This interactive Utah Physician Ebook contains 11 hours of continuing education. To complete click the Complete Your CE button at the top right of the screen.
Utah Continuing Medical Education
UTAH MEDICAL LICENSURE PROGRAM
MANDATORY EDUCATION REQUIRED FOR PRESCRIBERS OF CONTROLLED SUBSTANCES ENCLOSED PROGRAM INCLUDES: • 6 CREDIT HOURS Controlled Substances (DOPL Approved) • 5 CREDIT HOURS Medical Ethics (Elective)
InforMed is Accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
CME FOR:
AMA PRA CATEGORY 1 CREDITS ™ MIPS MOC STATE LICENSURE
CME DEADLINE: MD/APRN: 1/31/2026 • DO/PA/DDS: 5/31/2026 DPM/OD: 9/30/2026
AVAILABLE ONLINE AT: UT.CME.EDU
UTAH PHYSICIAN
UTAH MANDATORY CME REQUIREMENT ON CONTROLLED SUBSTANCE PRESCRIBING
Dear Colleagues,
Beginning with the licensing period that begins after January 1, 2024, as a condition precedent for license renewal, each controlled substance prescriber shall complete at least 3.5 continuing education credit hours in an SBIRT-training class. These hours must be earned in the current renewal cycle and may be counted toward your overall required CME hours. The enclosed Utah Medical Licensure Program includes a Controlled Substance Prescribers Course approved by the Utah Division of Occupational and Professional Licensing; found on the DOPL website: https://dopl.utah.gov/wp-content/uploads/2023/04/cs-approved-ce-courses.pdf. This course satisfies the mandatory 3.5 credit hour controlled substance requirement for all prescribers.
To complete the program online, visit BOOK.CME.EDU, enter the book code MDUT1125 in the box then click GO .
Thank you for choosing lnforMed as your CME provider. We strive to create a high-quality, streamlined program for our colleagues. Please contact us with any questions, concerns, or suggestions.
Best Regards,
The lnforMed CME Team
We are a nationally accredited CME provider. For all board-related inquiries please contact:
Division of Professional Licensing | State of Utah Department of Commerce P.O. Box 146741 |Salt Lake City, UT 84114-6741 | (801) 530-6628
1-800-237-6999
BOOK CODE: MDUT1125
BOOK.CME.EDU
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What’s Inside
01
EFFECTIVE MANAGEMENT OF ACUTE AND CHRONIC PAIN WITH OPIOID ANALGESICS, 2ND EDITION COURSE ONE | 6 CREDITS THIS COURSE IS APPROVED BY THE UTAH DIVISION OF PROFESSIONAL AND OCCUPATIONAL LICENSING TO SATISFY THE MANDATORY 3.5 CREDIT HOUR CONTROLLED SUBSTANCE REQUIREMENT FOR ALL PRESCRIBERS. This course is designed for all physicians and other health care professionals involved in the management of patients with pain. It is designed to increase physician knowledge and skills about guideline-recommended principles of pain management, the range of opioid and non-opioid analgesic treatment options, and specific strategies for minimizing opioid analgesic prescription, diversion, and abuse. This activity discusses the management of chronic and acute pain in a variety of patient populations. It reviews evidence for non-opioid therapies, including non-drug and non-opioid drug options, as well as current evidence regarding opioid efficacy, harms, and overdose prevention with naloxone, and how to slowly and safely taper opioid doses.
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MEDICAL ETHICS FOR PHYSICIANS COURSE TWO | 5 CREDITS
Medical ethics, also known as bioethics, is an amalgam of medicine, law, and religion. It is also influenced by cultural beliefs. In this course, we will define the most common ethical principles and note their relationship to the basic theories of ethics. Some of the prominent court cases that have dictated the basis of physician-patient relationships, especially in end-of-life care, are presented. Also, the Patient Self-Determination Act is outlined with explanations of advance directives—better known as physician directives and durable power of attorney for health care. Finally, a possible method of setting up a workable ethical decision-making framework is presented in some detail. Hopefully, this will be useful in the event of a conflict or when a decision involving ethical issues confronts us or our fellow physicians. This course should allow us to comprehend the basic precepts of medical ethics and afford us the general knowledge of how to apply them in our everyday practice of medicine.
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FINAL EXAMINATION ANSWER SHEET REQUIRED TO RECEIVE CREDIT
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MOC/MIPS CREDIT INFORMATION
Participants can earn MOC points equivalent to the amount of CME credits claimed for designated activities. InforMed currently reports to the following specialty boards: ABA, ABIM, ABS, ABPath and ABP. To be awarded MOC points, you must obtain a passing score, complete the corresponding activity evaluation, and provide required information necessary for reporting.
