Defensible, Rational, and Compassionate Pain Management

Transcription

1 Defensible, Rational, and Compassionate Pain Management Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. HEIT TEMPLATE.PPT 1 Board Certified in Internal Medicine and Gastroenterology/Hepatology Diplomate in Addiction Medicine Certified as a Medical Review Officer Chronic Pain Specialist Assistant Clinical Professor, Georgetown University Pain is the most common complaint for which individuals seek medical attention! HEIT TEMPLATE.PPT 2 Foley K. JAMA. 2000;283(1):115. Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 1

2 Chronic pain Pain that has outlived its usefulness Acute pain An adaptive, beneficial response necessary for the preservation of tissue integrity HEIT TEMPLATE.PPT 3 Oaklander AK. Neuroscientist. 1999;5(5): Barriers to Pain Management Addiction/Misuse/Diversion of Controlled Substances HEIT TEMPLATE.PPT 4 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 2

3 Addiction (Academic) Addiction is a primary, Chronic, i neurobiologic i disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired Control over drug use, Compulsive use, Continued use despite harm, and Craving (5 Cs). HEIT TEMPLATE.PPT 5 American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, Definitions Related to the Use of Opioids for the Treatment of Pain. 2001, American Academy of Pain Medicine: Glenview, IL. Five C s of the Disease of Addiction Chronic Control (lack of) Compulsive (use/behavior) Continued (use despite harm) Cravings HEIT TEMPLATE.PPT 6 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 3

4 Addiction (Practical) Charlie Parker,,g great jazz saxophonist, on addiction: You know, you can get the drugs out of your body, but you can t get them out of your brain. HEIT TEMPLATE.PPT 7 Physical Dependence Physical dependence is a state of adaptation that is manifested by a drugclass-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels of the drug, and/or administration of an antagonist HEIT TEMPLATE.PPT 8 American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, Definitions Related to the Use of Opioids for the Treatment of Pain. 2001, American Academy of Pain Medicine: Glenview, IL. Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 4

5 Physical dependence is neither sufficient nor necessary to diagnose addiction*: Physical dependence is a neuropharmacological phenomenon while addiction is both a neuropharmacological and behavioral phenomenon**. *HA Heit DL Gourlay. The Treatment of Chronic Pain in Patients with History of Substance Abuse JC Ballantyne, JP Rathmell, S M Fishman (eds) Bonica s Management of Pain, Fourth Edition. Lippincott Williams & Wilkins. Chapter 59. In Press HEIT TEMPLATE.PPT 9 **HA Heit Addiction, Physical Dependence, and Tolerance: Precise Definitions to Help Clinicians Evaluate and Treat the Patient with Chronic Pain. J Pain and Palliative Care Pharmacotherapy. March/April : Addiction: A Complex Brain Disease Environment Genetics Drug HEIT TEMPLATE.PPT 10 Wise, R. A. Addiction becomes a brain disease. Neuron 26(1): 27-33;2000 Leshner, A. I. Addiction is a brain disease, and it matters. Science 278(5335): 45-7;1997 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 5

6 Tolerance Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug s effects over time Key: All other conditions being constant BAD: Disease or syndrome is progressing GOOD: Functional activity is increasing HEIT TEMPLATE.PPT 11 American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, Definitions Related to the Use of Opioids for the Treatment of Pain. 2001, American Academy of Pain Medicine: Glenview, IL. History of AA AA/NA compatible with treatment of all medical and mental disorders Should be considered essential in treatment of addictive disorders HEIT TEMPLATE.PPT 12 John Chappel, MD, FASM, Professor Emeritus, University of Nevada at Reno ASAM Review Courses on the 12-Step Programs Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 6

7 Prevalence of Addiction in the General Population Approximately 10% (3% - 16%) Relapse rate with long-term opioid use is unknown HEIT TEMPLATE.PPT 13 Portenoy RK, Savage SR. J Pain Sympt Manage. 1997;14(3):S Opioid Treatment for Pain and Addiction Addiction to opioids in the context of pain treatment has been reported to be rare in those with no history of addictive disorders Portenoy, R.K., Savage, S.R. J of Pain and Symptom Management. 14 (3 )(Suppl.) Sept HEIT TEMPLATE.PPT 14 Fishbain DA, Cole B et al. Pain Medicine 9(4): 2008; Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 7

