PHARMACOLOGY OF CHRONIC PAIN MANAGEMENT

1. PHARMACOLOGY OF CHRONIC PAIN MANAGEMENT April 15, 2011 Michael J. Schwartz, M.D. Founder & Director OKLAHOMA PainCare, Inc.

2. CHRONIC PAIN - CNS

3. PAIN ROADMAP • Noxious stimulus in periphery transduced into electrical activity • Bidirectional process with both ascending and descending inputs • Normal response is protective and adaptive • Persistent pain → maladaptive • Neuroplastic changes that affect pain perception • Ultimately pain sensations out of proportion

4. CHRONIC PAIN - CNS

5. Acute vs Chronic Pain

6. Pain-Sensing System Malfunction in Chronic Pain Normal Pain • Pain-sensing signals are initiated in response to a stimulus • They elicit a pain-relieving response Chronic Pain • Pain signals are generated for no reason and may be intensified • Pain-relieving mechanisms may be defective or deactivated

7. Pain-Sensing System Malfunction in Chronic Pain • Sensitization of peripheral nociceptors → ↑magnitude and speed • Hyperalgesia • Activation of low-threshold mechanreceptors • Allodynia • Touch → pain

8. Central sensitization • Loss of inhibitory effects of myelinated primary afferents • Reorganization of spinal cord connections after deafferentation • Spontaneous activity in deafferented spinal pain transmission neurons • Prolonged excitation or sensitization of spinal pain transmission neurons

9. CHRONIC PAIN Pain Sensing • Pain signals are generated without physiologic significance

10. CHRONIC PAIN • Pain signal outlived its use • Becomes faulty wiring • ‘Wind-up’ of the pain signal • Louder and faster • CNS sub-optimal pain perception & processing • No longer a healthy pain response

11. BASICS • The International Association for the Study of Pain (IASP) defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage” • Pain is the most common reason people seek medical attention • Pain is a ubiquitous phenomenon • The same set of circumstances can cause significant pain in one patient, and little or none in another • Pain is both a sensory and an emotional experience

12. HOUSE of PAIN • Pain is a dirty 4-letter word • HONESTY of patient and physician • Weakness • Suck it up; “buck-up” • Avoid responsibilities • Work, family dynamics, parenting • Worthless; guilt; ‘no way out’

13. Importance of Chronic Pain • When improperly managed, pain can lead to decreased productivity and diminished quality of life • Estimates show that chronic pain affects approximately 90 million Americans each year • The burden placed on our society in financial terms is tremendous! • Approximately ≥ $100 billion per year including medical expenses, lost wages, and decreased productivity

14. TYPES OF PAIN • Acute nociceptive • Inflammatory/joint • Hypersensitive response to tissue damage and inflammation • Visceral nociceptive • IBS; IBD; IC; Crohn’s; endometriosis; etc • Neuropathic • Constant alarm without emergency, maladaptive, spontaneous, flunctuating • DPN; vascular neuropathy; TGN; PHN; etc

15. Pain coaching Life counseling CBT; ACT Pain psychologist Sleep evaluation Rehabilitation Interventional Blocks SCS; IT pump Neurolytic procedures Pharmacology Opioid Non-opioid adjuvants SMRs; AEDs; SNRIs; SSRIs; NSAIDs (non-selective COX-I and selective COX-II; anxiolytics; hypnotics; dopaminergics; etc Medical Management of Chronic Pain

16. Pharmacologic options • Opioids • Non-opioid adjuvants: • Antidepressants (SNRIs & SSRIs) • Anticonvulsants (AEDs) • NSAIDs, • non-selective COX-I • selective COX-II • Local anesthetics • SMRs • -adrenergic agents • Topical agents

17. DEFINITIONS Physical dependence: normal adaptation to a drug-class • Abrupt cessation, rapid↓dose, antagonist, etc →withdrawal syndrome Tolerance: drug exposure → ↓effect over time Addiction: primary, chronic, neurobiologic DZ with genetic, psychosocial & environmental influences

18. DEFINITIONS Addiction behaviors: • Impaired control over drug use • Compulsive use • Continued use despite harm • Craving • ‘Mad, sad or glad’

19. DEFINITIONS Abuse: • Illegal drug use • Self-administration of meds for non-medical purpose • Altered state of consciousness • ‘Getting high’ • Go to Disney World without leaving the couch