Table 1. MOC Recognition Statements Successful completion of certain enclosed CME activities, which includes participation in the evaluation component, enables the participant to earn up to the amounts and credit types shown in Table 2 below. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit. Board Programs
American Board of Anesthesiology’s redesigned Maintenance of Certification in Anesthesiology TM (MOCA®) program, known as MOCA 2.0®
ABA
ABIM
American Board of Internal Medicine’s Maintenance of Certification (MOC) program
ABS
American Board of Surgery’s Continuous Certification program
ABPath
American Board of Pathology’s Continuing Certification Program
ABP
American Board of Pediatrics’ Maintenance of Certification (MOC) program
Table 2. Credits and Type Awarded
AMA PRA Category 1 Credits T M
Activity Title
ABA ABIM ABS
ABPath
ABP
Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
6 Credits LL
6 Credits MK
6 Credits SA + AC
6 Credits LL
6 Credits LL
6 AMA PRA Category 1 Credits TM
5 Credits LL
5 Credits MK
5 Credits SA + AC
5 Credits LL
5 Credits LL+SA
5 AMA PRA Category 1 Credits TM
Medical Ethics for Physicians
Legend: LL = Lifelong Learning, MK = Medical Knowledge, SA = Self-Assessment, LL+SA = Lifelong Learning & Self-Assessment, AC = Accredited CME
DATA REPORTING: Federal, State, and Regulatory Agencies require disclosure of data reporting to all course participants. InforMed abides by each entity’s requirements for data reporting to attest compliance on your behalf. Reported data is governed by each entity’s confidentiality policy. To report compliance on your behalf, it’s mandatory that you must achieve a passing score and accurately fill out the learner information, activity and program evaluation, and the 90-day follow-up survey. Failure to accurately provide this information may result in your data being non-reportable and subject to actions by these entities.
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How to complete
Please read these instructions before proceeding. Read and study the enclosed courses and answer the final examination questions. To receive credit for your courses, you must provide your customer information and complete the mandatory evaluation. We offer two ways for you to complete. Choose an option below to receive credit and your certificate of completion.
ONLINE
FASTEST AND EASIEST!
• Go to BOOK.CME.EDU and enter code MDUT1125 in the book code box, then click GO. • Proceed to your exam. If you already have an account, sign in with your username and password. If you do not have an account, you’ll be able to create one now. • Follow the online instructions to complete your final examination. Complete the purchase process to receive course credit and your certificate of completion. Please remember to complete the online evaluation.
Enter book code
MDUT1125
GO
IF YOU’RE ONLY COMPLETING CERTAIN COURSES IN THIS BOOK: • Go to BOOK.CME.EDU and enter the code that corresponds to the course below, then click GO. Each course will need to be completed individually, and the specified course price will apply.
Complete the answer sheet and evaluation found in the back of this book. Include your payment information and email address. Mail to: InforMed, PO Box 997432, Sacramento, CA 95899
BY MAIL
Mailed completions will be processed within 2 business days of receipt, and certificates emailed to the address provided. Submissions without a valid email address will be mailed to the postal address provided.
Program Options
Price
Option
Code
Credits
ENTIRE PROGRAM • Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition • Medical Ethics for Physicians Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
$77
MDUT1125 11 Credits
$42
MDUT06EM 6 Credits
$35
Medical Ethics for Physicians
MDUT05ME 5 Credits
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v
MDUT03EM — 6 CREDITS R elease D ate : 1/6/2025 E xpiration D ate : 1/5/28
Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition In addition to receiving AMA PRA Category 1 Credit TM , physicians participating in Maintenance of Certification will receive the following points appropriate to their certifying board: 6 ABIM MOC Points, 6 ABS MOC Points, 6 ABA MOCA Points, 6 ABP MOC Points, 6 ABPath CC Points.
Faculty Dr. Chadwick A. Rawana is an educator, physician, and writer. He is a professor at Fanshawe College in the Health Care Administration Management Program. Dr. Rawana previously served as Associate Dean of Health Sciences at Baker College in Allen Park, Michigan, where he drew from his clinical experience of over 20 years in both hospital and clinic settings. Dr. Rawana obtained his medical degree from the University of Guyana. Faculty Disclosure Contributing faculty, Dr. Chadwick A. Rawana, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned. Division Planners John M. Leonard, MD Mary Franks, MSN, APRN, FNP-C Randall L. Allen, PharmD Senior Director of Development and Academic Affairs Sarah Campbell Division Planners/Director Disclosure The division planners and director have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned. Accreditations & Approvals In support of improving patient care, NetCE is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team. Designations of Credit NetCE designates this enduring material for a maximum of 3 AMA PRA Category 1 Credit(s) ™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 3 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent
HOW TO RECEIVE CREDIT
• Read the enclosed course. • Complete the final examination questions at the end. A score of 70% is required. • Return your customer information/answer sheet, evaluation, and payment to InforMed by mail or complete online at BOOK.CME.EDU.
Audience This course is designed for all physicians and other healthcare professionals involved in the management of patients with pain. Course Objective This learning activity is designed to increase physician knowledge and skills about guideline-recommended principles of pain management, the range of opioid and nonopioid analgesic treatment options, and specific strategies for minimizing opioid analgesic prescription, diversion, and abuse. Learning Outcomes Upon completion of this course, you should be able to: 1. Identify the range of therapeutic options for managing acute and chronic pain, including nonpharmacologic approaches and pharmacologic therapies. 2. Explain how to integrate opioid analgesics into a function-based pain treatment plan individualized to the needs of the patient, including counseling patients and caregivers about the safe use of opioid analgesics. 3. Discuss recommendations and rationale for incorporating emergency opioid antagonists into prescribing practice for training patients and family members on the use of naloxone. 4. Identify medications currently approved for the treatment of opioid use disorder and the ways these medications differ in terms of mechanisms of action, regulatory requirements, and modes of administration.
