pharmacology is the study of drugs and their action onliving organisms. A sound knowledge of basic pharmaco-logic principles is essential if the nurse is to safely admin-ister medications and to monitor patients who receivethese medications. This chapter gives a basic overview ofpharmacologic principles that the nurse must understandwhen administering medications. The chapter also dis-cusses drug development, federal legislation affecting thedispensing and use of drugs, and the use of botanicalmedicines as they relate to pharmacology.

DRUG DEVELOPMENT●

Drug development is a long and arduous process, takinganywhere from 7 to 12 years, and sometimes evenlonger. The United States Food and DrugAdministration (FDA) has the responsibility of approv-ing new drugs and monitoring drugs currently in use foradverse or toxic reactions. The development of a newdrug is divided into the pre-FDA phase and the FDA

UNIT I • Foundations of Clinical Pharmacology

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. Apanel of experts, including pharmacologists, chemists,physicians, and other professionals, reviews the appli-cation and makes a recommendation to the FDA. TheFDA then either approves or disapproves the drug foruse. This process of review takes approximately 2 years.After FDA approval, continued surveillance is done toensure safety.

Postmarketing surveillance occurs after the manufac-turer places the drug on the market. During this sur-veillance, an ongoing review of the drug occurs withparticular attention given to adverse reactions. Healthcare professionals are encouraged to help with this sur-veillance by reporting adverse effects of drugs to theFDA by using MedWatch (see Display 1-1).

SPECIAL FDA PROGRAMS●

Although it takes considerable time for most drugs to getFDA approval, the FDA has special programs to meet dif-ferent needs. Examples of these special programs includethe orphan drug program, accelerated programs forurgent needs, and compassionate use programs.

Orphan Drug Program

The Orphan Drug Act of 1983 was passed to encouragethe development and marketing of products used to treatrare diseases. The act defines a “rare disease” as a condi-tion affecting fewer than 200,000 individuals in theUnited States. The National Organization of RareDisorders reports that there are more than 6000 rare dis-orders that affect approximately 25 million individuals.Examples of rare disorders include Tourette’s syndrome,ovarian cancer, acquired immunodeficiency syndrome(AIDS), Huntington’s disease, and certain forms ofleukemia.

The act provides for incentives, such as researchgrants, protocol assistance by the FDA, and special taxcredits, to encourage manufacturers to develop orphandrugs. If the drug is approved, the manufacturer has 7 years of exclusive marketing rights. More than 100new drugs have received FDA approval since the lawwas passed. Examples of orphan drugs include thalido-mide for leprosy, triptorelin pamoate for ovarian cancer,tetrabenazine for Huntington’s disease, and zidovudinefor AIDS.

Accelerated Programs

Accelerated approval of drugs is offered by the FDA as ameans to make promising products for life-threateningdiseases available on the market, based on preliminaryevidence before formal demonstration of patient benefit.

2 UNIT I ● Foundations of Clinical Pharmacology

FIGURE 1-1. Phases of drug development. Adapted from (1997, Spring)PharmPhax, 3 (2), 2.

A drug must be used and studied for many years before all of theadverse reactions are identified. To help in identifying adverse reac-tions the nurse must be aware of reporting mechanisms. The FDAestablished a reporting program called MedWatch by which nurses orother health care professionals can report observations of seriousadverse drug effects by using a standard form (see Appendix A). TheFDA protects the identity of those who voluntarily report adversereactions. This form also is used to report an undesirable experienceassociated with the use of medical products (eg, latex gloves, pace-makers, infusion pumps, anaphylaxis, blood, blood components, etc.).It is important to submit reports, even if there is uncertainty aboutthe cause-effect relationship.

Nurses play an important role in monitoring for adverse reactions. TheFDA considers serious adverse reactions those that may result indeath, life-threatening illness, hospitalization, or disability or thosethat may require medical or surgical intervention.

Adverse drug reactions may be reported to the FDA by completing theMedWatch form and sending it to:MedWatch5600 Fishers LaneRockville, MD 20852-9787

Reports may be faxed to the following number:1-800-FDA-0178

Forms are available online and can be downloaded, completed, andreturned via mail, fax, or electronic mail. See the following website:www.fda.gov/medwatch/index.html

DISPLAY 1-1 ● How to Report Adverse Reactions

Pre-FDA Phases FDA Phases

Drug designed bymolecular modeling

or discoveredin extract

Live animal testingand

safety and efficacystudies

New drug moleculesynthesized or

produced

InvestigationalNew Drug

Application (IND)

Phase IV marketing

Post marketingsurveillance

Clinical TrialsPhases I-III

New DrugApplication (NDA)

Ongoing safetyand efficacy studies

In vitro testing

FDA submission

FDA submission

FDA submission

FDA approval

The approval that is granted is considered a “provisionalapproval,” with a written commitment from the pharma-ceutical company to complete clinical studies that for-mally demonstrate patient benefit. This program seeks tomake life-saving investigational drugs available beforegranting final approval to treat diseases that pose a sig-nificant health threat to the public. One example of a dis-ease that qualifies as posing a significant health threat isAIDS. Because AIDS is so devastating to the individualsaffected and because of the danger the disease poses topublic health, the FDA and pharmaceutical companiesare working together to shorten the IND approval processfor some drugs that show promise in treating AIDS. Thisaccelerated process allows primary care providers toadminister medications that indicate positive results inearly Phase I and II clinical trials, rather than wait untilfinal approval is granted. If the drug continues to provebeneficial, the process of approval is accelerated.

Compassionate Access to Unapproved Drugs

The compassionate access program allows patients toreceive drugs that have not yet been approved by theFDA. This program provides experimental drugs forpatients who could benefit from new treatments butwhose conditions are such that they most probablywould die before the drug is approved for use. Thesepatients are often too sick to participate in the con-trolled studies. Drug manufacturers make a proposal tothe FDA to target patients with the disease and, at thepharmaceutical company’s expense, provide the drugfree to patients. The pharmaceutical company analyzesand presents to the FDA data on the treatment. Thisprogram is not without problems. Because the drug isnot in full production, quantities may be limited, so thenumber of patients may be limited, and patients may beselected at random. Because patients receiving compas-sionate access often are sicker, they are at increased risk

for toxic reactions. This results in the newly developeddrug running the risk of obtaining a “bad reputation,”even before marketing begins.

DRUG NAMES●

Throughout the process of development, drugs mayhave several names assigned to them: a chemical name,a generic (nonproprietary) name, an official name, anda trade or brand name. This is confusing unless thenurse has a clear understanding of the different namesused. Table 1-1 identifies the different names and pro-vides an explanation of each.