20. DEFINITIONS Aberrant drug-use behavior: • Outside the boundaries of the agreed upon treatment plan established in the patient-physician relationship Misuse: • Use of medication for medical purpose other than as directed or as indicated, whether willful or unintentional, and whether harm results or not

21. DEFINITIONS Diversion: • Intentional transfer of a Controlled Dangerous Substance (CDS) medication for illegitimate use • Sell, trade, give, take, etc

22. HOUSE of PAIN • Pain patients practice to be worse • Pain Brain

23. Chronic pain circle

24. GOALS of the pharmacologic management of chronic pain Optimally contain the daily chronic pain Improved quality of life (QOL) • Improved function physically and emotionally Fewest adverse side effects (ASEs) Fewest cognitive side effects (CSEs)

25. Pharmacologic options • Opioids • Non-opioid adjuvants • Antidepressants (SNRIs & SSRIs) • Anticonvulsants (AEDs) • NSAIDs • Non-selective COX-I • Selective COX-II • Local anesthetics • SMRs • -adrenergic agents • Topical agents

26. OPIOIDS for daily use Extended-release preferred • Morphine • Oxycodone • Oxymorphine • Hydroxymorphine • Fentanyl • Buprenorphine

27. Immediate-release short-acting opioids (IRSAOs) AVOIDdaily use of repetitive doses • Increased need for dosage escalation • Increased risk of true addiction • Increased risk of cognitive and motor impairment • APAP combo meds →liver & renal toxicity

28. Long-acting opioid (LAO) Methadone • Unique characteristics • CAUTION! • For use only by clinicians familiar with its use and risks • A leading cause of inadvertent and accidental overdose and death

29. Methadone Must monitor: • K⁺, Na⁺⁺, Mg⁺⁺ • EKG • QT interval Dosing: • Q 6hr optimal – strict schedule

30. OPIOID POLICIES • Federal laws • State laws • Regulatory guidelines • Policy statements

31. MANAGING CHRONIC PAIN WITH OPIOIDS • Patient selection • One size does not fit all • Risk stratification • Informed consent and opioid management plan • Goals of treatment • Expectations • Risks and alternatives

32. MANAGING CHRONIC PAIN WITH OPIOIDS • Monitoring patients: • Level of function • Progress towards goals • Presence of adverse events • Compliance • Psychotherapeutic co-interventions • Driving and work safety • Breakthrough pain • Exit strategy

33. MANAGING CHRONIC PAIN WITH OPIOIDS • Monitoring patients: • 4 As • Analgesia • ADLs - level of function, progress towards goals • Adverse events – ASEs, CSEs • Aberrant medication use - compliance

34. PATIENT ASSESSMENT FOR OPIOID THERAPY • Chief complaint • Pain history • Pain medication history • Past history • Including psychiatric hx and substance use & abuse hx • Social history • Family history • Including psychiatric hx and substance use & abuse hx

35. PATIENT ASSESSMENT FOR OPIOID THERAPY • Physical examination • Features relevant to pain and substance use • Additional information: • Urine and/or serum drug test monitoring • Screening for risk of substance use or aberrant medication-use behavior • Outside medical records • Prescription monitoring reports (OBN PMP)

36. OPIOID RISK ASSESSMENT • Opioid Risk Test (ORT) • Screener and Opioid Assessment for Patient with Pain (SOAPP) • SOAPP-14, SOAPP-24, SOAPP-R (revised) • Current Opioid Misuse Measure (COMM) • Zung, HAM-D, HAM-A, etc • Other non-opioid eg. Epworth

37. Aberrant Drug-Taking Behaviors Probably more predictive: • Selling scripts • Prescription forgery • Stealing or borrowing meds • Obtaining scripts from nonmedical sources • Concurrent abuse of related illicit meds • Multiple unsanctioned dose escalations • Recurrent script or med losses

38. Aberrant Drug-Taking Behaviors Probably less predictive: • Aggressive complaining about pain intensity and need for higher doses • Drug hoarding • Requesting specific medications • Obtaining CDS meds from other medical source • Unsanctioned dose escalation 1-2 times • Use of med to tx other symptoms • Reporting psychic effects of meds

39. Opioid conversions Equianalgesic dose calculations of different opioids • Reduce amount by ≥ 50% • Methadone different animal • Propoxyphene off market • FDA banned in Feb 2011 • Meperidine not for chronic pain management • “Demerol blizzard”

