Pain and Its Relief Without Addiction

Clinical Issues in the Use of Opioids and Other Analgesics

Barry Stimmel

• Publisher: Routledge
• Year: 2014
• Print ISBN: 9781560249061
• eBook ISBN: 9781317826965
• Topic: Medicina
• Subtopic: Anestesiología y gestión del dolor

Pain and Its Relief Without Addiction will help people in pain understand why their pain is not always adequately relieved, as well as help reverse the failure of current medical practice to routinely alleviate pain. As noted by a 1992 publication of the United States Department of Health Services, this devastating trend contributes to unnecessary discomfort, longer recovery periods, and compromised patient outcomes. By reading this book, frustrated physicians and, perhaps more importantly, persons in pain can acquire a better understanding of the nature of pain, its connection to the emotions and psychological state of patients, and the impact particular drugs have on the body; this will facilitate relief from pain among a higher percentage of the population.Opioid analgesics comprise many of the chapters in Pain and Its Relief Without Addiction. Author Barry Stimmel, MD, describes the principles to be followed in prescribing opioid analgesics to relieve pain while maintaining one's daily activities without any limitation in function. The available opioids are described, and the differences between them are reviewed to allow you--as a physician, health care provider, or even a patient--to gain a better insight into the one(s) to use for both acute and chronic pain states. The point that is emphasized is that dependency on an analgesic to relieve pain is no different than dependency on medications to lower blood pressure, prevent heart attacks, treat diabetes, etc. What should be avoided is "addiction," a condition where function is impaired rather than enhanced.Pain and Its Relief Without Addiction is a guidebook designed to assist physicians and other health professionals in developing a practical approach to pain management and to give patients a fuller understanding of their pain. You'll gain specific information about:

• management of acute and chronic pain
• pain in children
• pain and cancer
• pain and AIDS
• psychological support of persons in pain
• theories of pain perception
• the anatomy of painIn Pain and Its Relief Without Addiction, you'll learn the basic concepts of drug dependence, tolerance, and withdrawal, the pharmacological actions and side effects of drugs used to provide analgesia, and the fundamental steps to be taken in proper pharmacological treatment of pain. The book produces more effective and more informed communication among physicians, other health professionals, and patients so that together they can achieve better pain relief. As Pain and Its Relief Without Addiction illustrates, it is crucial that both patients and physicians understand clearly the terms describing drug use and the behavioral, biochemical, and cellular concepts underlying dependence, tolerance, and withdrawal. Finally, you will acquire a knowledge of all the potential causes of pain and the appropriate steps for intervention.Medical students, new practitioners, and those wishing to reconsider their approaches to pain management will benefit from the book's coverage of general principles for pain control, the use of drug combinations to provide the most effective relief, methods for treating pain in different populations (such as the elderly and persons with chronic medical conditions), and alternative options for failed treatment. The scope of Pain and Its Relief Without Addiction reaches from nonprescription medications, such as aspirin, to NSAIDS, like ibuprofen, to narcotic analgesics to stimulants such as amphetamines and caffeine. It is the most comprehensive book available on various drugs, their desired effects and side effects, and their use to alleviate pain.

Section II:
Drugs Used to Relieve Pain

Chapter 5
Nonopioid Analgesics and Nonsteroidal Anti-Inflammatory Drugs

Introduction

The nonnarcotic analgesics are among the most widely used “pain killers” considered by both the public and by physicians to be effective and extremely safe, and, depending on the specific drug, may be purchased as over-the-counter (OTC) medications without prescriptions. The avidity of the American public for these drugs make them the most frequently purchased OTC medications responsible for approximately $650 million in purchases annually.¹ Unfortunately, these analgesics are also among the most common causes of inadvertent poisoning. In susceptible individuals, excessive use may also be associated with a number of complications.

