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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
This activity is supported by an independent educational grant from the Opioid Analgesic REMS Program Companies. Please see https://ce.opioidanalgesicrems.com/RpcCEUI/rems/pdf/resources/List_of_RPC_Companies.pdf for a listing of REMS Program Companies. This activity is intended to be fully compliant with the Opioid Analgesic REMS education requirements issued by the US Food and Drug Administration.
In collaboration with
Christopher Gharibo, MDAssociate ProfessorDepartments of Anesthesiology and Pain MedicineDepartment of OrthopedicsNYU School of Medicine;Medical Director of Pain MedicineNYU Langone HealthNew York, NY
Aaron Williams, MA Senior Director of Training and TA for Substance UseNational Council for Behavioral HealthWashington, DC
Program FacultyProgram FacultyTimothy J. Atkinson, PharmD, BCPS, CPEClinical Pharmacy Specialist, Pain ManagementDirector, PGY2 Pain Management & Palliative CareVA Tennessee Valley Healthcare SystemNashville, TN
NCBH SpeakerNCBH Speaker
Christopher Gharibo, MDAssociate ProfessorDepartments of Anesthesiology and Pain MedicineDepartment of OrthopedicsNYU School of Medicine;Medical Director of Pain MedicineNYU Langone HealthNew York, NY
Steering CommitteeSteering CommitteeCharles E. Argoff, MDProfessor of NeurologyAlbany Medical CollegeDirector, Comprehensive Pain CenterDirector, Pain Management FellowshipAlbany Medical CenterAlbany, NY
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
DisclosuresDisclosuresFaculty and Steering Committee Disclosures
The faculty and steering committee reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
Non-faculty DisclosuresNon-faculty content contributors and/or reviewers reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:
Rebecca Jimenez-Sanders, MD: Speaker’s Bureau: Amgen, Teva; Kathy Merlo; Blair St. Amand; Martin Myers, MD; Ashley Marostica RN, MSN, CCM; Brian Jack, MD; USF Health CPD staff: Nothing to disclose
Keypad NumberKeypad Number
• The FDA requires reporting of de-identified findings from this program; however, the provider needs your personal information for accreditation reporting. Your keypad number will be used in place of personal information for the FDA report.
• Your evaluation is stuffed into the syllabus, please take a minute to write in your keypad number at the top of the form
Educational ObjectivesEducational ObjectivesAt the conclusion of this activity, participants should be able to:
• Identify risk factors and vulnerabilities associated with addiction to opioid analgesics and provide patient/caregiver counselling when necessary
• Discuss the components of an effective treatment plan, including patient interactions, treatment goals, and collaboration within the healthcare team
• Analyze the specific benefits and risks to initiating non-medication therapies before utilizing long-term medications
• Recognize patients who are candidates for treatment with nonopioid pharmacologic analgesics
• Explain the decision to initiate long-term opioid analgesics, including ER/LA opioids, with consideration to providing in-home naloxone
• Determine when referral to a pain specialist is appropriate for a patient with chronic pain
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Please rate your confidence in your ability to develop a treatment plan for a patient with chronic pain:
1. Not confident
2. Slightly confident
3. Confident
4. Highly confident
5. Expert
Polling Question 1Polling Question 1
The Prevalence of Chronic Pain in the US Is HighThe Prevalence of Chronic Pain in the US Is High
• Approximately 100 million US adults experience chronic pain (33%)
• Consider appropriate nonpharmacologic, nonopioid options before starting opioids
• If an opioid is chosen consider benefit vs risk
IOM (Institute of Medicine). Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 2011; www.painpolicy.wisc.edu.
Ensure availability of opioids
for patients with pain
Establish systems of control
to prevent abuseAND
Adapted
Physical Social
Anger/Fear
Anger/Fear
• Relationships
• Ability to show affection/sexual function
• Isolation
• Function
• Activities of daily living
• Sleep/rest
Chronic Pain Affects Many Dimensions of Patient LifeChronic Pain Affects Many Dimensions of Patient Life
Borneman T, et al. Oncol Nurs Forum. 2003;30(6):997-1005.
Psychological
Anxiety/Depression
Anxiety/Depression
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
• Lack of access to interdisciplinary pain management
Opioid Morbidity and Mortality2017/2016 By the NumbersOpioid Morbidity and Mortality2017/2016 By the Numbers
• 72,300 drug overdose deaths
• 49,000 opioid overdose deaths
• 29,400 fentanyl overdose deaths
• 15,900 heroin overdose deaths
1. National Center for Health Statistics, CDC Wonder. 2. Volkow ND, McLellan AT. N Engl J Med. 2016;374:1253-1263.3. https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html.