8 Iatrogenic Addiction Occurs when a patient, with a negative personal or family history for alcohol or drug addiction or abuse, is appropriately prescribed a controlled substance and subsequently in the therapeutic course meets the diagnostic criteria for addiction to that substance. HEIT TEMPLATE.PPT 15 HA Heit, DL Gourlay. The Treatment of Chronic Pain in Patients with History of Substance Abuse. In S M Fishman, JC Ballantyne, JP Rathmell, (eds). Bonica s Management of Pain, Fourth Edition. Philadelphia: Lippincott Williams & Wilkins, 2010: Choice of Opioids for the Treatment of Acute, Chronic or Acute Pain Superimposed on Chronic Pain Long-acting opioids/cr/mr/sr opioids IR opioids RO opioids HEIT TEMPLATE.PPT 16 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 8

9 Pharmacokinetics of Drugs Drug Absorption Distribution Binding (or distribution) in tissue Biotransformation Excretion What the body does to the drug ASAM. Principles of Addiction Medicine. Second Edition. Graham A, Shultz T (eds). 1998; HEIT TEMPLATE.PPT 17 Pharmacodynamics of Drugs Drug Mechanism by which drugs produce their effect What the drug does to the body ASAM. Principles of Addiction Medicine. Second Edition. Graham A, Shultz T (eds). 1998; HEIT TEMPLATE.PPT 18 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 9

10 Pharmacogenetics of Drugs Genetic factors regulating the pharmacokinetics and pharmacodynamics of opioids contribute to variability in patient or group response Drug efficacy Drug safety/side effects The patient s response to a given drug is not known until after it is given Benefit or adverse reaction? HEIT TEMPLATE.PPT 19 Somogyi AA, Barratt DT, et al Clin Pharmacol Ther. 2007;81(3): Examples: Pharmacogenetics of Drugs HEIT TEMPLATE.PPT 20 Methadone Half-life life is hours Mark individual variation Extensive biotransformation in the liver Cytochrome P- 450 Enzyme System CYP 3A4 is main subtype enzyme» Atiit Activity can vary by as much as 50f 50-fold» Unpredictable in metabolism, effects, and side effects Inturrisi C Clinical Pharmacology of Opioids for Pain The Clinical Journal of Pain, 18(4);Supplement 2002, S1-11 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 10

11 Clinical Pearl of Prescribing of Methadone Deaths occur most often in the first 14 days Initial dose too high? Titrated up too fast? Drug-drug interaction? Be conservative Stabilize Then titrate t to effect Methadone has no sense of humor HEIT TEMPLATE.PPT 21 Weschules DJ, Baib KT et al Actual and Potential Drug Interactions Associated with Methadone Pain Medicine 9(30); 2008: Common Reward Pathway: Mesocorticolimbic Dopamine System HEIT TEMPLATE.PPT 22 Neuroanatomy and physiology of the brain reward system in substance abuse. Available at: Accessed April 10, Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 11

12 Properties of Medications Going Through the Common Reward Pathway Pharmacokinetic and pharmacodynamic properties Faster speed of dopamine elevation "Faster diminution of dopamine elevation." Positive reinforcement In genetically susceptible individuals "Slower speed of dopamine elevation "Slower diminution of dopamine elevation. Lack of positive reinforcement Volkow ND, Ding Y-S, et al. Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Archives of General Psychiatry 52: , HEIT TEMPLATE.PPT 23 WiseRA,NewtonP,etal. Fluctuations in nucleus accumbens dopamine concentration during intravenous cocaine self-administration in rats. Psychopharmacology 120:10-20, Treating Persistent Pain With Opioids: Theory Oral Patient Controlled Analgesia [OPCA] Minimum Effective Analgesic Concentration (MEAC) HEIT TEMPLATE.PPT 24 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 12

13 Opioid Blood Levels in Pain Management Chronic pain syndromes Opioids adjusted to just above the blood levels that relieves pain (MEAC) No euphoria Achieve functional goals HEIT TEMPLATE.PPT 25 Breakthrough Pain Transitory exacerbation of pain with relatively stable and adequately controlled baseline pain Incident pain End of dose pain Prevalence varies between 40 86% Usually lasts less than one hour HEIT TEMPLATE.PPT 26 Zeppetella, G. et al J Pain and Symptom Man. Vol.20 No. 2 August Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 13

14 Titrate to Effect All substances are poisons. The right dose differentiates a poison and a remedy. Paracelsus, AD HEIT TEMPLATE.PPT 27 Goals of Treating Chronic Pain Based on Patient Evaluation Decrease pain Increase function Use medications that do not have unacceptable side effects HEIT TEMPLATE.PPT 28 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 14