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Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition _ ________________
About the Sponsor The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare. Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice. Disclosure Statement It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.
to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. Successful completion of this CME activity, which includes participation in the evaluation component, enables the learner to earn credit toward the CME and Self-Assessment requirements of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit learner completion information to ACCME for the purpose of granting ABS credit. This activity has been approved for the American Board of Anesthesiology’s ® (ABA) requirements for Part II: Lifelong Learning and Self-Assessment of the American Board of Anesthesiology’s (ABA) redesigned Maintenance of Certification in Anesthesiology Program ® (MOCA ® ), known as MOCA 2.0 ® . Please consult the ABA website, www.theABA.org, for a list of all MOCA 2.0 requirements. Maintenance of Certification in Anesthesiology Program ® and MOCA ® are registered certification marks of the American Board of Anesthesiology ® . MOCA 2.0 ® is a trademark of the American Board of Anesthesiology ® . Successful completion of this CME activity, which includes participation in the activity with individual assessments of the participant and feedback to the participant, enables the participant to earn 6 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABP MOC credit. This activity has been designated for 6 Lifelong Learning (Part II) credits for the American Board of Pathology Continuing Certification Program. Through an agreement between the Accreditation Council for Continuing Medical Education and the Royal College of Physicians and Surgeons of Canada, medical practitioners participating in the Royal College MOC Program may record completion of accredited activities registered under the ACCME’s “CME in Support of MOC” program in Section 3 of the Royal College’s MOC Program.
Sections marked with this symbol include evidence-based practice recommendations. The level of evidence and/or strength of recommendation, as provided by the evidence-based source, are also included
so you may determine the validity or relevance of the information. These sections may be used in conjunction with the course material for better application to your daily practice.
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__________________ Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
Key Opioid-Related Terms
THE CHALLENGE OF PAIN MANAGEMENT Caring for patients in pain requires carefully balancing benefits of treatment with potential for harm. Opioids, one of the most commonly used classes of pain medications, are central to national efforts to stem the epidemic of opioid-related abuse, addiction, and overdose. In 2021, 106,699 drug overdose deaths occurred in the United States, the highest level of overdose deaths ever [1]. Nearly 88% of opioid-involved overdose deaths involved synthetic opioids, and more than one million people have died since 1999 from overdose. (See Figure 1.) Opioid use disorder (OUD, opioid addiction) affects over 16 million globally and 2.1 million in the United States [4]. In 2018, overdoses involving opioids killed nearly 47,000 people; 32% involved prescription opioids. The Substance Abuse and Mental Health Services Administration’s National Survey on Drug Use and Health estimated 10.1 million people aged 12 and older misused opioids in 2019 and approximately 80% of heroin users started after using oral opioid analgesics (prescribed or illicit) [1].
Opioid: any psychoactive chemical resembling morphine, including opiates, and binding to opioid receptors in the brain. This term describes opioid and opiates. Opiate : “ natural” opioids derived from the opium poppy (e.g., opium, morphine, heroin). Semi-synthetic opioids : analgesics containing both natural and manufactured compounds (e.g., oxycodone, hydrocodone, hydromorphone, oxymorphone). Synthetic opioids : fully-human-made compounds (e.g., methadone, tramadol, and fentanyl). Although the rates of opioid prescriptions have leveled off or declined slightly in recent years, the average days of supply per opioid prescription has risk [5]. Opioids are actually not very effective for relieving chronic noncancer pain in the long term and may be associated with increased pain, reduced functioning, and physical opioid dependenc [6][7]. There is an expanding range of both nonopioid medications and nonpharmacological therapies shown to be effective in reducing many common chronic pain conditions. (See box.) This course discusses the management of chronic and acute pain in a variety of patient populations. It reviews evidence for nonopioid therapies, including nondrug and nonopioid drug options, as well as current evidence regarding opioid efficacy, harms, and overdose prevention with naloxone, and how to slowly and safely taper opioid doses.
FIGURE 1. OPIOID-RELATED OVERDOSE DEATHS BY TYPE IN THE UNITED STATES
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Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition _ ________________
The Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based tool that screens for OUD and takes 5-10 minutes to administer [11]. SBIRT, endorsed by the Substance Abuse and Mental Health Services Administration (SAMHSA), should always be paired with referral to treatment [12]. SAMHSA recommends universal screening with oral or writing-based tools because of the high prevalence of substance use disorders in patients visiting primary care settings. In the context of pain care, however, the 2022 CDC guidelines recommend urine drug testing before initiating opioid therapy and probably at least annually when prescribing opioids for chronic pain. Other tools for universal substance abuse screening include: • Single screening question screening tool for drug use • Drug Abuse Screening Test (DAST) 10 • Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) • Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) • The CAGE questionnaire adapted to include drugs (CAGE-AID) DRUG MONITORING PROGRAMS Prescription drug monitoring programs (PDMPs) have been implemented in 49 of 50 states, the District of Columbia, and one U.S. territory (Guam). Information available through PDMPs varies based on reporting requirements and restrictions but may include Drug Enforcement Agency (DEA) schedules reported, timeliness of pharmacy dispensing information, access, and required reviews.