• 19,300 prescription opioid overdose deaths
• 3,280 methadone overdose deaths
• 52 million non-medical use all drugs
• 2.2 million non-medical use prescription opioids
• 1-8% become addicted
• 4% advance to heroin
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Woolf CJ. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, Curatolo M. Swiss Med Weekly. 2002;132:273-278; Woolf CJ, Wall PD. Nature.1983;306:686-688; Woolf CJ, et al. Nature. 1992;355:75-78.
Surgeryor
injurycauses
inflammation
Long-Term Consequences of Acute Pain Potential for Progression to Chronic PainLong-Term Consequences of Acute Pain Potential for Progression to Chronic Pain
SustainedActivation
PeripheralNociceptive
Fibers
Sensitization
CHRONIC PAIN
CNSNeuroplasticity
Hyperactivity
Structural Remodeling
Examples of nociceptive pain include which of the following?
Chronic Pain Conditions Can Be ClassifiedBased on Type of Pain PathophysiologyChronic Pain Conditions Can Be ClassifiedBased on Type of Pain Pathophysiology
Three Main Types of Pain PathophysiologyThree Main Types of Pain Pathophysiology
Nociceptive Neuropathic
Pain without identifiable nerve or tissue damage; thought to result from
persistent neuronal dysregulation, affective system disorder
EXAMPLES:Any pain
Pain without identifiable nerve or tissue damage; thought to result from
persistent neuronal dysregulation, affective system disorder
EXAMPLES:Any pain
Pain related to damage of somaticor visceral tissue, due to trauma
The Three Types of Pain, Separately or Together, Give Rise to Various Chronic Pain ConditionsThe Three Types of Pain, Separately or Together, Give Rise to Various Chronic Pain Conditions
Adapted from Stanos S, et al. Postgrad Med. 128:502-515.
Chronic low back painhas been acknowledged to have multiple potential mechanisms and is often viewed as a prototypical “mixed-pain state”
Which Person Has Pain?Which Person Has Pain?
Acute Postoperative Pain Has Been Associated With Chronic Pain After Common ProceduresAcute Postoperative Pain Has Been Associated With Chronic Pain After Common Procedures
Procedure Incidence of ChronicPostsurgical Pain
US Surgical Volumes(1000s)1
Amputation 57-62%2 159
Breast surgery 27-48%3,4 479
Thoracotomy 52-61%5,6 Unknown
Inguinal hernia repair 19-40%7,8 609
Coronary artery bypass 23-39%9-11 598
Caesarean section 12%12 220
1. Kehlet et al. Lancet. 2006;367:1618-1625; 2. Hanley et al. J Pain. 2007;8:102-10; 3. Carpenter et al. Cancer Prac. 1999;7:66-70; 4. Poleschuk et al. J Pain. 2006;7:626-634; 5. Katz et al. Clin J Pain. 1996;12:50-55; 6. Perttunen et al. Acta Anaesthesiol Scand. 1999;43:563-567; 7.Massaron et al. Hernia. 2007;11:517-525; 8. O’Dwyer et al. Br J Surg. 2005;92:166-170; 9. Steegers et al. J Pain. 2007;8:667-673; 10. Taillefer et al. J Thorac Cardiovasc Surg. 2006;131:1274-1280; 11. Bruce et al. Pain. 2003;104:265-273; 12. Nikolajsen et al. Acta Anaesthesiol Scand. 2004;48:111-116.
Factors correlated with the development of postsurgical chronic pain1:
1. Nerve injury2. Inflammation3. Intense acute
postoperative pain
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
• Goals for pain management should be specific, measurable, and patient-centered
• Goals focused solely on numeric pain ratings can be problematic• Clinical trials suggest that a 33% to 50% decrease in pain intensity
is meaningful • Goal setting
– Collaborative, focus on functional improvement• Be realistic
– Eliminating pain is often not realistic
http://prc.coh.org/pdf/Goals-FF%205-10.pdf.
Access to Interdisciplinary CareAccess to Interdisciplinary CareNation
No. Citizens / Clinic
Change in No. Clinics in Past Decade
Australia 255,555Belgium 1,222,222 Canada 172,413 Denmark 560,000 England and Wales 405,797 France 802,469 Israel 727,000 Netherlands 2,438,571 New Zealand 440,000 Spain 7,666,666 Sweden 339,285 United States (non-VHA*) 3,244,444 United States (VHA*) 369,491
Study results showed that a precipitous decrease in the number of interdisciplinary programs occurred in U.S. between 1999 and 2012, except among the Veteran’s Health Administration. During this same time period, the number of interdisciplinary programs in industrialized nations with National Health Services increased dramatically.
Study results showed that a precipitous decrease in the number of interdisciplinary programs occurred in U.S. between 1999 and 2012, except among the Veteran’s Health Administration. During this same time period, the number of interdisciplinary programs in industrialized nations with National Health Services increased dramatically.
Schatman ME. J Pain Res. 2015;8:885-887.
