1. FIGHTING ADDICTION PHARMACOLOGICALLY
MEDICATIONS
FIGHTING ADDICTION
PHARMACOLOGICALLY

2. Medication(s) should complement - not replace - psychosocial treatment

3. Medication Assisted Treatment (M.A.T.)
Increases patient retention
Decreases drug use
Decreases infectious disease transmission
Decreases criminal activity
Lowers risk of relapse
Reduce the risk of overdose

4. M.A.T.
Under utilized
million Americans with opioid abuse/dependence/addiction
Fewer than 1 million received M.A.T.

6. Barriers Paucity of trained prescribers
Negative attitudes & misunderstanding about addiction medications
Many treatment facilities favor an abstinence model
Provider skepticism
Prescribing inadequate doses - reinforces lack of faith in MAT, since resulting relapse to opioids perpetuates a belief in their ineffectiveness

7. Insurance Companies:
Limits on dosages prescribed
Annual or lifetime medication limits
Prior authorizations requirements
Re-authorization requirements
“FAIL FIRST” criteria requiring that other therapies be tried first
Minimal availability of substance abuse counseling services

8. Critiques of M.A.T.
“It’s just being hooked on another drug, a substitute addiction”
“You’re still addicted; you’re not in recovery”
“You can never get off it”

9. MEDICATION ASSISTED THERAPIES
Medications for detoxification
Medications for maintenance
Medications for psychiatric illnesses
Medical management of pain

10. MEDICATIONS FOR DETOXIFICATION
Librium … Alcohol and Benzodiazepine detoxification
Benzodiazepine & Phenobarbital … Benzodiazepine detoxification
Suboxone (Subutex) & Methadone …Opiate detoxification
Clonidine & Naltrexone … Opiate detoxification
Bromocryptine & Amantadine … Stimulant detoxification
Wellbutrin … Cannabis detoxification

11. MEDICATIONS FOR MAINTENENCE
Buprenorphine ….Opiate dependence
Methadone … Opiate dependence
Acamprosate … Alcohol dependence
Naltrexone … Alcohol and Opiate dependence
Vivitrol Alcohol dependence
Disulfram … Alcohol dependence
Nicotine Replacement …Nicotine dependence

12. Medications to Delay Relapse in Alcohol Dependence
Naltrexone
Vivitrol
Antabuse
Campral
Topamax
Zofran
Baclofen
Neurontin

17. MEDICATIONS TOPAMAX BACLOFEN BUPRENORPHINE PROVIGIL WELLBUTRIN ZOFRAN
MUCOMYST
GABTRIL
ABILIFY
TEGRETOL
AMITRIPTYLINE
STRATTERA
CYMBALTA
EFFEXOR
LAMICTAL
NAMENDA
DEPAKOTE

18. LUVOX
LYRICA
BUSPAR
CLONIDINE
VISTARIL
TRAZADONE
GUANFACINE
INDERAL
SEROMYCIN
RISPERDAL
AMANTADINE
BROMOCRIPTINE
MINIPRESS

19. Aldehyde dehydrogenase (Triggers aversive response)
Antabuse
Aldehyde dehydrogenase
(Triggers aversive response)

20. MU opioid receptor antagonist
Naltrexone
MU opioid receptor antagonist

21. Revia - Naltrexone Pure opioid antagonist
Effective in treatment of alcohol and opiate
addiction
Blocks craving
Blocks the ‘high’

22. MEAN CRAVING SCORES (shows less craving with naltrexone)
Volpicelli et al., 1992

27. GABA/Glutamate synthesis
Neurontin
GABA/Glutamate synthesis

28. Mood stabalizer
Chronic pain medication
Anti-craving medication

29. GABA Gamma Amino Butyric Acid ANTI-STRESS ANTI-ANXIETY ANTI-PANIC
ANTI-PAIN
FEEL CALM
MAINTAIN CONTROL
FOCUS

31. Suboxone Subutex “Subbies”
Buprenorphine
Suboxone
Subutex
“Subbies”

32. Drug Addiction Treatment Act of 2000 (DATA 2000)
Expands treatment options to include both the general health care system and opioid treatment programs.
Expands number of available treatment slots
Allows opioid treatment in office settings
Sets physician qualifications for prescribing the medication