DRUG CATEGORIES●

After approval of a drug, the FDA assigns the drug toone of the following categories: prescription, nonpre-scription, or controlled substance.

Prescription Drugs

Prescription drugs are drugs that the federal govern-ment has designated to be potentially harmful unlesstheir use is supervised by a licensed health careprovider, such as a nurse practitioner, physician, or den-tist. Although these drugs have been tested for safetyand therapeutic effect, prescription drugs may cause dif-ferent reactions in some individuals.

In institutional settings the nurse administers thedrug and monitors the patient for therapeutic effectand adverse reactions. Some drugs have the potential tobe toxic (harmful). The nurse plays a critical role inevaluating the patient for toxic effects. When thesedrugs are prescribed to be taken at home, the nurse pro-vides patient and family education about the drug.

CHAPTER 1 ● General Principles of Pharmacology 3

DRUG NAME AND EXAMPLE EXPLANATION

Chemical name Gives the exact chemical makeup of the drug and placing of Example: ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6] the atoms or molecular structure; it is not capitalized.

cycloheptal[1,2-b]-pyridin-11-ylidene)-1-piperidinecardisplayylate

Generic name (nonproprietary) Name given to a drug before it becomes official; may be used Example: loratadine in all countries, by all manufacturers; it is not capitalized.

Official name Name listed in The United States Pharmacopeia-National Example: loratadine Formulary; may be the same as the generic name.

Trade name (brand name) Name that is registered by the manufacturer and is followed Example: by the trademark symbol; the name can be used only by Claritin© the manufacturer; a drug may have several trade names,

depending on the number of manufacturers; the first letterof the name is capitalized.

TABLE 1-1 Drug Names

Prescription drugs, also called legend drugs, are thelargest category of drugs. Prescription drugs are prescribedby a licensed health care provider. The prescription (seeFig. 1-2) contains the name of the drug, the dosage, themethod and times of administration, and the signature ofthe licensed health care provider prescribing the drug.

Nonprescription Drugs

Nonprescription drugs are drugs that are designatedby the FDA to be safe (if taken as directed) and obtainedwithout a prescription. These drugs are also referred toas over-the-counter (OTC) drugs and may be purchasedin a variety of settings, such as a pharmacy, drugstore,or in the local supermarket. OTC drugs include thosegiven for symptoms of the common cold, headaches,constipation, diarrhea, and upset stomach.

These drugs are not without risk and may produceadverse reactions. For example, acetylsalicylic acid, com-monly known as aspirin, is potentially harmful and cancause gastrointestinal bleeding and salicylism (see Chap.17). Labeling requirements give the consumer importantinformation regarding the drug, dosage, contraindications,precautions, and adverse reactions. Consumers are urgedto read the directions carefully before taking OTC drugs.

Controlled Substances

Controlled substances are the most carefully moni-tored of all drugs. These drugs have a high potential forabuse and may cause physical or psychological depend-ence. Physical dependency is a compulsive need to usea substance repeatedly to avoid mild to severe with-drawal symptoms; it is the body’s dependence onrepeated administration of a drug. Psychologicaldependency is a compulsion to use a substance toobtain a pleasurable experience; it is the mind’s depend-ence on the repeated administration of a drug. One typeof dependency may lead to the other type.

The Controlled Substances Act of 1970 regulates themanufacture, distribution, and dispensing of drugs thathave abuse potential (see information under “FederalDrug Legislation and Enforcement” in this chapter).Drugs under the Controlled Substances Act are dividedinto five schedules, based on their potential for abuseand physical and psychological dependence. Display 1-2describes the five schedules.

Prescriptions for controlled substances must be writtenin ink and include the name and address of the patientand the Drug Enforcement Agency number of the pri-mary health care provider. Prescriptions for these drugscannot be filled more than 6 months after the prescription

4 UNIT I ● Foundations of Clinical Pharmacology

DEA #

CHARLES FULLER M.D.SUSAN LUNGLEY R.N., A.N.

1629 TREASURE HILLSHOUSTON, TX 79635

NAME

ADDRESS DATE

Rx

Label

Refill times PRN NRM.D.

To ensure brand name dispensing, prescriber must write ‘Dispense As Written’ onthe prescription.

FIGURE 1-2. Example of a prescription form.

SCHEDULE I (C-I)● High abuse potential● No accepted medical use in the United States● Examples: heroin, marijuana, LSD (lysergic acid diethylamide), peyote

SCHEDULE II (C-II)● Potential for high abuse with severe physical or psychological

dependence● Examples: narcotics such as meperidine, methadone, morphine,

oxycodone; amphetamines; and barbiturates

SCHEDULE III (C-III)● Less abuse potential than schedule II drugs● Potential for moderate physical or psychological dependence● Examples: nonbarbiturate sedatives, nonamphetamine stimulants,

limited amounts of certain narcotics

SCHEDULE IV (C-IV)● Less abuse potential than schedule III drugs● Limited dependence potential● Examples: some sedatives and anxiety agents, nonnarcotic analgesics

SCHEDULE V (C-V)*● Limited abuse potential● Examples: small amounts of narcotics (codeine) used as antitussives

or antidiarrheals

*Under federal law, limited quantities of certain schedule V drugs may be purchasedwithout a prescription directly from a pharmacist if allowed under state law. Thepurchaser must be at least 18 years of age and must furnish identification. All suchtransactions must be recorded by the dispensing pharmacist.

DISPLAY 1-2 ● Schedules of Controlled Substances

was written or be refilled more than five times. Under fed-eral law, limited quantities of certain schedule C-V drugsmay be purchased without a prescription, with the pur-chase recorded by the dispensing pharmacist. In somecases state laws are more restrictive than federal laws andimpose additional requirements for the sale and distribu-tion of controlled substances. In hospitals or other agen-cies that dispense controlled substances, the scheduleddrugs are counted every 8 to 12 hours to account for eachampule, tablet, or other form of the drug. Any discrepancyin the number of drugs must be investigated andexplained immediately.

FEDERAL DRUG LEGISLATION ANDENFORCEMENT

●

Many laws have been enacted over the last century thataffect drug distribution and administration. Thoseincluded here are the Pure Food and Drug Act; HarrisonNarcotic Act; Pure Food, Drug, and Cosmetic Act; andthe Comprehensive Drug Abuse Prevention and ControlAct. These laws control the use of the three categories ofdrugs in the United States (prescription, nonprescription,and controlled substances).