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• Be aware of risk of acute pain transitioning to chronic pain
• Psychosocial evaluation• Risk identification
– State prescription monitoring programs
• Special populations: pediatric, elderly, pregnancy
• State medical boards may have specific regulations, e.g., Medical Board of California:– History/Physical Examination
• “A medical history and physical examination must be accomplished. This includes an assessment of the pain, physical and psychological function; a substance abuse history; history of prior pain treatment; an assessment of underlying or coexisting diseases or conditions; and documentation of the presence of a recognized medical indication for the use of a controlled substance.”
Lalani I, Argoff CE. History and Physical Examination of the Pain Patient. In: Raj's Practical Management of Pain. 4th ed. 2008;177-88. Chou R, et al. J Pain. 2009;10:113-30.
Perform Thorough Evaluation and Assessment of PainPerform Thorough Evaluation and Assessment of Pain
Pain DescriptorsPain DescriptorsTen Components Questions to Ask
1. History of onset How/when did your pain begin? What was the last time you were pain free?
2. Location Where exactly is your pain?
3. Quality What does it feel like (e.g., sharp, dull, burning, cramping)?
4. IntensityHow would you rate your pain now? When is pain the least? At the worst? On average? Use an intensity scale appropriate to patient’s language, development and cognitive level.
5. Temporal patternIs your pain constant or intermittent? If intermittent, frequency and duration of episodes; variability according to time of day, etc.
6. Aggravating factors What factors make you pain worse?
7. Alleviating factors What factors decrease your pain?
8. Associated symptomsWhat other sensations are associated with your pain (e.g., nausea, vomiting, dizziness, weakness, incontinence, itching, vasomotor changes)?
9. Previous methods of treatmentWhat treatments have you tried for your pain, e.g., medications, behavioral strategies or alternative therapies such as acupuncture, massage, herbal therapies? How effective have they been?
10. Impact of pain on quality of lifeWhat effect has your pain had on your quality of life? This information many not be feasible to gather on the initial evaluation, due to time or pain intensity, but should be gathered on subsequent patient contact. Areas to assess include mood, sleep, appetite, functional status/activities of daily living.
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http://www.partnersagainstpain.com/hcp/pain-assessment/tools.aspx. Used for educational purposes only.
Pain and Function Assessment ToolsPain and Function Assessment Tools
• Graded Chronic Pain Scale– Pain and function
assessment
Von Korff M. Chronic Pain Assessment in Epidemiologic and Health Services Research: Empirical Bases and New Directions. Handbook of Pain Assessment: Third Edition. Dennis C. Turk and Ronald Melzack, Editors. Guilford Press, New York., In presshttp://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Used for educational purposes only.
Primary Care StrategiesPrimary Care Strategies
• If not already using pain assessment tools, then start with
– Chronic Pain Scale
– Assess pain and function at start and during therapy
• Consider having patients complete the Brief Pain Inventory at each visit while in the waiting room
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Paradigm Shift from Reducing Pain to Increasing FunctionParadigm Shift from Reducing Pain to Increasing Function
• Pain relief should improve function
• Lack of functional improvement always indicates treatment failure or other problems, e.g., misuse, diversion, addiction, mood disorders, side effects, etc.
FSMB | Responsible Opioid PrescribingTM: A Clinician’s Guide. Available at: http://www.fsmb.org/book/.
Outcomes to AssessOutcomes to Assess
• Progress towards therapeutic goals
• Changes in functional status
• Presence of opioid-related adverse effects
• Changes in underlying pain condition
• Changes in medical or psychological comorbidities
• Opioid tolerance
• Aberrant behaviors, addiction, diversion
The Goal of treatment in chronic pain is
to Improve Function
and Control the Pain
with minimal
side effects
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
A Depiction of How Therapeutic Choices May Affect Pain PathwaysA Depiction of How Therapeutic Choices May Affect Pain Pathways
Multiple Pathways of Pain Transmission Provide Multiple Targets for Pain ReliefMultiple Pathways of Pain Transmission Provide Multiple Targets for Pain Relief
Inhibiting ascending pathways1-4,6
• Opioids†
• Local anesthetics• Antiepileptics7
• NSAIDs/acetaminophen
*Theoretical mechanisms of action†It is well established that opioids inhibit the ascending trans-mission of nociceptive signals. Additional mechanisms have been reported in the literature, including the activation of descending inhibitory pathways and modulation of limbic system activity.1,3,4,6
1. National Pharmaceutical Council, Joint Commission on Accreditation of Healthcare Organizations. Pain: current understanding of assessment, management, and treatments. http://www.npcnow.org/resources/PDFs/painmonograph.pdf. December 2001. Accessed March 7, 2008.. 2.Pyati S, Gan TJ. Perioperative pain management. CNS Drugs.2007;21(3):185-211. 3. Vanderah TW. Pathophysiology of pain. Med Clin N Am. 2007;91:1-12. 4. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451. 5. Pertovaara A, Almeida A. Descending inhibitory systems. In: Cervero F, Jensen TS, eds. Pain: Handbook of Clinical Neurology. Vol 81. 3rd series. New York, NY: Elsevier; 2006:179-192. 6. Gutstein HB, Akil H. Opioid analgesics. In: Bruntin LL, ed. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006. 7. Knotkova H, Pappagallo M. Adjuvant analgesics. Med Clin N Am. 2007;91:113-124.
