Addiction Issues in Pain Management: From Opium to Buprenorphine

1. Addiction Issues in Pain Management:From Opium to Buprenorphine Challenges of Managing Pain Symposium UCSF Medical Center at Mount Zion Howard Kornfeld, M.D. June 7, 2007

2. Understanding addiction issues in pain management opens a window into 6,000 years of human experience with opium 100 years of opiate prohibition and the stigmatization of addiction 75 years of analgesic research at the NIH 35 years of evolving knowledge about both endogenous opioid systems and the pharmacology of buprenorphine

3. A History of OpiumMartin Booth, Opium, A History, St. Martin�s Press, New York, 1996 4th millennium BC, Switzerland Preserved remains of cultivated poppy seeds and pods discovered in the sites of Neolithic pile-dwelling village. 3400 BC, Mesopotamia Opium poppy cultivated in the Tigris-Euphrates river systems. The world�s first civilization and agriculturists, the Sumerians, used ideograms for the poppy that translate to �joy plant.� 200 AD, Greece Themes of opium in Greek legends and mythology. 800, AD Arab traders introduced opium to Persia, India and China. 980-1037, Persia Ibsina Avicenna, poet, intellectual and scholar, known as �the prince of physicians,� praises the poppy. He dies at fifty-eight, overdosing on opium and wine. 15th century, Europe Columbus, Casco de Gama and Magellan are all requested to find opium on their journeys. 1520, Europe Philippus Aureolus Theophrastus Bombastus von Hohenheim, known as Paracelsus, calls opium the �stone of immortality� and introduces the Latin word, laudanum, meaning �worthy of praise� in reference to opium.

4. A History of Opium 1600s, England Sydenham, known as the English Hippocrates says, among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium (Goodman and Gilman�s The Pharmacological Basis of Theraputics, Tenth Edition edited by Joel G. Hardman, et al) 1775-1835, Europe The Romantic Revival. For many of the great thinkers and poets of this era, opium and the liberation of thought it produced were key in the development of Romantic ideology. Late 1800s The Opium Wars 1914, United States The Harrison Narcotic Act is passed, eventually leading to the prosecution of over 25,000 doctors for prescribing narcotics to addicts.

5. opiophobia unreasonable & harmful fear of opiates leading to countless cases of untreated pain in the 20th century opiophilia unwarranted & harmful attraction to opiates leading to tremendous, unsupervised over-use of opiates in the 19th century opiognosis broad & inclusive knowledge of opiates leading to its wise use

6. Just as the actions of the legislative system contributed to the climate of opiophobia a century ago, now the California legislature mandates that physicians bring their often incomplete knowledge of pain treatment and opioid pharmacology up to current scientific levels.

7. Consequences of Opiophobia/Opiophilia Widespread under treatment of pain in the 20th century; the first report in the literature of treatment of non-malignant pain with long term opiates was made in 1986. Portenoy, RK & Foley, K,M Chronic use of analgesics in non-malignant pain: 38 cases, Pain. 1986 May;25(2):171-86 Iatrogenic generation of addiction 1.5 million arrests per year enforcing drug prohibition laws and 300,000 incarcerated for breaking drug laws 28,000,000 people use an illicit drug at least once a year Domestic violence linked to illicit drugs International violence (terrorism) linked to illicit drugs Stigmatization of addicts and addiction treatment

8. Possibilities of Opiognosis Knowledge of opium derived drugs is key to understanding other substance use problems in the illicit category Strengthen our capacities to deal with alcohol and nicotine addictions Prepare physicians and health professionals to be opinion leaders and educators for the general public Improve pain treatment and decrease the incidence and morbidity of opioid induced/aggravated pain syndromes

