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ii

Dedication

The Editors wish to express their sincere thanks and longstanding

admiration to the creators of Applied Therapeutics, Drs. Mary Anne

Koda-Kimble and Lloyd Young. They are truly educational visionaries

whom we deeply respect as the innovators and pioneers in the teaching of patient-centered drug therapeutics. Their passion has touched

the lives of countless health care professional students, clinicians, and

patients throughout the world. As their colleagues and friends, we are

forever indebted for their contributions and we consider it a privilege to

carry forward their legacy—renamed as Koda-Kimble and Young’s

Applied Therapeutics—into future editions.

iii

Preface

It has been nearly 40 years since the first edition of Applied Therapeutics: The Clinical Use of Drugs was published. The landscape

of health care has evolved radically during this time, much of it

spurred by remarkable advancements in drug discovery and clinical therapeutics. Despite these changes, the founding principle

for this innovative text—a patient-centric, case-based approach

to learning—remains integral to the current edition. Our authors

present more than 860 patient cases that stimulate the reader to

integrate and apply therapeutic principles in the context of specific clinical situations. Students and practitioners are provided

with a glimpse into the minds of clinicians as they assess and

solve therapeutic problems toward the development of their own

critical-thinking and problem-solving skills. Every chapter in this

edition has been revised and updated to reflect our ever-changing

knowledge of drugs and the application of this knowledge to the

individualized therapy of patients. Additionally, content within

several sections has been extensively reorganized, with new chapters introduced to expand important topics. Among these are

new chapters in the Arthritic Disorders, Women’s Health, Neurologic Disorders, Neoplastic Disorders, and Pediatrics sections.

Readers familiar with past editions of the text will notice some

welcome changes in the tenth edition. The overall design has

been updated for visual appeal and to allow the reader to more

quickly distinguish cases from surrounding text. In lieu of the traditional chapter outline, all chapters now contain a Core Principles section at the beginning, which provides the most important

“take home” information from the chapter. Each Core Principle

is mapped to specific cases within the chapter where the principle is discussed in detail. Key references and websites are listed at

the end of each chapter, whereas the full reference lists for each

chapter have been moved online.

A particularly significant change to the tenth edition is the

incorporation of online multimedia content, much of it authorcreated, for many of the chapters. These include images, videos,

narrated presentations, animations, and podcasts, which can be

found on the textbook’s website (see the “Additional Resources”

section, which follows this preface, for more information). The

incorporation of supplemental multimedia into the tenth edition marks a commitment on the part of the editorial team to

ensure that Koda-Kimble and Young’s Applied Therapeutics increases

its role as a viable and dynamic resource that can appeal to multiple learning styles and future generations. We welcome your

feedback as we undertake planning for the next edition.

The authors have drawn on information from the literature,

current standards, and their own clinical experiences to share the

process involved in making sound and thoughtful therapeutic

decisions. However, it remains the responsibility of every practitioner

to evaluate the appropriateness of a particular opinion in the context of

the actual clinical situation, bearing in mind any recent developments

in the field. We strongly urge students and practitioners to consult

several appropriate information sources when working with new and

unfamiliar drugs.

ACKNOWLEDGMENTS

We are deeply indebted to the many dedicated people who have

given of themselves to complete the tenth edition of Koda-Kimble

and Young’s Applied Therapeutics. As always, we are most grateful

to our contributing authors who have been attentive to meeting our stringent time deadlines and unique writing format. We

especially thank those authors who graciously provided multimedia to accompany their chapter, and we gratefully recognize

the additional time and effort this entailed. We hold their creativity in the highest regard. The exceptional work of our section

editors, Judith Beizer, Marcia Buck, Shareen El-Ibiary, Marcus

Ferrone, Patrick Finley, Timothy Ives, Mark Kirstein, Lisa Kroon,

Kelly Lee, Myrna Munar, Jean Nappi, Tricia Russell, and Joseph

Saseen, cannot be overstated. These content experts gave us critical feedback necessary in both the organizational structure of the

textbook and in the individual editing of chapters; without their

dedication and assistance, this edition would not be possible. We

would also like to thank Facts and Comparisons for allowing us

to use their data for the construction of some of our tables.

Two individuals from Lippincott Williams and Wilkins,

Meredith Brittain and Loftin (Paul) Montgomery, Jr., deserve

special recognition for their efforts. Their exceptional patience,

attention to detail, and firm guidance helped us all stay on task.