Pure Food and Drug Act

This act, passed in 1906, was the first attempt by thegovernment to regulate and control the manufacture, dis-tribution, and sale of drugs. Before 1906, any substancecould be called a drug, and no testing or research wasrequired before placing the drug on the market. Beforethis time, drug potency and the purity of many drugswere questionable, and some were even dangerous forhuman use.

Harrison Narcotic Act

This law, passed in 1914, regulated the sale of narcoticdrugs. Before the passage of this act, any narcotic couldbe purchased without a prescription. This law wasamended many times. In 1970, the Harrison NarcoticAct was replaced with the passage of the ComprehensiveDrug Abuse Prevention and Control Act.

Pure Food, Drug, and Cosmetic Act

In 1938, Congress passed this law that gave the FDAcontrol over the manufacture and sale of drugs, food,and cosmetics. Before the passage of this act, somedrugs, as well as foods and cosmetics, contained chem-icals that were often harmful to humans. This lawrequires that these substances are safe for human use.It also requires pharmaceutical companies to perform

toxicology tests before a new drug is submitted to theFDA for approval. Following FDA review of the testsperformed on animals and other research data,approval may be given to market the drug (see sectionson “Drug Development”).

Comprehensive Drug Abuse Preventionand Control Act

Congress passed this act in 1970 because of the growingproblem of drug abuse. It regulates the manufacture, dis-tribution, and dispensation of drugs that have the poten-tial for abuse. Title II of this law, the ControlledSubstances Act, deals with control and enforcement. TheDrug Enforcement Agency within the US Department ofJustice is the leading federal agency responsible for theenforcement of this act.

Drug Enforcement Administration

The Drug Enforcement Administration (DEA) withinthe US Department of Justice is the chief federal agencyresponsible for enforcing the Controlled Substances Act.Failure to comply with the Controlled Substances Act ispunishable by fine and/or imprisonment. With drugabuse so prevalent, nurses must diligently adhere to theregulation imposed by the FDA and the Nurse PracticeAct of their state. Any violation may result in the loss ofthe nurse’s license to practice. Nurses must also reportany misuse or abuse of these substances by other nursesto their State Board of Nursing. Most states have provi-sions within their Nurse Practice Act to assist nurseswho have problems with drug abuse.

DRUG USE AND PREGNANCY●

The use of any medication—prescription or nonpre-scription—carries a risk of causing birth defects in thedeveloping fetus. Drugs administered to pregnantwomen, particularly during the first trimester (3months), may cause teratogenic effects. A teratogen isany substance that causes abnormal development of thefetus leading to a severely deformed fetus. Drugs are onetype of teratogen.

In an effort to prevent teratogenic effects, the FDAhas established five categories suggesting the potentialof a drug for causing birth defects (Display 1-3).Information regarding the pregnancy category of a spe-cific drug is found in reliable drug literature, such as theinserts accompanying drugs and approved drug refer-ences. In general, most drugs are contraindicated duringpregnancy or lactation unless the potential benefits oftaking the drug outweigh the risks to the fetus or theinfant.

CHAPTER 1 ● General Principles of Pharmacology 5

During pregnancy, no woman should consider takingany drug, legal or illegal, prescription or nonprescrip-tion, unless the drug is prescribed or recommended bythe primary health care provider. Smoking or drinkingany type of alcoholic beverage also carries risks, such aslow birth weight, premature birth, and fetal alcohol syn-drome. Children born of mothers using addictive drugs,such as cocaine or heroin, often are born with an addic-tion to the drug abused by the mother.

DRUG ACTIVITY WITHIN THE BODY●

Drugs act in various ways in the body. Oral drugs gothrough three phases: the pharmaceutic phase, pharma-cokinetic phase, and pharmacodynamic phase. Liquidand parenteral drugs (drugs given by injection) gothrough the later two phases only.

Pharmaceutic Phase

The pharmaceutic phase of drug action is the dissolu-tion of the drug. Drugs must be in solution to beabsorbed. Drugs that are liquid or drugs given by injec-

tion (parenteral drugs) do not go through the pharma-ceutic phase. A tablet or capsule (solid forms of a drug)goes through this phase as it disintegrates into smallparticles and dissolves into the body fluids within thegastrointestinal tract. Tablets that are enteric-coated donot disintegrate until reaching the alkaline environmentof the small intestine.

Pharmacokinetic Phase

Pharmacokinetics refers to activities within the bodyafter a drug is administered. These activities includeabsorption, distribution, metabolism, and excretion(ADME). Another pharmacokinetic component is thehalf-life of the drug. Half-life is a measure of the rate atwhich drugs are removed from the body.

Absorption

Absorption follows administration and is the process bywhich a drug is made available for use in the body. Itoccurs after dissolution of a solid form of the drug orafter the administration of a liquid or parenteral drug. Inthis process the drug particles within the gastrointestinaltract are moved into the body fluids. This movement canbe accomplished in several ways: active absorption, pas-sive absorption, and pinocytosis. In active absorption acarrier molecule such as a protein or enzyme activelymoves the drug across the membrane. Passive absorptionoccurs by diffusion (movement from a higher concentra-tion to a lower concentration). In pinocytosis cells engulfthe drug particle causing movement across the cell.

As the body transfers the drug from the body fluids tothe tissue sites, absorption into the body tissues occurs.Several factors influence the rate of absorption, includingthe route of administration, the solubility of the drug, andthe presence of certain body conditions. Drugs are mostrapidly absorbed when given by the intravenous route, fol-lowed by the intramuscular route, the subcutaneous route,and lastly, the oral route. Some drugs are more soluble andthus are absorbed more rapidly than others. For example,water-soluble drugs are readily absorbed into the systemiccirculation. Bodily conditions, such as the development oflipodystrophy (atrophy of the subcutaneous tissue) fromrepeated subcutaneous injections, inhibit absorption of adrug given in the site of lipodystrophy.

Distribution

The systemic circulation distributes drugs to variousbody tissues or target sites. Drugs interact with specificreceptors (see Fig. 1-3) during distribution. Some drugstravel by binding to protein (albumin) in the blood.Drugs bound to protein are pharmacologically inactive.Only when the protein molecules release the drug canthe drug diffuse into the tissues, interact with receptors,and produce a therapeutic effect.

6 UNIT I ● Foundations of Clinical Pharmacology

PREGNANCY CATEGORY A● Controlled studies show no risk to the fetus.● Adequate well-controlled studies in pregnant women have not

demonstrated risk to the fetus.