These drugs are quite effective analgesics for mild and, at times, even moderate pain. Some of the newer nonsteroidal anti-inflammatory drugs are capable of providing pain relief equal to that seen with the more potent oral narcotic agents. Unlike the drugs in the opiate or narcotic group, a maximum analgesic effect is usually reached with increasing doses and tolerance does not appear to develop.

The Salicylates

History

Aspirin (acetylsalicylic acid) is the most extensively used nonnarcotic analgesic antipyretic and anti-inflammatory agent. The effectiveness of salicylates in relieving pain can be traced over 2,000 years ago when Hippocrates used the bark of the willow tree (salax) for relief of pain and fever. Many years later, in 1763, the Reverend Edward Stone reported the value of the willow bark in reducing fevers. The active ingredient of willow bark remained unknown until Laroux, in the early 1830s, was able to isolate salicin from the bark. This was followed by the preparation of salicylic acid from salicin, a substance found to exhibit all of the activity of the willow bark in much smaller doses. Synthetic production of salicylic acid was soon accomplished. However, its insolubility in water and its irritating and corrosive effects on the skin allowed only external application. The development of the sodium salt, sodium salicylate, and its subsequent use as an antipyretic for rheumatic fever in 1875, initiated recognition of their effectiveness.² In 1853, Von Gerhardt at the Bayer Chemical Works in Elberfield, Germany, synthesized acetylsalicylic acid (aspirin). It was not until a number of years later, however, that advantages of aspirin over sodium salicylate became well recognized with its use being widespread by the start of the twentieth century.

Available Preparations

At the present time, aspirin is the most extensively utilized of all the nonnarcotic analgesics, available in numerous OTC preparations (Tables 5.1 and 5.2) alone or in combination with mild narcotics to potentiate analgesia. A number of other salicylate preparations are also available (Table 5.3). Although some of these preparations differ from aspirin, with respect to absorption and toxicity, with the exception of diflunisal (Dolobid), none provide greater analgesia.

Available aspirin preparations can best be grouped as plain, buffered, or enteric coated tablets, timed-release caplets, and buffered solutions. Most recently, intravenous preparations of salicylate have been used to treat mild, postoperative pain. The following discussion concerning the effects of salicylates and their use as analgesics, however, will focus on aspirin as the prototype, unless otherwise noted.

Pharmacology

Absorption

Following ingestion, salicylates are absorbed from the stomach as well as the upper parts of the small intestine. All aspirin preparations, however, are not alike with respect to solubility or their ability to neutralize gastric acids (buffering capacity) (Table 5.2). Although plasma concentrations may be detected in less than 30 minutes after a single dose with ordinary aspirin tablets, maximal plasma levels may not be reached until more than two hours after ingestion. The administration of aspirin as a solution, such as effervescent aspirin, results in a maximum level within less than 30 minutes.³

TABLE 5.1. Selected Nonprescription Analgesic Combinations

TABLE 5.2. Aspirin Preparations

	Average daily dose (g)
Aspirin	3.6
Buffered Aspirin	3.6
Effervescent Aspirin	3.6
Enteric-Coated Aspirin	3.6
Timed-Release Aspirin	1.8

The precise plasma level at which analgesic effect may be obtained has been unable to be quantified. Controversy also exists as to the clinical significance of rapidity of absorption of different preparations. However, it has been suggested that with ordinary aspirin tablets, contrary to popular opinion, at least one hour may pass before analgesia can be objectively detected.⁴ This may be contrasted to the analgesic effect of aspirin given in solution, which may appear within 30 minutes.³

Absorption is rapid and mainly in the upper part of the small intestine, although absorption in the stomach can also occur. Increasing the pH results in a greater degree of ionization and a shortened time of dissolution. The first effect would tend to decrease the rate of absorption; the second would facilitate