TYPES OF PAIN Nociceptive and neuropathic pain respond differently to pain treatments. Neuropathic pain may respond poorly to both opioid analgesics and nonsteroidal anti-inflammatory (NSAID) agents. Other classes of medications, such as anti- epileptics, antidepressants, or local anesthetics, may provide more effective relief for neuropathic pain [8]. CHRONIC PAIN THAT DEVELOPS AFTER ACUTE PAIN Factors associated with an increased risk for chronic pain following acute pain or surgery include older age, psychological problems, higher levels of pre-procedural pain or pain sensitivity, type and duration of surgery, severity and number of comorbidities, and use of post-procedural radiation or chemotherapy [9]. SCREENING FOR OPIOID ABUSE RISK FACTORS Evaluations of the physical and psychological history can identify risk factors for substance misuse and overdose and help characterize pain to inform treatment decisions. Screening approaches include efforts to assess for concurrent substance use and mental health disorders that may place patients at higher risk for OUD and overdose. This includes screening for drug and alcohol use and the use of urine drug testing. These approaches enable providers to identify high-risk patients so that that they can consider whether to prescribe opioids, engage substance misuse and mental health interventions, and provide education materials to mitigate opioid misuse (Table 1).
TOOLS FOR PATIENT RISK ASSESSMENT
Tool
Use
Who Administers?
Length
Current Opioid Misuse Measure (COMM)
Monitor for misuse by patients currently on long- term opioid therapy
Patient self-report
17 items
Diagnosis, Intractability, Risk, Efficacy (DIRE)
Screen for risk of opioid addiction Screen for risk of opioid addiction Screen for risk of opioid addiction
Clinician
7 items
Opioid Risk Tool (ORT)
Clinician or patient self-report
5 yes/no questions
Screener and Opioid Assessment for Patients with Pain, Version 1 and Revised (SOAPP, and SOAPP-R)
Patient self-report
24 items
Source [9]
Table 1
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__________________ Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
NONDRUG APPROACHES Many nonpharmacologic and self-management treatment options have been found to be effective alone or as part of a comprehensive pain management plan, particularly for musculoskeletal pain and chronic pain [14]. Examples include, but are not limited to, psychological, physical rehabilitative and surgical approaches, procedural therapies (e.g., injections, nerve blocks), complementary therapies, and use of approved/ cleared medical devices for pain management. Primary care clinicians should know about the range of treatment options available, the types of pain that may be responsive, and when they should be used as part of a multidisciplinary approach to pain management. Clinicians should also be aware that not all nonpharmacologic options have the same strength of evidence to support their utility in the management of pain, and some may be more applicable for some conditions than others. MOVEMENT-BASED OPTIONS Movement therapies that may be helpful in patients with chronic pain include muscle-strengthening, stretching, and aerobic exercise (e.g., walking, aquatics). Recommended exercise programs typically occur one to three times a week for a total of 60-180 minutes per week, but any regimen must be carefully tailored to a patient’s existing level of physical conditioning, comorbidities, and cognitive status. WEIGHT LOSS Some pain syndromes, such as knee osteoarthritis, are worsened by obesity. For some patients, pain due to this condition is improved by reducing body weight because of reduced loads and physical stresses on the affected joints. The goal of body weight reduction is a baseline weight loss of 7%-10% by calorie reduction and increased activity using a balanced diet with less than 30% of calories from fat, 15%- 20% from protein, and 45%-60% from carbohydrates [15]. PASSIVE OPTIONS Acupuncture involves the stimulation of specific points on the body, most often involving skin penetration with fine metallic needles manipulated by hand but sometimes also including electrical stimulation or low-intensity laser therapy. Massage is the manual manipulation of the body to promote relaxation, reduce stress, and improve well-being. Handheld devices may also provide relief for some patients. Transcutaneous electrical nerve stimulation (TENS) machines generate mild electrical pulses that are applied cutaneously. The electrical stimulation from TENS may block or disrupt pain signals to the brain, reducing pain perception. TENS machines can be used at home or in conjunction with other interventions like physical therapy.
Recommendations for using a PDMP include: • Check the PDMP before starting anyone on opioid therapy. • Review the PDMP periodically throughout opioid therapy (at least every 3 months). • Look for prescriptions for other controlled substances, like benzodiazepines, that can increase risk of overdose death. • Review the total morphine milligram equivalent dose (MMED). Some states have specific requirements for PDMP use, such as requiring review prior to initial prescription or any time a specific prescription is written, such as for hydrocodone ER (Zohydro); clinicians should remain updated about the specific requirements of their state PDMPs. URINE DRUG TESTING Urine drug testing (UDT) is recommended before prescribing any opioid and at least annually thereafter [13]. Providers using urine drug screens should be familiar with the metabolites and expected positive results based on the opioid prescribed. If the prescribed opioid is not detected, discuss the finding with the patient and, if diversion is confirmed or suspected, reevaluate the pain management strategy or taper the opioid. If the patient tests positive for unprescribed drugs, schedule more frequent follow-up visits, consider opioid discontinuation, offer naloxone, or refer for treatment for substance use disorder. Decision tools and help with interpreting urine drug testing results are available at http://mytopcare.org/udt-calculator/ interpret-opiates-test-result. PAIN MANAGEMENT OVERVIEW Many pharmacologic and nonpharmacologic approaches to treating pain are available to primary care providers. These options should be employed using the following general principles: • Identify and treat the source of the pain, if possible, although pain treatment can begin before the source of the pain is determined. • Select the simplest approach to pain management first. This generally means using nonpharmacologic approaches as much as possible and/or trying medications with the least severe potential side effects and at the lowest effective doses. • Establish a function-based, individualized treatment plan if therapy is expected to be long- term.