15 No Pain Mild Pain Moderate Pain Severe Pain Very Severe Worst Possible HEIT TEMPLATE.PPT 29 One Drink: 12 oz Beer = 5 oz Wine = 1.5 oz Liquor (80 proof) Alcohol Alert. April 2005:65 U.S. Dept. of Health & Human Services NIH,NIAAA HEIT TEMPLATE.PPT 30 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 15

16 CAGE Questionnaire - AID Have you felt the need to Cut down on your drinking (or drug use)? Have people Annoyed you by criticizing your drinking (or drug use)? Have you ever felt bad or Guilty about your drinking (or drug use)? Have you ever needed an Eye-opener the first thing in the morning to steady your nerves or get rid of a hangover? HEIT TEMPLATE.PPT 31 Fiellin DA, et al. Ann Intern Med. 2000;133(10): Sensitivity and Specificity of CAGE Questionnaire Two out of four questions positive on CAGE questionnaire* Current diagnosis of alcohol misuse or dependency Sensitivity 77% - 94% Specificity 79% - 97% NIAAA and NIH recommends using the CAGE questionnaire** *Fiellin DA, et al. Ann Intern Med. 2000;133(10): HEIT TEMPLATE.PPT 32 **Alcohol Alert. April 2005:65 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 16

17 Stratifying Risk: Opioid Risk Tool Five-question clinical interview to assess patients Specifically developed to screen patients with chronic pain who will be using opioids Quantifies the level of risk for patient Three risk categories Low: 0-3 points Moderate: 4-7 points High: 8 points and above Webster, L.R. and R.M. Webster, Predicting aberrant behaviors in opioidtreated patients: preliminary validation of the Opioid Risk Tool. Pain Med, (6): p HEIT TEMPLATE.PPT 33 d FEMALE MALE Family history of substance abuse Alcohol 1 3 Illegal drugs 2 3 Prescription drugs 4 4 Personal history of substance abuse Alcohol 3 3 Illegal drugs 4 4 Prescription drugs 5 5 Age (if between 16-45) 1 1 History of preadolescent sexual abuse 3 0 Psychological disease Attention deficit disorder, Obsessive-compulsive Disorder, bipolar, schizophrenia 2 2 Depression 1 1 Scoring Totals: Treatment Agreements Treatment agreements are becoming more popular, especially for patients for whom controlled substances are being considered A treatment agreement is strongly recommended by the Federation of State Medical Boards, especially in those patients identified as high-risk Treatment agreements should be readable, reasonable and flexible HEIT TEMPLATE.PPT 34 Model Policy for the Use of Controlled Substances for the Treatment of Pain. Policy Statement: Federation of State Medical Boards of the United States, Inc; 2004 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 17

18 Creating and Implementing Treatment Agreements Treatment agreements Can improve the therapeutic relationship Must be based on mutual trust and honesty Should be part of an environment of care that emphasizes truthful, open dialogue A treatment agreement should not be called a contract A contract suggests a legally binding document This is not consistent with patient-centered care HEIT TEMPLATE.PPT 35 HA Heit, DL Gourlay. The Treatment of Chronic Pain in Patients with History of Substance Abuse. In S M Fishman, JC Ballantyne, JP Rathmell, (eds). Bonica s Management of Pain Fourth Edition. Philadelphia: Lippincott Williams & Wilkins, 2010: Creating and Implementing Treatment Agreements Purpose of agreement To facilitate and document informed consent Patient education The risk/benefits of the proposed treatment plan Potential consequences of agreement departures Establishes the responsibilities and expectations of physician-to-patient and patient-to-physician HEIT TEMPLATE.PPT 36 HA Heit, Creating and Implementing Opioid Agreements. Disease Management Digest, (1): p. 2-3 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 18

19 Creating and Implementing Treatment Agreements Establishes boundaries and consequences for aberrant behavior including opioid misuse, abuse or diversion Noncompliance with the agreement can aid in the diagnoses of the disease of addiction or substance abuse relapse This could require a change in the treatment plan HEIT TEMPLATE.PPT 37 HA Heit. Creating and Implementing Opioid Agreements. Disease Management Digest, (1): p. 2-3 Will versus May Avoid using absolute terms in your agreement such as will or shall as opposed to may This basic terminology gives the clinician the flexibility to make a patients-centered decision once more information is obtained HEIT TEMPLATE.PPT 38 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 19