Undertreatment of Pain May Involve Multiple FactorsUndertreatment of Pain May Involve Multiple Factors
Combination of factors
Physician factors
Patient factors
Fear of disciplinary action or prosecution1-3
Potential for abuse2,9
Lack of training in opioid titration8
Fear of addiction, tolerance & side effects10
Socioeconomic and psychological factors1-7,10
Poor patientknowledge10
Communication between physician and patient10
Governmental and public policy on payment for opioid analgesics5,10
Undertreatment of chronic pain
1. Richard J. Reidenberg MM. J Pain Symptom Manag. 2005;29:206-212.2. Gilson AM et al. J Pain. 2007;8:682-691.3. Jung B. Reidenberg MM. Pain Med. 2006;7:353-357.4. McCracken LM, et al. J Pain. 2006; 7:726-734.5. Primm BJ, et al. J Natl Med Assoc. 2004;96:1152-1161.
6. Edwards CL, et al. Pain. 2001;94:133-137.7. Green CR, et al. J Pain. 2005;6:689-699.8. Mercadante S. Eur J Pain. 2007;11:823-830.9. Manchikanti L. Pain Phys. 2006;9:287-321.10. Glachen M. J Am Board Fam Pract. 2001;14:211-218.
Special Considerations: Pregnant WomenManaging Chronic Pain in Pregnant Women is Challenging,and Affects Both Mother and Fetus
Special Considerations: Pregnant WomenManaging Chronic Pain in Pregnant Women is Challenging,and Affects Both Mother and Fetus
• Potential risks of opioid therapy to the newborn include:– Low birth weight– Premature birth– Hypoxic-ischemic brain injury
• Given these potential risks, clinicians should:– Counsel women of childbearing potential about risks & benefits of opioid therapy during
pregnancy & after delivery– Encourage minimal/no opioid use during pregnancy unless potential benefits outweigh risks
• If chronic opioid therapy is used during pregnancy, anticipate and manage risks to the patient and newborns
Special Considerations: Children (<18 years)Special Considerations: Children (<18 years)• Safety and effectiveness of most ER/LA opioids unestablished
– Pediatric analgesic trials pose challenges– Transdermal fentanyl approved in children aged ≥2 yrs
• Most opioid studies focus on inpatient safety– Opioids are common sources of drug error
• Opioid indications are primarily life-limiting conditions– Few children with chronic pain due to non-life-limiting conditions should receive
opioids
• When prescribing opioids to children:– Consult pediatric palliative care team or pediatric pain specialist or refer to a
specialized multidisciplinary pain clinicBerde CB, et al. Pediatrics. 2012;129:354-64. Gregoire MC, et al. Pain Res Manag 2013;18:47-50. Mc Donnell C. Pain Res Manag. 2011;16:93-8. Slater ME, et al. Pain Med. 2010;11:207-14.
American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57:1331-46. Chou R, et al. J Pain. 2009;10:113-130.
• Respiratory depression more likely in elderly, cachectic, or debilitated patients– Altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance
– Monitor closely, particularly when
• Initiating & titrating ER/LA opioids
• Given concomitantly w/ other drugs that depress respiration
– Reduce starting dose to 1/3 to 1/2 the usual dosage in debilitated, non-opioid-tolerant patients
– Titrate dose cautiously
• Older adults more likely to develop constipation– Routinely initiate a bowel regimen before it develops
• Is patient/caregiver likely to manage opioid therapy responsibly?
Special Considerations: Elderly PatientsDoes Patient Have Medical Problems That Increase Riskof Opioid-related AEs?
“Nothing is intrinsically good or evil but its manner of usage may make it so”
Thomas Aquinas
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Consider referring high-risk patients or any patient you have concerns about to a pain specialist
Primary Care StrategiesPrimary Care Strategies• If not using any risk assessment tools, then start with
– ORT to screen for potential for ADRBs
– PHQ-9 to screen for depression
– CAGE-AID to screen for alcohol and/or drug problems
– PEG for pain, function, and quality of life
• For monitoring at follow-up visits, start with– 2-4 weeks determined by risk
• Check state prescription monitoring program at first visit and continuously monitor during treatment (interval often stipulated by medical board)
• Comply with local regulations and laws
Know the Risk Factors for Respiratory DepressionKnow the Risk Factors for Respiratory Depression• Generally preceded by sedation and decreased respiratory rate
• Risk factors for respiratory depression include:
The Joint Commission. Sentinel Event Alert. August 8, 2012;49. www.jointcommission.org.