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COGNITIVE AND BEHAVIORAL OPTIONS Cognitive behavioral therapy (CBT) is a structured, time- limited (typically 3-10 weeks) intervention focused on how thoughts, beliefs, attitudes, and emotions influence pain and can help patients use their minds to control and adapt to pain. This therapy includes setting goals, often with recommendations to increase activity to reduce feelings of helplessness [16]. MEDITATION Mindfulness meditation programs typically include a time- limited (8 weeks; range 3-12 weeks) trainings with group classes and home meditation. The objective is to inculcate a long-term practice that helps patients refocus their minds on the present, increase awareness of self and surroundings, and reframe experiences [17]. NONOPIOID DRUG APPROACHES A wide range of medications can be used to treat pain, including: • Acetaminophen • NSAIDs (oral or topical) • Antidepressants ‒ serotonin and/or norepinephrine reuptake inhibitors ‒ tricyclic antidepressants (TCAs) ‒ selective serotonin reuptake inhibitors (SSRIs) • Anticonvulsants
Some early trials suggested that COX-2 inhibitors, as a class, were associated with higher risks for myocardial infarction and stroke compared to other NSAIDs, and the COX-2 inhibitor rofecoxib (Vioxx) was removed from the market in 2004 because of such concerns [20]. More recent trials and meta-analyses, however, provide strong evidence that the risks of CV events with celcoxib are no greater than those of other NSAIDs, and in 2018 two Food and Drug Administration (FDA) advisory panels recommended that the FDA change its advice to physicians regarding celecoxib’s safety [21]. SELECTIVE SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS SNRIs such as duloxetine, venlafaxine, and milnacipran are characterized by a mixed action on norepinephrine and serotonin, though their exact mechanism of action for pain reduction is unknown. These agents affect the descending pain pathways to facilitate pain relief. Side effects (e.g., nausea, dizziness, and somnolence) may limit treatment. Monitoring is suggested for blood pressure (duloxetine and venlafaxine), heart rate (venlafaxine), and drug interactions (duloxetine). SNRIs can be very helpful in patients who have central sensitization. TCAS TCAs inhibit reuptake of norepinephrine and serotonin. These agents act on descending pain pathways, but their mechanism of action for pain relief is unknown. Examples of TCAs studied for the management of chronic pain include amitriptyline, desipramine, and nortriptyline. Side effects, such as anticholinergic effects (e.g., dry mouth, constipation, dizziness) and QTc prolongation limit the use of TCAs in elderly patients. The majority of side effects occur at the typically higher doses used to treat depression. SSRIS SSRIs, such as citalopram, fluoxetine, and paroxetine, block the reuptake of serotonin in the brain, making more serotonin available in the synapse. The mechanism of SSRIs for pain remains unknown. Compared to SNRIs and TCAs, there is relatively little evidence to support the use of SSRIs in treating chronic pain conditions [22]. Potential side effects of SSRIs include weight gain, sexual dysfunction, and QTc prolongation, especially with citalopram. ANTICONVULSANTS Anticonvulsants, such as gabapentin, pregabalin, oxcarbazepine, and carbamazepine, are often prescribed for neuropathic pain and are thought to exert their analgesic effect by inhibiting neuronal calcium channels. Potential side effects include sedation, dizziness, and peripheral edema. Pregabalin and gabapentin have low abuse potential in the general population, are currently classified as Schedule V by the DEA, and prescriptions for these drugs are tracked by some state PDMPs. Anticonvulsants can be very helpful in patients who have central sensitization and neuropathic pain.
• Topical lidocaine or capsaicin • Cannabinoid-based therapies • Ketamine
ACETAMINOPHEN Lower doses of acetaminophen are recommended to decrease risk of side effects. Patients should not exceed 1,000 mg in a single dose. The maximum recommended dose for healthy adults is 4,000 mg/day [18]. The most severe potential side effect of acetaminophen is liver toxicity. Acetaminophen is the most common cause of acute liver failure, accounting for 46% of all cases [19]. Patients should stay within recommended doses to help prevent side effects and should only be prescribed one acetaminophen- containing product at a time. NSAIDS Chronic use of NSAIDs may be limited by gastrointestinal (GI) toxicity, including GI bleeding, upper GI symptoms, ulcers, and related complications. In addition to GI side effects, NSAIDs have been associated with an increased risk of renal and cardiac complications. Side effects with NSAIDs are typically lower with topical formulations.
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__________________ Effective Management of Acute and Chronic Pain with Opioid Analgesics, 2nd Edition
TOPICAL LIDOCAINE AND CAPSAICIN Topical lidocaine inhibits the conduction of nociceptive nerve impulses. Irritation at the application site is the most common side effect. The most common products for chronic pain management are lidocaine 5% patches, available by prescription, and lidocaine 4% patches available over the counter. Capsaicin is an active component of chili peppers and has moderate analgesic properties at 8% concentrations for neuropathic pain, specifically postherpetic neuralgia and diabetic neuropathic pain of the feet [23]. The most common side effect is a mild-to-severe burning sensation at the application site. CANNABINOID PREPARATIONS There has been increased interest among patients for the use of cannabis or cannabis derivatives (e.g., cannabidiol [CBD]) for pain relief. The CB1 and CB2 receptors have been shown to mediate the analgesic effects of cannabinoids [24] and some evidence suggests a potential benefit for chronic pain. A 2022 study concluded that oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain. The evidence for a benefit of cannabinoids on acute pain is extremely limited and mixed. A 2020 systematic review showed that there was moderate evidence to support cannabinoids in treating chronic, noncancer pain at 2 weeks and found moderate evidence that cannabinoids can exert analgesia [25]. Cannabis preparations pose both short-term and long- term risks. Short-term effects include impaired memory, motor coordination, and judgment. Paranoid ideation and psychotic symptoms, while rare, may occur with high doses of THC. Possible long-term effects include impaired brain development in young adults, potential for habituation, and increased risk of anxiety or depression. Abrupt cessation of marijuana in long-term users may cause withdrawal symptoms such as anxiety, irritability, craving, dysphoria, and insomnia. There is an increased risk of chronic bronchitis, respiratory infections, and pneumonia with inhaled products [26]. One study showed that states legalizing medical cannabis actually experienced a 22.7% increase in opioid overdose deaths [27]. FDA-approved cannabinoids including dronabinol (Marinol) and nabilone (Cesamet) are not indicated for the treatment of pain. When recommending cannabis for patients with chronic pain, clinicians may inform patients that the analgesic properties are due to both the CBD and THC components, which act on different pain pathways [28].