33. Buprenorphine Properties
Presentation May 17, 2005
Buprenorphine Properties
High affinity to the opiate receptor
Long duration of action (24-72hr)
Strong safety profile
Little respiratory depression
Little overdose potential
Safety – O.D. ceiling effect
Adam J. Gordon, MD, MPH

34. Buprenorphine’s Properties: Partial Agonist
Presentation May 17, 2005
Buprenorphine’s Properties: Partial Agonist
-10 -9 -8 -7 -6 -5 -4 10 20 30 40 50 60 70 80 90
100
“Activity” or
“Response”
Log DOSE
Full Agonist
(Methadone)
Partial Agonist
(Buprenorphine)
Antagonist (Naloxone)
PARTIAL AGONISTS:
BIND TO & ACTIVATE RECEPTOR
WEAK MORPHINE-LIKE EFFECTS WITH STRONG RECEPTOR AFFINITY
INCREASING DOSE DOES NOT PRODUCE AS GREAT AN EFFECT AS DOES INCREASING DOSE OF A FULL AGONIST
EXAMPLES OF PARTIAL AGONISTS:
BUPPRENORPHINE
TALWIN
PARTIAL AGONIST AT MU RECEPTOR
HIGH AFFINITY FOR MU RECEPTOR WILL DISPLACE FULL AGONIST (HEROIN OR METHADONE)
ANTAGONIST AT KAPPA RECEPTOR
SLOWLY METABOLIZED
Gordon, Counterdetails 2006
Adam J. Gordon, MD, MPH

35. Receptor Sends Pain Signal to the Brain
Buprenorphine
Opioid
Empty Receptor
Withdrawal Pain
Receptor Sends Pain Signal to the Brain
Courtesy of NAABT, Inc. (naabt.org)
Neuro receptor in withdrawal and craving opioids. Once dependent the body cannot produce enough natural opioids to satisfy the many new receptors that were produced while taking large doses of opioids over time. The unsatisfied receptor sends pain signals to the brain. This is withdrawal.

36. Perfect Fit - Maximum Opioid Effect
Empty Receptor
Euphoric Opioid Effect
No Withdrawal Pain
Courtesy of NAABT, Inc. (naabt.org)
Neuro receptor satisfied with an opioid. The strong opioid effect from painkillers, or heroin, stops the withdrawal symptoms for a short time. (4-24 hours) The person is high. After prolonged use, the patient is no longer getting high so much as just preventing the withdrawal symptoms.

37. Imperfect Fit – Limited Euphoric Opioid Effect
Courtesy of NAABT, Inc. (naabt.org)
Opioids replaced and blocked by Buprenorphine. Opioids cannot get to the neuro receptor while occupied by Buprenorphine. The person no longer feels sick (in withdrawal) and is unable to get high even if he/she uses other opioids. Buprenorphine produces a limited opioid effect, and cravings are reduced or eliminated.

38. Buprenorphine Still Blocks Opioids as It Dissipates
Courtesy of NAABT, Inc. (naabt.org)
Over time (24-72 hours) Buprenorphine dissipates, but still creates a small opioid effect (enough to prevent withdrawal) and still block opioids from attaching to the receptors. This means if someone were to take an opioid, they still would not get high.

39. HOW EFFECTIVE IS SUBOXONE?
Stops the symptoms of opiate withdrawal
Stops the cravings for opiates
Reduces illicit opioid use
Blocks the effects of other opioids
Helps patients stay in treatment

40. The Basic Idea Behind Suboxone
Drug is good when taken as directed
Drug is bad when taken any other way
Dose preparation safe and effective for take home dosing

41. Most often heard quotes with Buprenorphine
Presentation May 17, 2005
Most often heard quotes with Buprenorphine
“Doc, I feel normal”
“I wake up not sick”
“I have my life back”
Treatment in normal medical settings:
Encourages continuity of medical/specialty care
Encourages relationship building with clinicians
Legitimize opioid dependence as a normal, treatable, chronic illness
Adam J. Gordon, MD, MPH

46. It may not be that the med(s) stopped working, but……
The patient stopped the medication
The patient stopped the medication AND used drugs and/or alcohol…...
OR lowered the medication and used…
OR used on top of the medication….
OR used twice the dose on one day and nothing the next….
Stimulants ( cocaine, amphetamines, methamphetamines) are most destructive.

