FMA Pain Management Journal - August 2006 by Florida Medical Association

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CME Objectives After participating in this enduring material, participants should be able to: • Recognize that the process of treating pain requires a combination of compassion, clinical insight, and regulatory knowledge • Identify safe and effective mechanisms for evaluating and treating chronic pain • Describe the basic pharmacotherapy of opioid and nonopioid pain medications • Explain the various complementary nonpharmacological options available for treating chronic pain • Better understand the fundamental issues of addiction and how they can affect the process of pain management • Prescribe narcotic pain medication safely with comprehensive knowledge and appreciation for the legal requirements and ethical expectations imposed by Florida law • Access practical information and samples that will assist in treating pain patients Planner and Author Credentials and Disclosure Information: This information is being provided to CME learners in compliance with the ACCME’s policies for disclosure and commercial support. The information below identifies planner and faculty relationships/affiliations and financial relationships with any commercial interest that produces health care goods or services related to the content of the educational material in which they are involved. As an accredited CME provider, the FMA is obligated to resolve to the best of its abilities any potential conflicts of interest that may arise from a planner’s or speaker’s financial relationships with commercial interests that produce health care goods or services related to the content of the educational presentation in which that speaker is involved. The following biographical and disclosure information is provided for the learner’s benefit: Editorial Board Editor Bernd Wollschlaeger, M.D., Owner/Manager, Aventura Family Medicine & Clinical Assistant Professor, Department of Family Medicine, University of Miami Miller School of Medicine, Miami, Florida Member: Florida Medical Association, Florida Academy of Family Physicians & Florida Society of Addiction Medicine Co-Chair, FMA Committee on CME & Accreditation Disclosure: No relevant financial relationships Associate Editor Neel Karnani, M.D., Medical Director, Haven Hospice of North Central Florida, Gainesville, Florida Member: Florida Medical Association & Florida Academy of Family Physicians Vice Chair, FMA Committee on CME & Accreditation Disclosure: No relevant financial relationships Contributing Members Edward Frankoski, D.O., Director of Pain Management Services, Aventura Hospital Medical Center Member: Florida Osteopathic Medical Association Disclosure: No relevant financial relationships Fred Furgang, M.D., Assistant Professor of Clinical Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida Member: Florida Medical Association, Florida Society of Anesthesiologists & Florida Academy of Pain Medicine Disclosure: Speaker’s Bureau: Eli Lilly Joseph Krzanowski, Jr., Ph.D., Professor of Pharmacology & Molecular Therapeutics, University of South Florida College of Medicine, Tampa, Florida Disclosure: No relevant financial relationships Larry McPherson, J.D., Executive Director, Florida Board of Medicine, Medical Quality Assurance, Florida Department of Health, Tallahassee, Florida Disclosure: No relevant financial relationships Robin Moorman Li, Pharm.D., Ambulatory Pharmacist with emphasis in Pain Management, University of Florida Health Science Center, Jacksonville, Florida Disclosure: No relevant financial relationships Robert McCollough, M.D., Associate Medical Director, Haven Hospice of North Central Florida & Clinical Instructor in Medicine, University of Florida College of Medicine, Gainesville, Florida Member: Florida Medical Association Disclosure: No relevant financial relationships

J. Florida M.A. September 2006 Vol. 90, No. 2

CME Objectives Dennis Patin, M.D., Associate Professor of Clinical Anesthesiology, University of Miami Miller School of Medicine; Chief of Anesthesiology & Pain Management, University of Miami Hospital and Clinics, Sylvester Comprehensive Cancer Center Member: Florida Medical Association, Florida Society of Anesthesiologists & Florida Academy of Pain Medicine Disclosure: Speaker’s Bureau: Janssen, Cephalon, Pfizer, Endo & Merck Heidi Pomm, Ph.D., Director of Behavioral Science, Family Medicine Residency Program, St. Vincent’s Medical Center, Jacksonville, Florida; Clinical Associate Professor, NSU College of Osteopathic Medicine & Voluntary Assistant Professor, University of Miami Miller School of Medicine, Department of Family Medicine & Community Health Disclosure: No relevant financial relationships Raymond Pomm, M.D., Medical Director, Professionals Resource Network/Impaired Practitioners Program of Florida, Fernandina Beach, FL & Clinical Assistant Professor, University of Florida College of Medicine, Gainesville, Florida Member: Florida Medical Association & Florida Society of Addiction Medicine Disclosure: No relevant financial relationships Gary Reisfield, M.D., Associate Medical Director, Haven Hospice of North Central Florida and Assistant Professor & Director, Division of Palliative Medicine, Department of Community Health & Family Medicine, University of Florida Health Science Center, Jacksonville, Florida Member: Florida Medical Association Disclosure: No relevant financial relationships Penny Tenzer, M.D., Vice Chair & Director, Department of Family Medicine, University of Miami Miller School of Medicine, Miami, Florida Member: Florida Medical Association & Florida Academy of Family Physicians Disclosure: No relevant financial relationships Andrea Trescot, M.D., Owner/Manager, The Pain Center, Orange Park, Florida Member: Florida Medical Association, Florida Academy of Pain Medicine & Florida Society of Interventional Pain Physicians Disclosure: Speaker’s Bureau: Pfizer, Searle, Pharmacia, Janssen, Ortho-McNeil, Wallach & Alpha Pharma Financial Acknowledgments: This educational activity was made possible by the receipt of funds from the Office of the Attorney General of Florida. Other Acknowledgments: The FMA would like to express its appreciation to all of the organizations which participated in the planning process including the Office of the Attorney General of Florida, Florida Society of Anesthesiology, Florida Academy of Pain Medicine, and Florida Society of Addiction Medicine. Accreditation/Designation Statement The Florida Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical educational activities for physicians. The Florida Medical Association designates this educational activity for a maximum of six (6) AMA PRA Category 1 CreditsTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. Estimated time to complete this educational activity: Six Hours Expiration Date for the Activity: September 1, 2008 INSTRUCTIONS FOR OBTAINING CME CREDIT • Read all of the educational articles included in this monograph. • Complete the post-test using the answer sheet provided. Participants must correctly answer at least 70% of the questions to receive credit. • Complete the evaluation questions on the bottom of the answer sheet • Mail the answer sheet/evaluation form to: Florida Medical Association ATTN: Nancy Wisham 123 South Adams Street Tallahassee, FL 32301

Or fax the answer sheet/evaluation form to: 850.224.6627 ATTN: Nancy Wisham

• Call the FMA Education Department at 800.762.0233 or email education@medone.org if you have questions. • Once the answer sheet is graded and a score of at least 70% is achieved, a certificate of credit will be mailed to you. Retain a copy of your certificate for your records.

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Introduction As the Editor of this publication and Co-Chair of the Florida Medical Association CME & Accreditation Committee, I am pleased to present you with this complimentary copy of the FMA Journal on Pain Management which focuses on the role of physicians in treating pain and controlling the abuse of pharmaceutical narcotics and other pain medications. This publication was made possible by several organizations and numerous people, including the Office of the Attorney General of Florida, the FMA, and each one of the planners and contributors listed on the preceding page. The specialists and experts who generously contributed their time and talents worked hard to create an educational resource beneficial to every physician regardless of specialty or training. Pain affects us all and in its chronic form adversely impacts the quality of our lives. Pain is the chief complaint in 40 percent of primary care visits, and of these, 20 percent report chronic pain. Overall more than 75 million Americans suffer from chronic, debilitating pain. Pain is now considered the “fifth vital sign” by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). This fact implies that pain should not only be measured regularly in every patient, but also physicians should be familiar with the diagnosis and treatment of pain. Appropriate pain management remains a challenge for all physicians involved. Some may either resort to the intuitive utilization of several controlled substances regardless of the patient’s individual requirements, or limit the use of controlled substances out of concern for legal prosecution. We decided to create a guide for the practicing physician, which can be used as a reference tool or resource for clinical care. For that purpose we have gathered a team of experts including pain management experts, primary care physicians, addiction specialists, pharmacists and psychologists to provide a comprehensive overview of the complex issue in question. Within the pages of this monograph, you will find information about the evaluation and treatment of pain, the legal and ethical aspects of prescribing scheduled drugs, and the facts that every physician should know about substance abuse and addiction. We tried to supplement the material included with additional resources whenever possible. In the initial planning stages, we all agreed that the content should focus on the “ABCs” of pain management, focusing on what physicians can do, what they should not do, how they can justify the prescriptions they write, and when referral to a pain specialist is appropriate. There are never easy answers but our consensus was that approaching the issue of pain using evidence-based medicine and practical samples would be most valuable. Ultimately it is crucial that we as physicians feel competent to address, diagnose and treat our patients who complain about pain, and that we model our care plan along legal responsibilities and ethical prescribing modalities. The profession of medicine is best served when physicians are able to treat every patient thoroughly and compassionately with no fear of legal reprisal. Once you complete your review of this enduring material, I encourage you to take the CME examination on page 57 and claim your AMA PRA Category 1 creditTM. We distribute this monograph with high hopes that the content will de-mystify the elusive nature of pain, illuminate the process of pain management as both an art and a science, and create confidence in physicians to treat pain systematically. Our goal continues to be that the FMA functions as every patient’s best advocate, which hopefully serves as one of the best examples of how the FMA can benefit you as a practicing physician. Best Regards,

Bernd Wollschlaeger, M.D.

J. Florida M.A. September 2006 Vol. 90, No. 2

Introduction

J. Florida M.A. September 2006 Vol. 90, No. 2

CONTENTS 6

Evaluation of Pain Evaluation of Pain Penny Tenzer, M.D. & Bernd Wollschlaeger, M.D.

Treatment of Pain

Opioid Pharmacology

Nonopioid Pain Medications

Approach to the Management of Pain in the Patient with Cancer

Andrea Trescot, M.D. Andrea Trescot, M.D.

Neel Karnani, M.D.

From Chaos to Control: Nonpharmacologic Treatment of Chronic, Nonmalignant Pain Heidi A. Pomm, Ph.D.

Addiction and Pain Management

Pain & Addiction By Bernd Wollschlaeger, M.D. Raymond Pomm, M.D. Gary Reisfield, M.D.

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances

Basic Guidelines for Prescribing Physicians: The Laws and Rules Relating to Pain Management Larry McPherson, Esquire, Executive Director of the Florida Board of Medicine

Resources for Physicians

CME Post-Test

CME Answer Sheet

Conclusion

COVER Pain management can often be a complex dilemma for physicians, a practice that requires perceptive diagnostic skills, compassion, integrative treatment, and specifi c knowledge of Florida law. Physicians must balance the needs and welfare of their patients with their own clinical, legal and ethical obligations. The Florida Medical Association is proud to partner with the Offi ce of the Attorney General of Florida to present this complimentary educational resource to all physicians licensed in Florida.

Copyright ÂŠ 2006 The Journal of the Florida Medical Association is copyrighted by the Florida Medical Association, Inc. Views expressed in this issue represent those of the individual authors and may not necessarily represent the views of the Florida Medical Association, Inc.123 South Adams Street ~ Tallahassee, Florida ~ 32301 ~ 850.224.6496 or the Offi ce of the Attorney General of Florida.

Evaluation of Pain Evaluation of Pain By Penny Tenzer, M.D. & Bernd Wollschlaeger, M.D. Pain is one of the most common reasons people seek medical attention, and it remains one of the most prevalent medical complaints in the United States. Nine out of 10 Americans over the age of 18 report suffering from some kind of pain at least once a month, and 42 percent of them report experiencing pain every day. 1,2 The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience, which we primarily associate with tissue damage or describe in terms of such damage, or both.” Accordingly, pain is a combined sensory, emotional, and cognitive phenomenon. Therefore when assessing and treating pain, one must take into account its effects on all these parameters. Chronic pain patients may experience pain without obvious physical pathology. Conceptually, pain can be thought of as being composed of three hierarchical levels: a sensory-discriminative component (e.g., location, intensity, quality), a motivational-affective component (e.g., depression, anxiety), and a cognitive-evaluative component (e.g., thoughts concerning the cause and significance of the pain)3,4 Nociceptive pain is defined as pain in response to noxious stimuli. It is important to understand that chronic, particularly neuropathic pain, often does not have to correlate with an identifiable source of injury. Neuropathic pain involves damage to normal neurologic pathways and often leads to the development of abnormal pathways. Neuropathic pain is considered more frustrating for patient and physician alike, because neuropathic pain is not only a symptom, but a disease process which can be complex and difficult to treat. Neuropathic pain is often chronic, with the pain caused by damage to the nervous system itself. This damage can lead to abnormal nervous system pathways and processes such as peripheral sensitization, central sensitization, windup, central reorganization, and loss of inhibitory controls. Peripheral sensitization: membrane hyperexcitability with ectopic discharges prolonging the pain perception

Central sensitization: prolonged depolarization of dorsal horn neurons leads to sustained increased excitability. Windup: Sensitization of peripheral nociceptors that leads to a barrage of repetitive impulses, which elicit an augmented response in dorsal horn neurons. Central reorganization: Damage to nerves (Ab fibers) that normally carry sensations of touch can result in the sensation being perceived as pain instead. This may lead to Allodynia, a hallmark of neuropathic pain in which a stimulus normally not painful such as touch or warmth is perceived as pain. Loss of inhibitory controls: Neurons in the dorsal horn can facilitate or inhibit transmission of sensation, inhibition is mediated by gamma-aminobutyric (GABA) and glycine. Nerve injury may decrease GABA and glycine levels, and downregulates GABA and opioid receptors. When inhibition is lost, excitatory mechanisms dominate. Recognizing chronic pain as a serious condition with significant impact on the lives and functions of our patients and their families, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has issued Pain Assessment and Management Standards. JCAHO mandates that all JCAHOaccredited hospitals, ambulatory care facilities, long-term care facilities and other health care settings: • Recognize the right of patients to appropriate assessment and management of pain • Assess the existence and, if so, the nature and intensity of pain in all patients • Record the results of the assessment in a way that facilitates regular reassessment and follow-up • Establish policies and procedures which support the appropriate prescription or ordering of effective pain medications • Educate patients and their families about effective pain management • Address patient needs for symptom management in the discharge planning process

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Evaluation of Pain In the absence of objective pain measurement (i.e. laboratory tests), the clinician relies on the patient’s selfdescription and report of pain, even in the absence of a demonstrable source of tissue injury. The use of paper, verbal pain scales, or numeric scales can help rate the degree or intensity of the pain. Caricature representation of the human body can be used for children or patients with developmental disabilities (see Resources – Available Pain Rating Scales). These pain scales have been validated, and used consistently on the same person, can be a reliable indicator of pain measured over time. As responsible clinicians, we are challenged to apply a comprehensive and reliable tool to assess and follow pain. A systematic pain evaluation will strengthen the physicianpatient relationship and provide more appropriate, individualized approaches in pain management.

We advocate the “HAMSTER” model as a means to assess and follow pain:

HAMSTER Model H -- History A -- Assessment (including patient’s function, psychological state, and use of medications) M -- Mechanism of pain S -- Social and psychological factors T -- Treatment E -- Education R – Reassessment

History The history includes the chief complaint, history of the present illness, review of systems, and past, family, and/or social history. History of the present illness is a chronological description of the development of a patient’s present illness from the first sign and/or symptom. One suggested method for attaining a history is the PQRST approach. J. Florida M.A. September 2006 Vol. 90, No. 2

PQRST Approach • •

• • •

Assess Provocative (aggravating) and Palliative (relieving) factors Assess the Quality of the pain: burning, stabbing, stinging, dull, sharp, throbbing, shooting, aching, tingling, heaviness, tightness Assess the Region (location) of the pain, Radiation Assess the Severity of the pain (use pain intensity scale) Assess the Timing of the pain (when does it occur, how long does it persist),

Review of systems involves taking an inventory of body systems obtained by asking a series of questions that seek to identify signs and/or symptoms that the patient may be experiencing or has experienced. The assessment of past medical history, family, and social history are important components in chronic pain patients seeking care with opioids. Appropriate assessment requires 1. ) a thorough review of the entire history of the patient (including past experiences, illnesses, operations, injuries, and treatment); 2.) a thorough family history (including a review of medical events in the patient’s family, hereditary diseases, and other factors); and 3) a social history appropriate for age, reflecting past and current activities. A past history in interventional pain management includes a review of all past pain problems, including motor vehicle, occupational, or nonoccupational injuries; disorders such as arthritis, fibromyalgia, complex regional pain syndrome, or collagen vascular diseases; drug dependency, alcoholism, or drug abuse; and psychological disorders such as depression, anxiety, schizophrenia, mental status changes or suicidal ideations. It is important to recognize that the presence of addiction or prescription drug dependence does not preclude the use of pain management modalities, including opioids. We recommend the use of a signed pain contract/agreement in all patients using opioids for long-tem pain management. The treating physician may also choose to collaborate with a certified addiction and/or pain specialist. The “undertreatment” of pain in such a patient population may trigger drug-seeking behavior, which is iatrogenically induced through inadequate treatment of pain (also known as pseudoaddiction). In pseudoaddiction, preoccupation and pursuit of drugs is driven primarily by need for pain control and not for moodaltering effects. Again, family history is essential, and should include not only the history of different pain syndromes, including degenerative disorders, but also familial disorders such as drug or chemical dependency, alcoholism, or drug

Evaluation of Pain abuse and psychological disorders such as depression, anxiety, schizophrenia, and suicidal tendencies, particularly in first degree relatives. Social history is of central importance when administering opioids, and should include the collection of environmental information and demographics relating to education, marital status, children, habits, hobbies, occupational history, family support system, and recreational drug usage. Effect on Functional Status Some aspects specific to controlled substance abuse and chronic pain include evaluation of effect of pain on physical and psychological function, such as activities of daily living and sedation. It is also advisable to determine a Treatment and Medication History which should include the following questions: “What medications have been tried in the past?,” “Which medications have helped?,” and “Which medications have not helped?” Physical Examination Physical examination involves general, musculoskeletal, and neurological examinations. Examination of other systems, specifically cardiovascular, lymphatic, skin, eyes and cranial nerves is recommended based on the presenting symptomatology. Laboratory and diagnostic studies should be ordered as deemed appropriate; for example, glucose and renal function tests in a patient with peripheral neuropathy to assess the presence of diabetes or chronic renal disease. MRIs, CT, bone scans, electrophysiologic studies such as EMG and nerve conduction studies, and blood work may also be performed as guided by the history and physical examination. Psychological Evaluation Psychological evaluation is an extension of the evaluation process similar to the laboratory evaluation, imaging techniques, electromyography and nerve conduction studies. By definition, pain is a subjective description of the patient’s perception of actual or potential tissue damage. The distinction between pain and suffering should be established. A patient may suffer due to pain, but may have other reasons for suffering, as well. The assessment of a patient’s overall condition should be made at the initial evaluation and frequently thereafter. It is the goal of the physician to assist in the relief of suffering, no matter the cause. Financial, emotional, cultural, familial physical, and spiritual factors may contribute to the patient’s suffering. Relief of the underlying reasons for suffering, as well as the pain, will lead to optimal treatment.

Medical Decision Making and Treatment Plan Medical decision-making refers to the complexity of establishing a diagnosis and selecting an appropriate management option. The process consists of three components: 1. 2. 3.

Establishing the diagnosis and evaluating treatment options Reviewing all previous medical records (if available) Assessing the risks of each treatment option as compared to the existing comorbidities associated with the patient’s medical condition

Diagnostic interventional techniques may assist in making the proper diagnosis by following an algorithmic approach. It has been shown that in approximately 70 to 85 percent of patients with spinal pain, an accurate diagnosis may not be provided in spite of the available history, physical examination, EMG nerve conduction studies, and radiological evaluation. With precise diagnostic interventional techniques, the chances of diagnosis may be improved substantially, and proper treatment may be offered. Therapeutic interventional techniques may be utilized for pain management and functional improvement. The effectiveness of various interventional techniques has been evaluated in systematic reviews.5 A written treatment plan should document objectives that will be used to evaluate treatment success, including pain relief and improved physical and psychosocial function, and should indicate if additional diagnostic tests, consultations, or treatments are planned. After starting treatment, the physician should adjust with care the pharmaceutical therapy to meet the individual medical needs of each patient. In the continuum of treatment, other modalities, including interventional techniques, rehabilitation, and cognitive behavioral therapy will often be necessary depending on the etiology of pain and the extent to which pain is associated with physical, functional, and psychosocial impairment. Overall, we recommend a multimodal approach involving the patient and their support systems. Consultation We suggest that the physician consider consultation with a pain management expert and/or addiction medicine specialist, if they have used various treatment regimens without achieving desired results or if they feel uncomfortable with the medication or other treatment regimens being utilized.

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Evaluation of Pain Physicians should be willing to refer a patient as clinically indicated for additional evaluation to achieve treatment objectives. Special attention should be given to those patients who are at risk of misusing their medications and those whose living arrangements create a risk for medication misuse or diversion. The management of patients with a history of substance abuse or with a coexisting psychiatric disorder may require extra care, monitoring, documentation, and consultation with or referral to an addictionologist and/or addiction psychiatrist.

and their families in the care plan are all part of a structured approach, which should optimize care. A systematic approach toward pain evaluation, assessment, and management can assist the physician in feeling more comfortable with the treatment of pain. The goal of pain management is to improve function, reduce anxiety, physical suffering and co-morbidities, and improve overall quality of life.

Informed Consent and Controlled Substance Agreement At the outset, the physician should discuss the risks and benefits of the use of controlled substances with the patient or surrogate, including the risk of tolerance and drug dependence. It is advisable to employ the use of a written agreement/ contract between physician and patient outlining patient responsibilities.

1. Parrott T. Pain Management in Primary-Care Medical Practice. In: Tollison CD, Satterthwaithe JR, Tollison JW, eds. Practical Pain Management. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002:729-759.