KETAMINE Ketamine has been successfully used to treat such acute pain conditions as sickle cell crises, renal colic, and trauma. Recently the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists released the first joint recommendations for subanesthetic ketamine (including transdermal ketamine) for acute pain [29]. PSYCHOSTIMULANTS Psychostimulants have a higher likelihood of being misused due to their effects on the central nervous system. Psychostimulants with abuse potential include both illegal drugs (cocaine, methamphetamine, and ecstasy) and prescription stimulants. Approximately 3.9 million people aged 12 or older misused prescription stimulants in 2023 [30].
OPIOIDS
MECHANISM OF ACTION Opioids exert their analgesic effects by acting on the mu, kappa, and delta opioid receptors. Individual agents may be classified as agonists or partial agonists of those receptors: • Agonists (e.g., morphine, codeine, hydromor- phone, hydrocodone) stimulate at least one of the opioid receptors and provide continued analgesia with increasing doses. • Partial agonists (e.g., buprenorphine) have high affinity at mu-receptors, have a ceiling for analgesic effect, and are less likely to cause respiratory depression. Opioids are classified by the DEA according to their presumed
abuse and addiction potential. RELATIVE EFFECTIVENESS
The analgesic efficacy of opioids for treating acute pain has been known for centuries, and they continue to be reliable agents for moderate-to-severe acute pain, although they are not without risks. But the evidence for opioid efficacy for acute pain cannot be extended to chronic pain with a few exceptions discussed subsequently. Neuronal and physiologic adaptations to long-term opioid use can result in reduced analgesic effectiveness, or even, paradoxically, increased pain or sensitivity to pain [31]. Opioid-induced hyperalgesia is different pharmacologically from the phenomenon of opioid tolerance, although both can lead to an increased need for opioids, and disentangling the two clinically can be difficult [32].
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For chronic pain, the evidence that opioids reduce pain and improve function more than placebo is relatively weak. A 2018 systematic review and meta-analysis of 96 trials comparing various opioids versus placebo or nonopioid analgesics in 26,169 patients with chronic noncancer pain found that opioids may slightly reduce pain and increase physical functioning compared to placebo, but not compared to nonopioids [33]. In 76 trials comparing opioids versus placebo with follow-up ranging from 1 to 6 months, the reduction in pain scores with opioids (on a 10-point scale) was only 0.69 points. Physical function scores (on a 100-point scale) improved with opioids by 2.04 points, which may not be clinically important. The risk of vomiting with opioids, however, was more than 4 times higher than with placebo [33]. The same meta-analysis compared opioids to nonopioid analgesics including NSAIDs, TCAs, anticonvulsants, and synthetic cannabinoids. No significant differences were found in physical functioning scores for any of the comparisons, and no significant differences were found in pain scores for comparisons with NSAIDs, TCAs, or cannabinoids. EXCEPTIONS: CHRONIC OPIOID USE IN LIMITED PATIENT SUBSETS Sickle cell disease as an example for which chronic opioid therapy may be appropriate in some patients. The risk for opioid death in patients with sickle cell disease comprises a small fraction of the total number of opioid-related deaths. Opioids were involved in 80,411 overdose deaths in 2021 (75.4% of all drug overdose deaths) [1]. The pain experienced by patients includes both acute and chronic aspects through multiple mechanisms that are not completely understood. The American Society of Hematology 2020 guidelines endorse the use of chronic opioid therapy for patients with sickle cell disease with pain that is refractory to multiple other treatments using the lowest effective dose and with regular monitoring [34; 35]. OPIOID FORMULATIONS Prescription opioids are available in immediate-release and extended-release/long-acting (ER/LA) formulations. Immediate-release agents are recommended in opioid-naïve patients and for all acute pain conditions, with ER/LA agents reserved for patients or conditions in which the longer duration of action and smoother pharmacodynamics are preferred. A trial comparing immediate release to an ER/LA opioid did not find evidence that the continuous, time-scheduled use of ER/ LA opioids was more effective or safer than intermittent use of the immediate-release opioid [36]. According to the FDA, ER/LA opioids should only be used for patients who tolerate 60 MMED for at least one week.