PREGNANCY CATEGORY B● There is no evidence of risk in humans.● Animal studies show risk, but human findings do not.● If no adequate human studies have been done, animal studies are

negative.

PREGNANCY CATEGORY C● Risk cannot be ruled out.● Human studies are lacking, and animal studies are either positive for

fetal risk or lacking.● The drug may be used during pregnancy if the potential benefits of

the drug outweigh its possible risks.

PREGNANCY CATEGORY D● There is positive evidence of risk to the human fetus.● Investigational or postmarketing data show risk to the fetus.● However, potential benefits may outweigh the risk to the fetus. If

needed in a life-threatening situation or a serious disease, the drugmay be acceptable if safer drugs cannot be used or are ineffective.

PREGNANCY CATEGORY X● Use of the drug is contraindicated in pregnancy.● Studies in animals or humans or investigational or postmarketing

reports, have shown fetal risk that clearly outweighs any possiblebenefit to the patient.

Regardless of the pregnancy category or the presumed safety of thedrug, no drug should be administered during pregnancy unless it isclearly needed and the potential benefits outweigh potential harm tothe fetus.

DISPLAY 1-3 ● Pregnancy Categories

As the drug circulates in the blood, a certain bloodlevel must be maintained for the drugs to be effective.When the blood level decreases below the therapeuticlevel, the drug will not produce the desired effect.Should the blood level increase significantly over thetherapeutic level, toxic symptoms develop. Specific ther-apeutic blood levels are discussed in the subsequentchapters when applicable.

Metabolism

Metabolism, also called biotransformation, is the processby which a drug is converted by the liver to inactive com-pounds through a series of chemical reactions. Patientswith liver disease may require lower dosages of a drugdetoxified by the liver, or the primary care provider mayselect a drug that does not undergo a biotransformation bythe liver. Frequent liver function texts are necessary whenliver disease is present. The kidneys, lungs, plasma, andintestinal mucosa also aid in the metabolism of drugs.

Excretion

The elimination of drugs from the body is called excre-tion. After the liver renders drugs inactive, the kidneyexcretes the inactive compounds from the body. Also,some drugs are excreted unchanged by the kidney with-out liver involvement. Patients with kidney disease mayrequire a dosage reduction and careful monitoring of

kidney function. Children have immature kidney func-tion and may require dosage reduction and kidney func-tion tests. Similarly, older adults have diminished kid-ney function and require careful monitoring and lowerdosages. Other drugs are eliminated by sweat, breastmilk, breath, or by the gastrointestinal tract in the feces.

Half-Life

Half-life refers to the time required for the body toeliminate 50% of the drug. Knowledge of the half-life ofa drug is important in planning the frequency of dosing.For example, drugs with a short half-life (2–4 hours)need to be administered frequently, whereas a drug witha long half-life (21–24 hours) requires less frequent dos-ing. It takes five to six half-lives to eliminate approxi-mately 98% of a drug from the body. Although half-lifeis fairly stable, patients with liver or kidney disease mayhave problems excreting a drug. Difficulty in excreting adrug increases the half-life and increases the risk of tox-icity. For example, digoxin (Lanoxin) has a long half-life(36 hours) and requires once-daily dosing. However,aspirin has a short half-life and requires frequent dos-ing. Older patients or patients with impaired kidney orliver function require frequent diagnostic tests measur-ing renal or hepatic function.

PHARMACODYNAMIC PHASE●

Pharmacodynamics deals with the drug’s action andeffect within the body. After administration, most drugsenter the systemic circulation and expose almost allbody tissues to possible effects of the drug. All drugsproduce more than one effect in the body. The primaryeffect of a drug is the desired or therapeutic effect.Secondary effects are all other effects, whether desirableor undesirable, produced by the drug.

Most drugs have an affinity for certain organs or tis-sues and exert their greatest action at the cellular levelon those specific areas, which are called target sites.There are two main mechanisms of action:

1. Alteration in cellular environment2. Alteration in cellular function

Alteration in Cellular Environment

Some drugs act on the body by changing the cellularenvironment, either physically or chemically. Physicalchanges in the cellular environment include changes inosmotic pressures, lubrication, absorption, or the condi-tions on the surface of the cell membrane. An exampleof a drug that changes osmotic pressure is mannitol,which produces a change in the osmotic pressure inbrain cells, causing a reduction in cerebral edema. A

CHAPTER 1 ● General Principles of Pharmacology 7

FIGURE 1-3. Drug-receptor interactions. (Adapted from Reiss & Evans,Pharmacological Aspects of Nursing Care, 3rd ed.)

Receptor Receptor

Receptor Receptor

A. Macromolecule B. Poor receptor fit. Nopharmacologic effect.

C. Some drug-receptor fit.Slight therapeutic responsepossible.

D. Agonist—excellentreceptor fit. Therapeuticresponse.

drug that acts by altering the cellular environment bylubrication is sunscreen. An example of a drug that actsby altering absorption is activated charcoal, which isadministered orally to absorb a toxic chemical ingestedinto the gastrointestinal tract. The stool softenerdocusate is an example of a drug that acts by altering thesurface of the cellular membrane. Docusate has emulsi-fying and lubricating activity that causes a lowering ofthe surface tension in the cells of the bowel, permittingwater and fats to enter the stool. This softens the fecalmass, allowing easier passage of the stool.

Chemical changes in the cellular environment includeinactivation of cellular functions or the alteration of thechemical components of body fluid, such as a change inthe pH. For example, antacids neutralize gastric acidityin patients with peptic ulcers.

Alteration in Cellular Function

Most drugs act on the body by altering cellular function.A drug cannot completely change the function of a cell,but it can alter its function. A drug that alters cellularfunction can increase or decrease certain physiologicfunctions, such as increase heart rate, decrease bloodpressure, or increase urine output.

Receptor-Mediated Drug Action

The function of a cell alters when a drug interacts witha receptor cell. A receptor is a specialized macromol-ecule (a large group of molecules linked together) thatattaches or binds to the drug molecule. This alters thefunction of the cell and produces the therapeuticresponse of the drug. For a drug–receptor reaction tooccur, a drug must be attracted to a particular receptor.Drugs bind to a receptor much like a piece of a puzzle.The closer the shape, the better the fit, and the betterthe therapeutic response. The intensity of a drugresponse is related to how good the “fit” of the drugmolecule is and the number of receptor sites occupied.