We recommend the use of pain management agreements as a necessary component of the documentation and management plan for all patients at high risk for medication abuse or those who have a history of substance abuse. Suggested components of a controlled substance agreement between a physician and patient include: 1. 2.

Designate one prescribing doctor and one drug dispensing pharmacy Include a requirement that the patient must undergo urine/serum drug screening when requested by the physician Establish the fact that there will be no early refills and no medications called in (if medications are lost or stolen, a police report could be required before considering additional prescriptions) Document the reasons for which opioid drug therapy may be discontinued, such as violation of a documented doctor/patient agreement.

References:

2. Pain in America: highlights from a Gallup survey. Arthritis Foundation[Web site]. June 9, 1999. Available at: www.arthritis. org/conditions/speakingopain/factsheet.asp. Accessed March 31, 2003. 3. Melzack R. Neurophysiological foundation of pain. In: Sternbach RA, ed. The Psychology of Pain. New York: Raven Press; 1986:1-12. 4. Melzack R, Casey KL. Sensory, motivational, and central control determinants of pain: A new conceptual model. In: Kenshalo D, ed. The Skin Senses. Springfield, IL: Charles C. Thomas; 1968:423-429. 5.. Kapural L, Goldner J.Interventional pain management: when/what therapies are best for low back pain. Curr Opin Anaesthesiol. 2005 Oct;18(5):569-75.

Conclusion Pain is a common, and at times, complex problem encountered by physicians on a daily basis. As our population continues to age, it stands to reason that the number of patients with chronic pain syndromes will rise as well. Utilizing an adequate history, physical examination, pain scales, documentation with agreements/contracts as needed, while involving the patients J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain Opioid Pharmacology Andrea Trescot, M.D. “Millions of people suffer needlessly from agonizing pain because physicians have been reluctant to use ‘high-risk’ opioids.” Crain and Shen 2000 The opium poppy was cultivated as early as 3400 B.C. in Mesopotamia. The term opium refers to a mixture of alkaloids from the poppy seed. Opiates are naturally occurring alkaloids such as morphine or codeine. Opioid is the term used broadly to describe all compounds that work at the opioid receptors. The term narcotic (from the Greek word for stupor), originally was used to describe medications for sleep, then was used to describe opioids, but now is a legal term for drugs that are abused. Opioids are analgesics that provide pain relief by modulation of ascending and descending spinal pathways. Opioids may be classified by their function as agonists, mixed agonistsantagonists, or antagonists as well as by their actions at various opioid receptors. Much of our opioid prescribing techniques are based on opinion rather than on evidence, since chronic non-cancer pain opioid use is still an orphan area. This is due in part because the studies are difficult to perform and in part because the drugs themselves are mostly older, and therefore do not have pharmaceutical industry support.

Opioid receptors There are opioid receptors within the CNS as well as throughout the peripheral tissues. These receptors are normally stimulated by endogenous peptides (endorphins, enkephalins, and dynorphins) produced in response to noxious stimulation. Greek letters, based on their prototype agonists, designate various opioid receptors: • Mu (m) (agonist morphine) receptors are found primarily in the brainstem and medial thalamus; these receptors mediate supraspinal analgesia, respiratory depression, euphoria, and sedation. • Kappa (k) (agonist ketocyclazocine) receptors mediate spinal analgesia, sedation, dyspnea, and dependence. • Delta (d) (agonist delta-alanine-delta-leucineenkephalin) effects are not well studied. • Sigma (s) (agonist N-allylnormetazocine) receptors mediate psychomimetic effects, dysphoria, and stressinduced depression. They are no longer considered opioid receptors, but rather the target site for phencyclidine (PCP) and its analogs.

There are also now known to be receptor subtypes: • Mu1- related to analgesia, euphoria, and serenity • Mu2- related to respiratory depression, pruritus, prolactin release, dependence, anorexia, and sedation The varying effects of opioids may therefore be related to varying degrees of affinity for the various receptors. For instance, fentanyl is 60-80 times more potent than morphine, having a much higher affinity for the Mu1 receptor than morphine. Opioid agonist

Mu (m)

Morphine

Agonist

Codeine

Weak agonist

Fentanyl, sufentanil

Strong agonist

Meperidine

Agonist

Methadone

Agonist

Delta (d)

Kappa (k) Weak agonist

Weak agonist

Agonist

Opioid receptors, concentrated in the ventral tegmental and periaqueductal grey areas, presynaptically inhibit the transmission of excitatory pathways: acetylcholine, catecholamine, serotonin, and substance P. Activation of the opioid receptor inhibits adenylate cyclase. All opioid receptors are G protein-linked structures embedded in the plasma membrane of neurons; and activation releases a portion of the G protein, which moves in the membrane until it reaches its target (either an enzyme or an ion channel). These targets alter protein phosphorylation and/or gene transcription. Opioids and endogenous opioids activate presynaptic receptors on GABA neurons, which inhibit the release of GABA in the ventral tegmental area. This allows dopaminergic neurons to fire more vigorously. The resulting extra dopamine in the nucleus accumbens is interpreted as intensely pleasurable.

Endogenous opioids The opioid receptors were discovered in 1972, and the first endogenous opioid (or endorphin) was discovered in 1975. Their location in the CNS allows them to function as neurotransmitters, and they may play a role in hormone secretion, thermoregulation, and cardiovascular control.

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Treatment of Pain Opioid Antagonists Naloxone (Narcan ) is a pure competitive antagonist at µ, k, and d receptors (strongest at µ). It rapidly reverses opioids, but the action is short lived, and therefore has the potential for “renarcotizing.” ®

Naltrexone (ReVia®, Depade®) is used orally in high doses to detoxify opioid addicts. Its primary effect is from its metabolite, 6-b-naltrexol.

Opioid agonist-antagonists This class of drugs is classified into the following two types: • Partial agonists at µ receptor such as buprenorphine (Subutex®, Suboxone®), have a high affinity but low efficacy at the µ receptor. • Agonist/partial agonist at k receptor, such as nalorphine (Nalline®), pentazocine (Talwin®, Talacen®), nalbuphine (Nubain®), and butorphanol (Stadol®), act as k agonists but are also competitive µ antagonists, with a high affinity but no efficacy at the µ receptor. Methylnaltrexone and alvimopan have poor oral absorption and are under investigation for use as oral agents to reverse the decreased GI motility of opioid agonists. These agonist-antagonists are analgesics with a ceiling effect and therefore have a potentially reduced capacity for abuse. It must be remembered that their antagonist properties may precipitate withdrawal when used in patients who are on chronic opioids.

Controlled Substances Act (CSA) The CSA places all substances that are regulated under existing federal law into one of five schedules. This placement is based upon the substance’s medicinal value, harmfulness, and potential for abuse or addiction.

basal rate of metabolism is determined by genetic makeup, gender, age, as well as environment including diet, disease state, and concurrent use of medications. There is no clear evidence of renal metabolism, though the kidney is an important site of excretion. Most opioids are metabolized by glucuronidation or by the P450 (CYP) system. There are about 30 different isoenzymes, of which CYP3A4 is the most abundant (about one quarter of the total).1 Levels of CYP3A4 may vary as much as 30-fold between individuals,2 leading to large variability in blood levels. Other enzymes include CYP1A2, CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP2C19. CYP2D6 is entirely absent in some populations (for example, six to 10 percent of Caucasians are 2D6 deficient3) while other persons have high levels of this enzyme, leading to rapid metabolism of the medicines. • Codeine is a pro-drug, and has no effect until it is metabolized to morphine. Unfortunately, genetic deficiencies, and multiple drugs interactions can lead to ineffectiveness.4 It is converted to morphine via CYP2D6, and patients who are CYP2D6 deficient or on CYP2D6 inhibitors will have no analgesia. It was first isolated from opium in 1832. • Propoxyphene (Darvon®, Darvocet®) is a weak opioid that is metabolized by glucuronidation to an active metabolite, norpropoxyphene, which has local anesthetic affects similar to amitriptyline and antiarrhythmic agents such as lidocaine and quinine. It therefore has the potential to cause seizures in large doses. Propoxyphene and norpropoxyphene are both renally excreted and have the potential for accumulation in elderly patients and those with renal failure. • Morphine undergoes glucuronidation, predominately in the liver (though there are extra-hepatic sites of metabolism postulated). Ninety percent of the drug

Schedule

Criteria

Examples

No medicinal use; high addiction potential

Heroin, marijuana, PCP

Medicinal use; high addiction potential

Morphine, oxycodone, methadone, fentanyl, amphetamines

III

Medicinal use; moderate addiction potential

Hydrocodone, codeine, anabolic steroids

Medical use; low abuse potential

Benzodiazepines, meprobamate, butorphanol, pentazocine, propoxyphene

Medical use; low abuse potential

Buprenex, Phenergan with codeine

Opioid metabolism Many of the effects of opioids, as well as their side effects, may be related to the opioid metabolites. It is generally assumed that most of the metabolism of opioids occurs in the liver. The J. Florida M.A. September 2006 Vol. 90, No. 2

is metabolized, with up to 55 percent metabolized to morphine-3-glucuronide (M3G) and about 15 percent to morphine-6-glucuronide (M6G), as well as small amounts of normorphine. About 90 percent is excreted in the urine.

Treatment of Pain

•

M6G and normorphine are both opioid agonists; M6G is three to four times more potent than morphine when injected subcutaneously, and 45 times more potent after intracerebroventricular injections in mice.5 M3G has a low affinity for the opioid receptor, and may be responsible for the side effects of hyperalgesia (an increase in pain seen with high doses of opioids), and myoclonus.6 Liver7 and renal8 disease may significantly prolong the effect of morphine. Accumulation of morphine metabolites (especially M6G) becomes significant as creatinine clearance declines below 50 ml/min.9 Steady state for long acting preparations (e.g., MSContin®, Kadian®, Avinza®) is usually reached in one to two days. Hydrocodone (Lortab®, Lorcet®,Vicodin®, Norco®, Zydone®) is metabolized to hydromorphone (Dilaudid®) via the CYP2D6 enzyme system. Hydrocodone is one of the most abused prescription medications and is very popular as a street drug. In 2000, Nevada doctors wrote prescriptions for more than 42 million doses of hydrocodone - or about 17 pills for every adult in the state. Perhaps this metabolic pathway explains the popularity of this drug. It may also explain why practitioners often hear: “The only medicine that works for me is Dilaudid®.” If the patient is 2D6 deficient or taking a CYP2D6 inhibitor, hydrocodone may not be effective. Hydromorphone (Dilaudid®) is significantly more potent than morphine, and is highly water-soluble, which allows for very concentrated formulations. In patients with renal failure, it may be preferred over morphine, which has the possible risk of accumulation of toxic metabolites. Oxycodone (Percocet®, Tylox®, OxyContin®) is metabolized by glucuronidation to noroxycodone (which has less than one percent of the analgesia potency of oxycodone), and by CYP2D6 to oxymorphone. Oxycodone has activity at multiple receptors, but oxymorphone has high affinity for the µ receptor with negligible interaction with k and d receptors,10 and is about 10 times more potent than morphine. Oxymorphone is not affected by CY2D6 or CY3A4. If the patient is 2D6 deficient or taking a CYP2D6 inhibitor, oxycodone may not be as effective. Methadone is metabolized primarily by CYP3A4 (and CYP2D6 secondarily).11 The l-isomer is the opioid compound; the d-isomer blocks the N-methylD-aspartate (NMDA) receptor, making it particularly

•

useful for neuropathic pain and “opioid-resistant” pain states. Methadone has several other advantages in the treatment of chronic pain. It has excellent oral bioavailability (up to 100 percent absorbed12), and it can be crushed or dissolved to deliver down an NG tube. It can be used in patients with a true morphine allergy. There is low risk of accumulation in renal failure patients. It may cause less constipation than morphine and it is extremely inexpensive. There are also low rates of drug escalation and drug seeking. However, methadone redistributes extensively and can accumulate in the muscle and fat tissues after prolonged administration. It has a slow onset of action (half life ranges from 12 to 150 hours). The duration of action is between four and eight hours, reaching steady state in five to seven days. Methadone may cause torsade de pointes, a potentially fatal arrhythmia caused by a lengthening of the QT interval. Methadone also has multiple drug interactions. Plasma levels of methadone are increased by concomitant administration of CYP3A4 inhibitors such as cimetidine, erythromycin, ketoconazole, and fluvoxamine. Conversely, plasma levels are decreased by concomitant administration of CYP3A4 inducers such as ethenyl, barbiturates, phenytoin, carbamazepine, isoniazid, and rifampin, as well as HIV retrovirals ritonavir, nevirapine, and possibly efavirenz. Methadone may be unique in its lack of profound euphoria. Unfortunately, self-directed re-dosing coupled with a long half-life may result in accumulation, with ultimate adverse outcomes including respiratory depression and death. Even when prescribed in low doses, and used appropriately by individuals experienced with opioids, the long half-life of methadone may be underestimated while dosing is titrated to analgesic effect. Furthermore, the list of drug interactions with methadone is extensive, and further alteration in metabolism may occur innocently and unexpectedly, without the prescribing physician’s awareness. Fentanyl (Duragesic®) is metabolized by 3A4 to inactive and nontoxic metabolites. It is extremely lipophilic, with rapid crossing of the blood-brain barrier. Formulations include IV, transdermal (Duragesic®), intranasal and transoral. The transdermal formulation has a lag time of six to 12 hours to onset of action after application, and typically reaches steady state in three to six days. When a patch is removed, a subcutaneous reservoir remains, and drug clearance may take up to 24 hours.

J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain •

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Meperidine (Demerol®) is metabolized by glucuronidation to normeperidine, which stimulates the CNS and may result in seizures, especially with high doses or renal insufficiency. Normeperidine has a half-life of eight to 12 hours so significant amounts can accumulate. Its effects are not reversed by naloxone. It is probably not appropriate for long-term use. Levorphanol (Levo Dromoran®) is metabolized by glucuronidation. It is four to eight times as potent as morphine and lasts eight to 12 hours. The average oral dose is 3mg and 1.5mg by injection (equivalent to 10 to 15mg IM or IV morphine) It is the optical isomer of dextrorphan (an over the counter cough suppressant like dextromethorphan). Tramadol (Ultram®) is a synthetic analogue of codeine.13 The M1 derivative (O-demethyl tramadol) produced by CYP2D6 has a higher affinity for the µ receptor than the parent compound. Tramadol is a racemic mixture of two enantiomers - one form is a selective µ agonist and inhibits serotonin reuptake, while the other mainly inhibits norepinephrine. Maximum dose is 400mg/day. Toxic doses cause CNS excitation and seizures. CYP2D6 inhibitors (such as Prozac® or Paxil®) will not only decrease the effectiveness of the analgesia, but will also decrease the excretion, leading to an increased potential for toxicity. It is now available in an extended release form.

Adverse effects The majority of the adverse effects of opioids reflects the effects of opioids at multiple organ systems. Many of these “side effects” are used to clinical advantage.14

increasing intracranial tension (ICP). Miosis may mask changing neurologic status.

Respiratory system o Direct respiratory depression effect on the medulla, results in dose-dependant depression of the response to hypercarbia and hypoxia. There is also depression of the cough centers in the medulla, but this is a different mechanism than that of analgesia, since dextro-isomers of opioid such as dextromethorphan are potent cough suppressants but have relatively little direct analgesic effect. o First, the response to hypercarbia and hypoxia decreases and then the respiratory rate decreases. This effect is potentiated by sleep. o Respiratory depression is the major toxicity of opioids and is almost always the cause of death. o Equipotent doses of opioids cause equal decreases in respiratory function. o It is clear that volunteers not in pain who are given opioids develop respiratory depression. For patients with “opioid-sensitive pain,” there is minimal respiratory suppression when given appropriate analgesic doses of opioids. o It has been observed that patients in pain, on opioids, who are given acute pain relief (such as with a nerve block), will need a decrease in their opioid to avoid respiratory depression.15 o It is therefore clear that opioids need to be titrated to pain relief and not to some arbitrary blood level or dosing schedule.

Ocular system Central nervous system o o o o o o

Processing of pain information is inhibited by opioids by direct spinal effect at the dorsal horn, probably through inhibition of substance P. There is activation of inhibitory descending pathways. Emotional wellbeing and euphoria are mediated at the limbic system. There are opioid receptors at the peripheral tissues that may be involved in the pain from inflammation. Adverse effects include drowsiness, sedation, difficulty concentrating, or hallucinations. Dysphoria and agitation may occur. Accumulation of meperidine metabolites may result in seizures. o Opioids are usually avoided in head injuries, because decreased ventilation (see below) can increase pCO2, J. Florida M.A. September 2006 Vol. 90, No. 2

o Miosis occurs through the parasympathetic ganglion of the eye (Edinger-Westphal nucleus). o Antagonized by naloxone, atropine, and ganglion blockers.

Gastrointestinal system o Direct stimulation of the chemoreceptor trigger zone (CTZ) on the floor of the fourth ventricle. Signals enhanced by vestibular input (such as head movement). o Spasm of smooth muscle throughout the GI tract; delay of intestinal transit time and spasm of anal sphincter leads to constipation (with little or no tolerance occurring). Loperamide (Imodium®) may be used therapeutically with poorly absorbed opioids.

Treatment of Pain o Delayed gastric emptying leads to altered absorption of medication and decreased appetite, bloating, or reflux.

face of 2D6 inhibitors, might have better relief from an equipotent dose of fentanyl, which is not 2D6 inhibited.

Physical dependence Genitourinary o Urinary retention due to smooth muscle contraction. o Sexual dysfunction (central vs. peripheral).

o Withdrawal symptoms include runny nose, shivering, “gooseflesh,” diarrhea, and mydriasis. o Small doses of short acting opioids or alpha2 adrenergic agonists such as clonidine may be useful.

Cardiovascular

Addiction

o Decreased central sympathetic tone which decreases systemic vascular resistance. o Vagal stimulation causes bradycardia; little or no direct myocardial depression.

o Felt to be relatively rare in the face of chronic pain. See accompanying section.

Musculoskeletal system o Muscle rigidity with large doses of IV opioids, perhaps due to dopamine synthesis and inhibition of GABA. o Myoclonus can occur, especially with large oral or intrathecal doses.16

Immune system o Itching is common. This is due to a direct histamine release (especially with morphine); not an allergic reaction.17 Mouse studies of injected morphine have shown a dose-dependant increase in facial scratching but no increased scratching at the injection site, suggesting that the itching is related to central opioid µ receptors.18 The symptoms resolve with treatment by low dose opioid antagonists. Generally, true allergy to one class of opioids does not mean a person is allergic to another class.

Pregnancy and neonate o All opioids cross the placenta. o No teratogenic effects. o Neonatal depression possible if used during labor.

Drug interactions A drug interaction occurs when the amount or the action of a drug are altered by the administration of another drug or multiple drugs.19 Multiple drug interactions can influence opioid drug levels.20 (See Chart on Next Page) Methadone has multiple drug interactions, as described on the next page. Phenytoin, carbamazepine, rifampin, erythromycin, barbiturates, and several anti-retrovirals induce methadone metabolism, resulting in decreased blood levels and the potential for withdrawal. The azole antifungals, selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) may increase methadone levels.21 Methadone may also increase TCA levels. Overmedication occurring within a few days is usually due to P450 (CYP) inhibition, while withdrawal reactions taking a week or more are usually due to CYP induction.22 Methadone also has the potential to cause cardiac arrhythmias, specifically prolonged QTc interval and/or torsade de pointes under certain circumstances.23 Combining methadone with a CYP3A4 inhibitor such as ciprofloxacin24 can increase that risk.25 In Florida, methadone-related deaths jumped from 209 in 2000 to 357 in 2001 to 254 in the first six months of 200226 It is recommended that a switch to methadone from another opioid be accompanied by a large (50 to 90 percent) decrease in the calculated equipotent dose.27

Tolerance o Usually presents as decreased duration of analgesia and then decreased effectiveness. o Cross-tolerance exists to other opioids. Possibly related to adaptive response to adenylyl cyclase; however, perhaps changing to an opioid metabolized differently might help. For instance, a patient on high doses of hydrocodone, in the J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain Tricyclic antidepressants

Inhibit morphine glucuronidation leading to blood levels - Nortriptyline inhibits non-competitively - Amitryptyline and clomipramine inhibit competitively

Methadone & Morphine

metabolism of desipramine, leading to toxicity

Quinine

conversion of codeine to morphine leading to analgesia

Metoclopramide

Earlier peak plasma levels with controlled-released opioids

Meperidine

MAO inhibitors trigger hyperpyrexia

Propoxyphene

carbamazepine, doxepin, metoprolol, propranolol levels excretion of benzodiazepines, leading to accumulation and overdose

Erythomycin

opioid effects

Rifampin

opioid effects

CY2D6 Inhibitors

tramadol levels analgesia from hydrocodone/codeine

CY2D6 Inhibitors

tramadol levels because of competition for metabolism

Neuropathic pain Classically, physicians have been taught that opioids do little to relieve nerve or neuropathic pain. There have been very few controlled trials, and most did not take into account differences in previous opioid exposure. Jadad et. al28 used patient-controlled analgesia (PCA) and direct nurse observations to evaluate two concentrations of morphine in a randomized, cross-over protocol. Half of the patients who were felt to have neuropathic pain achieved a good response, whereas all of the nociceptive patients obtained relief. Tolerance Clinicians are divided as to whether tolerance is due to true up-regulation of the receptor or progression of the disease. It is clear that some patients are able to maintain relief at the same dose for prolonged periods of time, while others require rapid escalation of their dose for continued analgesia. Animal models, however, have shown both acute and chronic opioid tolerance.29 Administration routes There may be significant differences in analgesia between various opioid administration routes. For example, oral bioavailability of morphine may vary considerably (ranging from 10 to 50 percent), and depends on formulation, fasting status, and time of day. Administration routes for opioids include oral, rectal, intravenous (IV), intramuscular (IM), nasal, transoral, transdermal, and subcutaneous (SC).

medications, bioavailability of different formulations (such as seen with brand name versus generic medications), and concurrent disease (for instance, renal or hepatic disease) can influence the “expected” blood level of a medication. Therefore, any conversion table should be used as a rough guide only. In general, a concerted effort should be made to convert short acting medications to long acting formulations, at the lowest dose, with breakthrough medications as needed as the dose is titrated to analgesia. “You can always add more but you cannot take it back.” Drug conversions: • Hydrocodone to morphine o Converted on a 1:1 basis o Example: Six tablets per day of hydrocodone 5/500 =30mg hydrocodone = 30mg morphine (15mg BID or 30mg q daily) • Oxycodone to morphine o Converted on a 2:3 ratio (increase oxycodone dose by 50%) o Example: OxyContin® 20mg BID = 40mg oxycodone X 1.5 = 60mg morphine (30mg BID or 50 to 60mg q day (usually pick a lower dose to start)

Drug Conversions: It is critical to realize that there is a vast range of “equivalent doses” when changing from one opioid to another. Differences in genetic status (such as CYP activity), co-administered J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain Hydromorphone to morphine o Convert on a 1:4 ratio o 7.5mg hydromorphone equal 30mg morphine o Example: hydromorphone 2mg q 4hrs= 12mg X 4 = 48mg morphine (20mg BID or 40mg q day) Oral morphine 30mg is equivalent to 10mg morphine IV. 10mg morphine IV is equivalent to 1.5mg hydromorphone IV •

References 1.