CASE STUDY 1 Wayne is an 86-year-old who lives at home with his wife. He was diagnosed with Amyotrophic lateral sclerosis (ALS) 6 months ago, with deterioration occurring first in his diaphragm. He has been experiencing increasing muscle weakness in his legs and uses a walker or a wheelchair to get around in his home. He uses a bilevel positive airway pressure device except when eating or bathing and finds it helpful. He takes the following medications: fish oil, a statin, a thiazide diuretic, and a nonbenzodiazepine sedative to help him sleep. Lately he has been complaining of pain and stiffness in both of his knees and hips, which interferes with his sleep. He is physically deconditioned due to a lack of exercise and has become increasingly withdrawn socially, which worries his wife and family members. He asks if you can prescribe something to ease his pain. Case study questions: 1. Is Wayne a good candidate for an ER/LA opioid? Why or why not? 2. Is he a better candidate for an immediate-release opioid? Why or why not? 3. Would Wayne’s current medication need to be adjusted if he were to be prescribed an ER/LA opioid? 4. What kinds of nonopioid treatments might be tried to help Wayne with his pain?
ATYPICAL OPIOIDS: TRAMADOL AND TAPENTADOL
Tramadol and tapentadol are mu receptor agonists and norepinephrine reuptake inhibitors. Their mechanisms of action are unknown, but their analgesic effects are similar to morphine. Patients taking tramadol should be monitored for nausea, vomiting, constipation, and drowsiness, all of which are similar to side effects with opioids. There is potential risk of serotonin syndrome when tramadol is combined with SSRIs, SNRIs, or tricyclic antidepressants. As noted previously, tramadol is classified as Schedule IV, which has led some to view it as less potent or safer than other opioids. The 2022 National Survey on Drug Use and Health shows that of the 14.6 million people aged 12 and older who used tramadol products (e.g., Ultram, Ultram ER, Ultracet) in the past year, 9.4% of these individuals misused the drug. In addition, a 2019 cohort study of 88,902 patients with osteoarthritis showed increased risks of death at one year compared to NSAIDs naproxen, diclofenac, and celecoxib [33]. Abrupt cessation of tramadol is associated with opioid withdrawal, restlessness, and drug cravings (similar to those associated with other opioids) as well as hallucinations, paranoia, extreme anxiety, panic attacks, confusion, and numbness/tingling in extremities (which are less typical of other opioids).
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Tapentadol is FDA-approved for treating neuropathic pain associated with diabetic peripheral neuropathy, although it is also used for musculoskeletal pain. During treatment, tapentadol reduced pain intensity more than placebo. PROBLEMATIC OPIOID USE Although evidence for the long-term effectiveness of opioids for chronic pain is weak, evidence for opioid-related harm is abundant and strong. In 2023, nearly 8.6 million Americans 12 years and older reported misusing prescription opioids in the past year [34]. It is important to recognize and differentiate problematic use from adverse side effects of opioids. For instance, tolerance and opioid withdrawal occur with long- term use of prescribed opioids. Clinicians should be able to differentiate this from problematic use. Among adults without a prescription, 41% obtained prescription opioids from friends or relatives for their most recent episodes of misuse [36]. For prescription opioids, long- term therapy is associated with an increased risk of accidental overdose and death. Combining opioids with sedating drugs such as benzodiazepines or alcohol increases the risk of respiratory depression and overdose death. Benzodiazepines have been linked with overdose fatalities in 50 to 80% of heroin overdoses and 40 to 80% in methadone-related deaths [37]. Patients prescribed benzodiazepines who are being initiated on opioids should have their benzodiazepine tapered and discontinued whenever possible. For patients being co-managed by mental health professionals, coordinate a plan regarding continuing or tapering benzodiazepines in the setting of opioid co-prescribing. OTHER ADVERSE EVENTS In addition to risks of misuse, addiction, respiratory depression, and overdose death, there are many well-known side effects associated with chronic opioid use that can significantly compromise quality of life, including constipation, nausea or vomiting, sedation, pruritus, erectile dysfunction, menstrual changes, fracture, immunosuppression, hallucinations, and bhyperalgesia. GASTROINTESTINAL SIDE EFFECTS Constipation is one of the most common opioid-related adverse events, affecting most patients to at least some degree, and usually does not resolve with continued exposure. To mitigate this side effect, patients should use a mild stimulant
laxative such as senna or bisacodyl and increase the dosage in 48 hours if no bowel movement occurs. Physicians should perform a rectal examination if no bowel movement occurs in 72 hours. If there is no impaction, consider other therapies such as an enema, suppository, or magnesium citrate. Medications for refractory, opioid-induced constipation include naloxone derivatives: naloxegol (Movantik), methylnaltrexone (Relistor), or naldemedine (Symproic). Naloxegol is an oral tablet that is used daily while methylnaltrexone is a subcutaneous injection or oral tablet used daily. For nausea or vomiting, physicians should consider a prophylactic antiemetic, add or increase nonopioid pain control agents (e.g., acetaminophen as an opioid-sparing drug), and decrease opioid dose by 25% if analgesic is satisfactory. SEDATION Sedation is the first warning sign of a patient being at risk for opioid overdose. If a patient complains of sedation, determine whether sedation is related to the opioid, eliminate nonessential depressants (such as benzodiazepines or alcohol), reduce dose by 10% to 15% if analgesia is satisfactory, and add or increase nonopioid or nonsedating adjuvant for additional pain to reduce opioid dose. Patients should also be co-prescribed naloxone for opioid overdose reversal. TAMPER-RESISTANT/ABUSE-DETERRENT OPIOIDS One strategy to mitigate the risk of opioid abuse has been the development of “abuse-deterrent” formulations of opioids that make it more difficult to alter for non-oral consumption (e.g., injecting, snorting, or smoking). However, these opioids are more aptly named as “tamper-resistant” formulations instead of “abuse-deterrent” since they are no less potentially addictive than regular opioids when taken by mouth. Tamper- resistant formulations often contain a higher opioid dose than immediate-release preparations. PATIENT EDUCATION An important consideration in framing treatment, and a key message to communicate to patients, is that the goal is not “zero pain” but rather a level of analgesia that maximizes a patient’s physical and mental functioning [38]. A multimodal approach, using both drug and nondrug treatments, should be encouraged.
