Painkillers History, Science, and Issues, 1st Edition

Visit the link below to download the full version of this book:

https://medipdf.com/product/painkillers-history-science-and-issues-1st-edition/

Click Download Now

Copyright © 2016 by ABC-CLIO, LLC
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by
any means, electronic, mechanical, photocopying, recording, or otherwise, except for the inclusion of brief quotations in a review,
without prior permission in writing from the publisher.
Library of Congress Cataloging-in-Publication Data
Names: Stolberg, Victor B.
Title: Painkillers : history, science, and issues / Victor B. Stolberg.
Other titles: Pain killers
Description: Santa Barbara, California : Greenwood, [2016] | Series: The story of a drug | Includes bibliographical references
and index.
Identifiers: LCCN 2015047059 | ISBN 9781440835315 (hard copy : alk. paper) | ISBN 9781440835322 (ebook)
Subjects: LCSH: Analgesics. | Analgesics—History.
Classification: LCC RM319 .S76 2016 | DDC 615.7/83—dc23
LC record available at http://lccn.loc.gov/2015047059
ISBN: 978–1–4408–3531–5
EISBN: 978–1–4408–3532–2
20 19 18 17 16 1 2 3 4 5
This book is also available on the World Wide Web as an eBook.
Visit www.abc-clio.com for details.
Greenwood
An Imprint of ABC-CLIO, LLC
ABC-CLIO, LLC
130 Cremona Drive, P.O. Box 1911
Santa Barbara, California 93116-1911

This book is printed on acid-free paper

Manufactured in the United States of America

This book discusses treatments (including types of medication and mental health therapies), diagnostic tests for various
symptoms and mental health disorders, and organizations. The authors have made every effort to present accurate and up-to-
date information. However, the information in this book is not intended to recommend or endorse particular treatments or
organizations, or substitute for the care or medical advice of a qualified health professional, or used to alter any medical therapy
without a medical doctor’s advice. Specific situations may require specific therapeutic approaches not included in this book. For
those reasons, we recommend that readers follow the advice of qualified health care professionals directly involved in their
care. Readers who suspect they may have specific medical problems should consult a physician about any suggestions made in
this book.
 I would like to dedicate this book to my immediate family, particularly my wife, Marie Rose,
and our two young sons, Victor and George, for their support and tolerance during my work on
this project.
 Contents
Series Foreword
Preface
Acknowledgments

Chapter 1: A Case Study: Misery and Relief

Case 1: Misery
Case 2: Relief
Review

Chapter 2: What Are Painkillers?

Different Classes of Painkillers
Opiates
Opioids
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
COX-2 Inhibitors
Other Painkillers
Other Approaches to Pain Management
Acupuncture
Biofeedback
Chiropractic
Massage
Exercise
Hypnosis
Relaxation
Nutrition
Aromatherapy
Electrotherapy
Document: Major Categories of Pain Treatments
Chapter 3: Painkillers: A Brief History
Early Evidence of Opium
Antiquity
Mesopotamia
Egypt and the Ancient Near East
Greece and Rome
Gods and Goddesses
Middle Ages and Beyond
Cross-Cultural Evidence
Middle East
India
Asia
Empires
China
Immigration
Opium Trade
Development of Morphine
Morphine Use
Serturner’s Isolation
Spread of Use
Modern Era
Other Opiates
Heroin and More
Illicit Production of Heroin
Other Painkillers
Document: “Bayer’s Pharmaceutical Specialities”
Document: “Perry Davis’ Painkiller”

Chapter 4: How Painkillers Work

What Is Pain?
Acute Pain
Chronic Pain
Nociceptive Pain
Inflammatory Pain
Dysfunctional Pain
Neuropathic Pain
Pain Assessment
Neurotransmission
Neuron: Structure and Function
Impulse Transmission
Cellular Level of Pain
Mechanisms of Painkiller Action
Document: Nociceptive versus Neuropathic Pain
Chapter 5: Effects and Applications
Ways to Use Painkillers
Administration
Combinations
Smoking
Strategic Resource
Patent Medicines
Therapeutic Levels and Effects
Opiates and Opioids
Morphine
Over-the-Counter and Other Painkillers
Document: Bioavailability and Potency of Different Opioids