Breimer DD. Genetic polymorphism in drug metabolism:

clinical implications and consequences in ADME studies. In: The Relevance of Ethnic Factors in the Clinical Evaluation of Medicine (S. Walker et al, Eds). Kluwer Academic Publishers (Dor-drecht/Boston 1994), p 13-26. 2.

Leavitt SB, Shinderman M, Maxwell s, Eap CB, Paris P. When

“enough is not enough”: new perspectives on optimal methadone maintenance dose. Mt. Sinai J Med.2000; 67(5-6):404-411. 3.

Evans DA, Mahgoub A, Sloan TP, Idle JR, Smith RL. A family

and population study of the genetic polymorphism of debrisoquine

The following algorithm for switching to methadone has been proposed:30 • “Start low and go slow” o Calculate the total daily dose of short acting opioids and convert to morphine equivalents. Decrease dose by 50 percent. o Divide dose by three and dose q8 hours o Example: hydrocodone 10mg TID = 30mg morphine Decrease by 50 percent=15mg methadone Divide dose by 3 = methadone 5mg q8 hrs • Larger doses of opioids need to be started even lower (10 percent of morphine dose) o OxyContin® 80mg BID = 160 x1.5 = 240 mg morphine Decrease by 90 percent = 24mg methadone Divide dose by 3 = 8mg; start 10mg q 8 hours Increase by 5 to 10mg q day every five to seven days

oxidation in a white British population. J Med Genet 1980;17(2):102-5. 4.

and side effects. Eur. J. Clin. Pharmacol. 51, p. 289-295. 5.

Shimomura K, Kamata O, Ueki S, Ida S, Oguri K,Yoshimura H,

Tsukamoto H (1971) Analgesic effect of morphine glucuronides. Tohoku Journal of Experimental Medicine 105:45-52. 7.

Twycross RG, Lack S (1983) Symptom Control in Far

Advanced Cancer; Pain Relief. Pitman, London, 1983. 8.

Kaiko RF, Wallenstein SL, Rogers AG, Grabinski PY, Houde

RW (1982) Narcotics in the elderly. Medical Clinics of North America 66:1079-1089. 9.

Bodd E, Jacobsen D, Lund E, Ripel A, Mørland J, Wiik-Larsen

E (1990) Morphine-6-glucuronide might mediate the prolonged opioid effect of morphine in acute renal failure. Human & Experimental Toxicology 9:317-21. Metzger TG, Paterlini MG, Ferguson DM, Portoghese PS.

Investigation of the selectivity of oxymorphone and naltrexonederived ligands via site-directed mutagenesis of opioid receptors: exploring the ‘address’ recognition locus. J Med Chem 2001; 44(6):857-62. 11.

“If it were not for the great variability among individuals, medicine might as well be a science and not an art” William Osler (1892)

Woolf CJ (1981) Intrathecal high dose morphine produces

hyperalgesia in the rat. Brain Research 29:491-495.

10.

Extended release medications may need to be paired with a short acting medication to treat breakthrough pain. Do not use extended-release opioids for rescue or breakthrough treatment.

Poulsen L et al. (1996). Codeine and morphine in extensive

and poor metabolizers of sparteine: pharmacokinetics, analgesic effect

Eap CB, Buclin T, Baumann P. Interindividual variability of the

clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin Pharmacokinet. 2002; 41(14):1153-1193.

J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain 12.

Moolchan ET, Umbricht A, Epstein D. Therapeutic drug

monitoring in methadone maintenance: choosing a matrix. J Addict Dis.

24.

Methadone, ciprofloxacin, and adverse drug reactions Herrlin

K, Segerdahl M, Gustafsson LL, Kalso E. Lancet, 2000; 356(9247):2069-70.

2001; 20(2):55-73. 25. 13.

Dayer P, Desmeules J, Collart L. Pharmacology of tramadol.

De Bels D, Staroukine M, Devriendt J. Torsades de Pointes

Due to Methadone. Ann Intern Med.2003; 139: 58.

Drugs 1997; 53 suppl 2:18-24. 26. 14.

Harvard-MIT Division of Health Sciences and Technology,

Belluck P. Methadone suddenly grows as a killer drug. New

York Times. 9 Feb 2003.

HST.151: Principles of Pharmacology (Opioid Pharmacology). 27. 15.

Hanks GW, Twycross RG, Lloyd JW (1981) Unexpected

Gazelle G, Fine PG. Methadone for the treatment of pain. J

Palliat Med 2003; 6:621-2.

complication of successful nerve block. Anaesthesia 36:37-39. 28. 16.

Ferris DJ. Controlling myoclonus after high-dosage morphine

Jadad AR, Carroll D, Glynn CJ, Moore RA, McQuay HJ.

Morphine responsiveness of chronic pain: double-blind randomized

infusions. American Journal of Health System Pharmacy. 1999 May 15;

crossover study with patient-controlled analgesia. Lancet

56(10):1009-10.

1992;339:1367-71.

17.

29.

Kam P,Tan K. Pruritus-itching for a cause and relief?

Anaesthesia 1996; 51: 1133 - 8.

Colpaert FC, Niemegeers CJE, Janssen PAJ, Maroli AN (1980).

The effects of prior fentanyl administration and of pain on fentanyl analgesia: tolerance to and enhancement of narcotic analgesia. Journal of

18.

Kuraishi Y,Yamaguchi T, Miyamoto T. Itch-Scratch responses

Pharmacology & Experimental Therapeutics 213:418-426.

induced by opioids through central mu opioid receptors in mice. J Biomed Sci 2000 May;7(3):248-252.

30.

Goodman F, Jones WN, Glassman P, et al. Methadone dosing

recommendations for treatment of chronic pain, December 20, 2001. 19.

Bochner F. Drug interactions with methadone:

pharmacokinetics. In Hummeniuk R, Ali R, White J, Hall W, Farrell M.

Additional resources:

Proceeding of Expert Workshop on the Induction and Stabilization of Patients Onto Methadone. Monograph Series 39.

http://opioids.com

Canberra: Commonwealth of Australia; 2000: 93-110. Available at: http://www.health.gov.au. 20.

Jackson, KC, Lipman AG. Opioid Analesics. In: Talison CD,

Satterwaite JR, Tollison JW (eds). Practical Pain Management, 3rd edition. Philadelphia: Lippincott Williams & Wilkins; 2001:216-231. 21.

Iribarne C, Picart D, Dreano Y, Berthou F. In vitro interactions

between fluoxetine or fluvoxamine and methadone or buprenorphine. Fundam Clin Pharmacol. 1998; 12 (2): 194-9. 22.

Wolff K, Rostami-Hodjegan A, Hay AWM, Raistrick D,

Tucker G. Population based pharmacokinetic approach for methadone monitoring of opiate addicts: potential clinical utility. Addiction. 2000;95(12):1771-1783. 23.

Leavitt SB, Krantz MJ. Cardiac Safety in MMT. Addiction

Treatment Forum. Special Report; 2003. Available at: http://www.atforum. com/cardiacmmt.shtml.

J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain Nonopioid Pain Medications Andrea Trescot, M.D. Nearly all men die of their medicines, not of their diseases. Moliere (1622-1672) Although most people (physicians and patients alike) think of opioids when thinking of pain medications, there are multiple medications that can be used effectively to treat pain, alone or in combination with opioids. These medications are useful but are not without their own risks. Rational prescribing of medications requires an understanding of the types of pain being treated. Described in greater detail elsewhere in this issue, pain in general can be described as nociceptive or neuropathic. Nociceptive pain can be considered the activation of “healthy” receptors, responding in an appropriate manner to a noxious stimulus. Neuropathic pain is defined as pain secondary to injury or dysfunction of the peripheral or central nervous system. There are a variety of medications that are effective for pain management, some of which include: 1. Anti-inflammatories 2. Antidepressants a. Tricyclic antidepressants (TCA’s) b. Selective serotonin uptake inhibitors (SSRI’s) c. Serotonin/norepinephrine reuptake inhibitors (SNRI’s) 3. Anticonvulsants 4. Muscle relaxants 5. Anxiolytics 6. Stimulants 7. Triptans 8. Other agents Anti-inflammatories: In general, pain is caused by inflammation. This is certainly true in traumatic conditions such as burns, broken bones, and surgical trauma. Tissue trauma releases cell membrane phospholipids, which are metabolized to arachidonic acid molecules, and then further metabolized into prostaglandins, which mediate pain, inflammation, and fever. Steroids possess the most powerful anti-inflammatory activity as a result of their action blocking the production of arachidonic acid. Unfortunately, they are associated with serious side effects including osteoporosis, increased blood sugar, tissue fragility, and adrenal suppression. Nonsteroidal antiinflammatories (NSAIDs) do not have these side effects. They

work by inhibiting the action of cyclo-oxygenase, the enzyme mediating the production of prostaglandins. Unfortunately again, the body is very frugal, and it uses prostaglandins for a variety of other functions such as platelet aggregation and gastric mucosal cytoprotection. Therefore, inhibition of prostaglandins by NSAIDs has the potential for causing gastrointestinal (GI) bleeding as well as inappropriate anticoagulation due to platelet function inhibition. A newer group of NSAIDs, which inhibit cyclo-oxygenase 2 (COX2), has been developed. Although the risk of GI bleeding decreased, there were concerns about cardiovascular (CV) effects. Of the three that were released, two were withdrawn (rofecoxib and valdecoxib). The third, celecoxib (Celebrex®) is still available. There have been several recent studies supporting its lack of CV effects as well as its efficacy in acute and chronic pain. However, unlike the two other COX2 inhibitors, celecoxib is relatively insoluble and must be given in higher initial doses (a “bolus” of 400 to 600mg) to provide acute pain relief. Antidepressants: Since patients who are hurting may often become depressed, antidepressants were one of the early adjuvant medications. For many years TCAs have been used for various indications including headaches, peripheral neuropathy and fibromyalgia. These agents are felt to block the reuptake of norepinephrine and serotonin. Unfortunately, their use in the elderly is limited by common side effects including sedation, as well as anticholinergic effects such as dry mouth, increased intraocular pressure, constipation, and orthostatic hypotension. Examples of TCAs include amitriptyline (Elavil®), doxepin (Sinequan®), and trazodone (Desyrel®). In general, although they are excellent antidepressants, the SSRIs have not been shown to be useful in painful conditions. In addition, fluoxetine (Prozac®) and paroxetine (Paxil®) more than sertraline (Zoloft®) or escitalopram (Lexapro®) will inhibit CYP2D6. Since many of the commonly used opioids are activated by CYP2D6, care must be taken to avoid decreased analgesia in these patients in pain. More recently, the serotonin/norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor®) and duloxetine (Cymbalta®) have been studied in painful conditions. They are less potent inhibitors of dopamine reuptake and have been shown to be effective for diabetic peripheral neuropathy (DPN). Duloxetine was approved in 2005 for depression as well as DPN. Caution should be used, however, since duloxetine cannot J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain be used with monoamine oxidase (MAO) inhibitors, and may cause hepatotoxicity, activation of hypomania, seizures, or increased blood pressure. Serotonin syndrome may occur when these medications are taken along with other serotonin agents. Symptoms may include confusion, manic activity, confusion, myoclonus, shivering, hypertension, and even death. Anticonvulsants: Nerves that are firing off on their own inside the brain cause seizures; nerves that are firing off on their own (ectopically) outside the brain can cause paroxysms of pain described in neuropathic terms. Spontaneous discharges in the peripheral or central neurons, often triggered by localized demyelination or abnormal expression of sodium channels, are the proposed mechanism of neuropathic pain. It is for this reason that anticonvulsants or anti-epileptic drugs (AEDs) have been used for burning, stabbing, or “knife-like” pains. The older AEDs such as phenytoin (Dilantin®), valproic acid (Depakote®), and carbamazepine (Tegretol®) alter calcium, sodium and potassium cellular flux. Unfortunately, these medicines are severely limited by their side effect profile. Phenytoin has a very narrow therapeutic window and has the potential to cause Stevens-Johnson syndrome and liver toxicity. Valproic acid increases GABA levels, decreasing nerve firing, but can cause hepatotoxicity. Carbamazepine has been reported to cause life threatening aplastic anemia. All three drugs need to be monitored with periodic blood level sampling to maintain therapeutic levels. Newer AEDs such as gabapentin (Neurontin®), lamotrigine (Lamictal®), and topiramate (Topamax®) have much wider therapeutic windows with much milder side effect profiles. This has led to expansion of their uses in such diverse conditions as complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, migraine headaches, post herpetic neuralgia (PHN), and peripheral neuropathy. Pregabalin (Lyrica®) was approved in 2005 specifically for painful diabetic peripheral neuropathy (DPN) and PHN, the first AED to have primary pain indications. Muscle relaxants: Much of what is called “musculoskeletal pain” involves isolated muscle spasms called “trigger points.” These painful bands or foci were codified by Janet Travell and David Simons in the two-volume set Myofascial Pain and Dysfunction (Williams and Wilkins). Unlike muscle soreness from overuse of a muscle, these spasms may arise seemingly J. Florida M.A. September 2006 Vol. 90, No. 2

untriggered and may refer pain to many distant structures. Standard muscle relaxants such as diazepam (Valium®), methocarbamol (Robaxin®), or cyclobenzaprine (Flexeril®) appear to work by decreasing central nervous system signals. Unfortunately, trigger points “do not pay attention to what the brain is saying,” and are not well treated by these medications. Instead, medications that were originally used for cerebral palsy or spinal cord injuries such as baclofen (Lioresal®) and tizanidine (Zanaflex®) appear to be more effective because of their central effect on alpha-2 adrenergic receptors. In addition, we should mention a special note regarding carisoprol (Soma®). Though widely used, it is felt to be highly addictive and is condemned by most contemporary pain management physicians. It is metabolized to meprobamate, an old major tranquilizer (Miltown®) that has been taken off the market. Meprobamate potentiates the euphoric effects of opioids, and is now a schedule IV medication; there is a strong regulatory effort to ban it altogether. Anxiolytics: Pain is often associated with anxiety and depression, and they are sometimes difficult to separate. Traditional anxiolytics, such as lorazepam (Ativan®) and diazepam (Valium®), come primarily from the benzodiazepine family, which constitute the largest group of prescribed drugs in the US today. Benzodiazepines act on the GABA receptors to inhibit excitatory neurons, and act on glycine receptors to reduce muscle spasms. Unfortunately, all benzodiazepines interfere with Stage 4 sleep, and all except flurazepam (Dalmane®) interfere with REM sleep. Withdrawal causes seizures in 70 percent of patients and has been shown to cause at least a 12-point drop in IQ scores in 60 percent of patients1. Serotonin is inhibited, making them depressants, not antidepressants. Given their addictive properties, they are mostly condemned by pain management specialists, though there is a role for the longer acting benzodiazepines such as clonazepam (Klonopin®). Other options include the azapirones such as buspirone (BuSpar®) and gepirone (Ariza®), which have a direct effect on 5HT1A receptors. Phenothiazine tranquilizers such as chlorpromazine (Thorazine®) block norepinephrine as well as block dopamine postsynaptically, and have a strong atropine-like effect. Fluphenazine (Prolixin®) will also block dopamine but there is less norepinephrine blockade and less atropine-like effects. Butyrophenones like haloperidol (Haldol®) are the most potent dopamine and norepinephrine blockers and have the least acetylcholine release. Antihistamines such as hydroxyzine (Vistaril®, Atarax®) can also be used as anxiolytics.

Treatment of Pain Stimulants: Because many medications for pain (especially opioids) are associated with sedation, stimulants may be useful both in increasing the usable dose of other medications and by acting as an analgesic as well. Methylphenidate (Ritalin®), as an example, is used for anhedonistic withdrawal as well as psychomotor retardation and sedation caused by opioids. A newer agent, modafinil (Provigil®), has been approved for narcolepsy as well as the sedation from sleep apnea. Although not specifically FDA-approved for opioid sedation, clinically this class of medications may be very useful.2

Whether as first line therapy or as add-on therapy in conjunction with opioids, the use of non-opioid medications for pain should be considered as part of the pain treatment armamentarium. Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in humans of whom they know nothing. Voltaire (1694-1778) References 1.

Triptans: Vascular headaches have been treated with serotonin agents such as ergotamines (which are nonselective) and triptans (which are selective 5HT1b/1d receptor agonists). One proposed pharmacotherapeutic effect is vasoconstriction of dilated cerebral blood vessels. For a group of patients, these drugs have provided a significant improvement in quality of life. Sumatriptan (Imitrex®) was the first, and is available in an injection, nasal, and oral form. Zolmitriptan (Zomig®) and rizatriptan (Maxalt®) have rapid oral dissolving forms, while naratriptan (Amerge®) and frovatriptan (Frova®) are longer onset but longer acting. Other options include almotriptan (Axert®) and eletriptan (Relpax®).

Tata, P.R., Rollings, J., Collins, M., Pickering, A., Jacobson,

R.R. Lack of cognitive recovery following withdrawal from long-term benzodiazepine use. Psychological Medicine (1994) 24(1): 203-213. 2.

Webster L, Andrews M, Stoddard G. Modafinil treatment of

opioid-induced sedation. Pain Med. 2003 Jun; 4(2):135-40.

Other agents: Alpha2 agonists such as clonidine (Catapres®) as well as alpha adrenergic blocking agents such as phenoxybenzamine and phentolamine can promote improved blood flow in the face of sympathetic vasoconstriction. L-dopa blocks prolactin levels, and has been used in restless leg syndrome and for bone metastases from prostate cancer. Betablockers are used for vascular headaches and may be used early in the course of complex regional pain syndromes. Antiarrhythmics such as mexiletine and bretylium act by inhibiting release of norepinephrine from the post-ganglionic neurons and were used in the past. However, because of cardiovascular effects such as heart block, for the most part they have been replaced by the newer anticonvulsants (see above). Corticosteroids such as dexamethasone and methylprednisolone are indicated for the pain from metastatic bone pain, soft tissue infiltration, acute nerve compression, increased intracranial pressure, acute spinal cord compression, and acute rheumatologic flare. Bisphosphonates can inhibit osteoclast mediated bone reabsorption, and has been reported to provide relief from the bone metastases from breast cancer. Topical local anesthetics such as EMLA® and Lidoderm® may be quite useful in the treatment of surface pain problems such as post herpetic neuralgia, as well as the treatment of painful regions where the skin is thin such as ribs, knees and shoulders.

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Treatment of Pain Approach to the Management of Pain in the Patient with Cancer Neel Karnani, M.D. The large majority of patients with cancer will require treatment for pain at some stage of their disease. Using a combination of opioids and various adjunctive therapies, good pain relief can be achieved in the large majority of patients.1 Unfortunately, the lack of adequate treatment of pain continues to be a dilemma, for a variety of reasons which are largely related to limitations in clinical care, the health system and the under reporting of pain. The goals of therapy in patients with cancer are: 1- Optimize pain control; 2- Minimize side effects, adverse outcomes and costs; 3- Enhance quality of life by improving functional abilities and physical and psychological well being. The goals of care are dynamic, requiring repeated assessment, identification and responding to the changing clinical situation as the disease progresses. In the palliative care literature, the concept of “total pain” experienced by many dying patients, is described as being comprised of four elements, originally proposed by Dr. Cicely Saunders:2 1- Physical pain, usually due to multiple sources; 2- Emotional or psychic pain; 3- Social or interpersonal pain; 4- Spiritual or existential pain. In populations with life threatening illnesses, pain management is key to achieving relief of suffering. Although pain control alone is not sufficient to relieve suffering, there can be little progress in other spheres of being, if pain is uncontrolled. Pain management is an integral part of a larger therapeutic model known as palliative care. The aim of palliative care is to enhance the quality of life of the patient and family throughout the trajectory of the disease by addressing problems across the physical, psychological, social and spiritual domains. At the end of life, the need for interdisciplinary specialized care intensifies, requiring services provided by hospice and palliative care programs.3

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Cancer pain is defined as pain attributable to cancer or its therapy. However, it is important to keep in mind when evaluating pain in cancer patients, that in up to 10 percent of patients, the source may be due to other co-morbid conditions, such as osteoarthritis, diabetic neuropathy, etc. It is equally important to assess for nonphysical causes of pain. A therapeutic approach focused only on physical pain may not have meaningful benefit to a patient whose suffering is related to other factors, such as psychosocial or spiritual issues. After an initial assessment and treatment plan has been formulated, the practitioner needs to continually reassess the patient, especially when the pain remains uncontrolled. Using a team approach involving other members of the interdisciplinary panel such as the nurse, social worker, pharmacist, chaplain, physical therapist, and home health aides, etc., may provide the key to successful pain management. Pathophysiology A pathophysiologic classification of pain can have utility in treatment planning. Pain may be conceptualized as nociceptive, neuropathic, psychogenic and/or mixed. When a reasonable deduction cannot be made as to the pathophysiology of pain, it may be labeled as “idiopathic.”4 Pain is considered to be nociceptive, if it is due to tissue injury causing direct stimulation of intact mechanical, chemical or thermal nociceptors and transmission of impulses along normally functioning nerves. Nociceptive pain can be further subdivided into the following: •

Somatic pain - arises in skin, soft tissue, muscle and bone; described as aching, throbbing, stabbing, etc.