TABLE 5.3. Available Salicylate Preparations

it. The quantity of buffer actually present in buffered preparations, however, may not produce either a significant decrease in gastric acidity or a diminished incidence of gastrointestinal side effects.⁵ The use of buffers to shorten the time to relieve pain therefore is marginally effective. Buffered aspirin solutions contain more buffer than tablets and may cause less gastric irritation and bleeding. However, their high sodium content and their ability to rapidly increase urine pH can be associated with increasing urinary salicylate excretion, preventing effective long-term administration.^4,6 In addition, some preparations contain insufficient quantities of buffers to effectively change the pH. Enteric-coated aspirin probably provides the best protection against intestinal mucosal injury.⁵ Although a major drawback to the use of enteric-coated aspirin had been a variable dissolution and absorption, newer products are more dependable. These preparations are ideal for single dose administration. Time-delayed preparations, although able to be taken less frequently, are probably of limited value; with continued use of regular aspirin preparations, an extremely long half life in the plasma develops.

Absorption of aspirin may be delayed by the presence of food or other substances, the rate at which the stomach empties, the pH, and the concomitant use of antacids. Salicylic acid preparations that are nonacetated are associated with a lower incidence of gastrointestinal side effects. Both salicylic acid and methyl salicylate may be rapidly absorbed when applied cutaneously. Rectal absorption of salicylate is variable and slower than that seen with ingestion.

Distribution

Subsequent to absorption, aspirin is rapidly distributed to all body tissues, and rapidly hydrolyzed in the gastrointestinal mucosa and liver to salicylic acid so that plasma concentrations are usually difficult to detect. Plasma levels of aspirin are considerably higher when administered in solution. Approximately 80 percent to 90 percent of salicylate is bound to plasma proteins, predominantly albumin. The presence of hypoalbuminemia may be associated with a higher level of free salicylate, which may predispose to salicylate toxicity.

Biotransformation and Excretion

Metabolism occurs predominantly in the hepatic microsomal system. Excretion occurs mainly through the kidney as free salicylic acid (10 percent), acyl glucuronides (5 percent), and gentisic acid (less than 1 percent).^7,8 Renal excretion is so rapid that, under usual conditions, only salicylic acid can be detected in the body. Metabolism, however, is rate limited. Increasing aspirin doses above the body’s metabolic capacity will result in an increase in the proportion of salicylic acid found in the urine.⁸ Urinary pH greatly affects salicylate excretion. Alkalinization will be associated with over 30 percent excretion of free salicylate, whereas acidification of urine inhibits ionization and is accompanied by a back diffusion of salicylate, with the free salicylate excretion diminishing to as low as 5 percent.

Pharmacologic Effects

Analgesic Activity

Salicylates are effective analgesic agents best suited for relief of mild to moderate pain, especially when inflammation contributes to the painful experience. In such instances they are preferred to the more potent narcotic (opiate) analgesics. Tolerance does not develop and dependence is quite unusual. Aspirin and related drugs have long been considered peripheral analgesics; however, over the years, the evidence has accumulated suggesting that they may have an analgesic effect on the central nervous system as well.⁸ The peripheral effects of aspirin are felt to be related to the blocking of impulse generation.⁹ Pain, especially in the presence of inflammation, is felt to be initiated by prostaglandin release. Aspirin inhibits both synthesis and release of prostaglandins by blocking the activity of cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostaglandin. Recently two isoenzymes of COX have been identified. COX-1 is felt to have a “protective” role on the mucosa of kidney and stomach, whereas COX-2 is involved in the inflammatory response and production of pain. Since aspirin is rapidly hydrolyzed to salicylic acid, which has minimal analgesic activity, other mechanisms may also be i...

Table of contents

• Cover Page
• Half Title page
• Title Page
• Copyright Page
• Dedication
• About the Author
• Contents
• Preface
• Acknowledgments
• Section I Physiological Concepts of Pain and Dependence
• Section II Drugs Used to Relieve Pain
• Section III The Practical Management of Pain
• Section IV Management of Pain in Special Populations
• Index