Sleep apnea or a sleep disorder diagnosis
Morbid obesity with a high risk of sleep apnea Snoring
Risk increases with age (>60) No recent opioid usePost-surgery
(particularly upper abdominal or thoracic)
Use of other sedating agents (CNS depressants), such as
benzodiazepines and alcohol
Preexisting pulmonary or cardiac disease or dysfunction
or major organ failureSmoking
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BreakBreak• The onsite evaluation form can be found in your syllabus and must be
completed to receive credit – please feel free to take it out and start this during the break
• If you have not done so already - please be sure to include your 3-digit keypad number on the evaluation form
Components to an Effective Treatment Plan and General Principals of
Nonpharmacologic Approaches
Components to an Effective Treatment Plan and General Principals of
Nonpharmacologic Approaches
Principles of Responsible Opioid PrescribingTreatment Plan Principles of Responsible Opioid PrescribingTreatment Plan • I have resolved key points before initiating opioid therapy
– Diagnosis established and opioid treatment plan developed– Established level of risk– I can treat this patient alone/I need to enlist other consultants to co-
manage this patient (pain or addiction specialists) • I have considered nonopioid modalities
– Pain rehabilitation program– Behavioral strategies– Non-invasive and interventional techniques
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Fine PG, et al. J Support Oncol. 2004;2(suppl 4):5-22; Portenoy RK, et al. In: Lowinson JH, et al, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:863-903.
Definition of Integrative Pain TreatmentDefinition of Integrative Pain Treatment
“Integrative pain treatment is the practice of caring for individuals with pain that focuses on the whole person, reaffirms the importance of the relationship between practitioner and patient, uses the least invasive treatments whenever possible, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing.”
Cochrane Reviews (CAM)Cochrane Reviews (CAM)• Touch Therapy: Areas of the body where energy field is weak or congested are assessed,
and practitioner uses his/her hands to direct energy into the field to balance it, thereby relieving pain1
• Music Therapy: Music may have beneficial effects on anxiety, fatigue, depression, pain, and quality of life for patients with cancer; reduces the need for pain medication after surgery2
• P6 Therapy for Post-op Nausea: P6 acupoint stimulation is comparable to antiemetics in preventing postoperative nausea and vomiting after anesthesia and surgery3
• Aromatherapy: Essential oils are massaged into the skin, inhaled, or placed in baths to relieve stress, anxiety, and other ailments, such as pain2
• Caffeine: Use of an analgesic plus caffeine resulted in a higher number of patients with good pain relief compared with use of an analgesic alone4
EFNS, European Federation of Neurological Societies; IASP, International Association for the Study of Pain; NeuPSIG, Neuropathic Pain Special Interest Group
OpioidTramadol
First line
Second line
Third line
TCAGBP/PGB
Lidocaine 5% plaster
SNRI(Opioid)
OpioidLamotrigineCapsaicin
Canadian Pain Society
TCAGBP/PGB
SNRILidocaine 5%
Opioid (except methadone)
TCA, SNRIGBP/PGB
Lidocaine 5%Opioid
(specific circumstances)
EFNS, Europe Neurology IASP NeuPSIG
ParoxetineBupropion
NMDAantagonist
Fourth line Methadone
Neuropathic PainRecommendations of Various SocietiesNeuropathic PainRecommendations of Various Societies
Pharmacotherapeutics IGeneral Principles of Pharmacologic
Analgesic Therapy
Pharmacotherapeutics IGeneral Principles of Pharmacologic
Analgesic Therapy
The most effective and safe way to manage pain with medication is:
1. NSAIDs and antidepressants
2. Anticonvulsants
3. Immediate-release opioids
4. As part of multimodal plan of care
Polling Question 6Polling Question 6
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Although formal pain management treatment protocols are lacking, most experts propose conservative nonpharmacological modalities as primary and adjunctive treatment, with opioids reserved for those patients who fail to respond to other therapies
Used for educational purposes only.
Rational PolypharmacyRational Polypharmacy
Advantages• Multimechanistic effect
• Improved efficacy
• Reduction in end organ toxicity
• Reduction in side effects
• Functional improvement
Disadvantages
• Requires knowledge of drugs, PK data, and pharmacodynamics
• Every analgesic has its own unique adverse event profile
• May increase drug-drug interactions
1. Sinatra RS. Ann Meeting Cleveland Soc of Anesthesiology. Nov 2010.2. Kehlet H, Wilmore DW. Am J Surg. 2002;183:630-41.
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Non-opioids Limited by Efficacy and AEsNon-opioids Limited by Efficacy and AEs
Devries F, et al. Br J Clin Pharm. 2010;70:429-438. Solomon SD, et al. N Engl J Med. 2005;352:1071-1080.Roumie CL, et al. Stroke. 2008;39:2037-2045. Used for educational purposes only.