20 Universal Precautions in Pain Medicine The term Universal Precautions originated from the infectious disease model Careful 10-point assessment of all persistent pain patients within the biopsychosocial model Appropriate boundary setting before writing the first prescription Triage scheme for estimating risk for management and referral By using this approach to the pain patient t Stigma can be reduced Patient care improved HEIT TEMPLATE.PPT 39 Overall risk of pain management be reduced Gourlay D, Heit HA et al. Pain Med. 2005;6(2): Universal Precautions in Pain Medicine 1. Diagnosis with appropriate differential 2. Psychological assessment including risk of addictive disorders 3. Informed consent (verbal vs written/signed) 4. Treatment agreement (verbal vs written/signed) 5. Pre/post intervention assessment of pain level and function HEIT TEMPLATE.PPT 40 Gourlay D, Heit HA et al. Pain Med. 2005;6(2): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 20

21 Universal Precautions in Pain Medicine 6. Appropriate trial of opioid therapy +/- adjunctive medication 7. Reassessment of pain score and level of function 8. Regularly assess the Four A s of pain medicine Analgesia, Activity, Adverse reactions, & Aberrant behavior 1 9. Periodically review pain diagnosis and comorbid conditions, including addictive disorders 10.Documentation HEIT TEMPLATE.PPT 41 1 Passik SD, Weinreb HJ. Adv Ther. 2000;17(2): Gourlay D, Heit HA et al. Pain Med. 2005;6(2): Universal Precautions: Triage It is important to continually reassess risk over time Group 1 Primary care patients Who is your patient? Group II Primary care patient with specialist support Who is our patient? Group III Specialty care patients HEIT TEMPLATE.PPT 42 Who is my patient? Gourlay D, Heit HA et al. Pain Med. 2005;6(2): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 21

22 Purpose of Urine Drug Test Urine drug testing in clinical practice Consensual diagnostic test Full explanation to and for the benefit of the patient Assists in objective documentation of compliance with the mutually agreed upon treatment plan Aids in the diagnosis and treatment of the disease of addiction or drug misuse Advocate for the patient in family and social issues Not for forensics purposes DL Gourlay, HA Heit (co-authors), YH Caplan. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice. 4 th Edition. May HEIT TEMPLATE.PPT 43 HA Heit, D L Gourlay: Urine Drug Testing in Pain Medicine: J Pain Sympt Manage. 2004:27(3): Urine Drug Test Assess only the presence of a particular drug and/or metabolite in a specific concentration ti at a specific moment in time A A positive result does not diagnose Drug addiction Physical dependence Impairment DL Gourlay, HA Heit (co-authors), YH Caplan. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice. 4 th Edition. May HEIT TEMPLATE.PPT 44 HA Heit, D L Gourlay: Urine Drug Testing in Pain Medicine: J Pain Sympt Manage. 2004:27(3): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 22

23 Urine Drug Test Initial testing is done with class-specific specific immunoassay drug panels Typically do not identify individual drugs within a class This is followed by a technique such as gas chromatography/mass spectrometry (GC/MS) To identify or confirm the presence or absence of a specific drug and/or its metabolites Must identify the specific opioid in a pain practice DL Gourlay, HA Heit (co-authors), YH Caplan. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice. 4 th Edition. May HEIT TEMPLATE.PPT 45 HA Heit, D L Gourlay: Urine Drug Testing in Pain Medicine: J Pain Sympt Manage. 2004:27(3): Immunoassay Drug Testing Opiates Responsive for natural opioids such as morphine and codeine Does not distinguish which one is present Low or no sensitivity for semisynthetic / synthetic opioids Semisynthetic: oxycodone, hydrocodone, hydromorphone, buprenorphine Synthetic: fentanyl and methadone A negative test does not exclude these analytes Unless the immunoassay is specific for that drug DL Gourlay, HA Heit (co-authors), YH Capaln. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice. 4 th Edition. May HEIT TEMPLATE.PPT 46 HA Heit, D L Gourlay: Urine Drug Testing in Pain Medicine: J Pain Sympt Manage. 2004:27(3): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 23