49. IS IT PAIN OR IS IT THE ADDICTION?

50. CHRONIC PAIN SYNDROME Chronic pain: an altered brain
Any opioid treatment is directed to the altered brain than it is to any peripheral injury
Chronic pain of any nature means pain arising from the brain

51. Treating this syndrome is not treating the condition that precipitated the syndrome ie., low back pain
But is treating the change in the brain caused by the persistence of the pain

52. “All Pain is in the Brain”

53. Pharmacologic Agents Affect Pain Differently
BRAIN
Descending Modulation
Anticonvulsants
Opioids
Tricyclic/SNRI Antidepressants
Spinal
Cord
CNS
Dorsal
Horn
Central Sensitization
PNS
Available drug treatments for chronic pain currently include simple analgesics such as acetaminophen, salicylates and other nonsteroidal anti-inflammatory drugs, traditional opioid drugs, and adjuvant agents (eg, antidepressants, anticonvulsants). Typically, the choice of a drug is made by balancing the indications for treatment, the clinical efficacy of the drug, and its toxicity. An understanding of the mechanism of action of these drugs helps to establish their role in therapy.
Better understanding of the pathophysiology of acute and chronic pain has led to numerous advances in pharmacologic management of painful disorders, including low back pain, migraine headache, fibromyalgia, postherpetic neuralgia, osteoarthritis, rheumatoid arthritis, and cancer-related neuropathic pain.
Opioids mimic the actions of endogenous opioid peptides by interacting with mu, delta, or kappa opioid receptors. The opioid receptors are coupled to G1 proteins and the actions of the opioids are mainly inhibitory. They close N-type voltage-operated calcium channels and open calcium-dependent inwardly-rectifying potassium channels. This results in hyperpolarization and a reduction in neuronal excitability. They also decrease intracellular cAMP which modulates the release of nociceptive neurotransmitters (eg, substance P).
Inhibition of prostaglandin synthesis by cyclooxygenase is the principal mode of the analgesic and anti-inflammatory actions of NSAIDs. Cyclooxygenase is inhibited irreversibly by aspirin and reversibly by other NSAIDs. The widespread inhibition of cyclooxygenase is responsible for many of the adverse effects of these drugs. NSAIDs also reduce prostaglandin production within the CNS. This is the main action of paracetamol.
Argoff CE. Pharmacologic management of chronic pain. J Am Osteopath Assoc. 2002;102(suppl 3):S21-S27.
Aronson MD. Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain. Clin Ther. 1997;19:420-32; discussion
Bovill JG. Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs. Eur J Anaesthesiol Suppl.1997;15:9-15.
Anticonvulsants
Opioids
NMDA-Receptor Antagonists
Tricyclic/SNRI Antidepressants
Peripheral
Sensitization
Local Anesthetics
Topical Analgesics
Anticonvulsants
Tricyclic Antidepressants
Opioids

54. Adjuvant Analgesic Medications
Not analgesics in true pharmacological sense
Contribute significantly to pain relief
Used alone or in combination

55. Antidepressants Tricyclics - amitriptyline, desipramine, nortriptyline
SSRI’S – Prozac, Celexa, Luvox, Paxil, Zoloft, Viibryd
SNRI’S – Cymbalta, Effexor, Savella

56. Anticonvulsants Carbamazepine – Tegretol Gabapentin - Neurontin
Lamotrigine - Lamictal
Oxcarbazepine - Trileptal
Pregabalin - Lyrica
Valproic Acid - Depakote

57. Levetiracetam - Keppra
Phenytoin - Dilantin
Topiramate - Topamax
Zonisamide - Zonegran

58. Skeletal Muscle Relaxants
Baclofen
Cyclobenzaprine - Flexeril
Tizanidine - Zanaflex

59. Topical Therapy
Capsaicin
Lidocaine
Flector patches
Voltaren gel

60. Miscellaneous Memantine - Namenda
Tramadol - Ultram ( Norepinephrine & serotonin reuptake inhibitor)
Alpha-2 agonists - Catapres, Guanfacine

62. THE EXPERIENCE OF PAIN IS ENTIRELY IN THE BRAIN

63. Patients with chronic pain are at risk for addiction or overdose when treated with opioid medication
Many people with addiction also have chronic pain
Many patients path to addiction started with a prescription for pain medication & progressed to heroin

64. BOTTOM LINE: OPIOIDS ARE RARELY THE ANSWER