Considerations for AntidepressantsConsiderations for Antidepressants
• TCAs vs Beer’s Criteria*
• Pharmacology– TCAs
– SNRIs
• See http://www.paindr.com/antidepressant%20chart.pdf
• Drug Interactions to consider– 2D6, 3A4, others
*Beer’s Criteria: guidelines for healthcare professionals to help improve the safety of prescribing medications for older adults.
– SARIs
– Atypicals
AnticonvulsantsAvailable in US, Excluding BenzodiazepinesAnticonvulsantsAvailable in US, Excluding Benzodiazepines
Inflammation Ongoing Chemical Activation of Pain Sensors
Inflammation Ongoing Chemical Activation of Pain Sensors
Sensitize, activate
NSAIDsCoxibs COX1/2
H+5HTNa+, K+,
Ca2+
channels
C-fiber
NGF
cytokines
Nerve Growth FactorNerve Growth FactorDirect Peripheral, Direct and Indirect Gene Effects Conditions of Tissue Damage, Deep Inputs, NeuromasDirect Peripheral, Direct and Indirect Gene Effects Conditions of Tissue Damage, Deep Inputs, Neuromas
Sensory nerve fiber-sprouting and neuroma-like structures2
Potential functions and mechanisms of action of NGF in development of post-injury pain1
1. Xian CJ, Zhou XF. Nat Clin Pract Rheumatol.. 2009;5:92-98; 2. Jiminez-Andrade JM, Mantyh PW. Arthritis Res Ther. 2012;14:R101..
NGF In Lower Back PainNGF In Lower Back Pain
Takahashi K, et al. Eur Spine J. 2008;17:S428-S431.
Fusion surgery
Sensitization
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American Medical Association, Arizona Center for Education and Research on Therapeutics, Critical Path Institute. Pharmacogenomics: increasing the safety and effectiveness of drug therapy. Chicago, IL: American Medical Association; 2011. Report 10-0290:5/11:jt. https://crediblemeds.org/files/3913/6973/9557/pgx-brochure2011.pdf.
Looking at pharmacogenetic variability and response, what percentage of the general population has phenotype variability:
1. 5-8%
2. 10-15%
3. 25-35%
4. 40-60%
Polling Question 8Polling Question 8
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Cavallari LH, Limdi NA. Curr Opin Mol Ther. 2009;11(3):243-251. Lynch T, Price A. Am Fam Physician. 2007;76:391-396.Ma JD et al. J Pharm Pract. 2012;25:417-427..
http://www.arupconsult.com/assets/graphics/OpiatesAndOpiodMetabolism.jpg. Used for educational purposes only.
Opiates and Opioid MetabolismOpiates and Opioid Metabolism
How would you proceed if you inherited a patient prescribed both a benzodiazepine for sleep and high-dose opioids after 9 spinal surgeries?
1. Continue both as prescribed2. Reduce the dosages of both medications3. Discontinue the opioid or benzodiazepine therapy 4. Consider an alternative medication, such as an
anticonvulsant or low-dose trazodone
Polling Question 9Polling Question 9
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Benzodiazepines and Chronic Pain PatientsBenzodiazepines and Chronic Pain Patients• Enhance the respiratory depressant effects of opioids
– Frequently co-prescribed with opioids (up to 50% of patients)• In 1 population, 80% of patients prescribed high-dose opioids were co-prescribed
benzodiazepines
• More common in chronic pain patients with substance use disorders
• Consider an alternative– For anxiety disorders
– When a sleep aid is indicated, e.g., an anticonvulsant or low-dose trazodone• For patients with neuropathic pain, low-dose trazodone at bedtime may be dually
beneficial
Webster LR. Pain Med. 2013;14:959-961. Webster LR, et al. Postgraduate Med. 2015;127:27-32. Deyo RA, et al. J Am Board Fam Med. 2011;24:717-727. King SA, Strain JJ. Clin J Pain. 1990;6:143-147. Manchikanti L, et al. Pain Physician. 2009;12:259-267. Braden JB, et al. Arch Intern Med. 2010;170:1425-1432. Dasgupta N. Opioid analgesic prescribing and overdose mortality in North Carolina [dissertation]. Chapel Hill, NC: University of North Carolina at Chapel Hill; 2013. Weisner CM, et al. Pain. 2009;145:287-293.