24 Metabolism of Opioids* codeine morphine** 6-MAM heroin hydrocodone hydromorphone oxycodone oxymorphone or 15%? *DL Gourlay, HA Heit (co-authors), YH Caplan. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice 4 th Edition. May **E.J. Cone, H.A. Heit, Y.H. Caplan, D. Gourlay: J. Anal. Toxicol.: Evidence of Morphine Metabolism to Hydromorphone in Pain Patients Chronically Treated with Morphine, 2006;30(1):1-5. HEIT TEMPLATE.PPT 47 Drug Amphetamines Barbiturates Benzodiazepines Cocaine Metabolite Ethanol Methadone Opiates Propoxyphene Cannabinoids Phencyclidine HEIT TEMPLATE.PPT 48 Approximate Retention Time 48 Hours Short acting (e.g., secobarbital) 24 hours Long acting (e.g., phenobarbital) 2-3 weeks 3 days if therapeutic dose ingested Up to 4-6 weeks after extended dosage (I.e., one or more years) 2-4 days (benzoyl ecgonine) 2-4 hours Approximately 3 days 2 days 6-48 hours Moderate smoker (4 times/week) 5 days Heavy smoker (smoking daily) 10 days Retention time for chronic smokers may be 20 days - 28 days Approximately 8 days Up to 30 days in chronic users (mean value = 14 days) Note: Interpretation of retention time must take into account variability of urine specimens, drug metabolism and half-life, patient s physical condition, fluid intake, and method and frequency of ingestion. These are general guidelines only. Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 24

25 HEIT TEMPLATE.PPT 49 Conclusions for UDTs Urine drug testing is important, but it s only one of many tools that should be included in a comprehensive risk management strategy All tests have strengths and limitations Unanticipated results should open up rather than close communication with the patient UDT in clinical management of pain is NOT about mistrusting the patient It s about providing optimum patient care DL Gourlay, HA Heit (co-authors), YH Caplan. Urine Drug Testing in Clinical Practice: The Art & Science of Patient Care. California Academy of Family Practice. 4 th Edition. May Buprenorphine and Pain Management: New Tricks for an Old Molecule HEIT TEMPLATE.PPT 50 HA Heit, DL Gourlay. Buprenorphine: New Tricks With an Old Molecule for Pain Management. The Clinical J Pain. February 2008; 24(2): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 25

26 Federal Regulations Drug Addiction Treatment Act of 2000 Office-based opioid treatment (OBOT) S/L Buprenorphine with or without naloxone Prescribed by certified and specially trained physicians Has received a waiver from the requirement to register as an NTP from the Center for Substance Abuse Treatment (CSAT) of the Substance Abuse and Mental Health Services Administration (SAMHSA) NTP = narcotiv treatment plan United States Department of Health and Human Services, SAMHSA. Drug Addiction Treatment Act of 2000 (DATA). Accessed June 3, 2007 at: HEIT TEMPLATE.PPT 51 Can One Use S/L Buprenorphine with or without Naloxone for Analgesia? The off-label use of the sublingual formulations buprenorphine with or without naloxone for the treatment of pain is not prohibited under DEA requirements One does not need a wavier from CSAT but a valid license to prescribe a schedule III controlled substance (CS) DEA = Drug Enforcement Agency Heit HA, Covington E, Good PA (Former Chief Liaison and Policy Section Office of Diversion Control): Dear DEA. Pain Medicine, 2004, Vol.5, No. 3: HEIT TEMPLATE.PPT 52 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 26

27 Buprenorphine: Old: Buprenex Injectable New: S/L Buprenorphine with or without Naloxone HEIT TEMPLATE.PPT 53 Buprenorphine Semi-synthetic Highly lipophilic opioid id Partial mu agonist Kappa antagonist Dissociates very slowly from opioid receptors High affinity Heel RC, et al. Drugs. 1979;17: ; Boas RA, Villiger JW. Br J Anaesth. 1985;57: HEIT TEMPLATE.PPT 54 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 27

28 Buprenorphine HEIT TEMPLATE.PPT 55 Agonist substitute for the disease of opioid addiction Upper mu limit of ~60 mg equivalents of methadone (~240 mg of MS) Blockade of receptor persists for more than 24 hours 1 Combine with naloxone in a 4:1 ratio may reduce euphoria with IV misuse 2 Average dose of buprenorphine with or without naloxone as an agonist for maintenance therapy 8 to 32 mg/day MS = morphine sulfate 1 Boas RA, Villiger JW. Br J Anaesth. 1985;57: Comer SD, Collins ED. J Pharmacol Exp Ther. 2002;303: HEIT TEMPLATE.PPT 56 Agonist Therapy with S/L Buprenorphine and Pain Effective analgesia is achieved at relatively low receptor occupancy % Degree of analgesia is not related to plasma concentration of the drug 2 The dissociation at the receptor site will lag behind plasma concentration 0.4 mg of buprenorphine = mg of morphine At least 30 times more potent than morphine 3 Analgesic effects mg 1 Tyers MB. Br J Pharmacol. 1980;69: Boas RA, Villiger JW. Br J Anaesth. 1985;57: Budd K. Anaesthesia. 1981;36: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 28