•

Visceral pain - originates in abdominal viscera, lung, etc.; results from stimulation of the autonomic nervous system and is described as crampy, gnawing, etc.

Pain is labeled neuropathic when it is thought to be sustained by abnormal somatosensory processing in the peripheral (e.g., post herpetic neuralgia) or the central nervous system (e.g., phantom pain).Verbal descriptors such as “burning,” “shocklike,” or “electrical” are suggestive of neuropathic mechanisms.

Treatment of Pain In addition, the physical examination may reveal allodynia (pain in response to normally innocuous stimuli) or hyperalgesia (exaggerated and prolonged response to painful stimuli). If psychological factors predominate in a clinical picture devoid of any obvious cause for pain, the pain may be considered to be psychogenic. Management of Persistent Cancer Pain can be broadly categorized into the following:5 •Primary Therapy -

chemorainhdt,eirap,y surgery, immunotherapy

•Symptomatic Therapy - pharmacotherapy, ,seiti lm adolacisyhp interventional therapy, ,ypahert laco igho cylps complementary and alternative medicine

Conversely, the “burden” of treatment may test the practitioner’s skill at symptom management. Treatment may possibly intensify pain and other troubling symptoms. Additionally, treatment may have adverse financial, logistical and psychosocial implications, which will require an inter-disciplinary team approach to deal with these issues. Pharmacotherapy Effective pain management requires proficiency in the administration of three categories of analgesic medications: nonsteroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, and adjuvant analgesics.5 The term “adjuvant

WHO ANALGESIC LADDER analgesic” is applied to a diverse group of drugs that have primary indications other than pain but can be effective analgesics in specific circumstances, such as the treatment of neuropathic pain.

In 1986, the World Health Organization (WHO) recommended a step-wise approach to treating pain based on its severity. This three-step approach of administering the right drug in the right dose at the right time is inexpensive and effective in 80-90 percent of patients.2 Step 1: recommends the use of acetaminophen, aspirin or one of the other NSAIDs to control mild pain. Step 2: As the level of pain escalates, this step requires the addition of an opioid such as codeine, hydrocodone or oxycodone. These are administered on an around-the-clock basis with additional PRN doses for breakthrough or incident pain (see below). Step 3: As pain persists or increases, stronger opioids such as morphine, oxycodone, hydromorphone (Dialudid®) and fentanyl (Duragesic®) are needed. Some authors have advocated adding a “fourth step” consisting of interventional procedures, such as nerve blocks, surgical procedures, and cognitive behavioral therapies to treat patients with intractable symptoms. Some caveats are as follows: a) Climbing each step of the ladder sequentially is not necessary. Patients presenting with moderate to severe pain are started on Step 2 or 3 of the ladder. b) Adjuvant drugs or “co-analgesics” may be used at any step to enhance analgesia. NSAIDs are especially useful in patients with bone pain or pain related to inflammatory lesions. They have an opioidsparing effect, which may enable the practitioner to use lower doses of opioids thereby preventing dose-related side effects. Given the high prevalence of gastrointestinal (GI) side effects and concerns about platelet function in many cancer patients undergoing chemotherapy, it is justifiable to consider the COX2 selective drug celecoxib (Celebrex®) as a first-line choice in this population. Non-acetylated salicylates, such as, salsalate (Disalcid®) and choline magnesium salicylate (Trilisate®) may be preferable over other NSAIDs. They have less GI toxicity and do not exhibit any detrimental effect on platelet function. Gastrointestinal adverse effects can be minimized by the addition of a proton-pump inhibitor, such as esomeprazole (Nexium®). Misoprostol (Cytotec®) is also approved for prevention of NSAID-induced GI ulcers but its use is limited by diarrhea. Given the potential for nephrotoxicity and cardiotoxicity, NSAIDs should be used cautiously in patients with known renal insufficiency and those at high risk for congestive heart failure and coronary thrombosis. The old adage “start low and go slow” is applicable here. J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain Opioids Discussed in greater detail in the Opioid Pharmacology chapter, opioids are the safest and most effective agents for most types of cancer-related pain. Inadequate dosing adjustment is probably the most common reason for unsuccessful longterm relief of cancer pain. Significant respiratory depression is highly uncommon in the clinical setting of careful titration of opioids for relief of cancer pain. It is always accompanied by somnolence. Monitoring the respiratory rate should help to avoid this rare adverse event.   The dose of an opioid should be increased until acceptable analgesia is produced or side effects become intolerable and uncontrollable. There is no maximum dose of a pure agonist opioid. In clinical situations where the dose of opioid cannot be escalated due to adverse events and analgesia is incomplete, several strategies can be utilized: 1) Switching to another opioid is warranted, given the large individual variation in response to the different opioids. 2) Addition of pharmacologic (e.g., NSAID) or nonpharmacologic (e.g., neural blockade) treatment that allows reduction in the opioid requirement may permit a lower dose of the opioid to be effective. 3) Instituting measures to control the side effects may improve the efficacy of the drug and convert a poorly responsive patient to one who has a satisfactory response. 4) Nonphysical pain must be addressed with compassionate listening and involvement of other members of the interdisciplinary team. Chronic pain in patients with cancer is usually continuous and where this is so, therapeutic plasma levels of analgesics must be maintained. This can only be achieved when the drug is given regularly at correct intervals, according to the pharmacokinetic and pharmacodynamic profile of the drug. Patients who are opioid-naïve typically are given an opioid at a dose of 5 to 10 mg of oral morphine (or its equivalent) every four hours. Immediate release morphine reaches its peak effect at 60-90 minutes when given orally. The dose is then escalated as needed to produce analgesia, keeping in mind that no ceiling exists on the number of times that a dose may be titrated. During a 24-hour period, some patients may require a 100 percent increase over their initial daily baseline dose. When titration has been successful, the total daily dose can be calculated and administered in divided doses at eight to12 hour intervals around the clock, in the form of a sustained release J. Florida M.A. September 2006 Vol. 90, No. 2

preparation, (e.g. MS Contin®, Oxycontin®). Slow-release tablets or patches should not be used for titration. Transitory flares of pain, known as “breakthrough pain” can be expected throughout the day. “Incident pain” is precipitated by some specific physical activity. When this pain lasts longer than a few minutes, additional doses of analgesics, known as rescue or breakthrough doses, will be required. A short acting opioid, (e.g., morphine sulfate immediate release, oxycodone) can be used for this purpose every two to four hours as needed. The dose is equal to five to 15 percent of the total daily opioid consumption.  Tolerance is the need for increasing dosage of opioid to produce the same desired therapeutic effect. It is a normal physiologic occurrence in any person who takes opioids for more than a few days. However this is not a frequent occurrence. The need for increasing doses of opioids in cancer patients is usually a reflection of disease progression rather than due to tolerance or inappropriate use of opioids. Hence, at some point, patients with stable pain may need gradually escalating doses.5 Increasing doses of opioids should not be withheld because of concern of addiction. Evidence has shown that cancer patients who have a fear of tolerance or addiction to opioids tend to experience a higher intensity of pain.6 The clinical implication is that patient anxiety regarding opioids needs to be allayed through education and medication, if necessary.7 Pure agonist opioids are recommended as they have no ceiling effect, allowing their upward titration in moderate to severe pain. Partial agonist and mixed agonist-antagonists, such as pentazocine (Talwin®), butorphanol (Stadol®) and nalbuphine (Nubain®) should not be used in the patient already taking a pure agonist opioid as this may precipitate an acute withdrawal reaction. Most experts would argue that these drugs have a very limited role, if any, in the treatment of cancer pain. When a short acting agent is used initially or to treat breakthrough pain, caution is necessary if the agent is combined with acetaminophen. The dose of the opioids that are combined in a single tablet with acetaminophen can only be escalated until the total daily dose of acetaminophen is reached, taking into account over the counter use as well. This is usually a maximum of four g/d (<4 g/d in patients with known liver disease or a history of heavy ethanol ingestion). Propoxyphene (Darvocet®) and meperidine (Demerol®) should not be used at higher doses or over prolonged periods because of the risk of accumulation of neurotoxic metabolites.

Treatment of Pain Morphine, used in accordance with WHO guidelines remains the strong opiate of choice in the management of cancer pain. Oxycodone and fentanyl are other long acting choices. In the small minority of patients who respond poorly to morphine and other opioids, methadone may prove to be a successful alternative. Financial considerations have propelled a significant increase in the role of methadone in pain management. It is effective in neuropathic pain as well, possibly because of its ability to function as an N-methyl-D-aspartate (NMDA) antagonist.8 It has a relatively high potency and a long half-life, which adds to its favorable characteristics. However, given its highly variable half-life and unexpected potency, its use presents the challenges of dose selection, adjustment and monitoring. It is prudent to adjust the dose only every four to seven days. In high doses it may prolong the QT interval, predisposing patients to fatal ventricular arrhythmias (torsades de pointes). Some of the commonly used drugs that increase methadone levels (CYP3A4 inhibitors) are SSRI antidepressants, clarithromycin, erythromycin, quinolones, haloperidol, ketoconazole and fluconazole amongst others. When patients are switched from one opioid drug to another, the dose of the new drug is calculated from an equianalgesic dose table. Basic guidelines are mentioned in the section on opioids. The dose of the new drug is then reduced to decrease the risk of toxicity caused by incomplete cross-tolerance by 25-50 percent. The two exceptions are: 1) transdermal fentanyl, the calculated dose is considered the equianalgesic dose (a safety factor has already been built into the conversion), and 2) methadone, the dose must be reduced by a significantly larger proportion depending on the dose of the opioid to be converted. Side effects that are common and should be anticipated are constipation, nausea/vomiting, somnolence and cognitive impairment. As with opioid therapy, the most effective laxative regimen for the control of constipation is one that follows a step-wise approach and is ongoing, instead of being administered on an as-needed basis. Osmotic laxatives (e.g., lactulose) and/or stimulant cathartics (e.g., senna) are needed in adequate doses, to counter the constipating effect of opioids. Standard anti-emetics, such as prochlorperazine (Compazine®), promethazine (Phenergan®), haloperidol (Haldol®) or metoclopramide (Reglan®) may be required for a few days to treat nausea and vomiting. Usually the antiemetic can be phased out after several days or weeks. Nausea and vomiting is less likely to occur if the patient has been taking regular doses

of other opioids such as hydrocodone or oxycodone before starting morphine. Temporary sedation and drowsiness may occur when opioids are initiated. This is usually self-limited and clears within two to five days. Accumulated exhaustion and sleep deprivation caused by uncontrolled pain are the major contributing factors to somnolence. When pain relief is achieved, the patient finally may be able to sleep for long periods of time. If sedation continues to be a problem, reducing the dose or switching to another opioid at a lower dose may be an effective strategy. A few patients may require a stimulant such as methylphenidate (Ritalin®) 5 to 15 mg in the morning and at noon. Alternatively, modanifil (Provigil®), which has less sympathomimetic cardiovascular side effects, may prove to be helpful. Urticaria and pruritus are frequently encountered (most commonly with morphine) and occur as a result of mast cell destabilization. This is not a true allergic reaction and can usually be managed by the administration of nonsedating antihistamines or mast cell stabilizers. These symptoms are rarely a problem with chronic opioid administration. Adjuvant Analgesics These drugs play a pivotal role in cancer pain management at all stages of treatment. These medications are described more fully in earlier chapters. In addition to their use in neuropathic pain, corticosteroids are empirically used to treat the pain and symptoms associated with a number of medical conditions: lymphedema, bowel obstruction, metastatic bone pain, headache associated with intracranial mass lesions, hepatic capsular distension and acute spinal cord compression. Dexamethasone (1-4 mg) or prednisone(10-20 mg) are the most commonly used steroids. Antidepressants, anticonvulsants and other adjuvant drugs have analgesic properties in neuropathic pain. There is significant evidence for the analgesic activity exhibited by the antiepileptic drugs gabapentin (Neurontin®) and pregabalin (Lyrica®), a newer agent with a similar mode of action and for the tricyclic antidepressants, particularly amitriptyline (Elavil®). The lack of drug interaction with gabapentin gives it an edge in patients on multiple medications.9 The use of amitriptyline is often limited by its anticholinergic side effects. Nortriptyline (Pamelor®) or desipramine (Norpramin®) is often better tolerated than amitriptyline, particularly in the elderly.

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Treatment of Pain Newer antidepressants, particularly the serotonin and norepinephrine selective reuptake inhibitors (SSNRIs), venlafaxine (Effexor®) and duloxetine (Cymbalta®) also are analgesic and may be better tolerated in patients with cancer. Other anticonvulsants that may be used include the newer and better tolerated drugs: lamotrigine (Lamictal®), tiagabine (Gabitril®), topiramate (Topamax®), oxcarbazepine (Trileptal®), zonisamide(Zonegran®), and levetiracetam (Keppra®). Mexiletine (Mexitil®), an antiarrythmic, may be considered if efforts using the previously mentioned drugs, are not successful. A baseline EKG is recommended before this drug is initiated. Topical agents, such as, a five percent lidocaine patch (Lidoderm®) and capsaicin (Zostrix®) - a peptide that depletes substance P from sensory neurons that mediate cutaneous pain - have been helpful in some patients with neuropathic pain, e.g., postherpetic neuralgias, postmastectomy syndrome. The burning sensation that accompanies capsaicin may wane spontaneously in some patients and can be reduced in others with the prior administration of an oral analgesic or cutaneous application of lidocaine ointment. Bisphosphonates, such as pamidronate (Aredia®) and zoledronic acid (Zometa®), are useful in treating pain due to painful bony metastasis. Other drugs used with the same intent include corticosteroids, calcitonin and the radiopharmaceuticals, strontium-89 and samarium-153. Adjuvant analgesics also are commonly employed in the setting of advanced bowel obstruction. Treatment usually involves the combination of steroids, anticholinergic drugs (e.g., scopolamine or glycopyrrolate), octreotide and opioids. Other Analgesic Approaches/End-of-life Care Most patients can be managed well with pharmacotherapy. Only a small proportion of patients will require invasive procedures for adequate analgesia. Interventional therapy includes neuraxial drug delivery, spinal cord stimulation and neural blockade. Opioids and local anesthetics can be delivered to the vicinity of neural tissue, obviating the need for systemic absorption as a means to reach receptor sites. Neuraxial drug delivery (i.e., epidural, subarachnoid, intraventricular) is usually considered when treatment with an opioid causes intolerable and uncontrolled side effects despite maximal therapy. Epidural or subarachnoid drug administration may be performed by either percutaneous catheterization, reservoir or implantation of a catheter and pump. J. Florida M.A. September 2006 Vol. 90, No. 2

Stimulation of afferent neural pathways may result in analgesia. Examples include transcutaneous electrical nerve stimulation (TENS), percutaneous electrical nerve stimulation, spinal cord (dorsal column) stimulation and deep brain stimulation. Unfortunately, relief is usually not sustained. Neural blockade comprises a diverse group of procedures that block sympathetic nerves, somatic nerves, or both. Somatic nerve blocks reduce afferent nociceptive input, and sympathetic nerve blocks are used to block afferent input from viscera. Neuroablation is often initiated, early in the natural history of the cancer pain, in the presence of selected focal somatic lesions (e.g., rib metastasis), visceral (e.g., celiac plexus blockade in pancreatic cancer) or neuropathic pain (e.g., craniofacial) pain that is thought to be highly responsive to neuroablation with limited risk.10 After performance of a successful neuroablation, the dose of opioids should be reduced, to reduce the possibility of respiratory failure. However, they should not be abruptly discontinued, to avoid precipitation of a withdrawal reaction. In some cancer patients, therapeutic blocks with local anesthetic are used repeatedly to obtain substantial relief if they demonstrate adequate response to an initial temporary block. More prolonged neural blockade can be achieved through techniques of perineural or epidural infusion. Prolonged infusion of epidural local anesthetic is the most common approach.3 Certain modalities of physical therapy, such as the use of heat, cold, ultrasound and electrical stimulation, appear to benefit some patients, thereby improving quality of life. The use of orthoses or prostheses may be beneficial, e.g., bracing a limb with a painful metastatic fracture. Range of motion exercises may lessen pain associated with immobility, trigger points and ankylosis. Some patients or families who present with severe psychological distress may benefit from a multidisciplinary approach in which specific psychological interventions are emphasized within a program designed to palliate symptoms and provide family support. Specific cognitive and behavioral approaches have also been applied successfully in the management of pain and related symptoms. Cognitive approaches include relaxation training, distraction techniques, hypnosis, and biofeedback, which may enhance a patient’s sense of personal control over the pain and result in pain reduction. These are discussed in more detail in the next chapter.

Treatment of Pain Therapies that are typically considered complementary or alternative have had a growing role in pain management. This holistic approach offers hope and an element of self-control to patients at a time when both are needed. The following methods can be invaluable for improving quality of life and enhancing the efficacy of drug therapy: •

Distraction: music, art, movies, reading, books on tape

•

Guided imagery or hypnosis

•

Progressive relaxation

•

Meditation

•

Massage therapy

•

Acupuncture

That physician will hardly be thought very careful of the health of his patients if he neglects his own. Galen 130-200 A.D.11 Physician Health It is essential to recognize that optimal patient care can be adversely affected if the health of the clinician is disturbed.12 The practitioner faces a unique set of challenges when caring for seriously ill patients. At a time when patients are emotionally vulnerable during their illness, the clinician may respond to such emotions and needs with strong emotions of their own.

Health care practitioners have the unenviable task of striking a balance between their concerns for patient safety while respecting their patient’s pursuit of complementary treatments that have little or no documented evidence of being beneficial. The National Institutes of Health (www.nccam.nih.gov) continues to support research in this area. While most patients experience excellent relief from suffering with the support of a hospice or palliative care team, some patients continue to suffer from intractable end-of-life problems. Sedation at the end of life and voluntary refusal of food and fluids are ethical and effective means of coping with intractable suffering, without resorting to assisted suicide. Potential pitfalls:11 1. Using extended release preparations for initial dose titration. 2. Mixing opioids. 3. Stool softeners at conventional doses are not enough to relieve the constipating effect of opioids. 4. Failing to distinguish sleepiness caused by exhaustion once pain is relieved from sedation caused by overmedication. Monitoring the patient’s respiratory rate will help to identify the somnolence caused by opioids. 5. Using opioids to control terminal delirium, which may worsen as a result. 6. Unproven fear of respiratory depression resulting in undertreatment of pain leading to unnecessary pain and suffering.

If these emotions (e.g., guilt, grief, anger, frustration, etc.) are not consciously acknowledged and examined, the unintended consequences may result in physician distress, disengagement, burnout and poor judgement.13 It is important to accept that such emotions are normal and inevitable. It is equally important to acknowledge life’s imperfections and the limitations of modern medicine. Developing a personal philosophy that provides meaning for illness, death and the physician’s own role helps to alleviate the negative feelings. Discussing troubling professional issues with empathetic health professionals helps to alleviate isolation. Other coping strategies include ministering to the mind, body and spirit as well. By engaging in activities that provide a sense of rejuvenation - psychological, physical or spiritual - the clinician can learn to transcend their own role attachments and co-exist with their very normal feelings of fear, guilt and grief. Such activities include meditation, yoga, worship, enjoying the outdoors, nature appreciation, being with family, etc. It is essential to participate in activities for their intrinsic enjoyment and not for reward or acclaim.14 “Smelling the roses” is not necessarily a cliché.

7. Unfounded concern for tolerance and addiction.

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Treatment of Pain References 14. 1.

Portenoy, R and Lesage, P. AMA Pain Management On line

Series Module 10. Overview and assessment of cancer pain. Dec 2005. 2.

Storey, P and Knight, C. UNIPAC Five: Caring for the

terminally ill: communication and the physicianâ&#x20AC;&#x2122;s role on the interdisciplinary team. 2nd edition 2003. Mary Ann Liebert Inc Publishers, Larchmont, New York 10538-1962.

Storey, P and Knight, C. UNIPAC Three: Assessment and

treatment of Pain in the terminally ill. 2nd edition 2003. Mary Ann Liebert Inc Publishers, Larchmont, New York 10538-1962. 3.

Portenoy, R and Lesage, P. AMA Pain Management Online

Series Module 12. Management of cancer pain:Other analgesic approaches and end-of-life care. Dec 2005. 4.

Brown EF. AMA Pain Management Online series Module 1.

Pathophysiology of pain and Pain Assessment. Dec 2005. 5.

Portenoy, R and Lesage, P. AMA Pain Management Online

Series Module 11. Cancer pain pharmacotherapy. Dec 2005. 6.

