Addiction Issues in Pain Management: From Opium to Buprenorphine

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Addiction Issues in Pain ManagementFrom Opium
to Buprenorphine

• Challenges of Managing Pain Symposium
• UCSF Medical Center at Mount Zion
• Howard Kornfeld, M.D.
• June 7, 2007

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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

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A History of OpiumMartin Booth, Opium, A
History, St. Martins 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 worlds 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.

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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 Gilmans 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.

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• 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

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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.
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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 May25(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

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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

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Addiction The 5 Cs

• Continued use despite adverse consequences
• Chronic
• Control, loss of
• Compulsive
• Craving

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DSM-IV Criteria for Substance Dependence
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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)

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Correlations the 5 Cs 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/Compuls
  ive- 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/Compuls
  ive- 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)

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Pain Treatment The 4 As of Assessment

• Analgesic?
• Adverse Effects?
• Activities of Daily Life?
• Aberrant Behaviors?/Predictors of Opioid Misuse

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Opioid Chronic Pain Guidelines Aberrant
Behaviors Predictors of Opioid Misuse From
the VA/DOD Opioid/Chronic Pain GuidelinesJune,
2003
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I. Illegal or Criminal Behavior

• Diversion (sale of provision of opioids to
  others)
• Prescription forgery
• Stealing or borrowing drugs from others

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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

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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

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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.)

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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.

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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.

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

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• 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 elses
  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.

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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

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Anti-hyperalgesia properties of
buprenorphineRusso, MA, Pain, 2005 Nov 118
(1-2) 15-22
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Training HIV Physicians to Prescribe
Buprenorphine for Opioid DependenceSullivan, et
al, Substance Abuse, 2006l 27(3)13-18
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The Twelve Steps of Alcoholics AnonymousAlcoholic
s 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.

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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.