This edition would not have come to completion without their

partnership. Mary Tod (copyediting), Ed Schultes, Jr. (multimedia

production), and Jeri Litteral (typesetting) all played key roles in

the production of the tenth edition, and we sincerely thank them

for their assistance in completing this edition. Most importantly,

we would be remiss not to acknowledge the love, understanding,

and support of our spouses, children, and in some cases, grandchildren. They selflessly gave to us the many early mornings, late

nights, and weekends we spent writing and editing.

As in past editions, we continue to dedicate our work to our

students who inspire us and to the many patients we have been

privileged to care for. Our patients have repeatedly taught us how

critical it is to tailor our knowledge to their specific circumstances,

to listen well, and to welcome them as true partners in their care.

Brian K. Alldredge

Robin L. Corelli

Michael E. Ernst

B. Joseph Guglielmo

Pamala A. Jacobson

Wayne A. Kradjan

Bradley R. Williams

iv

Additional Resources

The Tenth Edition of Koda-Kimble and Young’s Applied Therapeutics: The Clinical Use of Drugs includes additional resources for

both instructors and students, available on the book’s companion website at http://thepoint.lww.com/AT10e.

STUDENT RESOURCES

Students who have purchased Koda-Kimble and Young’s Applied

Therapeutics: The Clinical Use of Drugs, Tenth Edition have access

to the following additional resources for each chapter:

 An audio recording of that chapter’s core principles

 A full online reference list for that chapter

In addition, at least one of the following supplements each chapter to enhance the chapter content:

 Audio files (most recorded by author)

 PowerPoints (most created by author)

 PowerPoints with audio (most created/recorded by author)

 Animations

 Videos (some created by author)

 Additional content (created by author)

 Interactive versions of the algorithms found in the book

 Full-color images

INSTRUCTOR RESOURCES

Approved adopting instructors will be given access to the following additional resources:

 PowerPoint slides

 Image bank (includes all images and tables in the book)

 Pathophysiology image collection

In addition, purchasers of the text can access the searchable Full

Text On-line by going to the Koda-Kimble and Young’s Applied

Therapeutics: The Clinical Use of Drugs, Tenth Edition website at

http://thepoint.lww.com/AT10e. See the inside front cover for

more details, including the passcode you will need to gain access

to the website.

v

EPIDEMIOLOGY

1 In 2009, 2.48 million poisonings were reported to the American Association of

Poison Control Centers. Half of these exposures occur in children younger than

6 years of age and usually involve a single substance that is found in the home such

as personal care items, analgesics, and cleaning agents. The elderly have access to

numerous and dangerous medications and have a higher rate of completed suicide

attempts than other age groups.

Case 4-1 (Questions 2, 3)

GENERAL MANAGEMENT

1 The most important aspect of patient management is to support airway, breathing,

and circulation (the “ABCs”). There is no “cookbook” method to treat all poisoned

patients, so it is important to treat the patient, not the poison or the laboratory

values. The assessment and treatment of the potentially poisoned patient can be

separated into seven functions: (a) gather history of exposure, (b) evaluate clinical

presentation (i.e., “toxidromes”), (c) evaluate clinical laboratory patient data,

(d) remove the toxic source (e.g., irrigate eyes, decontaminate exposed skin),

(e) consider antidotes and specific treatment, (f) enhance systemic clearance, and

(g) monitor patient outcome.

Case 4-4 (Questions 1, 5, 6)

GASTROINTESTINAL DECONTAMINATION

1 The most appropriate method for gastrointestinal (GI) tract decontamination is

unclear because sound comparative data for different methods of GI

decontamination are not available. Lavage, emesis, and cathartics are rarely

performed as there is no evidence they improve patient outcome. Activated

charcoal is generally safe to use, but it should not be administered if the benefit is

not greater than the risk. Whole bowel irrigation using a polyethylene glycol–

balanced electrolyte solution can successfully remove substances (iron, lithium,

sustained-release dosage forms) from the entire GI tract in a period of several

hours.

Case 4-3 (Questions 6, 7),

Case 4-4 (Questions 11, 12,

16), Case 4-5 (Question 3)

ANTIDOTES

1 An antidote is a drug that neutralizes or reverses the toxicity of another substance.

Some antidotes displace drugs from receptor sites (e.g., naloxone for opioids,

flumazenil for benzodiazepines), and some can inhibit the formation of toxic

metabolites (e.g., N-acetylcysteine [NAC] for acetaminophen, fomepizole for

methanol).

Case 4-4 (Questions 2, 4)

continued

65

66 Section 1 General Care

CHAPTER CASES