Paice JA, Toy C, Shott S. Barriers to cancer pain relief: fear of

tolerance and addiction. J Pain Symtom Manage 1998; 16:1-9. 7.

Whitecar P, Jonas A.,Clasen M. Managing pain in the dying

patient. Am Fam Physician 2000; 61:755-64. 8.

Morley JS and Makin MK. The use of methadone in cancer

pain poorly responsive to other opioids. Pain Reviews 1998:8:51-58. 9.

McDonald A, Portenoy R. How to use antidepressants and

anticonvulsants as adjuvant analgesics in the treatment of neuropathic cancer pain. JSupportOncol 2006; 4:043-052. 10.

A Report by the American Society of Anesthesiologists Task

Force on Pain Management, Cancer Pain Section. Anesthesiology 1996; 84:1243-57 ÂŠ1996 American Society of Anesthesiologists, Inc, LipincottRaven Publishers. 11.

Education for physicians on end-of-life care (EPEC) Project.

1999. Robert Wood Johnson Foundation. 1996-2003. 12.

Beatty WK. Galen. Of protecting the Health, book V. In: Sleep

Thieves: An eye-opening exploration into the science and mysteries of sleep. New York: The Free Press;1996:205. 13.

Meier D, Back AL, Morrison S. The inner life of physicians and

care of the seriously ill. JAMA 2001; 286:3007-3014.

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Treatment of Pain From Chaos to Control: Nonpharmacologic Treatment of Chronic, Nonmalignant Pain Heidi A. Pomm, Ph.D. Pain affects all aspects of the individual: physical, cognitive, emotional, social, occupational, sexual and spiritual. 1,2 However, most interventions used to treat pain in the medical setting are pharmacologic and/or procedural in nature. These interventions, while very effective and useful, do not fully address the global, multi-faceted, nature of pain. A combination of pharmacologic/ procedural and nonpharmacologic interventions, which touch on all aspects of pain, appears to yield the best results.3,4 Some of the most widely-used nonpharmacologic modalities for treating pain are cognitive behavioral techniques5,6,7, acupressure8, diaphragmatic breathing9, relaxation techniques9,10,11, guided imagery12, chiropractic/osteopathic manipulation13,14, distraction15, acupuncture16,17, biofeedback18, hypnosis19, exercise20, yoga21, and massage.22 Another nonpharmacologic modality which has been demonstrated to be an efficacious adjunct for pain reduction in specific conditions is physical therapy.23,24,25 While a thorough review of each of these interventions is beyond the scope of this brief section, patients can access this information directly through The National Pain Foundation’s website, “Using Complementary Therapy to Relieve Pain” (http://www.nationalpainfoundation.org/MyTreatment/News_ Complementary.asp). Two specific pragmatic techniques, which can be most easily adapted to the office-based setting are as follows: 1- Cognitive-restructuring - a component of cognitive-behavioral therapy; 2- Diaphragmatic breathing. These strategies, as well as recommendations for enhancing the doctor-patient relationship, will be discussed. Cognitive Restructuring If you are distressed by anything external, the pain is not due to the thing itself but to your own estimate of it; and this you have the power to revoke at any moment -Marcus Aurelius Cognitive-behavioral therapy (CBT) is one of the most widely used and studied interventions for the nonpharmacologic treatment of chronic pain. The essence of CBT theory is, simply, “We Feel What We Think.” That is, our thoughts are created because of our perceptions about situations (people, places and events), and these thoughts, in turn, create feelings.

From a medical psychology perspective, feelings then influence our physical sensations by activating the sympathetic nervous system and “fight or flight” response. Our feelings, and the accompanying physical sensations, then affect the choices we make (behaviors). This can be best illustrated by the struggle faced by most patients who are living with chronic pain: Perceptions of a situation as threatening their available coping resources>>>negative, distorted cognitions>>>distressful feelings>>>>tightened muscles and increased blood pressure>>>>greater perceptions of pain>>>short-term rewarding, long-term defeating behaviors (greater use of narcotics, avoidance behaviors which, in the long run, make pain worse, etc.)>>>more negative outlook on life>>>distressful feelings, and so on. 26 It is as if the patient is on a roller-coaster of negativity and chaos---the cognitive-emotional-physicalbehavioral cycle continues and the patient experiences a tremendous loss of control over his/her life and circumstances; a kind of “reality vertigo.” 1,2,27 Probably the most important goal that you, the physician, can accomplish is to help your patients with chronic pain “get in touch” with the aspect of their cognitive process that is NOT negative or distorted by fear. This is what might be referred to as the “wise” or “balanced” part of each individual; the part that yearns for peace of mind and freedom from the roller coaster of chaos, which is chronic pain. Cognitive restructuring is the practice of changing one’s negative, distorted thinking, or “self-talk,” into more balanced, accurate cognitions. For example, a patient with pain may state, “My pain will never go away…I will always be in pain!” When thinking thoughts such as these, your patient is undoubtedly feeling very anxious, depressed and physiologically aroused which, in turn, increases perceptions of severity of pain. To teach your patient cognitive restructuring, you might ask him/her, “What can you tell yourself (or, “What would the wise part of you tell you) that would make you feel less anxious (or sad, scared, depressed, angry, etc.)?” Most patients are able to come up with a thought to refute, or to work as an “antidote” against, their negative self-talk. Using the example above, your patient might then be able to change the negative statement, “My pain will never go away…I will always be in pain” into a more balanced (and much less distressing) thought, such as, “I am doing everything my doctor has recommended and I will take everything one day at a time and hope that things will get better.” Of course, your patient will not believe this new thought as much as s/he believes the previous, negative one! S/he should be reassured J. Florida M.A. September 2006 Vol. 90, No. 2

Treatment of Pain that this is normal and will take time and practice. The physician might assign “homework” to continue practicing cognitive restructuring between visits. When your patient returns for follow-up, you can focus on the homework you prescribed and identify both successes and difficulties in your patient’s ability to cognitively restructure negative, distorted self-talk. This “focusing” by asking about homework and/or elements of the previous visit, tends to help keep the visit “on track” and brief--you have a goal in mind (decreasing pain by having the patient change thoughts to change feelings) and all other dialogue can be continuously brought back to this goal. Diaphragmatic Breathing Another office-based practical strategy for managing pain is diaphragmatic breathing. 9 The physician can teach patients this technique by instructing them to breathe deeply from their lower diaphragm, rather than from their upper thorax. The patient is directed to place one hand on the chest and another on the stomach. The physician then encourages the patient to focus on “moving” their lower hand, by breathing in deeply.1,2,26 Diaphragmatic breathing appears to assist in pain reduction by invoking the parasympathetic nervous system, as well as through distraction, or directing one’s attention away from the pain. The Doctor-Patient Relationship One of the most powerful variables in improving patient outcomes is the development and maintenance of a good relationship between the physician and patient. The physician can enhance this relationship by acting in an empathic manner toward the patient in pain, helping the patient to feel heard and understood, involving the patient in her/his treatment plan, and seeing the patient for regularly scheduled visits.1,2,27,28,29 Past research indicates that patients with chronic pain rate “listening” and “being believed” as the most important qualities in their physician, regardless of whether or not the doctor can actually help them with their pain.30 However, this may be easier said than done--pain patients can be very difficult! Hence, the challenge for the physician is to demonstrate an empathic, caring style with a patient who may be problematic in many respects. 1,2,28,31 Some communication strategies for increasing empathy include asking questions such as, “Is there anything else?” and “Let me see if I understood you correctly.” 1,2,32 In addition, acknowledging the patient’s experience with statements such as, “It must be very difficult to live with pain,” and “Pain affects all areas of a person’s life—this must be very hard for you,” may be very beneficial in helping the patient feel understood. Finally, it is of utmost importance that physicians practice their own “self-care” in order to avoid becoming “burned out” from treating such a difficult patient population. Self-care should J. Florida M.A. September 2006 Vol. 90, No. 2

include the setting of appropriate boundaries with your more difficult patients. For example, “boundary setting” might include informing the patient at the start of each visit what the timeframe is and what your expectations are for the visit, while also informing the patient that you value and welcome what s/he wants to discuss. This definition of expectations can aid both you and the patient in feeling more “in control.” Other forms of physician self-care include engaging in pleasurable activities outside of medicine, getting adequate time alone as well as time spent with loved ones, and discussing feelings of frustration about patients with trusted colleagues. 1,2,31 By putting oneself first, the physician is better able to care for their patients with chronic pain, and to help them move forward--from chaos to control. References 1.

Pomm HA. Psychological aspects of chronic, nonmalignant

pain: Moving from “reality vertigo” to hope. Northeast Florida Medicine 2005; Summer: 31-3. 2.

Pomm HA. Regaining balance after “reality vertigo:” Teaching

learners to attend to the psychological aspects of patients with chronic, nonmalignant pain. Family Medicine 2006; 38(2):86-9. 3.

Berman BM. Integrative approaches to pain management: how

to get the best of both worlds. BMJ 2003; 326: 1320-1321. 4.

Nicholas MK, Molloy AR, Brooker C. Using opioids with

persisting noncancer pain: a biopsychosocial perspective. Clin J Pain 2006;22(2):137-46. 5.

Moseley GL, Nicholas MK, Hodges PW. A randomized

controlled trial of intensive neurophysiology education in chronic low back pain. Clin J Pain 2004;20(5):324-30. 6.

Goldenburg DL, Burckhardt C, Crofford L. Management of

fibromyalgia syndrome. JAMA 2004; 292(19):2388-95. 7.

Turner JA, Mancl L, Aaron LA. Brief cognitive-behavioral

therapy for temporomandibular disorder pain: effects on daily electronic outcome and process measures. Pain 2005; 117(3):377-87. 8.

Hsieh LL et al. Acupressure may be more effective than

physical therapy at relieving low back pain. BMJ 2006 (in press). 9.

Moskowitz L. Psychological management of postsurgical pain

and patient adherence. Hand. Clinic 1996; 12(1):129-37.

Treatment of Pain 10.

Lin YC, Lee AC, Kemper KJ, Berde CB. Use of complementary

22.

Plews-Ogan M, Owens JE, Goodman M, Wolfe P, Schorling

and alternative medicine in pediatric pain management service: a survey.

J. A pilot study evaluating mindfulness-based stress reduction and

Pain Med. 2005; 6(6):452-8.

massage for the management of chronic pain. J Gen Intern Med 2005; 20(12):1136-8.

11.

Lindberg DA. Integrative review of research related to

meditation, spirituality, and the elderly. Geriatr Nurs 2005; 26(6):372-7.

23.

Wen DY. Approach to shoulder pain in primary care. Mo Med

2006; 103(2):169-174. 12.

Menzies V, Taylor AG, Bourguignon C. Effects of guided

imagery on outcomes of pain, functional status, and self-efficacy in

24.

Vassiliou T, Kaluza G, Putzke C, Wulf H, Schnabel M. Physical

persons diagnosed with fibromyalgia. J Altern Complement Med 2006;

therapy and active exercises - An adequate treatment for prevention of

12(1):23-30.

late whiplash syndrome? Randomized controlled trial in 200 patients. Pain 2006; May 9 (Epub ahead of print).

13.

Beyerman KL, Palmerino MB, Zohn LE, Kane GM, Foster

KA. Efficacy of treating low back pain and dysfunction secondary to

25.

osteoarthritis: chiropractic care compared with moist heat alone. J

controlled trial investigating the efficiency of musculoskeletal

Goldby LJ, Moore AP, Doust J, Trew ME. A randomized

Manipulative Physio Ther 2006; 26(2): 107-14.

physiotherapy on chronic low back disorder. Spine 2006; 31(10):108393.

14.

Kuchera ML. Osteopathic manipulative medicine

considerations in patients with chronic pain. J Am Osteopath Assoc

26.

2005;105(9 Suppl 4):S29-36.

in primary care (in press). Springer Publishing: New York.

15.

27.

Veldhuijzen DS, Kenemans JL, de Bruin CM, Oliver B,Volkerts

ER. Pain and attention: attentional disruption or distraction? J Pain 2006;

Pomm HA, Pomm RM. Management of the addicted patient

Tenzer P & Stanley (Pomm) H. Helping Patients Get Off the

Wheel of Chronic Pain. Home Health Care Consultant 2000; 17:35-39.

7(1):11-20. 28. 16.

Linde K, Weidenhammer W, Streng A, Hoppe A, Melchart D.

Acupuncture for osteoarthritic pain: an observational study in routine

Wasan AD, Wootton J, Jamison RN. Dealing with difficult

patients in your pain practice. Regional Anesthesia and Pain Medicine. 2005; 30:184-192.

care. Rheumatology 2006; 45(2): 222-7. 29. 17.

Cabyoglu MT, Ergene N, Tan U. The mechanism of acupuncture

Gillette RD. Problem patients: A fresh look at an old vexation.

Fam Pract Manag 2000; 7:57-62.

and clinical applications. Int J Neurosci;116(2):115-25. 30. 18.

Ryan M, Gevirtz R. Biofeedback-based psychophysiological

treatment in a primary care setting: an initial feasibility study. Appl

Abyholm AS, Hjortdahl P. Being believed is what counts: A

qualitative study of experiences with the health service among patients with chronic back pain. Tidsskor Nor Laegeforen 1990; 119: 1630-2.

Psychophysiol Biofeedback 2004; 29(2):79-93. 31. 19.

Jensen M, Patterson DR. Hypnotic treatment of chronic pain. J

Pomm HA, Shahady E, Pomm RM. The CALMER approach:

Teaching learners six steps to serenity when dealing with difficult

Behav Med 2006; Jan 11:1-30.

patients. Fam Med. 2004 Jul-Aug; 36(7):467-9.

20.

32.

Gusi N et al. Exercise in waist-high warm water decreases

Coulehan JL, Platt FW, Egener B, Franel R, Lin CT, Lown B,

pain and improves health-related quality of life and strength in the

SDalazar WH. â&#x20AC;&#x153;Let me see if I have this right!â&#x20AC;? Words that help build

lower extremities in women with fibromyalgia. Arthritis Rheum 2006;

empathy. Ann Intern Med 2001; 135: 221-27.

55(1):66-73. 21.

Williams et al. Effect of Iyengar yoga therapy for chronic low

back pain. Pain 2005; 115(1-2):107-17.

J. Florida M.A. September 2006 Vol. 90, No. 2

Addiction and Pain Management Pain and Addiction By Bernd Wollschlaeger, M.D., FAAFP Raymond Pomm, M.D. Gary Reisfield, M.D.

and physical dependence to pain medications. This may explain the augmented pain response and decreased tolerance to pain in the presence of addiction.

Previous chapters have addressed the evaluation of the pain patient, and reviewed the neuroanatomy, neurophysiology, classification, and mechanisms of pain. Opioid and nonopioid pharmacology has been presented, along with nonpharmacologic approaches and a special patient population, the patient with cancer. In this chapter, we will first discuss the topic of addiction, then focus on the difficult task of providing pain relief in a patient with aberrant drug use and/or addiction.

These facts will complicate pain management in the presence of addiction, but do not preclude the use of opioids in addicted individuals with chronic pain. Unfortunately, many physicians believe that addicted individuals should be able to exert more control over the aberrant use of their drug(s) of choice. When this is the predominant belief, feelings of frustration, intolerance, and anger result and affect physicians’ responses to these patients and, in turn, patients’ responses to physicians. In addition, decisions relating to the treatment plan are also affected.

Addiction is now understood to be a primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Patients with addiction and patients with chronic pain are two of the most challenging populations in clinical medicine. Diagnosis and management become especially difficult when attempting to discern between inadequately treated chronic pain and addiction, or when confronted with the combination of both disorders. In these settings the doctor-patient relationship can become severely strained; many doctors consider these individuals to be “problem patients” and are reluctant to prescribe appropriate pharmacotherapies. Patients, in turn, can become hostile and demanding. Yet, the therapeutic relationship itself is one of the most important factors in determining adherence with, and maximum benefit from, treatment. Unfortunately, individuals with addictive disease remain at risk for under treatment of pain. Multiple factors contribute to this problem, including inadequate training of physicians in pain management and addiction medicine; concerns over rekindling addictive behavior by using powerfully reinforcing medications; prejudices toward patients with addiction; and physicians’ fear of regulatory scrutiny related to opioid prescribing.1 Successful management of co-existing pain and addiction requires a thorough understanding of the underlying bidirectional aberrant physiological responses: the addictive response is altered by the physiological response to the presence of pain, and pain responses are altered by the physiological presence of addiction.2 Neuroplastic changes in the pathways of pain processing and the mesolimbic reward system can affect pain perception, tolerance, J. Florida M.A. September 2006 Vol. 90, No. 2

When the biopsychosocial and genetic factors come into play, and an individual has “crossed the line” from substance abuse to addiction, the ability to say “no” without appropriate intervention and treatment, has been lost as an option. The primary disease of addiction is now present. This is a concept agreed upon by most major medical specialty societies, including the American Psychiatric Association, the American Society of Addiction Medicine, as well as the American Medical Association. The disease of addiction manifests in the same manner as many other diseases: 1. the illness can be described 2. the course of the illness is predictable 3. the disease is primary, i.e., it is not just a symptom of an underlying disorder 4. it is permanent 5. if left untreated, it is often terminal The etiology of addiction remains unclear, as it does for many other diseases, including diabetes and hypertension. Most physicians, however, do not hold diabetic or hypertensive patients responsible for their disease in the same way addicted individuals are held responsible! This difference in physicians’ responses may be the result of factors such as social stigma, perceived weakness of character, and poor willpower, all of which are consistent with the societal view that drug addiction is a choice rather than a disease. A critical question in dealing with patients with current or past histories of potentially aberrant drug use is, “What do the patient’s potentially aberrant behaviors represent?” Is this addiction, abuse, or a type of misuse (including pseudoaddiction)?

Addiction and Pain Management Our discussions should be based on a common understanding of the terms used: The definition of substance use disorders, and its constituents, substance dependence and substance abuse as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), are problematic in the context of medically sanctioned opioid therapy. For example, of the seven criteria for substance dependence, four criteria – tolerance, the potential for withdrawal, chronicity of use, and time spent attempting to procure the drug – lack the sensitivity and specificity to distinguish (some) pain patients whose opioid use is in compliance with prescription instructions from those whose use is highly aberrant (Brown 1996; Portenoy 1996). Similarly, the DSM-IV definition of substance abuse requires substantial demonstrable harm, thereby posing significant problems with sensitivity. We will use the following terms and definitions to classify the various forms of aberrant drug use: Addiction, as defined by the American Society of Addiction Medicine, the American Academy of Pain Medicine, and the American Pain Society, is characterized by the “four Cs” of addictive drug use:

Four C’s of Addictive Drug Use 1. loss of control 2. compulsive use 3. craving 4. continued use despite harm The phenomena of opioid analgesic tolerance and physical dependence are important in this discussion because they are often mistakenly conflated with opioid addiction. Opioid analgesic tolerance, defined as a diminished level of analgesia over time with a stable opioid dose (or, conversely, the need for a greater opioid dose to maintain a stable level of analgesia), is uncommon, absent the progression of the underlying pathological process. Physical dependence is the presence of a withdrawal phenomenon when the opioid is suddenly stopped, the dose precipitously reduced, or an opioid antagonist (or agonist/antagonist) is administered. The phenomena of tolerance and physical dependence represent neurophysiologic adaptations to chronic opioid administration and are not analogous to, nor sufficient to establish the diagnoses of, addiction, abuse, or misuse. Substance abuse has been defined by the National Institute on Drug Abuse as the repeated, intentional use of illegal drugs or the inappropriate use of legal drugs to produce pleasure, to alleviate stress, and/or to alter or avoid reality. This pattern of drug use does not meet

the diagnostic criteria for addiction; the “four C’s” that characterize addiction are not necessary to establish a diagnosis of drug abuse. Note that this definition of abuse differs from that offered in the DSM-IV, chiefly in that it does not require demonstrable substancerelated role failure, legal problems, social/interpersonal problems, or substance use in hazardous situations. Substance misuse will be defined here as inappropriate use of prescription medication that does not meet criteria for addiction or abuse. This orphan category includes such heterogeneous and unrelated behaviors as pseudoaddiction – aberrant drug-related behaviors that are due to iatrogenic under-treatment of pain (Weissman, 1989), and which resolve when pain is properly treated; diversion – for example, selling or trading prescription opioids for money or sex; miscomprehension – as seen in patients with limited health literacy (Reisfield) or cognitive dysfunction3; impulsive use – as seen in some psychiatric disorders; and hoarding – accumulating a supply of opioids during a period of reduced pain for use in the future when it is feared that pain will be uncontrolled and opioids insufficiently available. Drugs of abuse have distinctive and multiple modes of action in the brain, but all share the ability to increase dopaminergic activity in the mesolimbic system, which in animal models has been shown to be responsible for the reinforcing and rewarding effects of drugs of abuse. Since the more complex neurobiological responses as related to specific drugs of abuse are beyond the scope of this monograph, the role of most of the critical neurochemical transmitters known to date is summarized below: •

•

• • • •

Dopamine: All drugs of abuse, pleasure (ventral tegmental area (VTA)/nucleus accumbens (NA)mediated). Endogenous opioids (e.g., endorphins, enkephalin): All drugs of abuse, reward and pleasure. Possibly involved in the communication between the NA and the prefrontal cortex (PFC). Norepinephrine: Stimulants. Serotonin: Hallucinogens. GABA: Sedatives and alcohol. Glutamate and NMDA: Withdrawal and stimulation.

A more complete review of all related material can be found through the National Institute of Drug Abuse J. Florida M.A. September 2006 Vol. 90, No. 2

Addiction and Pain Management (NIDA , http://www.nida.nih.gov ) the National Institute on Alcohol and Alcoholism (NIAAA www.niaaa.nih.gov) and the Substance Abuse and Mental Health Services Administration (SAMHSA http://www.samhsa.gov).