29 Opioid Tolerance One mu gene for opioids At least (?) genetic versions of the mu receptors Tolerance 10-20(?) mu receptor sites I I I I I I I I I I I I I I I I I I Opioid A Opioid B Drug A and B have incomplete cross tolerance Neither Drug A or B occupies this genetic version of the mu receptor sites Drug A and B are tolerate to the same mu receptor sites Pasternak GW. The Neuroscientist. 2001;7: HEIT TEMPLATE.PPT 57 H A Heit IP&CD conference, June, 2007 HEIT TEMPLATE.PPT 58 Agonist Therapy with S/L Buprenorphine and Pain Effective analgesia is achieved at relatively low receptor occupancy % Degree of analgesia is not related to plasma concentration of the drug 2 The dissociation at the receptor site will lag behind plasma concentration 0.4 mg of buprenorphine = mg of morphine At least 30 times more potent than morphine 3 Analgesic effects mg 1 Tyers MB. Br J Pharmacol. 1980;69: Boas RA, Villiger JW. Br J Anaesth. 1985;57: Budd K. Anaesthesia. 1981;36: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 29

30 Agonist Therapy with S/L Buprenorphine and Pain High receptor site affinity may interfere with effectiveness of other full mu analgesics Not easily reversed with antagonist agents HEIT TEMPLATE.PPT 59 HA Heit, DL Gourlay. Buprenorphine: New Tricks With an Old Molecule for Pain Management. The Clinical J Pain. February 2008; 24(2): Agonist Therapy with S/L Buprenorphine and Pain Partial l mu agonists Contraindicated in opioid dependent patients May precipitate withdrawal Secondary to strong affinity to the mu receptor HEIT TEMPLATE.PPT 60 Sporer KA. Ann Emerg Med. 2004;43: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 30

31 Agonist Therapy with S/L Buprenorphine and Pain There may be a possible risk of mu receptor up regulation 2 to 3 days after discontinuing S/L buprenorphine May result in increased sensitivity to a full mu agonist treatment Therefore, carefully titrate the full mu agonist to effect to prevent withdrawal and treat the pain HEIT TEMPLATE.PPT 61 HA Heit, DL Gourlay. Buprenorphine: New Tricks With an Old Molecule for Pain Management. The Clinical J Pain. February 2008; 24(2): HEIT TEMPLATE.PPT 62 S/L Buprenorphine Pearls Starting S/L buprenorphine when a patient is physically dependent on a full opioid agonist Could precipitate acute withdrawal Dose limited for acute or chronic pain treatment 6-8 mg in a tid or qid dosing schedule is probably the maximum dose per day S/L buprenorphine may not be suitable in a patient requiring a large methadone dose Greater than 60 mg of methadone/day Simones S et al. Br J Gen Pract. 2005;55: ; Mattick RP, et al. Cochrane Database Syst Rev Accessed June 3, 2007 at: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 31

32 S/L Buprenorphine Pearls Chronic pain management 6-8 hour analgesic duration As with methadone tid or qid dosing OAT Stabilizing drug Long duration of action ( >24 h) qd dosing HEIT TEMPLATE.PPT 63 HA Heit, DL Gourlay. Buprenorphine: New Tricks With an Old Molecule for Pain Management. The Clinical J Pain. February 2008; 24(2): S/L Buprenorphine Pearls S/L buprenorphine full mu agonist Will not precipitate it t withdrawal Full mu agonist May precipitate withdrawal to S/L buprenorphine HEIT TEMPLATE.PPT 64 HA Heit, DL Gourlay. Buprenorphine: New Tricks With an Old Molecule for Pain Management. The Clinical J Pain. February 2008; 24(2): Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 32

33 Can You Treat Pain in a Patient Who is on OAT with S/L Buprenorphine? HEIT TEMPLATE.PPT 65 Anticipated Pain HEIT TEMPLATE.PPT 66 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 33