Agonists are drugs that bind with a receptor to pro-duce a therapeutic response. Drugs that bind only par-tially to the receptor will most probably have some,although slight, therapeutic response. Figure 1-3 identi-fies the different drug–receptor interactions. Partialagonists are drugs that have some drug receptor fit andproduce a response but inhibit other responses.

Antagonists join with a receptor to prevent theaction of an agonist. When the antagonist binds moretightly than the agonist to the receptor, the action of theantagonist is strong. Drugs that act as antagonists pro-duce no pharmacologic effect. An example of an antag-onist is Narcan, a narcotic antagonist that completelyblocks the effects of morphine, including the respiratorydepression. This drug is useful in reversing the effects ofan overdose of narcotics.

Receptor-Mediated Drug Effects

The number of available receptor sites influences theeffects of a drug. If only a few receptor sites are occu-pied, although many sites are available, the responsewill be small. If the drug dose is increased, more recep-tor sites are used and the response increases. If only afew receptor sites are available, the response does notincrease if more of the drug is administered. However,not all receptors on a cell need to be occupied for a drugto be effective. Some extremely potent drugs are effec-tive even when the drug occupies few receptor sites.

DRUG REACTIONS●

Drugs produce many reactions in the body. The follow-ing sections discuss adverse drug reactions, allergic drugreactions, drug idiosyncrasy, drug tolerance, cumulativedrug effect, and toxic reactions. Pharmacogenetic reac-tions can also occur. A pharmacogenetic reaction is agenetically determined adverse reaction to a drug.

Adverse Drug Reactions

Patients may experience one or more adverse reactions(side effects) when they are given a drug. Adverse reac-tions are undesirable drug effects. Adverse reactions maybe common or may occur infrequently. They may bemild, severe, or life threatening. They may occur afterthe first dose, after several doses, or even after manydoses. An adverse reaction often is unpredictable,although some drugs are known to cause certain adversereactions in many patients. For example, drugs used inthe treatment of cancer are very toxic and are known toproduce adverse reactions in many patients receivingthem. Other drugs produce adverse reactions in fewerpatients. Some adverse reaction is predictable, but manyadverse drug reactions occur without warning.

Some texts use both terms side effect and adverse reac-tions. These texts distinguish between the two terms byusing side effects to explain mild, common, and nontoxicreactions; adverse reaction is used to describe moresevere and life-threatening reactions. For the purposesof this text only the term adverse reaction is used, withthe understanding that these reactions may be mild,severe, or life threatening.

Allergic Drug Reactions

An allergic reaction also is called a hypersensitivityreaction. Allergy to a drug usually begins to occur aftermore than one dose of the drug is given. On occasion,the nurse may observe an allergic reaction the first timea drug is given because the patient has received or takenthe drug in the past.

8 UNIT I ● Foundations of Clinical Pharmacology

A drug allergy occurs because the individual’simmune system views the drug as a foreign substance orantigen. The presence of an antigen stimulates the anti-gen–antibody response that in turn prompts the body toproduce antibodies. If the patient takes the drug afterthe antigen–antibody response has occurred, an allergicreaction results.

Even a mild allergic reaction produces serious effectsif it goes unnoticed and the drug is given again. Anyindication of an allergic reaction is reported to the pri-mary health care provider before the next dose of thedrug is given. Serious allergic reactions require con-tacting the primary health care provider immediatelybecause emergency treatment may be necessary.

Some allergic reactions occur within minutes (evenseconds) after the drug is given; others may be delayedfor hours or days. Allergic reactions that occur immedi-ately often are the most serious.

Allergic reactions are manifested by a variety of signsand symptoms observed by the nurse or reported by thepatient. Examples of some allergic symptoms include itch-ing, various types of skin rashes, and hives (urticaria).Other symptoms include difficulty breathing, wheezing,cyanosis, a sudden loss of consciousness, and swelling ofthe eyes, lips, or tongue.

Anaphylactic shock is an extremely serious allergicdrug reaction that usually occurs shortly after theadministration of a drug to which the individual is sen-sitive. This type of allergic reaction requires immediatemedical attention. Symptoms of anaphylactic shock arelisted in Table 1-2.

All or only some of these symptoms may be present.Anaphylactic shock can be fatal if the symptoms are notidentified and treated immediately. Treatment is to raisethe blood pressure, improve breathing, restore cardiacfunction, and treat other symptoms as they occur.

Epinephrine (adrenalin) 0.1 to 0.5 mg may be given bysubcutaneous or intramuscular injection. Hypotensionand shock may be treated with fluids and vasopressors.Bronchodilators are given to relax the smooth musclesof the bronchial tubes. Antihistamines may be given toblock the effects of histamine.

Angioedema (angioneurotic edema) is another typeof allergic drug reaction. It is manifested by the collec-tion of fluid in subcutaneous tissues. Areas that aremost commonly affected are the eyelids, lips, mouth,and throat, although other areas also may be affected.Angioedema can be dangerous when the mouth isaffected because the swelling may block the airway andasphyxia may occur. Difficulty in breathing or swellingto any area of the body is reported immediately to theprimary health care provider.

Drug Idiosyncrasy

Drug idiosyncrasy is a term used to describe anyunusual or abnormal reaction to a drug. It is any reactionthat is different from the one normally expected of a spe-cific drug and dose. For example, a patient may be givena drug to help him or her sleep (eg, a hypnotic). Insteadof falling asleep, the patient remains wide awake andshows signs of nervousness or excitement. This responseis an idiosyncratic response because it is different fromwhat the nurse expects from this type of drug. Anotherpatient may receive the same drug and dose, fall asleep,and after 8 hours be difficult to awaken. This, too, isabnormal and describes an overresponse to the drug.

The cause of drug idiosyncrasy is not clear. It isbelieved to be due to a genetic deficiency that makes thepatient unable to tolerate certain chemicals, includingdrugs.

Drug Tolerance

Drug tolerance is a term used to describe a decreasedresponse to a drug, requiring an increase in dosage toachieve the desired effect. Drug tolerance may developwhen a patient takes certain drugs, such as the narcoticsand tranquilizers, for a long time. The individual whotakes these drugs at home increases the dose when theexpected drug effect does not occur. The development ofdrug tolerance is a sign of drug dependence. Drug toler-ance may also occur in the hospitalized patient. Whenthe patient receives a narcotic for more than 10 to 14 days, the nurse suspects drug tolerance (and possiblydrug dependence). The patient may also begin to ask forthe drug at more frequent intervals.