9. Addiction: The 5 C�s Continued use despite adverse consequences Chronic Control, loss of Compulsive Craving

10. DSM-IV: Criteria for Substance Dependence

11. A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by 3 (or more) of the following, occurring at any time in the same 12-month period Tolerance, as defined by either of the following: a need for markedly increased amounts of the substance to achieve intoxication or desired effect markedly diminished effect with continued use of the same amount of the substance Withdrawal, as manifested by either of the following: the characteristic withdrawal syndrome for the substance the same (or a closely related substance is taken to relieve or avoid withdrawal symptoms The substance is often taken in larger amounts over a longer period than was intended There is a persistent desire or unsuccessful efforts to cut down or control substance use 5. A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), using the substance (e.g., chain-smoking), or recovering from its effects 6. Important social, occupational, or recreational activities are given up or reduced because of substance use 7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition that an ulcer was made worse by alcohol consumption) DSM-IV, 1994DSM-IV, 1994

12. Correlations: the 5 C�s of Addiction and the DSM-IV Chronic- A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by 3 (or more) of the following, occurring at any time in the same 12-month period Loss of Control- The substance is often taken in larger amounts over a longer period than was intended Loss of Control/Craving- There is a persistent desire or unsuccessful efforts to cut down or control substance use Continued use despite adverse consequences/Compulsive- A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), using the substance (e.g., chain-smoking), or recovering from its effects Continued use despite adverse consequences- Important social, occupational, or recreational activities are given up or reduced because of substance use Continued use despite adverse consequences/Compulsive- The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition that an ulcer was made worse by alcohol consumption)

13. Pain Treatment: The 4 A�s of Assessment Analgesic? Adverse Effects? Activities of Daily Life? Aberrant Behaviors?/Predictors of Opioid Misuse

14. Opioid Chronic Pain Guidelines: Aberrant Behaviors & Predictors of Opioid Misuse From the VA/DOD Opioid/Chronic Pain GuidelinesJune, 2003

15. I. Illegal or Criminal Behavior Diversion (sale of provision of opioids to others) Prescription forgery Stealing or �borrowing� drugs from others

16. II. Dangerous Behavior Motor vehicle crash/arrest related to opioid or illicit drug or alcohol intoxication or effects Intentional overdose or suicide attempt Aggressive/threatening/belligerent behavior in the clinic

17. III. Behavior that Suggests Addiction Use of prescription medications in an unapproved or inappropriate manner (such as cutting time-release preparation, injecting oral formulations and applying fentanyl topical patches to oral or rectal mucosa) Obtaining opioids outside of medical settings Concurrent abuse of alcohol or illicit drugs Repeated requests for dose increases or early refills, despite the presence of adequate analgesia Multiple episodes of prescription �loss� Repeatedly seeking prescriptions from other clinicians or from emergency rooms without informing prescriber, or after warnings to desist Evidence of deterioration in the ability to function at work, in the family, or socially, which appears to be related to drug use Repeated resistance to changes in therapy despite clear evidence of adverse physical or psychological effects from the drug Positive urine drug screen-other substance use

18. IV. Aberrant Behavior that Requires Attention Aggressive complaining about needing more of the drug Drug hoarding during periods of reduced symptoms Requesting specific drugs Openly acquiring similar drugs from other medical sources Unsanctioned dose escalation or other noncompliance with therapy on one or two occasions Unapproved use of the drug to treat another symptom Reporting psychic effects not intended by the clinician Resistance to a change in therapy associated with �tolerable� adverse effects, with expressions of anxiety related to the return of severe symptoms Missing appointment(s) Not following other components of the treatment plan (physical therapy, exercise, etc.)

19. Forms of Buprenorphineavailable in the United States Buprenex (buprenorphine HCI) Injectable. Supplied in clear glass snap-ampuls of 1ml (0.3mg buprenorphine) for parenteral use. Suboxone (buprenorphine HCI and naloxone HCI dihydrate sublingual tablets) Hexagonal orange tablets containing 2mg & 8mg buprenorphine with 0.5mg or 2mg naloxone, respectively. Subutex (buprenorphine HCI) Sublingual. Oval white tablets containing 2mg & 8mg buprenorphine. compounded gelatin troche, wide range of strengths from 0.1mg to 4mg sublingual.

20. Analgesic Equivalence Parenteral, non tolerant subject, 0.3mg buprenorphine equivalent to 10mg morphine sulfate. Buprenorphine sublingual approximately 50% absorption Morphine oral approximately 33% absorption Therefore 30mg morphine PO roughly equivalent to 0.6mg buprenorphine SL.