Chapter 6: Risks, Misuse, and Overdose

Adverse Effects, Dependence, and Misuse
Risk Potential and Semisynthetic Opioids
Over-the-Counter and Related Painkiller Concerns
Misuse
Abuse and Addiction
Risk of Dependence
Addiction Treatments
Methadone
Fentanyl
Etorphine and Dihydroetorphine
LAAM
Buprenorphine
Opioid Antagonists
Overdose
Over-the-Counter Painkiller Overdose
Other Problems
Document: How Different Misusers of Pain Relievers Get Their Drugs
Document: Overdose Deaths Involving Opioid Analgesics, Cocaine, and Heroin

Chapter 7: Production, Distribution, and Regulation

Policy Issues
Early Initiatives
Pure Food and Drug Act
Opium Exclusion Act
Harrison Narcotics Act
United Kingdom and the League of Nations
Narcotics Drug Import and Export Act
Porter Narcotic Farm Act
Enforcement Initiatives
 Boggs Act
Treatment Initiatives
United Nations Conventions
Rehabilitation Shift
Historical Policy Lessons
More Recent Moves
Clinical Trials
Phase I Clinical Trials
Phase II Clinical Trials
Phase III Clinical Trials
Phase IV Clinical Trials
Meta-analysis
Critiques of the Clinical Trial System
Sample Selection
Publication Concerns
Role of the Controlled Substances Act
Scheduling of Drugs
Opiates
Synthetic Opioids
Phenylpiperidine Group
Diphenylpropylamine Derivatives
Benzomorphan Derivatives
Anilidopiperidine Family
Oripavine Derivatives
Morphinan Derivatives
Tramadol and Others
Non-Opioid Painkillers
Aspirin
Ibuprofen
Acetaminophen
Other Analgesics
Document: How Drugs Are Developed and Approved

Chapter 8: The Social Dimension of Painkillers

Social Reform Pressures
20th Century
Stigma
21st Century
Treatment Approaches
Early Treatments
Substitution
Detoxification
Elsewhere
 Behavioral Approaches
Therapeutic Communities
Methadone Treatment
Agonist and Antagonist Medications
Overdose Fatalities
Special Populations
Document: “What Every Individual Needs to Know About Methadone Maintenance
Treatment”

Chapter 9: The Future of Painkillers

Development of New Painkillers
Reducing Abuse
Criminal Justice Initiatives
Patient Rights
Summary
Document: A Model Policy for the Use of Painkillers

Directory of Resources
Glossary
Bibliography
Index
 Series Foreword
While many books have been written about the prevalence and perils of recreational drug use,
what about the wide variety of chemicals Americans ingest to help them heal or to cope with
mental and physical issues? These therapeutic drugs—whether prescription or over the counter
(OTC), generic or brand name—play a critical role in both the U.S. health care system and
American society at large. This series explores major classes of such drugs, examining them
from a variety of perspectives, including scientific, medical, economic, legal, and cultural.
For the sake of clarity and consistency, each book in this series follows the same format.
We begin with a fictional case study bringing to life the significance of this particular class
of drug. Chapter 2 provides an overview of the class as a whole, including discussion of
different subtypes, as well as basic information about the conditions such drugs are meant to
treat. The history and evolution of these drugs is discussed in Chapter 3. Chapter 4 explores
how the drugs work in the body at a cellular level, while Chapter 5 examines the large-scale
impacts of such substances on the body and how such effects can be beneficial in different
situations. Dangers such as side effects, drug interactions, misuse, abuse, and overdose are
highlighted in Chapter 6. Chapter 7 focuses on how this particular class of drugs is produced,
distributed, and regulated by state and federal governments. Chapter 8 addresses professional
and popular attitudes and beliefs about the drug, as well as representations of such drugs and
their users in the media. We wrap up with a consideration of the drug’s possible future,
including emerging controversies and trends in research and use, in Chapter 9.
Each volume in this series also includes a glossary of terms and a collection of print and
electronic resources for additional information and further study. To supplement the main text,
Chapters 2 through 9 include end-of-chapter primary documents, which offer readers
additional insights.
It is our hope that the books in this series will not only provide valuable information, but
will also spur discussion and debate about these drugs and the many issues that surround them.
For instance, are antibiotics being overprescribed, leading to the development of drug-resistant
bacteria? Should antipsychotics, usually used to treat serious mental illnesses such as
schizophrenia and bipolar disorder, be used to render inmates and elderly individuals with
dementia more docile? Do schools have the right to mandate vaccination for their students,
against the wishes of some parents?
As a final caveat, we wish to emphasize that the information we present in these books is no
substitute for consultation with a licensed health care professional, and we do not claim to
provide medical advice or guidance.