Cumulative Drug Effect

A cumulative drug effect may be seen in those withliver or kidney disease because these organs are themajor sites for the breakdown and excretion of most

CHAPTER 1 ● General Principles of Pharmacology 9

Respiratory BronchospasmDyspnea (difficult breathing)Feeling of fullness in the throatCoughWheezing

Cardiovascular Extremely low blood pressureTachycardia (heart rate > 100 bpm)PalpationsSyncope (fainting)Cardiac arrest

Integumentary UrticariaAngioedemaPruritus (itching)Sweating

Gastrointestinal NauseaVomitingAbdominal pain

TABLE 1-2 Symptoms of Anaphylactic Shock

drugs. This drug effect occurs when the body is unableto metabolize and excrete one (normal) dose of a drugbefore the next dose is given. Thus, if a second dose ofthis drug is given, some drug from the first dose remainsin the body. A cumulative drug effect can be seriousbecause too much of the drug can accumulate in thebody and lead to toxicity.

Patients with liver or kidney disease are usuallygiven drugs with caution because a cumulative effectmay occur. When the patient is unable to excrete thedrug at a normal rate the drug accumulates in the body,causing a toxic reaction. Sometimes, the primary healthcare provider lowers the dose of the drug to prevent atoxic drug reaction.

Toxic Reactions

Most drugs can produce toxic or harmful reactions ifadministered in large dosages or when blood concentra-tion levels exceed the therapeutic level. Toxic levelsbuild up when a drug is administered in dosages thatexceed the normal level or if the patient’s kidneys arenot functioning properly and cannot excrete the drug.Some toxic effects are immediately visible; others maynot be seen for weeks or months. Some drugs, such aslithium or digoxin, have a narrow margin of safety, evenwhen given in recommended dosages. It is important tomonitor these drugs closely to avoid toxicity.

Drug toxicity can be reversible or irreversible,depending on the organs involved. Damage to the livermay be reversible because liver cells can regenerate.However, hearing loss due to damage to the eighth cra-nial nerve caused by toxic reaction to the anti-infectivestreptomycin may be permanent. Sometimes drug toxic-ity can be reversed by the administration of anotherdrug that acts as an antidote. For example, in seriousinstances of digitalis toxicity, the drug Digibind may begiven to counteract the effect of digoxin toxicity.

Nurses must carefully monitor the patient’s bloodlevels of drugs to ensure that they remain within thetherapeutic range. Any deviation should be reported tothe primary health care provider. Because some drugscan cause toxic reactions even in recommended doses,the nurse should be aware of the signs and symptoms oftoxicity of commonly prescribed drugs.

Pharmacogenetic Reactions

A pharmacogenetic disorder is a genetically deter-mined abnormal response to normal doses of a drug.This abnormal response occurs because of inheritedtraits that cause abnormal metabolism of drugs. Forexample, individuals with glucose-6-phosphate dehy-drogenase (G6PD) deficiency have abnormal reactionsto a number of drugs. These patients exhibit varyingdegrees of hemolysis (destruction of red blood cells) if

these drugs are administered. More than 100 millionpeople are affected by this disorder. Examples of drugsthat cause hemolysis in patients with a G6PD defi-ciency include aspirin, chloramphenicol, and thesulfonamides.

DRUG INTERACTIONS●

It is important for the nurse administering medicationsto be aware of the various drug interactions that canoccur, most importantly drug–drug interactions anddrug–food interactions. The following section gives abrief overview of drug interactions. Specific drug–drugand drug–food interactions are discussed in subsequentchapters.

Drug—Drug Interactions

A drug–drug interaction occurs when one drug inter-acts with or interferes with the action of another drug.For example, taking an antacid with oral tetracyclinecauses a decrease in the effectiveness of the tetracycline.The antacid chemically interacts with the tetracyclineand impairs its absorption into the bloodstream, thusreducing the effectiveness of the tetracycline. Drugsknown to cause interactions include oral anticoagu-lants, oral hypoglycemics, anti-infectives, antiarrhyth-mics, cardiac glycosides, and alcohol. Drug–drug inter-actions can produce effects that are additive, synergistic,or antagonistic.

ADDITIVE DRUG REACTION. An additive drugreaction occurs when the combined effect of two drugsis equal to the sum of each drug given alone. Forexample, taking the drug heparin with alcohol willincrease bleeding. The equation one � one � two issometimes used to illustrate the additive effect of drugs.

SYNERGISTIC DRUG REACTION. Drug synergismoccurs when drugs interact with each other andproduce an effect that is greater than the sum of theirseparate actions. The equation one + one = four maybe used to illustrate synergism. An example of drugsynergism is when a person takes both a hypnotic andalcohol. When alcohol is taken simultaneously orshortly before or after the hypnotic is taken, the actionof the hypnotic increases. The individual experiences adrug effect that is greater than if either drug was takenalone. On occasion, the occurrence of a synergistic drugeffect is serious and even fatal.

ANTAGONISTIC DRUG REACTION. An antagonisticdrug reaction occurs when one drug interferes with theaction of another, causing neutralization or a decrease in

10 UNIT I ● Foundations of Clinical Pharmacology

the effect of one drug. For example, protamine sulfate is aheparin antagonist. This means that the administrationof protamine sulfate completely neutralizes the effects ofheparin in the body.

Drug—Food Interactions

When a drug is given orally, food may impair orenhance its absorption. A drug taken on an emptystomach is absorbed into the bloodstream at a faster ratethan when the drug is taken with food in the stomach.Some drugs (eg, captopril) must be taken on an emptystomach to achieve an optimal effect. Drugs that shouldbe taken on an empty stomach are administered 1 hourbefore or 2 hours after meals. Other drugs, especiallydrugs that irritate the stomach, result in nausea or vom-iting, or cause epigastric distress, are best given withfood or meals. This minimizes gastric irritation. Thenonsteroidal anti-inflammatory drugs and salicylatesare examples of drugs that are given with food todecrease epigastric distress. Still other drugs combinewith a drug forming an insoluble food–drug mixture.For example, when tetracycline is administered withdairy products, a drug–food mixture is formed that isunabsorbable by the body. When a drug is unabsorbableby the body, no pharmacologic effect occurs.

FACTORS INFLUENCING DRUGRESPONSE

●

Certain factors may influence drug response and are con-sidered when the primary health care provider prescribesand the nurse administers a drug. These factors includeage, weight, gender, disease, and route of administration.