Opioid Formulations: Points to ConsiderOpioid Formulations: Points to Consider• Dose-limiting issues and toxicity with co-analgesics
– 4 g/day acetaminophen limit
• Importance of titration– Risk of overdose, challenges of dose conversion during rotation
• Pharmacokinetics vs temporal patterns of pain• Issues that influence the opioid selection
– Pain pattern– Genetic factors that can influence metabolism– Comorbid medical conditions that may alter drug metabolism or clearance– Past history with opioid therapy and route of administration issues
• Adherence and care-giving issues• Cost and convenience
• Full impact cannot be realized until all opioids are abuse-deterrent
• FDA’s goal: ADFs for all major opioids
Abuse-deterrent formulations (ADFs) One Component to Address Prescription Opioid EpidemicAbuse-deterrent formulations (ADFs) One Component to Address Prescription Opioid Epidemic
Prescribing Guidelines
Insurance Reform
Physician & Patient Education
Research New Safer Therapies
Prescription Drug
MonitoringAbuse-Deterrent
FormulationsApproach to
Address Opioid Epidemic
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Speed of CNS Entry and Concentration Determines Liking
The “abuse potential” of a drug increases as the value of the AQ increases
Opi
oid
Con
cent
ratio
n
Time
Tmax
Cmax
Webster LR. Drug Discovery and Development. July, 30. 2009.
Cmax / TmaxIn this ratio, as Cmax INCREASES and as Tmax DECREASES, the ratio becomes relatively larger, signaling potentially increased attractiveness as a drug of abuse
Polling Question 10Polling Question 10
In converting patients from one extended release opioid to another extended release opioid:
1. Use conversion tables to determine the exact starting dose of the new opioid
2. Adjust dose of new opioid every 24 hours3. Start the new ER opioid at a lower dose or dose as if the patient
is opioid naïve4. Never use IR opioids during an opioid rotation
Help Minimize Harm Prescribing Opioids and Other Psychotherapeutics
1. Assess patients for risk of abuse before starting opioid therapy and manage accordingly2. Watch for and treat comorbid mental disease if present3. Conventional conversion tables can cause harm and should be used cautiously when rotating
(switching) from one opioid to another4. Avoid combining benzodiazepines with opioids, especially during sleep hours5. Start methadone at a very low dose and titrate slowly regardless of whether your patient is
opioid tolerant or not6. Assess for sleep apnea in patients on high daily doses of methadone or other opioids and in
patients with a predisposition7. Tell patients on long-term opioid therapy to reduce opioid dose during upper respiratory
infections or asthmatic episodes8. Avoid using long-acting opioid formulations for acute, post-operative, or trauma-related pain
Webster LR. Pain Med. 2013;14:959-961.
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Issues with Morphine Equivalent Daily Dose and Opioid ConversionIssues with Morphine Equivalent Daily Dose and Opioid Conversion
• Body weight
• Pharmacogenetic variability
• Drug interactions
• Lack of universal morphine equivalence
Fudin J et al. J Pain Res. 2016;9:153-156.Fudin J et al. Practical Pain Management. Sept. 2012. 46-51.Donner B et al. Pain. 1996;64:527–534.Breitbart W et al. Oncology. 2000;14:695-705.Shaw K, Fudin J. Practical Pain Management. 2013;13(7):61-66.
• Specific opioids that should never have an MEDD
– Methadone
– Buprenorphine
– Tapentadol
– Tramadol
Challenge of Equianalgesic ConversionChallenge of Equianalgesic Conversion
• Tables use for risk stratification and should not be used to establish equianalgesic conversion
• Subjects with limited opioid exposure
• Do not reflect clinical realities of chronic opioidadministration
Pereira J et al. J Pain Symptom Manage. 2001;22:672-687.
Risks for Opioid OverdoseRisks for Opioid Overdose
Substance abuse
High daily morphine
equivalent dose (MED)
Age Gender
Concomitant use of benzodiazepines and/or alcohol with or without
other sedative-hypnotics
Chronic lung disease
Chronic kidney and/or liver impairment
Sleep apnea
Accidental exposure to
young children in the home
Opioid Overdose Risk Assessment Checklist. Kaleo, Inc. May 2014. http://www.evzio.com/pdfs/Evzio-Opioid-Overdose-Risk-Assessment-Checklist.pdf. Evzio [package insert]. Richmond, VA: Kaleo, Inc.; 2014.Substance Abuse and Mental Health Services Administration. SAMHSA Opioid Overdose Prevention Toolkit. HHS Publication No. (SMA) 14-4742. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Which of the following is true?1. All aberrant behaviors are signs of addiction
2. All aberrant behaviors are signs of abuse
3. All patients on opioids eventually show signs of aberrant behaviors
4. All people with an opioid addiction misuse/abuse opioids
5. All people who misuse/abuse opioids are also opioid addicts
Opioid Use Disorder (OUD)Opioid Use Disorder (OUD)• DSM-I (1952-1968) – “Addiction” is usually symptomatic of a personality disorder.
• DSM-II (1968-1980) – “Addiction” requires evidence of habitual use ... withdrawal symptoms are not the only evidence of dependence.
• DSM-III (1980-1994) – Essential feature of “Opioid Abuse” ... pattern of pathological use for at least one month ... impairment in social or occupational functioning ... “Opioid Dependence” essential feature is tolerance or withdrawal.