—Peter L. Myers, PhD

Emeritus member, National Addiction Studies Accreditation Commission Past President,
International Coalition for Addiction Studies Education Editor-in-Chief Emeritus, Journal of
Ethnicity in Substance Abuse
 Preface
The title of this work might be a little misleading, as a discussion of painkillers is not simply
the story of “a” drug, but rather the story of several somewhat similar but also of many other
somewhat disparate drugs. There are, as you will discover in reading this work, many different
drugs that are used as painkillers. This book will present an overview of opium, morphine,
other opiates and opioids, and of other painkiller use and abuse from ancient times to the
contemporary era; these other painkiller drugs include non-steroidal anti-inflammatory drugs
and an array of many different other substances, some of which are available for sale over the
counter, while others are available only with a physician’s prescription, and some of which are
available both ways, usually with the higher dosages of the painkiller medication requiring a
prescription from a medical professional. Each painkiller drug, or at least groups of painkiller
drugs, has its own somewhat unique story; thus this story is composed of many different
stories.
The historical and cross-cultural background of painkiller use and abuse will be examined
along with considerations of various societal approaches of how to deal with these issues.
This consideration will utilize historical studies of respective painkiller drugs, principally
opium and morphine, from various time periods that can be used for developing a better
understanding of the historical background of such phenomena. Attention will first be
concerned with the early evidence for the use of opium, including discussion of Near Eastern
civilizations, particularly Egyptian and Mesopotamian, as well as those from elsewhere in the
world, notably including China and India. Cross-cultural evidence of painkiller use and abuse
elsewhere will also be presented. The development of morphine and other similar painkillers
will briefly be reviewed. Historical studies of opiates, opioids, and other painkiller drugs, as
well as those reviewing specific approaches to addressing abuse at various time periods, and
other related works will be used in an attempt to provide a richer and fuller appreciation of the
broad dimensions of the field. A brief review of the science of how different painkiller drugs
work will also be presented along with coverage of their respective effects and applications.
Attention will also be directed at some of the risks of painkiller use, their misuse, and potential
overdose concerns. We will also explore issues around the production, distribution, and
regulation of respective painkiller drugs. This discussion will include the early evidence of
painkiller use, cross-cultural evidence, modern developments, abuse patterns, treatment
approaches, policy issues, and several other additional perspectives.
This work is intended to broaden the scope of the participant’s frame of reference within the
area of historical and cultural foundations of addiction studies by focusing on the story of
painkiller drugs, examining the pharmacological basis of their effects and applications, risks,
production, distribution, and regulation, as well as reviewing some of the social dimensions of
the use and abuse of painkiller drugs, and thoughts on the future of these particular type of
drugs.
 Acknowledgments
I would like to acknowledge my family, particularly my wife and two young sons, for their
support and tolerance during this project. I would also like to thank all the staff behind the
scenes at ABC-CLIO. Chiefly, I would like to heartedly thank the series editor, my good friend
and colleague of nearly three decades, Dr. Peter L. Myers. His unwavering support and
friendship has been a stalwart base not only for much of my career advancement, but also for
my own personal growth and development. I am particularly indebted to his insightful
criticisms and helpful suggestions that have contributed to the completion of the present
volume.
Most importantly, I would like to acknowledge all of those individuals struggling with
painkillers and other drugs of abuse. The hard work of so many individuals in recovery
striving to improve their lives and health is a testament to humanity at its best.
 Chapter 1
A Case Study: Misery and Relief