21. Actions & Selectivities of Some Opioids at the Various Opioid Receptor Classes

22. Managing Pain Medicine in RecoveryDr. Stephen F. Grinstead, from Addiction Free Pain Management During early recovery postpone non-urgent dental work (except preventative or restorative) and elective surgical procedures requiring mind-altering medications. When you do need to be on medication, make sure that an addiction medicine practitioner/ specialist is used for consultation and/or prescribing that medication If you need to be on medication, have your sponsor, significant other, or an appropriate support person hold and dispense the medication. Keep only a 24-hour supply available (unless this is a chronic condition, then other precautions must be developed). Consult with an addiction medicine practitioner/specialist about using non-addictive medications such as an anti-inflammatory, or other over-the-counter analgesics. Be open to exploring all non-chemical pain management modalities. Some of the more common ones are acupuncture, chiropractic, physical therapy, massage therapy, and hydrotherapy. In addition, identifying and managing uncomfortable emotions may also decrease your pain significantly. Be aware of your stress levels and have a stress management program such as meditation, exercise, relaxation, music, etc. in place. If you lower your stress, you will usually lower your pain as a result. Take personal responsibility to augment your support group meetings in order to decrease isolation as well as urges and cravings Inform all of your health care providers about being in recovery and be aware of the importance of consulting with an addiction medicine practitioner/specialist in the event that mind-altering medication is needed.

23. Do not overwork, especially if you are in pain or sick. Add one extra day off to your return to work plan to avoid fatigue and promote healing. Be open and aware of the cross-addiction concept. Decline "helpful" offers to use someone else�s prescriptions. Any psychoactive chemical could trigger a relapse of your addiction because all mood-altering drugs enter the limbic system as Dopamine. This explains why non-poly-addicted alcoholics can relapse to alcohol after receiving opiates. As depression is common for people with chronic pain, consider the possibility of taking appropriate antidepressants if needed. Be aware of the importance of proper nutrition and exercise as a vital part of chronic pain recovery. Stretch slowly at first, then structure progressive walking at least once a day, or twice if necessary to complete the designated distance. Increase the distance as you are able. Add strengthening exercises if cleared by your health care provider. Remember, protein assists the healing of injuries, therefore; it is important to create a nutrition plan for tissue repair. Explore your past beliefs and role models from childhood regarding pain and pain management. Look for healthy role models for pain management in recovery.

24. Naltrexone as Adjunct to Buprenorphine Use Naltrexone shortened opioid detoxification with buprenorphine A. Umbricht, et al, NIDA Intramural Research Program Drug and Alcohol Dependence 56 (1999) 181-190

25. Anti-hyperalgesia properties of buprenorphineRusso, MA, Pain, 2005 Nov; 118 (1-2): 15-22

26. Training HIV Physicians to Prescribe Buprenorphine for Opioid DependenceSullivan, et al, Substance Abuse, 2006l 27(3):13-18

27. The Twelve Steps of Alcoholics AnonymousAlcoholics Anonymous, Fourth Edition We admitted we were powerless over alcohol-that our lives had become unmanageable. Came to believe that a power greater than ourselves could restore us to sanity. Made a decision to turn our will and our lives over to the care of God as we understood Him. Made a searching and fearless moral inventory. Admitted to God, to ourselves, and to another human being the exact nature of our wrongs. Were entirely ready to have God remove all these defects of character. Humbly asked God to remove our shortcomings. Made a list of all persons we had harmed and became willing to make amends to them all. Made direct amends to such people wherever possible, except when to do so would injure them or others. Continued to take personal inventory and when we were wrong promptly admitted it. Sought through prayer and meditation to improve our conscious contact with God, as we understood Him, praying only for knowledge of His will for us and the power to carry that out. Having had a spiritual awakening as the result of these steps, we tried to carry this message to alcoholics, and to practice these principles in all our affairs.

28. Serenity Prayer God grant me the serenity to accept the things I cannot change; courage to change the things I can; and wisdom to know the difference.