• DSM-IV (1994-2000) – “Opioid Dependence” includes ... compulsive, prolonged self-administration of opioid substances ... for no legitimate medical purpose ... doses that are greatly in excess of the amount needed for pain relief.
• DSM-V (2013-Present) – Categories of substance abuse and substance dependence have been eliminated and replaced with an overarching new category of “substance use disorders” with the specific substance defining the disorder.– Tolerance and withdrawal that previously defined dependence are normal responses.
Triangle of the Disease of Abuse/AddictionTriangle of the Disease of Abuse/Addiction
Genetics
Social /Environment
Drug Properties
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Vulnerability Factor: Drug PropertiesVulnerability Factor: Drug Properties
• Drug-induced effect
• On/Off; frequency
• Rate and quantity of dopamine release
Drug Properties
Kreek MJ. Update on the Neurobiological Linkages between Pain and Chemical Dependency. Pain Management and Clinical Dependency. December 7-9, 2000.Gardner E. Neurophysiology of Chemical Dependence. Pain Management and Clinical Dependency. December 7-9, 2000.
Adapted with permission. Webster publication pending
• Set, setting• Cuing• Peer pressure• Stress, stressors• Home
Kreek MJ. Update on the Neurobiological Linkages between Pain and Chemical Dependency. Pain Management and Clinical Dependency. December 7-9, 2000.Gardner E. Neurophysiology of Chemical Dependence. Pain Management and Clinical Dependency. December 7-9, 2000.
Adapted with permission Webster publication pending
• Approximately 50%• Many polymorphisms• Comorbidity with
mental disorders
Genetics
Kreek MJ. Update on the Neurobiological Linkages between Pain and Chemical Dependency. Pain Management and Clinical Dependency. December 7-9, 2000.Gardner E. Neurophysiology of Chemical Dependence. Pain Management and Clinical Dependency. December 7-9, 2000.
Adapted with permission Webster publication pending
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Big Tent - Mental health; addictions; children to older adults; not for profits, government, and peer run; housing, and school and employment services; hospital and community based; prevention, treatment, and recovery supports.
The National Council for Behavioral Health The National Council for Behavioral Health
• Serving 10 million + adults, children and families with mental illnesses and/or addictions.
• Drive mental health and addictions policy, practice, and education initiatives that improve access to effective care
The National Council for Behavioral Health Who Are WeThe National Council for Behavioral Health Who Are We• Over 3,000 Members providing or supporting treatment for Mental
Illnesses and Addiction
• Services– Mental Health First Aid – over 1 million trained
– Center for Integrated Health Solutions (HHS)
– CDC National Networks
– Improving Business & Clinical Practices
– Advocacy and Policy
– Medical Director Institute
National Council Resources National Council Resources
• Dedicated Webpages
• Infographics
• Assessment Tools
• Training and consultation services
• Online Training
• Medical Directors Institutehttps://www.thenationalcouncil.org/opioid-use-disorders/
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How would you proceed if you inherited a patient prescribed a benzodiazepine for sleep and high-dose opioids after 9 spinal surgeries?
1. Continue both as prescribed2. Reduce the dosages of both medications3. Discontinue the opioid or benzodiazepine therapy 4. Consider an alternative medication, such as an
anticonvulsant or low-dose trazodone
Polling Question 8Polling Question 8
Polling Question 9Polling Question 9
In converting patients from one extended release opioid to another extended release opioid:
1. Use conversion tables to determine the exact starting dose of the new opioid
2. Adjust dose of new opioid every 24 hours3. Start the new ER opioid at a lower dose or dose as if the patient
is opioid naïve4. Never use IR opioids during an opioid rotation
Polling Question 10Polling Question 10
Co-prescribing of take-home naloxone should be considered for patients:
1. Taking high doses of opioids (≥MME per day)
2. With a legitimate medical need for analgesia, coupled with suspected/confirmed substance abuse
3. Undergoing opioid rotation
4. Discharged from emergency medical care following opioid intoxication/poisoning
5. All of the above
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Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)
Which of the following is true?1. All aberrant behaviors are signs of addiction
2. All aberrant behaviors are signs of abuse
3. All patients on opioids eventually show signs of aberrant behaviors
4. All people with an opioid addiction misuse/abuse opioids
5. All people who misuse/abuse opioids are also opioid addicts
Patient/provider counseling strategies include all of the following except:
1. Cognitive Behavioral Therapy
2. Motivational Interviewing
3. CAP Counseling
4. Individual Counseling
5. Community Reinforcement Approach
Polling Question 12
Evaluation RemindersEvaluation Reminders• The onsite evaluation form must be completed to receive credit
• If seeking MOC credit, in addition to completing the onsite evaluation form, please visit www.rockpointe.com/remsmoc (this link is also provided on page 4 of your syllabus)
• You must include your 3-digit keypad number on the evaluation form
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