Age

The age of the patient may influence the effects of a drug.Infants and children usually require smaller doses of adrug than adults do. Immature organ function, particu-larly the liver and kidneys, can affect the ability of infantsand young children to metabolize drugs. An infant’simmature kidneys impair the elimination of drugs in theurine. Liver function is poorly developed in infants andyoung children. Drugs metabolized by the liver may pro-duce more intense effects for longer periods. Parentsmust be taught the potential problems associated withadministering drugs to their children. For example, a safedose of a nonprescription drug for a 4-year-old child maybe dangerous for a 6-month-old infant.

Elderly patients may also require smaller doses,although this may depend on the type of drug adminis-tered. For example, the elderly patient may be given thesame dose of an antibiotic as a younger adult. However,the same older adult may require a smaller dose of a drugthat depresses the central nervous system, such as a nar-cotic. Changes that occur with aging affect the pharma-cokinetics (absorption, distribution, metabolism, andexcretion) of a drug. Any of these processes may bealtered because of the physiologic changes that occurwith aging. Table 1-3 summarizes the changes that occurwith aging and the possible pharmacokinetic effect.

Polypharmacy is the taking of numerous drugs thatcan potentially react with one another. When practicedby the elderly, polypharmacy leads to an increase in thenumber of potential adverse reactions. Although multi-ple drug therapy is necessary to treat certain diseasestates, it always increases the possibility of adverse reac-tions. The nurse needs good assessment skills to detectany problems when monitoring the geriatric patient’sresponse to drug therapy.

CHAPTER 1 ● General Principles of Pharmacology 11

AGE-RELATED CHANGES EFFECT ON DRUG THERAPY

Decreased gastric acidity; decreased gastric motility Possible decreased or delayed absorption

Dry mouth and decreased saliva Difficulty swallowing oral drugs

Decreased liver blood flow; decreased liver mass Delayed and decreased metabolism of certain drugs; possible increased effect, leading to toxicity

Decreased lipid content of the skin Possible decrease in absorption of transdermal drugs

Increased body fat; decreased body water Possible increase in toxicity of water-soluble drugs; more prolonged effects of fat-soluble drugs

Decreased serum proteins Possible increased effect and toxicity of highly protein-bound drugs

Decreased renal mass, blood flow, and glomerular Possible increased serum levels, leading to toxicity of drugs filtration rate excreted by the kidney

Changes in sensitivity of certain drug receptors Increase or decrease in drug effect

Adapted from Eisenhauer, L., Nichols, L., Spencer, R., & Bergan, F. (1998). Clinical pharmacology and nursing management (5th ed., p. 189). Philadelphia:Lippincott-Raven. Used with permission.

TABLE 1-3 Factors Altering Drug Response in the Elderly

Weight

In general, dosages are based on a weight of approxi-mately 150 lb, which is calculated to be the “average”weight of men and women. A drug dose may sometimesbe increased or decreased because the patient’s weight issignificantly higher or lower than this average. Withnarcotics, for example, higher or lower than averagedosages may be necessary to produce relief of pain,depending on the patient’s weight.

Gender

The gender of an individual may influence the action ofsome drugs. Women may require a smaller dose of somedrugs than men. This is because many women aresmaller than men and have a body fat-and-water ratiodifferent from that of men.

Disease

The presence of disease may influence the action ofsome drugs. Sometimes disease is an indication for notprescribing a drug or for reducing the dose of a certaindrug. Both hepatic (liver) and renal (kidney) diseasecan greatly affect drug response.

In liver disease, for example, the ability to metabolizeor detoxify a specific type of drug may be impaired. Ifthe average or normal dose of the drug is given, the livermay be unable to metabolize the drug at a normal rate.Consequently, the drug may be excreted from the bodyat a much slower rate than normal. The primary healthcare provider may then decide to prescribe a lower doseand lengthen the time between doses because liver func-tion is abnormal.

Patients with kidney disease may exhibit drug toxic-ity and a longer duration of drug action. The dosage ofdrugs may be reduced to prevent the accumulation oftoxic levels in the blood or further injury to the kidney.

Route of Administration

Intravenous administration of a drug produces the mostrapid drug action. Next in order of time of action is theintramuscular route, followed by the subcutaneousroute. Giving a drug orally usually produces the slowestdrug action.

Some drugs can be given only by one route; for exam-ple, antacids are given only orally. Other drugs are avail-able in oral and parenteral forms. The primary healthcare provider selects the route of administration basedon many factors, including the desired rate of action.For example, the patient with a severe cardiac problemmay require intravenous administration of a drug thataffects the heart. Another patient with a mild cardiacproblem may experience a good response to oral admin-istration of the same drug.

NURSING IMPLICATIONS●

Many factors can influence drug action. The nurseshould consult appropriate references or the hospitalpharmacist if there is any question about the dosage ofa drug, whether other drugs the patient is receiving willinterfere with the drug being given, or whether the oraldrug should or should not be given with food.

Drug reactions are potentially serious. The nurseshould observe all patients for adverse drug reactions,drug idiosyncrasy, and evidence of drug tolerance(when applicable). It is important to report all drugreactions or any unusual drug effect to the primaryhealth care provider.

The nurse must use judgment about when adversedrug reactions are reported to the primary health careprovider. Accurate observation and evaluation of thecircumstances are essential; the nurse should record allobservations in the patient’s record. If there is any ques-tion regarding the events that are occurring, the nursecan withhold the drug but must contact the primaryhealth care provider.

HERBAL THERAPY ANDNUTRITIONAL SUPPLEMENTS

●

Botanical medicine or herbal therapy is a type of com-plementary/alternative therapy that uses plants or herbsto treat various disorders. Individuals worldwide useboth herbal therapy and nutritional supplements exten-sively. According to the World Health Organization(WHO), 80% of the world’s population relies on herbsfor a substantial part of their health care. Herbs havebeen used by virtually every culture in the worldthroughout history, from the beginning of time untilnow. For example, Hippocrates prescribed St. JohnsWort, currently a popular herbal remedy for depression.Native Americans used plants such as coneflower, gin-seng, and ginger for therapeutic purposes. Herbal ther-apy is part of a group of nontraditional therapies com-monly known as complementary/alternative medicine(CAM). Unfortunately, CAM therapies are not widelytaught in medical schools. A 1998 survey revealed that75 of 117 US medical schools offered elective courses inCAM or included CAM topics in required courses.Complementary therapies are therapies such as relax-ation techniques, massage, dietary supplements, heal-ing touch, and herbal therapy that can be used to “com-plement” traditional health care. Alternative therapies,on the other hand, are therapies used in place of orinstead of conventional or Western medicine. The termcomplementary/alternative therapy often is used as anumbrella term for many therapies from all over theworld.