40. Defects in Opioid Metabolism Genetic screening • Cytochrome 450 (CYP 450) • CYP 2D6; CYP 2C9 • Most common defect CYP 3A4 • Testing not available • Why? • Avoid drug interactions (ADRs) • High-dose opioids • Unusual or expensive regimen

41. Defects in Opioid Metabolism • Suspect genetic metabolic defect if when opioid blood levels are very high or very low • Screening costly • Insurance says “experimental”

42. Exit Strategy for discontinuing opioid therapy • Opioid risk-benefit ratio • Intolerable side effects • Opioid rotation failure • Deterioration of QOL • Poor compliance • Aberrant med-use behavior • PPP – mean disagreeable pts

44. American Academy of Pain Managementhttp://www.aapainmanage.org/ - The American Academy of Pain Management is a non-profit organization that educates clinicians about pain and its management through an integrative interdisciplinary approach. American Academy of Pain Medicinehttp://www.painmed.org/ - The American Academy of Pain Medicine (AAPM) is the medical specialty society representing physicians practicing in the field of Pain Medicine American Chronic Pain Associationhttp://www.theacpa.org/ - To facilitate peer support and education for individuals with chronic pain and their families so that these individuals may live more fully in spite of their pain. American Pain Foundationhttp://www.painfoundation.org/ - NPO site that contains newsletter, downloadable patient resources (MS Word), and discussion boards. American Pain Society (APS)http://www.ampainsoc.org/ - Multidisciplinary, scientific and professional society. Contains announcements of positions, fellowships, grants, etc. American Society for Action on Painhttp://www.druglibrary.org/schaffer/asap/ - Patient organization interested in pain management issues/concerns. American Society for Pain Management Nursinghttp://www.aspmn.org/ - Organization of professional nurses that provide support to pain management. Contains announcements and an e-mail list. American Society of Addiction Medicinehttp://www.asam.org/ - Site dedicated to increasing the quality of addiction treatment. Includes certification, publications, and conference info. American Society of Regional Anesthesia and Pain Medicine http://www.asra.com/ - Member info, web-based CME, and fellowship opportunities are some of the highlights. Drugs4Realhttp://www.drugs4real.com/ - An interactive prevention program that teaches adolescents about the influence of alcohol and drugs and strengthens their commitment to avoid taking these substances. International Association for the Study of Pain (IASP)http://www.iasp-pain.org/ - NPO consisting of health professionals. Access to web-based learning, grants/awards, opportunities, etc. National Pain Foundationhttp://www.painconnection.org/ - A non-profit organization that provides education and support resources for people in chronic pain, their families, and physicians. Pain & Policy Studies Group, University of Wisconsinhttp://www.painpolicy.wisc.edu/ - The Pain & Policies Studies Group website contains a wealth of information about pain relief and public policy, both domestic and international. Pain Medicine Newshttp://www.painedu.org/www.painmedicinenews.com - Pain Medicine News has timely frequently updated content designed to meet the needs of the spectrum of physicians involved in pain medicine. Pain Treatment Topicshttp://www.pain-topics.org/ - With pharmaceutical company support, a noncommercial resource for healthcare professionals, providing clinical news, information, research, and education for a better understanding of evidence-based pain-management practices. Pain.comhttp://www.pain.com/ - Free web-based CME, articles, and pain journals (all free to view). PainACTIONhttp://www.painaction.com/ - An online self-management program for pain patients, featuring individually-customized information, interactive skill-building tools, monthly newsletter and opportunities to share self-management tips. PainLinkhttp://www.edc.org/PainLink/ - Archived website that still contains applicable information. The Mayday Fundhttp://www.painandhealth.org/ - Extensive listing of internet resources relating to pain and pain management. Wisconsin Pain Initiativehttp://www.wisc.edu/wcpi - Grassroots organization of professionals that includes: pain management laws (WI), patient/public/professional education. Chronic Pain Resources

45. OPIOIDOLOGY • Universal Precautions for Opioid Pain Management • Federation of State Medical Licensure Boards • Guidelines of American Pain Society & American Academy of Pain Medicine • PHARMACOLOGY

46. Michael J. Schwartz, M.D. • OKLAHOMA PainCare, Inc. • drschwartzopc@coxinet.net • Opinions are like rear-ends – we’ve all got one – “and now I’ve shown you mine”