34 HEIT TEMPLATE.PPT 67 Agonist Therapy with S/L Buprenorphine and Pain Elective procedure/surgery (mild-to-moderate pain and not NPO) S/L Buprenorphine with or without naloxone Take the total qd dose of buprenorphine Give the total dose divided in tid or qid doses Titrate to effect with a maximum dose around 8 mg/dose If breakthrough medication is needed, use one with high receptor site affinity and potency Oral transmucosal fentanyl lozenges/tablets/film Hydromorphone PCA HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: Agonist Therapy with Buprenorphine and Pain Elective procedure/surgery (moderate-to to-severe pain and not tnpo) Discontinue S/L buprenorphine around three days before surgery Use full mu agonist such as methadone/mr/sr/ CR opioid Titrate the mu agonist to effect to prevent withdrawal and to the treat the pain If breakthrough medication is needed, use a IR full mu agonist HEIT TEMPLATE.PPT 68 HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 34

35 HEIT TEMPLATE.PPT 69 Agonist Therapy with S/L Buprenorphine and Pain Elective procedure/surgery (NPO) Discontinue S/L buprenorphine PCA with full mu agonist Titrate to effect to prevent withdrawal Then treat the pain with an opioid with high receptor site affinity and potency Fentanyl Hydromorphone» Second choice Avoid meperidine HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: Unanticipated Acute Pain HEIT TEMPLATE.PPT 70 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 35

36 Agonist Therapy with S/L Buprenorphine and Pain Acute pain patient on buprenorphine agonist therapy (mild- to-moderate t pain and not NPO) Divide S/L buprenorphine dose to tid or qid schedule Titrate to effect Up to 8 mg tid to qid of buprenorphine Limit of dose for pain? Alternative is to discontinue S/L buprenorphine Switch to full mu agonist if time permits Titrate the mu agonist to limit withdrawal Titrate to effect to treat the pain HEIT TEMPLATE.PPT 71 HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: HEIT TEMPLATE.PPT 72 Agonist Therapy with S/L Buprenorphine and Pain Acute moderate-to to-severe pain treated with IV opioids (NPO) Discontinue S/L buprenorphine PCA analgesic Titrate to effect to prevent withdrawal Then titrate to treat the pain Fentanyl» High receptor site affinity it and potency» May be easier to titrate Hydromorphone Avoid meperidine HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 36

37 Chronic Pain or Acute Pain Superimposed on Chronic Pain HEIT TEMPLATE.PPT 73 Agonist Therapy with S/L Buprenorphine and Pain (Mild-to-Moderate Pain) HEIT TEMPLATE.PPT 74 Acute pain superimposed on chronic pain Assumes S/L buprenorphine in divided doses was controlling pain Add IR/RO opioid with high receptor site affinity and potency Hydromorphone o o Oral transmucosal fentanyl lozenges/tablets/film Titrate to effect HA Heit, DL Gourlay. Buprenorphine in Pain and Addiction. In H Smith and SD Passik (eds). Pain and Chemical Dependency. New York: Oxford University Press, 2008: Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 37

38 Teamwork With the Dispensing Pharmacist The pharmacist is a critical member of the treatment team and the patients Circle of Care As such, an open dialog between prescriber and dispensing pharmacist will help minimize risk while enhancing patient care The unique role of the pharmacist may offer the prescriber valuable insights which could help to modify the treatment plan HEIT TEMPLATE.PPT 75 Wisdom From Lilly: Patient Assessment After placement of the Deep Brain Stimulator on December 19, 2007, I was walking hand in hand with my granddaughter ghter Lilly. She looks up at me and says: PopPop you are not crooked any more. Visual physical exam Your boo boo is getting better! Assessment of my pain generator That means you can play me with more right? Assessment of my functional activity HEIT TEMPLATE.PPT 76 Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 38

39 AA Serenity Prayer God, grant me the Serenity to accept the things I cannot change; Courage to change the things I can; and the WISDOM to know the difference. HEIT TEMPLATE.PPT 77 Conclusion Pain management Patient-centered Improving outcomes Focused on managing risk Defensible, Rational and Compassionate HEIT TEMPLATE.PPT 78 DL Gourlay, HA Heit Universal Precautions Revisited: Managing the Inherited Pain Patient Pain Medicine. 2009;10(S2):S115-S123. Howard A. Heit, M.D., F.A.C.P., F.A.S.A.M. 39