Not all individuals use drugs for the same reasons, nor will they all have the same experiences
with the use of a particular drug whether it is or is not a painkiller or any other type of drug.
Many individuals will try a particular drug, use it for a time, perhaps for only a short period of
time, and then leave it alone and move on with the rest of their lives. Other individuals relate
that from the very first time that they tried a particular drug, they became hooked and
progressively moved through the stages to addiction. Such varied tales, and many more, are
certainly true with respect to individual users of respective painkiller drugs. We will briefly
examine two fictitious case studies to examine some of the types of interactions that can occur
among those who come to use these painkiller drugs and the varied impacts that this practice
causes in their lives.

CASE 1: MISERY
Trevor is an African American male, age 47; he is 5 feet 10 inches tall and weighs 178
pounds. Trevor’s high school years were trying for him and his family; he got involved briefly
with a small street gang and was smoking marijuana and drinking alcoholic beverages almost
every day. Trevor was also very gifted intellectually and athletically. He was actually an
outstanding young student-athlete, winning many awards and trophies. He played basketball
and ran track. Trevor used to work part time as a mover while he was in his freshman year at
college. One day, while moving a large leather couch, he seriously hurt his lower back. He
went to see a doctor who gave him a prescription for Vicodin. Vicodin was the trade name for
a combination pharmaceutical product that contained doses of both acetaminophen and
hydrocodone. Hydrocodone, of course, is a powerful opioid painkiller medication, and
acetaminophen is a less potent non-steroidal anti-inflammatory drug, or NSAID, that increases
the effects of the hydrocodone. Vicodin was intended to be used for relief of moderate to
severe pain.
 Trevor was supposed to take 2 Vicodin pills twice a day as prescribed. He was initially
prescribed the formulation of Vicodin that consisted of 300 mg of acetaminophen and 5 mg of
hydrocodone. However, not long after starting to use the Vicodin, Trevor felt that the 2 pills
were not strong enough, so he started taking more. This should not be too surprising, as only
about 50% of prescribed medications are, according to the World Health Organization (WHO),
taken in accordance with directions. He soon then progressed to 3 pills twice a day, and not
too long thereafter, he was taking 3 pills 3 times a day as his tolerance increased. Trevor was
able to get his prescription changed to the stronger formulation of Vicodin that consisted of 500
mg of acetaminophen and 5 mg of hydrocodone. However, he was not much more satisfied with
that dosage, and not long thereafter, he found another doctor who gave him a prescription for
Vicodin HP, a formulation of Vicodin that consists of 600 mg of acetaminophen and 10 mg of
hydrocodone. However, Trevor’s pharmacist substituted the generic formulation of Vicodin,
which is manufactured by Norco, and each pill consists of 325 mg of acetaminophen and 10 mg
of hydrocodone. He was more than satisfied with its effects. The Vicodin did not just numb the
pain in his lower back, however; he really, really liked the way it made him feel. When using
the Vicodin, Trevor felt more relaxed than usual and he was less anxious about things in his
life. But he was tired a lot of the time, and on some days he even had to push himself to get out
of the house. In addition, he often became somewhat depressed and wondered if his life would
ever get any better while having these types of feelings. Trevor dropped out of college after the
beginning of his sophomore year; he would soon have been expelled for poor academic
performance anyhow.
One day Trevor’s Vicodin prescription ran out, and he quickly started to feel really sick. He
was soon sweating profusely without engaging in any physical activity, and his whole body
was in intense pain. He felt better only after he got his prescription refilled. Trevor had
developed high tolerance, and he was dependent on the drug at that point. He needed to take his
painkiller medication just to not feel in pain. His body started to show the wear and tear of his
drug abuse. The acetaminophen in the high levels of Vicodin he had consumed over the years of
abuse had caused severe deterioration to most of his vital body organs, particularly his liver.
Trevor started looking for different doctors so that he could get more Vicodin prescriptions.
He would lie to the doctors and tell them that he was in horrible pain, far worse than he really
was feeling. One day Trevor intentionally slammed a door on his finger and broke it. This