•

Having gained an understanding of the complex and often reinforcing relationship between pain and addiction, it is suggested that practitioners use a templated approach to the diagnosis and treatment of patients with co-occurring pain and addiction.

• •

Determine if the patient is actively addicted or in recovery: • Clinicians should address addiction as a medical disorder and be open and non-judgmental in discussing patients’ concerns. • Ask about consequences related to use (physical, occupational, legal, familial). • Identify related medical and psychiatric diagnoses (anxiety, depression, cardiovascular disease, gastrointestinal symptoms). • Identify components of pain (neuropathic, nociceptive), and impact of pain (e.g., sleep disturbance, mood disorder, stress). • Discuss risks/benefits of opioids, other analgesics, and sedative-hypnotics with patients in recovery. • Recommend increase in recovery-related activities (12-step meetings; psychotherapy) and discussion with recovery support community. • Establish treatment goals (see pain management agreement): o Analgesia (level of comfort) by using pain scales (see below) o Realistic level of function (social, occupational, etc.)

•

Maintain detailed Medical Record containing: • Diagnostic assessment (history and physical examination including biomechanical function and neurological exam), and mental status examination. Emphasize sensory examination for numbness, hypo- or hyperesthesia (reduced or exaggerated sensation to non-noxious stimuli, respectively), hypo- or hyperalgesia (reduced or exaggerated sensation to noxious stimuli, respectively), allodynia (pain sensation in response to non-painful stimuli) and hyperpathia (persistence of pain after cessation of pain stimuli). J. Florida M.A. September 2006 Vol. 90, No. 2

•

Document previous hospitalizations, diagnostic testing, and treatments by previous physicians (ideally old medical records should be attached). Obtain authorization for medical record release for all caregivers involved (past and present). Devise written treatment plan. Document all communications and discussions with other health care professionals regarding pain management. Detailed description of all medications used and patients’ response to them, including any adverse events. Use pain management agreement outlining patient’s rights and responsibilities. Utilize urine drug testing (UDT) to assess patient adherence to medication regimen and to detect any additional drugs of abuse. Physicians should be familiar with the interpretation of urine drug testing and, when in doubt, should consult with a certified medical review officer (MRO).

Prevent or Treat Withdrawal • Avoid abrupt cessation of opioids in opioid dependent patients, which may cause an acute increase in pain. Gradually taper opioids to prevent withdrawal. • Identify and treat withdrawal. According to the socalled “72-hour rule” it is permissible for a treating clinician to provide opioids (including methadone) to prevent withdrawal in a patient. Note: methadone for this purpose cannot be prescribed, so this must occur in a setting in which methadone can be dispensed (i.e., hospital or facility with dispensing license). Provide effective pain relief: • Non-opioids (NSAIDs, tricyclic antidepressants (TCAs), anticonvulsants, topical analgesics (e.g., capsaicin, lidocaine). • Opioids, if indicated. o Use long-acting or sustained released opioids to minimize the activity of the dopamine release-induced reward circuit in the brain. o Consider the use of less rewarding partial agonists (e.g., buprenorphine) or agonistantagonists (e.g., nalbuphine, pentazocine). Beware prescribing partial agonists and agonist-antagonists in these patients, as they can precipitate withdrawal in patients on pure agonist therapy (not in withdrawal).

Addiction and Pain Management REMEMBER: The exposure to drugs of abuse in actively addicted or recovering patients will not necessarily trigger a relapse. The distress of inadequate pain treatment may pose an even greater risk of relapse. Pain treatment in patients with addiction should be coupled with participation in recovery programs (12-step program, pyschosocial support and counseling, family therapy) to reduce stress associated with concurrent pain and addiction. In summary, addiction has been accepted as a disease by most experts and specialty societies. There is neurobiological and genetic evidence supporting this concept. Therefore, despite societal perception and stigma, addicted individuals, once having developed this disease, cannot just say “no.” They must be helped to overcome the commonly found strong denial system, and through appropriate treatment followed by a program of recovery, helped to maintain remission one day at a time. There is no cure! The following section provides answers to the most commonly asked questions regarding the management of pain in patients with current or past history of potentially aberrant drug use. Q: How do I recognize potentially aberrant drug-related behavior? A: It may not be immediately apparent what isolated, potentially aberrant behaviors represent. The significance of a report that a patient is crushing, dissolving, and injecting OxyContin® is unambiguous, and certainly represents addiction or serious drug abuse. But what is the significance of occasional requests for early opioid refills? Or of persistent complaints that the pain medication is not strong enough? There is little data addressing the significance of such behaviors in identifying or predicting the development of substance abuse or addiction (Butler; Dunbar). While these behaviors could be signs of abuse or addiction, they could also, however, represent more benign forms of drug misuse. Indeed, the meaning of potentially aberrant behaviors may initially be unclear, declaring themselves only over time and through careful observation. In analyzing such behaviors, clinicians need not be right. But clinicians should be thorough, thoughtful, and vigilant, and should clearly document their thinking.4

may create barriers in the therapeutic relationship, resulting in inadequate treatment of pain. Many of those patients are being stigmatized as “addicts” and have to struggle to obtain appropriate pain management. Clinicians must understand that patients’ drug seeking behavior may reflect inadequately treated pain (pseudoaddiction) rather than true addiction. Identify and document any clearly aberrant behaviors, e.g., forging prescriptions, reporting multiple occasions of prescription loss, selling drugs, or witnessed episodes of intoxication. Set appropriate boundaries in the physician-patient relationship utilizing the universal precaution paradigm5 described as follows: 1. Make diagnosis with appropriate differential: Treatable causes for pain should be identified as should co-morbid conditions that may exacerbate pain perception (e.g., depression). 2. Assess risk of addiction: Inquire about personal and family history of substance abuse including possible consequences suffered from abusing drugs (family, health, personal, legal). Utilize urine drug testing (UDT) to monitor adherence to the treatment regimen. A drug test that is positive for the prescribed medication and negative for illicit or non-prescribed drugs provides objective documentation about adherence to the treatment plan. Please be aware that UDTs alone should not be used to establish the diagnosis of addiction. There are multiple causes for both false positive and false negative drug screens. This points up the need for consultation with an MRO. 3. Informed consent: The proposed treatment plan, patients’ and physicians’ rights and responsibilities, and anticipated benefits/foreseeable risks should be clearly articulated and a consent form should be signed by the patient and the physician. (See form on page 53)

Q: How do I handle patients who request higher dosages of pain medication?

4. Pre-and post-intervention assessment of pain and functional levels: Ongoing careful and meticulous documentation of the pain scores and level of function will assure objective assessment of treatment failure or success.

A: Physicians are often concerned that patients might exaggerate their pain complaints in order to gain access to increased amounts of opioid medication. The fear of addiction

5. Appropriate trial of therapy: Individualized pharmacological approaches may include opioids. Such treatments should be titrated to make the J. Florida M.A. September 2006 Vol. 90, No. 2

Addiction and Pain Management pain tolerable. Tolerance needs to be taken into consideration and the dose adjusted accordingly. Medications can be adjusted on a fixed-time, around the clock (ATC) schedule and rescue doses of onequarter to one-half the ATC dose should be available. It is important to emphasize that the use of discretionary (“rescue” or “breakthrough pain”) doses in chronic pain patients with addiction is controversial and not universally embraced as a treatment modality.

receptors and is the stabilizing factor that permits addicted individuals to change their behavior and to discontinue heroin use.

Taken orally once a day, methadone suppresses opioid withdrawal for 24-36 hours. Because methadone is effective in eliminating withdrawal symptoms, it is used in detoxifying opioid addicted individuals. It is, however, only effective in cases of addiction to heroin, morphine, and other opioid drugs, and is not an effective treatment for other drugs of abuse. Methadone reduces the cravings and blocks the “rush” associated with the use of heroin and other opioids. Consequently, methadone patients do not experience the extreme highs and lows that result from the waxing and waning of heroin and other opioids in the brain. Ultimately, patients remain physically dependent on the opioid, but are freed from the uncontrolled, compulsive, and disruptive behavior seen in heroin addicts.

The Drug Addiction Treatment Act of 2000 (DATA 2000) expands the clinical context of medication-assisted opioid addiction treatment by allowing qualified physicians to dispense or prescribe specifically approved Schedule III, IV, and V opioids for the treatment of opioid addiction in treatment settings other than the traditional methadone clinic. In addition, DATA 2000 reduces the regulatory burden on physicians who choose to practice OAT by permitting qualified physicians to apply for and receive waivers of the special registration requirements defined in the Controlled Substances Act.

As a result, in October 2002 the FDA approved a buprenorphine monotherapy product, Subutex®, and a buprenorphine/naloxone combination product, Suboxone®, for use in OAT. The combination product is designed to decrease the potential for abuse by injection. Subutex® and Suboxone® are currently the only Schedule III, IV, or V medications to have received FDA approval for this indication.

Note that aside from Subutex® and Suboxone®, other forms of buprenorphine, e.g., Buprenex®, are not approved for treatment of opioid addiction.

Buprenorphine is a partial opioid and agonist. This means that although buprenorphine is an opioid, and thus can produce typical opioid agonist effects and side effects such as euphoria and respiratory depression, its maximal effects are less than those of full agonists like heroin, morphine, and methadone. At low doses buprenorphine produces

6. Regularly assess the “Five A’s” of opioid treatment: Routine assessment of analgesia, activity, adverse effects, affect and aberrant behavior will help to direct therapy.

Five A’s of Opioid Dependence 1. Analgesia 2. Activity 3. Adverse effects 4. Affect 5. Aberrant behavior 7. Periodically review pain, diagnosis and comorbidities: The treatment of pain in patients with addiction is a complex challenge. Psychiatric co-morbidities and behavioral disorders must be recognized and addressed in the choice of analgesic treatment options. 8. Documentation: The use of templates may assist in the consistent and comprehensive documentation of patient care. Such documentation may minimize medicolegal exposure and the risk of regulatory sanctions. Q: How do I treat pain in addicted individuals receiving “maintenance” opioids? A: The paradigm of opioid agonist therapy (OAT) with methadone is based on the premise that the use of a long acting opioid can mitigate the effects of opioids with more reinforcing characteristics. Methadone is a rigorously tested opioid that is safe and effective for the treatment of opioid withdrawal and addiction. For more than 40 years this synthetic opioid has been used to treat opioid addiction. The repetitive use of heroin releases an excess of dopamine in the mesolimbic system. In the absence of heroin the dopamine levels will decrease, thereby triggering craving and subsequent compulsive opioid use. Methadone occupies the opioid J. Florida M.A. September 2006 Vol. 90, No. 2

Addiction and Pain Management sufficient agonist effects to enable opioid-addicted individuals to discontinue their opioids of abuse without experiencing withdrawal symptoms. The agonist effects of buprenorphine increase linearly with increasing doses of the drug until, at moderate doses, they reach a plateau (the “ceiling effect”). Thus, buprenorphine has a lesser potential for abuse, addiction, and other adverse effects compared to full opioid agonists. In fact, in high doses and under certain circumstances, buprenorphine can actually block the effects of full opioid agonists and can precipitate withdrawal symptoms if administered to opioid-tolerant individuals while a full agonist is in the bloodstream. Buprenorphine has poor oral bioavailability, but its moderate sublingual bioavailability allows for its use in the form of sublingual tablets for OAT. Buprenorphine is highly bound to plasma proteins. It is metabolized by the liver via the cytochrome P4503A4 enzyme system into the active norbuprenorphine and other metabolites. The half-life of buprenorphine is 24–60 hours. Because of its ceiling effect and poor bioavailability, buprenorphine is safer in overdose than opioid full agonists. The maximal effects of buprenorphine appear to occur in the 16–32 mg dose range for sublingual tablets. Higher doses are unlikely to produce greater effects. Ideal candidates for OAT with buprenorphine are individuals who have been diagnosed with opioid addiction, are willing to follow a highly structured approach to treatment that includes a limited supply of buprenorphine, frequent office visits, random UDT, and a program of recovery or psychotherapy. Qualified physicians who wish to prescribe buprenorphine for the purpose of office-based opioid treatment (OBOT) must receive a waiver from the special registration requirements in the Controlled Substances Act for the provision of OAT. This waiver allows qualifying physicians to practice OAT with United States Food and Drug Administration (FDA) approved Schedule III, IV, or V opioids. To receive a waiver to practice OAT with approved Schedule III, IV, or V opioids, physicians must notify the Center for Substance Abuse Treatment (CSAT, a component of the Substance Abuse and Mental Health Services Administration) of their intent to begin dispensing or prescribing this treatment. This Notification of Intent must be submitted to CSAT before the initial dispensing or prescribing of opioid therapy. For more information see http://buprenorphine.samhsa.gov/waiver_qualifications.html.

The treatment of acute, including post-operative, pain in the patient receiving OAT is complex and warrants consultation with specialists in addiction or pain medicine who are thoroughly knowledgeable about the pharmacology of the maintenance opioid. As noted, OAT should not be considered adequate for the treatment of moderate to severe acute pain, chiefly due to previously established opioid tolerance and inadequate duration of analgesia from OAT. Thus, patients should receive their OAT (or equivalent) as a baseline to which other therapies, such as regional analgesic techniques, nonopioid analgesics, and additional opioids are added for acute pain management. The specifics of management are dependent, in part, on whether OAT involves methadone, a strong mu-opioid receptor (MOR) agonist or buprenorphine, a partial MOR agonist and kappa-opioid receptor (KOR) antagonist. For patients on methadone OAT who require additional opioid for acute pain, there are at least two options: 1.) Continue regular methadone maintenance dose and titrate additional opioid (methadone or another pure MOR agonist) to cover the acute pain. Note that: a) higher than “usual” opioid doses will be necessary because of previously established opioid tolerance, and b) in patients unable to take methadone by the oral route, the drug may be administered parenterally, as onehalf to two-thirds of the oral maintenance dose. 2.) Substitute an alternate MOR agonist for methadone (in equianalgesic, but divided doses) and titrate additional doses of the alternate opioid for acute pain. For patients on buprenorphine OAT who require additional opioid for acute pain there are several options, including: 1.) Continue regular buprenorphine maintenance dose (once daily or in divided doses), and add a pure MOR agonist for acute pain. Higher than “usual” doses may be necessary because the additional opioid must compete with the (high receptor affinity, low receptor efficacy, and slow receptor dissociation) buprenorphine at the MOR. 2.) To the regular buprenorphine maintenance dose titrate additional buprenorphine (in divided doses) to cover the acute pain (off-label use). Buprenorphine is available in this country for both sublingual and parenteral (i.m., i.v.) administration. 3.) Substitute a pure MOR agonist for buprenorphine and titrate to satisfactory analgesia.

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Addiction and Pain Management Note: With resolution of acute pain, the substituted opioid is discontinued and buprenorphine re-started with the first signs of opioid withdrawal, in accordance with an induction protocol.6 It is important to emphasize that: • Managing patients on methadone or buprenorphine (Suboxone®, Subutex®) requires specialized knowledge, training and skills. • Physicians who choose to manage such patients should be certified in addiction and/or pain medicine. •

Methadone is a full opioid agonist and its abuse increases the risk of fatal drug overdose. Therefore it should be prescribed carefully with limitation on dosage and refill.

Q: Is it still safe to use opioids in patients with addiction? A: Is there a current or recent history of addiction or abuse? Or is the patient in established, long-term recovery? In patients with histories of alcohol or other substance abuse, experts have long advised against the use of opioid therapy.7 Others believe that chronic opioid therapy can safely be employed in those with a past history of substance abuse, particularly if the history is remote and opioids were not the drugs of abuse.8,9,10 Dunbar et al.11 found that patients with a history of alcohol abuse alone, especially if they were involved in a recovery program, did not display aberrant drug-related behaviors. Similarly, those with a remote history of substance or polysubstance abuse displayed little propensity toward aberrant use. Those with a current or recent history of polysubstance abuse, however, were found to do poorly with chronic opioid therapy. As is the case for acute pain, patients in OAT (i.e., methadone or buprenorphine) programs for addiction require special consideration. Chronic opioid therapy with analgesic intent can be employed in well-selected patients with moderate to severe pain, who are in stable recovery, and have strong support systems (Rosenblum). Management should be done with full communication with the patient’s family, if applicable. It is important to understand that methadone or buprenorphine maintenance is inadequate for the treatment of most chronic pain, for two reasons: 1) The maintenance opioid dose necessary to prevent withdrawal is often inadequate to treat pain; and 2) The once-daily administration of the maintenance opioid does not match the drugs’ six to eight hour duration of effective analgesia. Titration of additional methadone or buprenorphine J. Florida M.A. September 2006 Vol. 90, No. 2

(an off label, but increasingly common practice) on a t.i.d. or q.i.d. schedule in this setting may be satisfactory, as both methadone and buprenorphine have been shown to be safe and effective in the management of chronic nonmalignant pain12 and cancer pain13. There is no evidence that chronic opioid therapy in this setting will lead to relapse; to the contrary, poorly controlled pain is more likely to trigger relapse (Alford; Manfredi). Active or recent abuse or addiction makes successful treatment with opioid therapy unlikely14,15. Occasionally however, opioid therapy will be necessary in these patients. In such cases, opioid therapy should be provided in the context of multidisciplinary management program16, involving specialists in addiction medicine17 and, perhaps, pain management and psychiatry. Clear treatment boundaries must be established, with patients being seen more frequently (sometimes weekly or even daily), as they may have little capacity to manage their opioid supplies. Furthermore, provision of opioids should be contingent upon participation in a recovery program18, preferably with a sponsor. It is imperative to remember that addiction is a chronic, relapsing disease, and that “slips” are to be expected and managed unless patient behavior makes it impossible to maintain safety with opioids19. Q: How should I approach opioid therapy in patients with substance abuse issues? A: Stratify risk. Low risk patients are those with no past or current history of substance abuse or addiction, no major psychopathology, and no family history of substance abuse or addiction. These patients can generally be managed safely by the knowledgeable primary care physician. Moderate risk patients are those with a past history of substance abuse or addiction, significant past or current psychiatric disorders, or family histories of substance abuse or addiction. Depending on the knowledge and skill of the primary care physician, these patients may benefit from specialist consultation20. High risk patients are those with active or recent substance abuse or addiction and/or major, untreated psychopathology. These patients are usually best co-managed with addiction specialists21 and, often, pain management and psychiatry. Establish clear goals of therapy. Realistic pain reduction goals should be set. As analgesia is likely to be incomplete22, elicit patients’ expectations for analgesia and work toward aligning these expectations toward more realistic goals of

Addiction and Pain Management partial analgesia. Without denying the validity of patients’ pain experience, broaden the focus beyond the single-minded pursuit of pain elimination23, and beyond opioids as the exclusive means of treatment. For example, one focus should include improving functional level as a means to improving quality of life. Certainly, quality of life depends significantly on fulfilling and maintaining roles and responsibilities, and one of the goals of opioid therapy should be to increase – or at least maintain – function in important life spheres24. Another focus should be to encourage the acceptance of some pain, guiding patients toward techniques for coping with residual pain, thereby reducing reliance on opioids.25 A third important focus in this patient population should be minimization of aberrant drug-related behaviors. Clarify expected behaviors and the consequences of aberrant use (see the section on opioid agreements below). Realize however, that for the highest risk patients, the stress of coping with pain and illness, coupled with the availability of prescription opioids can, at times, overwhelm impulse control, making perfect compliance an unrealistic goal. Balance this with the fact that poorly controlled pain may increase the rate of relapse for those in recovery and may increase the use of illicit drugs in those with active addictions.26 Rather, a harm reduction approach might be adapted.27 “Slips” should be expected and dealt with firmly but compassionately.

Q: Are there any specific opioid prescribing guidelines?

Q: What other options are available for these patients?

Minimize or eliminate the discretionary use of opioids for “breakthrough” pain. Evaluate appropriateness of discretionary dosing on a case-by-case basis, based on length and quality of recovery and patients’ demonstrated ability to responsibly manage their opioid prescriptions and adhere to the treatment plan. If discretionary dosing is prescribed, it should preferably be used on an activity- or time-contingent basis, to promote participation in important life spheres, thereby reinforcing functional gains. Pain-contingent, or “prn” dosing, may lead to a focus on pain, heightening the perception of pain, and thereby “justifying” additional opioid use.37

A: Non-opioid therapies may obviate the need for opioids, or may at least provide an opioid-sparing effect, and should be used to their fullest potential. First, diagnose and appropriately treat any correctable underlying pathology that may be responsible for the pain. Second, diagnose and treat major psychiatric co-morbidities that may impact pain perception and treatment compliance. Third, utilize nonpharmacologic methods, including: 1) behavioral techniques such as progressive relaxation, biofeedback, distraction techniques, and mindful breathing; 2) physical modalities such as heat, ice, massage, yoga, and rehabilitative therapies; and 3) interventional pain therapies such as nerve blocks, spinal cord stimulators, and intrathecal pumps. Fourth, use non-opioid analgesics such as NSAIDs – by themselves for mild nociceptive pain, and as co-analgesics for moderate and severe nociceptive pain; and analgesic adjuvants (e.g. tricyclic antidepressants, anticonvulsants, topical lidocaine) for neuropathic pain. Often, successful treatment will depend on the skillful integration of multiple therapies. Please refer to the Nonpharmacologic Treatment Chapter.