BEHAVIORS INDICATIVE OF OPIOID MISUSE
Behavior
Frequency in Patients with Opioid Misuse
Requested early refills Increased dose on own
47% 39% 35% 26% 18%
Felt intoxicated from pain medication
Purposely oversedated oneself
Used opioids for purpose other than pain
Source: [35]
Table 2
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In addition, patients should be educated about the safe storage and disposal of opioid medications. Safe use means following clinician instructions about dosing, avoiding potentially dangerous drug interactions (e.g., alcohol), and ensuring full understanding of how the medication should be consumed or applied. Remind patients that opioid pain medications are sought after by many people, and therefore opioids should be stored in a locked cabinet or, if a locked unit is not available, a place that is not obvious or easily accessed by others. Proper disposal methods should be explained: • Follow any specific disposal instructions on the prescription drug labeling or patient information that accompanies the medication. • Do not flush medicines down the sink or toilet unless the prescribing information specifically instructs to do so. • Return medications to a pharmacy, health center, or other organization with a take-back program. • Mix the medication with an undesirable substance
Multimodal analgesia (e.g., using drugs from two or more classes, or a drug plus a nondrug treatment) can produce synergistic effects, reduce side effects, or both. One example of multimodal analgesia is the use of both an NSAID and acetaminophen, plus physical approaches (e.g., cold, compression, or elevation) to manage postoperative pain. Demonstrated benefits of multimodal analgesia include earlier ambulation, earlier oral intake, and earlier hospital discharge for postoperative patients, as well as higher levels of participation in activities necessary for recovery (e.g., physical therapy). NONPHARMACOLOGICAL TREATMENTS FOR ACUTE PAIN When possible, nonpharmacologic methods should be used, alone or in combination with analgesics, to manage acute pain [44]. The degree to which this is possible depends on the severity, type, and origin of the pain, but many nonpharmacologic approaches can be very effective, and their use avoids the potential side effects and risks associated with pharmacological interventions. Physical methods of pain management can be helpful in all phases of care, including immediately after tissue trauma (e.g., rest, application of cold, compression, elevation) and later in the healing period (e.g., exercises to regain strength and range of motion). Physical therapy may be useful for a range of musculoskeletal issues and can be helpful in recovering from acute pain- producing traumas initially treated with other methods. A 2018 study reported that patients with low back pain who first consulted a physical therapist were less likely to receive an opioid prescription compared to those who first saw their primary care physician [45]. Exercise therapy can take many forms, including walking, swimming or in-water exercise, weight training, or use of aerobic or strength-training equipment. According to a CDC review, conditions that may improve with exercise therapy include low back pain, neck pain, hip and knee osteoarthritis pain, fibromyalgia, and migraine [46].
(e.g., used coffee grounds or kitty litter) and put it in the trash, or use special drug deactivation pouches that your healthcare provider may recommend.
MANAGING ACUTE PAIN Many of the problems and risks associated with managing chronic pain with opioids are also at work in the management of acute pain with opioids. A number of studies demonstrate increased risk of new persistent opioid use in opioid-naïve patients after having been prescribed opioids for acute pain [39; 42]. Although the risk of opioid misuse in patients prescribed opioids for acute post-surgical or post-procedural pain is relatively small (roughly 0.6% per year) [43] the volume of such procedures (there are well over 100 million outpatient surgeries performed each year in the United States) translates into large numbers of patients (i.e., approximately 600,000) who may develop dependence, abuse, or overdose every year. A central tenet of pain management, whether acute or chronic, is that the goal of treatment is a tolerable level of pain that allows the patient maximum physical and emotional functioning with the lowest risk of side effects, progression to chronic pain, or misuse or abuse. This requires an adroit balancing of patient-related factors (e.g., comorbidities, medical history, risk of abuse) and drug-related factors (e.g., potency, mechanism of action, expected side effects). This can be balanced by multimodal analgesia in which several therapeutic approaches are used, each acting at different sites of the pain pathway, reducing dependence on a single medication and reducing or eliminating the need for opioids and attendant risks and side effects.
NONOPIOID PHARMACOLOGIC TREATMENTS FOR ACUTE PAIN
ACETAMINOPHEN AND NSAIDS In general, mild-to-moderate acute pain responds well to oral nonopioids (e.g., acetaminophen, NSAIDs, and topical agents). Although they are weaker analgesics than opioids, acetaminophen and NSAIDs do not produce tolerance, physical dependence, or addiction, and they do not induce respiratory depression or constipation. Acetaminophen and NSAIDs are often added to an opioid regimen for their opioid- sparing effect. Since nonopioids relieve pain via different mechanisms than opioids, combination therapy can provide improved relief with fewer side effects.
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