helped him get even more pills. Another time he had a friend pull out a tooth so that he could
go to a dentist whom he had heard would write painkiller prescriptions for him. When he
visited his grandmother’s house, he would check her medicine cabinet for any pills he could
take.
Trevor had so many different prescriptions from so many different doctors that he had to go
to different pharmacies to fill his Vicodin prescriptions. One day he went to a pharmacy with
his mother, and the pharmacist told him that he could not fill his prescription. Their computer
records indicated that Trevor had already purchased a lot of Vicodin pills in a rather brief
period of time at many different pharmacies. He was embarrassed that he was caught, but he
was really ashamed that his mother heard the whole thing.
Vicodin was a potent painkiller that was a combination formulation of hydrocodone
bitartrate and acetaminophen. On December 9, 1988, the U.S. Food and Drug Administration
(FDA) approved the marketing of Vicodin by Abbvie; it was first produced as an oral tablet
composed of 500 mg of acetaminophen and 5 mg of hydrocodone bitartrate, but was on that
date approved as a 750 mg acetaminophen and 7.5 mg hydrocodone bitartrate combined-
formulation oral tablet. On September 23, 1996, the FDA approved the marketing of a more
potent 660 mg acetaminophen and 10 mg hydrocodone bitartrate combination formulation oral
tablet manufactured by Abbvie. This is the form of Vicodin that Trevor started using. In 2007,
99% of hydrocodone was consumed in the United States, and by 2012, it was the most
commonly prescribed opioid in the United States. However, there were mounting concerns
with Vicodin. On June 30, 2009, an FDA advisory panel voted to remove Vicodin from the
market because of the high likelihood of overdose. On October 6, 2014, hydrocodone was
moved from a Schedule III to a more controlled Schedule II drug.
Trevor was a very bright young man, and he well knew that he had reached the point of
having a very serious drug problem. However, he was too proud to ask anyone for help. He
had tried going cold turkey a few times, but as soon as the pain of the withdrawal symptoms
from this painkiller arose, he picked up again, and again. He then tried to taper off his use by
cutting down his daily dosage; he was able to make it for 2 days at half of his normal dose,
then he went a day and a half of being clean. The second day of not using, his regular supplier
showed up unannounced with a ready stash. Trevor purchased a bag of pills from his dealer,
but after an hour and a half of relying on his willpower to not pick up, he gave in to the
overwhelming temptation and was back to his habitual level of use. The next time that he tried
to detox by tapering off his use, he made it longer because he had gotten some Xanax, which is
a formulation of alprazolam, a benzodiazepine medication. Trevor found that taking 0.5 mg of
alprazolam every 3 hours helped him amazingly to cope with the withdrawal symptoms. He
made it a week clean from the Vicodin, but the Xanax was increasing his feelings of anxiety
and also gave him some very troubling insomnia. So he stopped the Xanax and relapsed back
to the Vicodin.
The next change in Trevor’s drug use came when he found a bottle of OxyContin at his
girlfriend’s mother’s house. The OxyContin pills contained the semisynthetic opioid oxycodone
as their active ingredient, and Trevor discovered that these pills not only covered the pain of
withdrawal, but made him feel really good. Oxycodone had thereby become his new drug of
choice. As it was getting progressively more difficult for Trevor to obtain prescriptions to
maintain his level of painkiller drug use, he moved into the world of illicit drug supplies. He
easily found a drug dealer in his neighborhood who, for a price, would supply him with as
many painkiller pills of whatever type as long as he could afford to pay for them.
While Trevor was taking the Vicodin, and when he switched over primarily to OxyContin,
he was always drinking alcoholic beverages and dabbling with assorted other drugs as well.
He was clearly an example of what is commonly referred to as a polydrug abuser. Since
polydrug abuse is regarded as being symptomatic of various underlying social or personality
disorders, its treatment can be rather complex. It is generally felt that outpatient detoxification
is rarely successful for this type of drug abuser. Withdrawal from this dependence on an
inpatient basis in a drug-free environment used to be the gold standard of care, but we have
since come to appreciate the value of medication-assisted treatment, particularly for the phase
of detoxification. The use of clonidine, for instance, is preferred by many clinicians.