A: Initiate an opioid trial, titrating to attain adequate analgesia and optimal function: Present opioid treatment as a trial – rather than an open-ended commitment to prescribing these medications – in which analgesia, functional level, and evidence of aberrant use will be continually reassessed, and with continued provision of opioids contingent on achieving and maintaining negotiated therapeutic goals. Long-acting or controlled-release opioids – rather than shortacting opioids – should be the mainstay of opioid therapy.28 Titrate expeditiously to achieve satisfactory analgesia, manageable side effects, and maximal functional level. Note that patients may require higher than “normal” dosing to achieve adequate analgesia because of previously established opioid tolerance.29,30 Avoid immediate-release, short-acting opioids. These formulations are thought to carry a greater risk of abuse because of the rapid delivery of opioid to the brain.31,32 Furthermore, they are believed to promote analgesic tolerance.33 These phenomena may promote compulsive drug use and loss of control, rekindling addiction.34,35,36

Avoid opioids with high “likeability” and high street value such as Demerol®, Dilaudid®, and OxyContin®.38 In patients with current or past histories of opioid abuse or addiction, avoid patients’ “opioid of choice” for aberrant use. Have patients bring all medication bottles to each clinic visit, including random unscheduled visits for “pill counts” to assess compliance. Avoid using opioids as monotherapy, but rather as part of a multimodal program that includes, when appropriate, other pharmacologic and nonpharmacologic techniques for analgesia and functional restoration.

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Addiction and Pain Management Assess and document all of your objective findings, results of diagnostic testing and treatment rationale. Conclusion: Clinicians are often reluctant to appropriately treat pain in patients with current or past histories of drug addiction or abuse. This can result in the inadequate treatment of legitimate pain, needless suffering, and a return to maladaptive drug-related behaviors. With our nascent understanding of the neurobiology of pain and addiction it becomes possible to use opioids effectively and safely in this patient population using structured treatment guidelines. This complex pain management often requires collaborative efforts of primary care physicians, addiction psychiatrists, and pain specialists.Templated documentation formats will minimize the medicolegal and regulatory exposure. References: 1. Savage SR. Addiction in the treatment of pain: significance, recognition, and management. J Pain Sympt Manage 1993; 8:265-278.

10. Weaver MF, Schnoll SH. Opioid treatment of chronic pain in patients with addiction. Journal of Pain & Palliative Care Pharmacotherapy 2002a; 16(3):5-26. 11.

Dunbar SA, Katz NP.

12. Malinoff HL, Barkin RL, Wilson G. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome. American Journal of Therapeutics 2005; 12:379-384. 13. Davis MP. Buprenorphine in cancer pain. Support Care Cancer 2005;13:878-887. 14.

Weaver MF, Schnoll SH.

15.

Gourlay DL, Heit HA, Almahrezi A.

16. Currie SR, Hodgins DC, Crabtree A, Jacobi J, Armstrong S. Outcome from integrated pain management treatment for recovering substance abusers. J Pain 2003; 4(2):91-100. 17. Savage SR. Opioid therapy of chronic pain: Assessment of consequences. Acta Anaesthesiol Scand 1999; 43:909-917.

2. Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med 2006; 144:127-134.

18.

Weaver MF, Schnoll SH.

19.

Ibid.

3. Passik SD, Kirsh KL. Opioid therapy in patients with a history of substance abuse. CNS Drugs 2004; 18(1):13-25.

20. Kalso E, Alan L, Dellemijn PLI, et al. Recommendations for using opioids in chronic non-cancer pain. European Journal of Pain 2003; 2:381-386.

4. Passik SD, Kirsh KL. Managing pain in patients with aberrant drug-taking behaviors. Journal of Supportive Oncology 2005; 3(1):83-86. 5. Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Medicine 2005; 6(2):107-112. 6.

Alford DP, Compton P, Samet JH.

7. Dunbar SA, Katz NP. Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Manage 1996; 11(3):163-170.

21.

Ibid.

22. Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of safety and efficacy. Pain 2004; 112:372-380. 23. Cohen MJM, Jasser S, Herron PD, Margolis CG. Ethical perspectives: opioid treatment of chronic pain in the context of addiction. Clin J Pain 2002; 18:S99-S107. 24.

Ibid.

25.

Savage SR. Opioid therapy of chronic pain.

8. Jage J. Opioid tolerance and dependence â&#x20AC;&#x201C; do they matter? European Journal of Pain 2005; 9:17-162.

26.

Ibid.

27.

Passik SD, Kirsh KL.

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Addiction and Pain Management 28.

Kalso E, Alan L, Dellemijn PLI, et al.

29. Prater CD, Zylstra RG, Miller KE. Successful pain management for the recovering addicted patient. J Clin Psychiatry 2002; 4(4):125-131. 30.

Weaver MF, Schnoll SH.

31.

Passik SD, Kirsh KL.

32.

Prater CD, Zylstra RG, Miller KE.

33. Ballyntyne JC, Mao J. Opioid therapy for chronic pain. New Engl J Med 2003; 349:1943-1953. 34.

Passik SD, Kirsh KL.

35. Currie SR, Hodgins DC, Crabtree A, Jacobi J, Armstrong S. 36.

Alford DP, Compton P, Samet JH.

37.

Savage SR. Opioid therapy of chronic pain.

38.

Prater CD, Zylstra RG, Miller KE.

Mitka M. Experts debate widening use of opioid drugs for chronic nonmalignant pain. JAMA 2003; 289(18): 2347-2348. Pawl RP. Addiction and pain medicine. Surgical Neurology 2006; 65:219-222. Roberts DM, Meyer-Witting M. High-dose buprenorphine: perioperative precautions and management strategies. Anaesth Intensive Care 2005; 33:17-25. Rosenblum A, Joseph H, Gong C, et al. Methadone maintenance therapy and chronic pain. In reply. JAMA 2003; 290(18):24032404. Trafton JA, Oliva EM, Horst DA, Minkel JD, Humphreys K. Treatment needs associated with pain in substance use disorder patients: implications for concurrent treatment. Drug Alcohol Depend 2004; 73:23-31.

Other resources Biller N, Caudill MA. Commentary: contracts, opioids, and the management of chronic nonmalignant pain. J Pain Symptom Manage 1999; 17(2):144-145. Brant JM. Let’s talk about challenges surrounding addiction in cancer pain. ONS News 2006; 21(1):8-9. Dodick DW. Clinical practice. Chronic daily headache. N Engl J Med 2006; 354(2):158-165. Doleys DM, Rickman L. Other benefits of an opioid “agreement.” J Pain Symptom Manage 1999; 25(5):402-403. Drake RE, Mercer-McFadden C, Mueser KT, et al. Review of integrated mental health and substance abuse treatment for patients with dual disorders. Schizophr Bull 1998; 24(4):589-608. Fishman SM, Kreis PG. The opioid contract. Clin J Pain 2002; 18: S70-S75. Manfredi PL, Gonzales GR, Cheville AL, Kornick C, Payne R. Methadone analgesia in cancer pain patients on chronic methadone maintenance therapy. J Pain Symptom Manage 2001; 21(2):169-174.

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Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances Basic Guidelines for Prescribing Physicians: The Laws and Rules Relating to Pain Management By Larry McPherson, Esquire, Executive Director of the Florida Board of Medicine Introduction Any physician who practices pain management or prescribes pain medication must have a working knowledge of Florida laws and rules. The perspective of this article is preventive: protecting your patients and your license. This article will outline the regulatory process; identify the prescribing laws and rules practitioners need to be familiar with and how to readily access them, and provide 10 practice suggestions for practitioners to help in the safe prescribing of controlled substances to their patients. Not taking the time to learn the laws can result in patient harm. Illicit practices by patients and practitioners as well as inappropriate prescribing is a major concern. A recent Florida Department of Law Enforcement/ Florida Medical Examiners report of drugs found in decedents reflected that prescription drugs continued to be found more often than illicit drugs in both lethal and non-lethal levels. In 2005, the Florida Board of Medicine joined with the Boards of Osteopathic Medicine, Nursing, and Pharmacy to issue a Joint Statement on Pain Management, which included support for a statewide drug verification system for controlled substances. This Joint Statement, the laws and rules cited in this article, as well as agendas, minutes of meetings and current items of interest to all health care practitioners can be found at the Department of Health’s Medical Quality Assurance Web site: www.doh.state.fl.us/mqa or www.flhealthsource.com. To automatically receive news that is posted on the Board of Medicine Web site, you can subscribe at no cost at www.doh.state.fl.us/mqa/medical. Ignorance of the law can also result in disciplinary action. The Florida Board of Medicine has disciplined hundreds of doctors for inappropriate prescribing with discipline ranging from fines, reprimands and restrictions to probation, suspension and revocation of license. The purpose of the regulatory process is not to discipline practitioners but to set out the standards and procedures to best ensure safe, quality practice. However, a small percentage of practitioners are disciplined every year. This regulatory process is separate and apart from the civil malpractice process, the criminal law process, or the hospital J. Florida M.A. September 2006 Vol. 90, No. 2

peer review process. Understanding how the regulatory process functions is the first step toward being a safe practitioner and protecting your license. The Regulatory Process Florida licenses more than 50,000 allopathic and osteopathic physicians. The following in-state health care practitioners are authorized to prescribe controlled substances: • • • • • •

Allopathic Physicians Dentists Veterinarians (DBPR) Osteopathic Physicians Podiatric Physicians Naturopaths

39,016 9,258 7,469 3,439 1,214 7

The 15-member Florida Board of Medicine licenses, sets practice standards, and disciplines allopathic physicians in Florida. The Board is part of the Department of Health, an executive agency that provides the overall regulatory support functions for all health care boards. The best way to illustrate the regulatory process is to take a walk in the shoes of a Florida licensed physician. Here is a case study of the fictional John Smith, M.D. •

Dr. Smith is notified that he has received his Florida license.

In Florida, licensure includes the ability to prescribe, subject to Drug Enforcement Administration (DEA) requirements on controlled substances and subject to 458.331(1)(v), Florida Statutes, which limits a physician to practicing within his scope of education, training and practice. Dr. Smith is well educated but has not read the laws and rules applicable to Florida physicians. In Florida, the legislature enacts the statutes and the Florida Board of Medicine implements the statutes via promulgation of rules and decisions relating to discipline. •

After obtaining his Florida license, Dr. Smith opens his practice, hires a physician assistant (PA) and a receptionist.

Dr. Smith goes to Chicago to attend a three-day convention. He leaves several pre-signed prescriptions with his PA as they are expecting patients who will need controlled substance

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances prescriptions while the doctor is away. In Florida, a PA is a licensed health care practitioner who may prescribe noncontrolled substances subject to the direction of the supervising physician and registration with the Department of Health. In our case study, the PA has been taking Lortab® for back pain and the physician he has been seeing has moved and his medical records are not available. Without performing a history and physical, Dr. Smith gives his PA a prescription for Lortab®. The PA uses one of the pre-signed prescriptions to prescribe Lortab® to himself while the doctor is gone. The pharmacist filling the prescription notes the multiple prescriptions to the PA and notifies the Department. •

A case is opened against Dr. Smith for inappropriate prescribing.

The complaint against Dr. Smith will get a thorough due process review, which begins with a review by a Department investigator who is assisted by medical consultants. In our case study, this review results in finding a possible violation of the Medical Practice Act, Chapter 458, Florida Statutes. This preliminary finding means only that the allegations, if true, would be a violation. However, this finding of legal sufficiency of a violation will result in an investigation of Dr. Smith. •

Two weeks later Dr. Smith receives a letter notifying him that he is the subject of a complaint.

The letter is from a Department investigator advising Dr. Smith of the complaint and asking for an interview. Dr. Smith is stunned. Fortunately, Dr. Smith talks to an attorney who explains that the investigation is confidential and that he has a right to see the complaint and supporting documents before the case goes any further. Dr. Smith and his attorney meet with the investigator and provide a response and a request a copy of the completed investigation. • The completed investigation is forwarded to the Prosecution Services Unit, where a physician consultant helps the Department to determine whether the case warrants further action or dismissal. Dr. Smith’s case is found to merit further action so it is forwarded to an expert in Dr. Smith’s specialty, for a formal written opinion. The opinion will set out the facts that demonstrate whether or not Dr. Smith’s actions violated the Medical Practice Act. The expert, who has been credentialed by

the Board of Medicine to perform such reviews, is provided a copy of the complete case file, including Dr. Smith’s response. The expert opines that Dr. Smith violated the Practice Act by failing to prescribe appropriately, by failing to maintain adequate medical records and by pre-signing prescriptions. A Department attorney reviews the file and takes it, together with any further response from Dr. Smith, to the Board’s probable cause panel. •

The decision to charge a physician with a violation is a matter for the licensing board, not the Department investigators or attorneys.

The board Probable Cause Panels (PCP) consist of physicians and lay members of the Board of Medicine. These panels meet in a closed session to review completed investigations. In our case study, the panel recommends that formal charges be filed against Dr. Smith. •

Dr. Smith receives formal charges, called an Administrative Complaint, and at this point the case becomes public, except for patient names.

Dr. Smith has the option of taking the matter to trial and disputing the facts (a formal hearing); not disputing the facts and going to the Board for imposition of penalty (informal hearing); or entering into an agreement on penalty (settlement agreement) with the prosecutor which, if accepted by the Board of Medicine, will result in final resolution of the case. Dr. Smith’s attorney works with the prosecutor and arrives at a settlement agreement, which is accepted by the Board of Medicine. The terms of Dr. Smith’s agreement include, as do many such cases involving inappropriate prescribing, completing the University of South Florida Course on Prescribing Abusable Drugs. This three-day comprehensive course includes the clinical, legal, and regulatory aspects of safe prescribing practice. •

Dr. Smith’s disciplinary action is a matter of public record.

All disciplinary actions are matters of public record. In our case study, Dr. Smith’s disciplinary action will be reflected on his practitioner profile, which is a public record and accessible online. Since 1997 all penalties imposed by the Board of Medicine have been compiled into a Subject Matter Index, available to the public. It will also be reported to the Federation of State Medical Boards (FSMB) and, if the Board imposes a major penalty, to the National Practitioners Data Bank (NPDB). The FSMB and NPDB reports are not matters of public record J. Florida M.A. September 2006 Vol. 90, No. 2

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances but the information may be made available to state regulatory agencies, hospitals, and certain organizations.

•The legible prescribing statute can be found at Section 456.42, Florida Statutes.

Accessing the laws & rules relating to controlled substance prescribing As the case of Dr. Smith illustrates, safe prescribing practice requires more than being a well-educated and caring physician. Just as you must keep pace with changes in medicine through continuing education and reading professional journals, the practitioner needs to stay abreast of the changing regulatory framework. This means being familiar with the relevant Florida laws (statutes) and Board of Medicine regulations (rules).

• The definition of inappropriate prescribing, Sections 458.331(1)(q), 459.015(1)(t), Florida Statutes.

The Florida Legislature has created a statutory framework for medical practice in Florida. The framework for prescribing practice is reflected in four separate areas or Chapters with which physicians need to be familiar with. These are readily accessible online at the following website, www.leg.state.fl.us. •Chapter 456, Florida Statutes, the regulatory “umbrella” which sets out general regulatory processes for all health care licensees, •Chapter 458, Florida Statutes, the Medical Practice Act, which provides the parameters for practice for M.D.s, including prescribing, •Chapter 459, Florida Statutes, the Osteopathic Medical Practice Act, which provides the parameters for practice for D.O.s, including prescribing, •Chapter 465, Florida Statutes, the Pharmacy Practice Act. This provision is relevant for physicians who provide samples as well as physicians registered as dispensing practitioners, and, •Chapter 893, Florida Statutes, controlled substance provisions. Within these Chapters, the following are important provisions for the prescribing practitioner: • Section 458.326, Florida Statutes, relates specifically to prescribing for intractable pain and offers guidance to practitioners who might otherwise be reluctant to prescribe controlled substances in appropriate cases. J. Florida M.A. September 2006 Vol. 90, No. 2

• The prohibition on self-prescribing of controlled substances, Sections 458.331(1)(r), 459.015(1)(u), Florida Statutes. • Prohibition on pre-signing prescriptions, Sections 458.331(1)(aa), 459.015(1)(ee), Florida Statutes. • Prohibition on prescribing Schedule II controlled substances for office use, Sections 458.331(1)(bb), 459.015(1)(ff), Florida Statutes. • Limitations and prohibitions on prescribing Schedule II amphetamine or Schedule II sympathomimetic amine drugs, Sections 458.331(1)(cc), 459.015(1)(gg), Florida Statutes, and • Requirements for dispensing practitioners, Section 465.0276, Florida Statutes. The Board of Medicine has implemented these laws with specific rules for safe prescribing. These rules are readily accessible in the Florida Administrative Code, which can be viewed at FAC Online at http://election.dos.state.fl.us. These important rules include the following: • Standards for the use of controlled substances for treatment of pain in Rule 64B8-9.013, FAC. These standards reflect the Board view on prescribing. The following is most instructive for prescribing practitioners:

“Physicians should not fear disciplinary action from the Board or other state regulatory or enforcement agencies for prescribing, dispensing, or administering controlled substances including opioid analgesics, for a legitimate medical purpose and that is supported by appropriate documentation establishing a valid medical need and treatment plan.”

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances • Florida was one of the first states to specifically address the issue of Internet prescribing, by promulgating Rules 64B8-9.014, FAC and 64B15-14.008, FAC. These rules prohibits doctors from prescribing to patients without performing an adequate history and physical. There are exceptions for on call and cross coverage and for emergency situations.

Based upon the above history and perspective, the following outline of practical suggestions and observations are respectfully offered. For many, this is familiar ground; however, I hope there will be something new for the prescribing practitioner.

• Prescribing of controlled substances by registered interns, residents, and fellows, Rule 64B8-6.010, FAC;

Practitioners should be able to recognize behaviors that identify a patient as a likely drug seeker. These patients may give the practitioners the following signals:

• Standards for Prescribing Obesity Drugs, Rules 64B8-9.012, FAC and 64B15-14.004, FAC.

1.BE PREPARED TO IDENTIFY AND DEAL WITH THE MANIPULATIVE PATIENT

• “I can only take Percocet®, the other medications don’t work for me.”

SuggestionsforSafePracticeandAvoidingRegulatory Problems Allopathicphysicians,(M.Ds.)byfaraccountforthegreatest number of controlled substance prescriptions written each year. During my 17 years of observing the Board of Medicine hear more than 4,000 disciplinary cases, I have seen good practitioners being disciplined because they did not know the rules, kept poor documentation in the charts, or were not paying attention in their busy practices. Controlled substance scenarios that typically end up badly for licensees include the following: • • • • • • •

Internet prescribing, Self-prescribing controlled substances, Selling scripts, Medication error/wrong strength, Prescribing without an examination, Not paying attention to drug history in chart, and Pre-signing scripts.

Between 1997 and October 2005, the Board disciplined 239 doctors for prescribing violations. Of these cases, 120 of them involved controlled substances. The penalties were not only for punitive reasons but often included education of the licensee. One such educational course is the University of South Florida course on prescribing abusable drugs. This three-day course provides a comprehensive review of clinical, legal, and regulatory aspects of prescribing controlled substances. Other penalties imposed by the Board during this period included: Revocation or relinquishment 42 Suspension 30 Probation 23 License restrictions 13

• “I can’t afford any tests, just give me the same meds I have been taking.” • “I lost my medical records from my prior treater, and I forgot his name” • “ I lost my prescription for Lortab® ….again.” There are several tools for handling these patients. • Use a detailed informed consent form that alerts the new patient prior to the first encounter of your policy on prescribing controlled substances. This will not only deter drug-seeking behavior but may also deter those who are only seeking your care as a source for controlled substances. • If the patient demands prescriptions which you do not find are indicated, you may advise the patient that your medical license does not allow you to prescribe a medication unless a clear medical need is documented in the patient’s chart. • Listen to your pharmacists. • Document, and • If all else fails, you can use a 30-day letter terminating care with that patient.

J. Florida M.A. September 2006 Vol. 90, No. 2

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances 2. DON’T FORGET THAT THE FAMILY/EMPLOYEE/ FRIEND IS A PATIENT • Records are required.

• Any prescription creates the physician/patient relationship. This means that when you write a prescription renewal for a friend, neighbor, or co-worker, you have created a physician-patient relationship and all the regulatory requirements that apply to your regular patients apply here. This includes family. If you write scripts for family members, you have to keep charts just as you do for your regular patients.

5. Do Not Pre-Sign Prescriptions • Board of Medicine Disciplinary Guidelines provide a maximum penalty for a first offense of: • Reprimand • $5,000 fine • 2 years probation 6. No Self-Prescribed Controlled Substances •

• Good employees can and have forged/altered scripts. • Family members may become adverse parties. Keeping records will help protect your license in the event a complaint is filed. 3. ON-CALL COVERAGE • Home calls: • Make notes of the call at home and put in the chart next morning. • Get the name and phone number of the pharmacist. • Office calls: • Read the chart and check the medication list. • Limit scripts. • See the patient if necessary. 4. CONTINUITY OF CARE • In a group practice setting, where several practitioners see long time patients, there may be a tendency to continue with the same treatment plan without taking fresh look at the patient chart. • Look at chart and review treatment history. • The progress notes should clearly justify: • Treatment • Medication • Dose • Duration • Talk with staff. • Limit renewals to office visits as appropriate. • Use a separate medication list.

J. Florida M.A. September 2006 Vol. 90, No. 2

•

Although physicians may lawfully treat themselves and prescribe non-controlled substances, any selfprescription of controlled substances is prohibited and a guaranteed trip for a mental and physical examination. Maximum penalty: revocation.

7. Get Good Legal/Business Advice •

•

Talk to the right kind of attorney when getting advice on your business practices. This is a complicated area, with both State and Federal prohibitions. Board has disciplined doctors who received bad business/legal advice.