12 UNIT I ● Foundations of Clinical Pharmacology

Although herbs have been used for thousands ofyears, most of what we know has been from observation.Most herbs have not been scientifically studied for safetyand efficacy (effectiveness). Much of what we knowabout herbal therapy has come from Europe, particularlyGermany. During the last several decades, European sci-entists have studied botanical plants in ways that seek toidentify how they work at the cellular level, what chem-icals are most effective, and adverse effects related totheir use. Germany has compiled information on 300herbs and made recommendations for their use.

Dietary Supplement Health andEducation Act

Because herbs cannot be sold and promoted in theUnited States as drugs, they are regulated as nutritionalor dietary substances. Nutritional or dietary substancesare terms used by the federal government to identify sub-stances not regulated as drugs by the FDA but that arepurported to be effective for use to promote health.Herbs, as well as vitamins and minerals, are classified asdietary or nutritional supplements. Because naturalproducts cannot be patented in the United States, it isnot profitable for drug manufacturers to spend the mil-lions of dollars and the 8 to 12 years to study and developthese products as drugs. In 1994, the US governmentpassed the Dietary Supplement Health and EducationAct (DSHEA). This act defines substances such asherbs, vitamins, minerals, amino acids, and other natu-ral substances as “dietary supplements.” The act permitsgeneral health claims such as “improves memory” or“promotes regularity” as long as the label also has a dis-claimer stating that the supplements are not approved bythe FDA and are not intended to diagnose, treat, cure, orprevent any disease. The claims must be truthful and notmisleading and be supported by scientific evidence.Some have abused the law by making exaggerated claims,but the FDA has the power to enforce the law, which ithas done, and these claims have decreased.

Center for Complementary andAlternative Health

In 1992, the National Institutes of Health established anOffice of Alternative Medicine to facilitate the study ofalternative medical treatments and to disseminate theinformation to the public. In 1998, the name was changedto National Center for Complementary and AlternativeMedicine (NCCAM). This office was established partlybecause of the increased interest and use of these thera-pies in the United States. It has been estimated thatapproximately 40% of all individuals in the United Statesuse some form of complementary/alternative therapy. In 1997, Americans spent more that $27 billion on thesetherapies. Among the various purposes of the NCCAM,

one is to evaluate the safety and efficacy of widely usednatural products, such as herbal remedies and nutritionaland food supplements. Although the scientific study ofCAM is relatively new, the Center is dedicated to devel-oping programs and encouraging scientists to investigateCAM treatments that show promise. The NCCAM budgethas steadily grown from $2 million in 1993 to more than$68.7 million in 2000. This funding increase reflects thepublic’s interest and need for CAM information that isbased on rigorous scientific research.

Educating the Client on the Use of Herbsand Nutritional Supplements

The use of herbs and nutritional supplements to treatvarious disorders is common. Herbs are used for variouseffects, such as to boost the immune system, treatdepression, and for relaxation. Individuals are becomingmore aware of the benefits of herbal therapies andnutritional supplements. Advertisements, books, maga-zines, and Internet sites abound concerning these top-ics. People, eager to cure or control various disorders,take herbs, teas, megadoses of vitamins, and variousother natural products. Although much information isavailable on nutritional supplements and herbal ther-apy, obtaining the correct information sometimes is dif-ficult. Medicinal herbs and nutritional substances areavailable at supermarkets, pharmacies, health foodstores, specialty herb stores, and through the Internet.The potential for misinformation abounds. Becausethese substances are “natural products,” many individ-uals may incorrectly assume that they are withoutadverse effects. When any herbal remedy or dietary sup-plement is used, it should be reported to the nurse andthe primary health care provider. Many of these botani-cals have strong pharmacological activity, and some mayinteract with prescription drugs or be toxic in the body.For example, comfrey, an herb that was once widelyused to promote digestion, can cause liver damage.Although it may still be available in some areas, it is adangerous herb and is not recommended for use as asupplement.

When obtaining the drug history, the nurse mustalways question the patient about the use of herbs, teas,vitamins, or other nutritional or dietary supplements.Many patients consider herbs as natural and thereforesafe. It is also difficult for some to report the use of an herbal tea as a part of the health care regimen.Display 1-4 identifies teaching points to consider whendiscussing the use of herbs and nutritional supplementswith patients. Although a complete discussion about theuse of herbs is beyond the scope of this book, it is impor-tant to remember that the use of herbs and nutritionalsupplements is commonplace in many areas of the coun-try. To help the student become more aware of herbaltherapy and nutritional supplements, Appendix B gives

CHAPTER 1 ● General Principles of Pharmacology 13

an overview of selected common herbs and nutritionalsupplements. In addition, Herbal Alerts are placed invarious chapters throughout the book, giving the stu-dent valuable information or warnings about the use ofherbs.

● Critical Thinking Exercises

1. Judy Martin, a student nurse, has just administered anantibiotic to Mr. Green. When she returns to the roomabout 30 minutes later, she finds Mr. Green flushed,reporting a lump in his throat, and experiencing diffi-culty breathing. Determine what actions the studentnurse should take.

2. Jenny Davis, age 25, is pregnant. Jenny’s primaryhealth care provider tells her that she may not take anymedication without first checking with the health careprovider during the pregnancy. Jenny is puzzled andquestions you about this. Discuss how you wouldaddress Jenny’s concerns.

3. Ms. James, an 80-year-old woman, is receiving a lowerdose of Demerol, a narcotic analgesic, postoperativelyfor pain. Her family questions the use of a lower dose.Determine what information you would give her familywhen they voice concerns that the dosage will not ade-quately relieve their mother’s pain. Analyze what

patient assessment, if any, you would need to makebefore talking with the family.

● Review Questions

1. Mr. Carter has a rash and pruritus. You suspect anallergic reaction and immediately assess him for othermore serious symptoms of an allergic reaction. Whatquestion would be most important to ask Mr. Carter?

A. Are you having any difficulty breathing?B. Have you noticed any blood in your stool?C. Do you have a headache?D. Are you having difficulty with your vision?

2. Mr. Jones, a newly admitted patient, has a history ofliver disease. In planning Mr. Jones’ care the nursemust consider that liver disease may result in a (an) .

A. increase in the excretion rate of a drugB. impaired ability to metabolize or detoxify a drugC. necessity to increase the dosage of a drugD. decrease in the