8. Internet Prescribing •

•

Prescribing without a history and physical is both a standard of care violation and a violation of Board rule. Physicians have been disciplined for this with penalties ranging from revocation to suspension, reprimands and fines. DO NOT JEOPARDIZE YOUR LICENSE-DO NOT PRESCRIBE BASED ON INTERNET QUESTIONNAIRES! [Rule 64B8-9.014, FAC]

Legal & Ethical Aspects of Pain Management & Prescribing Controlled Substances 9. ANY COMPLAINT ABOUT YOUR PRESCRIBING PRACTICE WILL BE REVIEWED BY A PHYSICIAN WITHIN YOUR SAME PRACTICE SPECIALITY. THE DECISION REGARDING WHETHER YOU ACTED WITHIN A STANDARD OF REASONABLE CARE WILL BE BASED UPON THE FOLLOWING: • • • • • • •

Evaluation (complete H & P) Treatment Plan Informed Consent Periodic Review Consultation Complete Medical Records Compliance with Laws and Rules

10. Keep in mind the four elements that the Board of Medicine Considers the hallmarks of good prescribing practice: Physicians should not fear disciplinary action from the Board or other state regulatory or enforcement agencies for prescribing, dispensing, or administering controlled substances including opioid analgesics, (1) for a legitimate medical purpose and that is (2) supported by appropriate documentation establishing a (3) valid medical need and (4) treatment plan.

Help For Impaired Practitioners Do you know a colleague or medical student with drug, alcohol, or psychiatric problems? You can get them help without subjecting them to disciplinary action. The Board has an excellent evaluation and rehabilitation program that is a phone call away: Professionals Resource Network (PRN) 1-800-888-8776. For most practitioners, this is a confidential process that offers help to those willing to change.

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Available Pain Rating Scales

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Available Pain Rating Scales

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Legal Resources The Florida Medical Association (FMA) recognizes that physicians often have questions about pain management and prescribing. With that in mind, this section includes some Frequently Asked Questions (FAQs). In addition, the Boards of Medicine, Osteopathic Medicine, Nursing, and Pharmacy have collectively addressed the topic of pain medicine and issued a Joint Statement on Pain Management. This is also included for the readerâ&#x20AC;&#x2122;s benefit. The following FAQs are provided for the benefit of the reader. The answers provided to these FAQs do not constitute legal advice and are presented for educational purposes only. The information contained within this section should not be taken as a substitute for legal advice, which should be obtained from personal legal counsel. The information presented in these articles is based upon current Florida and federal law and is subject to change based on changes in Florida and federal law. The FMA hopes that the information provided here and in its other publications continues to assist physicians in answering many of their most common legal questions allowing them to treat patients, instead of addressing legal concerns. When a clear answer is not forthcoming, it is often times beneficial to consult with a pain specialist for clinical and referral questions. In addition, it can be helpful to discuss problematic legal concerns with an attorney who is well-versed in the area of prescribing. Remember that although a law might not strictly prohibit a certain act, you should still consider broad requirements placed on Florida physicians, such as the requirement that you practice within the standard of care. FMA membership affords physicians the privilege of legal consultation in many situations. FMA members are encouraged to contact the FMA Legal Department when confronted with confusing legal questions. Other physicians may choose to seek consultation with a health care attorney.

Frequently Asked Questions Q.

Can I prescribe a controlled substance to a family member?

There is no strict prohibition on that, but you must maintain medical records, perform an adequate exam, history and physical, and otherwise treat the family member as you would any other patient including practicing within the standard of care. Florida law prohibits you from prescribing a controlled substance to yourself and from treating anyone with whom you have a sexual relationship.

Is there a limit on the number of pills or prescriptions that I can prescribe to a patient at any one time?

No, but a physician is required to prescribe appropriately (Section 458.331(1)(q), Florida Statutes) and practice within the standard of care (Section 458.331(1)(t), Florida Statutes). And note that each controlled substance prescription must be written on a different prescription blank (Section 893.02(20), Florida Statutes).

Can I prescribe more than a one-month supply?

There is no prohibition on prescribing more than a one-month supply of a drug to a patient, as long as you are prescribing appropriately and within the standard of care.

Can I authorize refills for controlled substances?

Section 893.04(1)(g), Florida Statutes, prohibits refills on Schedule II controlled substances. Other controlled substances can be authorized for refill but not more than five times within six months of the initial prescription, and only as long as other requirements are met (prescribing appropriately and treating within the standard of care, etc.)

Continued

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Legal Resources

How often do I need to see a patient to be in compliance?

There is no hard and fast rule. In most cases, you do need to ensure that an adequate history and physical exam has been performed outlining the indication and rationale for opioid-based pain management for the patient before writing a prescription, even if you have prescribed for the patient in the past. While there is no specific requirement that exams be performed with a particular degree of frequency, it is extremely important that you be able to demonstrate proper patient assessment and appropriate follow-ups, particularly when narcotics are prescribed. Ultimately this is determined by the standard of care for your profession. See Rules 64B8-9.014, FAC, and 64B15-14.008, FAC for more information on this topic. If you have any doubts about appropriate action, it is extremely advisable to consult an attorney.

How do I handle controlled substance prescriptions for patients seen by PAs and ARNPs?

In Florida, neither PAs nor ARNPs can prescribe controlled substances. If a patient seen by a PA or ARNP is in need of controlled substance prescription, a physician will need to write the prescription. The Board of Medicine rule on this topic does not prohibit a physician from relying on information (history, physical exam) collected by the ARNP or PA.

What is the role of the DEA?

The Drug Enforcement Administration (DEA) is the Federal agency that oversees substances that are controlled pursuant to Federal law. A state decides what type of practitioner may prescribe those substances, (for instance some states allow an ARNP to prescribe controlled substances), but the DEA controls which of those practitioners receive a license to write these prescriptions, and can take away that license. The DEA also investigates crimes relating to controlled substances.

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Legal Resources MEDICAL PRACTICE BULLETIN In response to questions regarding Drug Enforcement Agency (DEA) policy on controlled substance prescriptions, the Board of Medicine offers the following advice: 1. Pain management is an integral part of patient care and should be handled in a compassionate and comprehensive manner. Medical management will accommodate most patients with chronic pain but requires special attention, especially with respect to controlled substances. Florida physicians treating chronic pain patients are encouraged to continue expanding their knowledge in managing these sometimes difficult patients, in order to optimize patient care and minimize abuse and diversion. 2. DEA interpretations of regulations point out that writing refills, postdating or writing instructions to fill Schedule II controlled substance prescriptions at a later date is equivalent to unauthorized refills. 3. There is no DEA requirement to see patients on a monthly basis. The frequency of visits to the physician is a matter of professional judgment and should be established by the treating physician, after properly determining there is a legitimate medical purpose for that controlled substance and he/she is acting in the usual course of professional practice. This may result in more or less frequent office visits than monthly. 4. Patients on stable regimens may have their Schedule II prescriptions mailed to their home or the patientsâ&#x20AC;&#x2122; pharmacy. The latter may be facilitated by identifying a single pharmacy for patient use in the treatment agreement, if used. Alternatively, the patient may present to the office for prescription pickup, but does not necessarily need to see the physician. 5. There is no specific limit on the number of days worth that a physician may write per prescription. However, as stated above, this is a matter of professional judgment to be determined by the treating physician. 6. Physicians have a duty to ensure that their prescribing of controlled substances occur in a manner consistent with effective controls against diversion and misuse. These controls may include behavioral observation and documentation, discussions with family, urine/serum drug testing, addictionologist consultation and/or others as deemed indicated by the treating physician. Reference: Department of Justice/Drug Enforcement Administration [Docket No. DEAâ&#x20AC;&#x201C;271N] Clarification of Existing Requirements Under the Controlled Substances Act for Prescribing Schedule II Controlled Substances. Federal Register / Vol. 70, No. 165 / Friday, August 26, 2005/Notices J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Legal Resources Joint Statement on Pain Management By Coble, Dan As part of its ongoing mission to protect the health, safety, and welfare of the public in Florida and to implement the patient safety agenda advocated by the Institute of Medicine and other groups, the Board of Nursing initiated an effort to address the issue of pain management. Working with other regulatory boards, a meeting was held in Tallahassee this fall, hosted by the Board of Osteopathic Medicine. As a result of that meeting, the following Joint Statement on Pain Management was approved by representatives of the Boards of Medicine, Nursing, Osteopathic Medicine, and Pharmacy on September 19, 2005. The full Board of Nursing approved the joint statement at the October 13, 2005 meeting in Kissimmee. JOINT STATEMENT OF PAIN MANAGEMENT The Florida Boards of Medicine, Nursing, Osteopathic Medicine, and Pharmacy recognize that principles of quality medical practice dictate that the people of the state of Florida have access to appropriate and effective pain relief. The appropriate application of up-to-date knowledge and treatment modalities can serve to improve the quality of life for those patients who suffer from pain as well as reduce the morbidity and costs associated with untreated or inappropriately treated pain; including non-treatment, undertreatment, over-treatment, and the continued use of ineffective treatments. It is, therefore, incumbent upon Florida physicians, nurses and pharmacists to work cooperatively and effectively to address the dimensions of pain and to provide maximum pain relief with minimal side effects. Towards that end and in the interest of public protection, the Florida Boards of Medicine, Osteopathic Medicine, Nursing and Pharmacy issue the following joint statement. To effectively assist patients in the management of pain, health care professionals should, within their scope of practice: * Consistently and thoroughly assess all patients for pain. If pain is reported, the pain should be evaluated with a complete history and physical with laboratory and diagnostic testing, if indicated; * Work collaboratively in a multi-disciplinary approach to develop and implement an individualized, written treatment plan utilizing pharmacologic and non-pharmacologic interventions with specific objectives for the patient; * Regularly evaluate the effectiveness of the treatment plan, using a consistent, developmentally appropriate, standardized pain scale, and make adjustments as needed; * Document all aspects of pain assessment and care in a timely, clear, consistent, complete and accurate manner; 52

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Sample Forms Patient Informed Consent and Notice of Material Risks For Treatment of Intractable Pain With Contrtolled Substances Dear

This will confirm your diagnosis of

causing you intractable pain. I have recommended treating your condition with . I anticipate that this treatment will

, a condition

We have discussed the following alternative therapies: We have discussed potential side effects and risks of controlled substances, including: • sleepiness, confusion, difficulty thinking • nausea, vomiting, constipation • difficulty breathing, shortness of breath, wheezing • rash, itching • potential for allergic reaction • potential for interaction with other medications (increasing effects or side effects of drugs taken together) • potential for dose escalation/tolerance (need for higher doses for the same effect may occur with long term use) • potential for dependence (after the body adjusts to these medications, they cannot be stopped abruptly without physical symptoms) • potential for withdrawal (stopping medications abruptly may cause nausea, vomiting, abdominal pain, sweating, aching, abnormal heartbeat or other symptoms that can be life threatening; medication changes should be under provider supervision) • potential for addiction (compulsive drug use not related to pain relief) • potential for impaired judgment and/or motor skills (driving or operating machinery may be hazardous due to effects on the brain and nerves) • other: Continued on Next continued onPage back J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Sample Forms This confirms that I asked you if you wanted a more detailed explanation of the proposed treatment, the alternatives and the material risks, and you (check one):

Are satisfied with that explanation and desire no further information. Requested and received, in substantial detail, further explanation of the treatment, alternatives and material risks. If this form accurately represents our discussion, and if you are satisfied with the explanation

given, you must sign this document indicating your consent to the use of controlled substances in treating your intractable pain prior to commencing the treatment.

Signed:

Date:

Explained by me and signed in my presence: Signed:

Date:

J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Sample Forms SAMPLE FOR ADAPTATION AND REPRODUCTION ON PHYSICIAN LETTERHEAD PLEASE CONSULT WITH YOUR ATTORNEY

Long-term Controlled Substances Therapy for Chronic Pain SAMPLE AGREEMENT A consent form from the American Academy of Pain Medicine The purpose of this agreement is to protect your access to controlled substances and to protect our ability to prescribe for you. The long-term use of such substances as opioids (narcotic analgesics), benzodiazepine tranquilizers, and barbiturate sedatives is controversial because of uncertainty regarding the extent to which they provide longterm benefit. There is also the risk of an addictive disorder developing or of relapse occurring in a person with a prior addiction. The extent of this risk is not certain. Because these drugs have potential for abuse or diversion, strict accountability is necessary when use is prolonged. For this reason the following policies are agreed to by you, the patient, as consideration for, and a condition of, the willingness of the physician whose signature appears below to consider the initial and/or continued prescription of controlled substances to treat your chronic pain. 1.

All controlled substances must come from the physician whose signature appears below or, during his or her absence, by the covering physician, unless specific authorization is obtained for an exception. (Multiple sources can lead to untoward drug interactions or poor coordination of treatment.)

All controlled substances must be obtained at the same pharmacy, where possible. Should the need arise to change pharmacies, our office must be informed. The pharmacy that you have selected is: ____________________________________________

phone: _______________________.

You are expected to inform our office of any new medications or medical conditions, and of any adverse effects you experience from any of the medications that you take.

The prescribing physician has permission to discuss all diagnostic and treatment details with dispensing pharmacists or other professionals who provide your health care for purposes of maintaining accountability.

You may not share, sell, or otherwise permit others to have access to these medications.

These drugs should not be stopped abruptly, as an abstinence syndrome will likely develop.

Unannounced urine or serum toxicology screens may be requested, and your cooperation is required. Presence of unauthorized substances may prompt referral for assessment for addictive disorder.

Continued on Next Page J. Florida M.A. September 2006 Vol. 90, No. 2

Resources for Practitioners - Sample Forms 8.

Prescriptions and bottles of these medications may be sought by other individuals with chemical dependency and should be closely safeguarded. It is expected that you will take the highest possible degree of care with your medication and prescription. They should not be left where others might see or otherwise have access to them.

Original containers of medications should be brought in to each office visit.

10.

Since the drugs may be hazardous or lethal to a person who is not tolerant to their effects, especially a child, you must keep them out of reach of such people.

11.

Medications may not be replaced if they are lost, get wet, are destroyed, left on an airplane, etc. If your medication has been stolen and you complete a police report regarding the theft, an exception may be made.

12.

Early refills will generally not be given.

13.

Prescriptions may be issued early if the physician or patient will be out of town when a refill is due. These prescriptions will contain instructions to the pharmacist that they not be filled prior to the appropriate date.

14.

If the responsible legal authorities have questions concerning your treatment, as might occur, for example, if you were obtaining medications at several pharmacies, all confidentiality is waived and these authorities may be given full access to our records of controlled substances administration.

15.

It is understood that failure to adhere to these policies may result in cessation of therapy with controlled substance prescribing by this physician or referral for further specialty assessment.

16.

Renewals are contingent on keeping scheduled appointments. Please do not phone for prescriptions after hours or on weekends.

17.

It should be understood that any medical treatment is initia lly a trial, and that continued prescription is contingent on evidence of benefit.

18.

The risks and potential benefits of these therapies are explained elsewhere [and you acknowledge that you have received such explanation].

19.

You affirm that you have full right and power to sign and be bound by this agreement, and that you have read, understand, and accept all of its terms.

Physician Signature

Patient Signature

Date

Patient Name (Printed)

Approved by the AAPM Executive Committee on April 2, 2001. AAPM 4700 W. Lake Avenue Glenview, IL 60025-1485 847/375-4731 Fax 877/734-8750 E-mail aapm@amctec.com Web site http://www.painmed.org/

“Long-term Controlled Substances Therapy for Chronic Pain: Sample Agreement” is a copyrighted work of the American Academy of Pain Medicine. © 1998 American Academy of Pain Medicine.” © 2001 American Academy of Pain Medicine J. Florida M.A. September 2006 Vol. 90, No. 2

CME POST-TEST CME Post-Test Multiple Choice Questions. Please choose the most appropriate answer for each question and indicate the corresponding letter on the answer sheet provided. 1.

Which of the following opioid medications is NOT recommended for the long-term control of pain in cancer patients: a. Oxycodone b. Demerol£ c. Morphine d. Fentanyl

As presented in this discussion, cognitive-behavioral theory/medical psychology proposes that: a. Physical sensations lead to feelings which then create thoughts b. Feelings create thoughts which impact physical sensations c. Thoughts create feelings which, in turn, influence physical sensations d. None of the above

Meperidine a. Has been used for many years and is appropriate for chronic use b. May cause side effects that cannot be reversed by opioid antagonists c. Is safe to use in elderly patients d. Is metabolized by CYP2D6 e. Becomes more effective over time, because of an active metabolite

When selecting and dosing opioids: a. There is no ceiling dose for combination analgesics b. Use long acting opioids for as-needed pain c. Use short acting opioids for around-the-clock pain d. There is no ceiling dose for pure agonists e. Agonist-antagonist opioids are appropriate breakthrough medications

The Five “A’s” of opioid treatment does NOT include routine assessment of which of the following: a. Analgesia b. Acute pain c. Adverse effects d. Affect e. Aberrant behavior

Meprobamate is the active metabolite of which skeletal muscle relaxant? a. Carisoprodol (Soma®) b. Cyclobenzaprine (Flexeril®) c. Methocarbamol (Robaxin®) d. Celecoxib (Celebrex®) e. Gabapentin (Neurontin®)

Which of the following is NOT one of the four elements that the Board of Medicine considers to be the hallmarks of good prescribing practice: a. A legitimate medical purpose b. Appropriate documentation c. Routine urine screens d. Treatment plan

Continued on Next Page

J. Florida M.A. September 2006 Vol. 90, No. 2

CME Post-Test 8.

Which one of the following effects is unlikely to occur during treatment with amitriptyline? a. Orthostatic hypotension b. Diarrhea c. Dry mouth d. Sedation e. Urinary retention

True/False Questions. Please indicate whether the following statements are true or false on the answer sheet provided. (T = True and F = False) 9.

Findings from one study demonstrate that patients with chronic pain rate “listening” and “being believed” as the most important qualities in their physician, regardless of whether or not the doctor can actually help them with their pain.

10. Pain is an objective description of the patient’s perception of actual or potential tissue damage. 11. Physicians may pre-sign prescription blanks to be completed by their office staff while they are out of town. 12. Tolerance, or the need for increasing dosage of opioid to produce the desired therapeutic effect, is a normal physiologic occurrence when opioids are taken for more than a few days. 13. A physician may self-prescribe controlled substance medication but only if he/she maintains appropriate medical records to justify the prescription. 14. Relief of pain in cancer patients can be achieved by addressing the cause of the physical pain. 15. Physicians can prescribe methadone for the purpose of preventing withdrawal in a patient.

J. Florida M.A. September 2006 Vol. 90, No. 2

CME Answer Sheet Pain Management CME Post-Test Answer Sheet EXPIRATION DATE OF THIS ACTIVITY AND ANSWER SHEET: September 1, 2008 NO CME CREDIT GRANTED FOR ANSWER SHEETS RECEIVED AFTER THIS DATE 1. 2. 3.

4. 5. 6.

7. 8. 9.

10. 11. 12.

13. 14. 15.

Make a copy of your completed answer sheet for your files. EVALUATION 1.

The activity fulfilled the stated CME objectives?

Very Much

Somewhat

Not at all

The articles were effectively written? Evaluation of Pain Opioid Pharmacology Nonopioid Medications Management of Pain in the Patient With Cancer Nonpharmacologic Treatment of Chronic Pain Pain and Addiction The Laws and Rules Relating to Pain Management

My knowledge of the topic was enhanced?

Very Much

How could we have improved the activity?

Please list 2-3 things you will do differently as a result of this activity:

What CME topics would you like to see presented in future FMA journals?

(See Page 1)

Very Much Very Much Very Much Very Much Very Much Very Much Very Much

Somewhat Somewhat Somewhat Somewhat Somewhat Somewhat Somewhat

Somewhat

Not at all Not at all Not at all Not at all Not at all Not at all Not at all

Not at all

PLEASE PRINT OR USE AN ADDRESS LABEL Name:

Degree:

Address: City/State/Zip: Phone: E-mail: Mail the answer sheet/evaluation form to: Florida Medical Association ATTN: Nancy Wisham 123 South Adams Street Tallahassee, FL 32301

J. Florida M.A. September 2006 Vol. 90, No. 2

Or fax the answer sheet/evaluation form to: 850.224.6627 ATTN: Nancy Wisham

Conclusion I hope that you enjoyed this publication from the Florida Medical Association in partnership with the Office of the Attorney General. With improved technology, methods, and better understanding of pain, physicians are able to provide enhanced care to suffering patients. I am excited that the FMA is able to provide you with such a practical and collaborative journal. The FMA works on your behalf by partnering with regulatory agencies to keep you up-to-date on health matters that concern you and your patients. Throughout the year, FMA staff serves as your liaison to legislators to protect you and your physicians and their practice. FMA members have access to a knowledgeable staff and tremendous benefits, including asset protection, financial services, HIPAA tools, and of course, continuing medical education. By joining the efforts of the FMA, you will benefit your profession and your practice. Please consider becoming a member of the FMA if you are not already a member. Simply call (800) 762-0233 to speak to the membership department, or you may join online at www.fmaonline.org. If you are currently a member of the FMA, I appreciate your continued support. Informed and committed members are the necessary element for the future growth of the FMA. Finally I would like to recognize each of the contributing authors and editors who worked tirelessly to publish this CME monograph for the benefit of their colleagues. I am particularly grateful to Dr. Bernd Wollschlaeger and Dr. Neel Karnani, the Chair and Vice Chair of the FMA CME Committee for their efforts to manage this time consuming educational project.Thanks to them, you will be eligible to earn six CME credits upon successful completion of the test on page 57. With the assistance of organizations like the Attorney Generalâ&#x20AC;&#x2122;s office, I am confident the FMA will continue to serve Florida physicians . With Best Regards,

Troy M. Tippett, MD, President Florida Medical Association

J. Florida M.A. September 2006 Vol. 90, No. 2

CME Opportunities Brought to you by the Florida Medical Association

Coming Summer 2007