Physiology of Addiction by Carl Christensen

Slideshow Transcript

1. Slide 1: Physiology of Addiction Carl Christensen, MD PhD Dawn Farm Education Series October 25, 2007
2. Slide 2: History: Tommy Walker Tommy Walker has been sent to you for  addiction evaluation.  He began drinking when he was 13.  His mother also admits to drinking during her pregnancy with him.  When he was born, he was small, irritable and was “slow to grow” Dawn Farm Education Series Oct 25, 2007 2
3. Slide 3: Neuroplasticity/Neurotoxicity Neuro = brain   Plasticity = change  toxicity = damage  Exposure to drugs and alcohol in the womb can cause permanent damage  Most extreme example: Fetal Alcohol Syndrome (FAS) Dawn Farm Education Series Oct 25, 2007 3
4. Slide 4: FAS Dawn Farm Education Series Oct 25, 2007 4
5. Slide 5: Fetal Alcohol Syndrome Dawn Farm Education Series Oct 25, 2007 5
6. Slide 6: Tommy Walker: Genetics? Tommy’s father was an alcoholic and was  also addicted to heroin.  His older brother died of a heroin overdose. Dawn Farm Education Series Oct 25, 2007 6
7. Slide 7: Genetics? The biological children of alcoholics are  more likely to become alcoholics.  If they are raised by another family, they are STILL more likely to become alcoholics.  Non-alcoholic offspring raised in alcoholic homes are NOT more likely to become alcoholics. Dawn Farm Education Series Oct 25, 2007 7
8. Slide 8: POSSIBLE FAMILIES OF RISK FACTORS  Alcoholics metabolize alcohol BETTER (= tolerance)  Alcoholics are impulsive  Alcoholics are more likely to have personality disorders Dawn Farm Education Series Oct 25, 2007 Stolen from Shuckitt et al…….  8
9. Slide 9: Tommy Walker: Tolerance He found that he could “drink anyone  under the table” by the time he was 15.  TOLERANCE: a predictor of later alcoholism.  Future alcoholics are able to drink MORE than their peers.  The one who “can’t handle their liquor” is LESS likely to become an alcoholic. Dawn Farm Education Series Oct 25, 2007 9
10. Slide 10: Tommy: Hedonic Tone? He describes feeling “uncomfortable in his  own skin” unless he was drunk .  Hedonic Tone: your “set point” for feeling pleasure/normal. – Addicts feel better when given amphetamine, normal people feel worse. Addiction: seeking to regain hedonic  tone? Salsitz, 2006 ASAM  Dawn Farm Education Series Oct 25, 2007 10
11. Slide 11: Polysubstance abuse He began smoking cigarettes when he was  14.  At age 17 he began using marijuana, LSD and ecstasy. He later starts using cocaine.  He finds that when he stops using one drugs, he simply switches to another. Dawn Farm Education Series Oct 25, 2007 11
12. Slide 12: “Hi…I’m Joe. I’m cross addicted” Dawn Farm Education Series Oct 25, 2007 12
13. Slide 13: The Pleasure Center Nucleus Accumbens   Responds to dopamine (DA)  Responds to drugs  Responds to food  Responds to sex  Sends signals to your frontal cortex  THE PLEASURE CENTER IS ABNORMAL (DAMAGED) IN ADDICTION Dawn Farm Education Series Oct 25, 2007 13
14. Slide 14: Dawn Farm Education Series Oct 25, 2007 14
15. Slide 15: The Pleasure Center Dawn Farm Education Series Oct 25, 2007 15
16. Slide 16: Addicts have abnormal pleasure centers…. and abnormal responses to visual cues of their addictions…..
17. Slide 17: Dawn Farm Education Series Oct 25, 2007 17
18. Slide 18: Dawn Farm Education Series Oct 25, 2007 18
19. Slide 19: Dawn Farm Education Series Oct 25, 2007 19
20. Slide 20: Dawn Farm Education Series Oct 25, 2007 20
21. Slide 21: Dawn Farm Education Series Oct 25, 2007 21
22. Slide 22: Dawn Farm Education Series Oct 25, 2007 22
23. Slide 23: Tommy’s story cont’d…. He comes to see you , his doctor, now because he has  found that he cannot stop drinking and using drugs. His wife has left him several times, but when he quits, he  finds he cannot stay sober. She is getting a divorce. He has tried “controlled drinking” several times, but finds  that he drinks more than he plans to. Whenever he starts drinking, he finds that he starts using  cocaine again He constantly thinks about drinking and using drugs.  Diagnosis???  Dawn Farm Education Series Oct 25, 2007 23
24. Slide 24: Substance Dependence - DSM IV Maladaptive pattern with three or more:  – Tolerance – Withdrawal Using more and/or using for longer times – A desire or repeated attempts to cut down – Lots of time using or recovering – Reduced activities: social, work, recreation – Recurrent use despite physical and psychological – problems Dawn Farm Education Series Oct 25, 2007 24
25. Slide 25: Addiction/chemical dependence: A chronic progressive disease characterized by the following  physical and psychological symptoms (the four (five) C’s): Craving  Compulsion  Loss of Control  Continued use despite consequences, and  Chronic use  Dawn Farm Education Series Oct 25, 2007 25
26. Slide 26: Addiction? He comes to see you now because he has found that he  cannot not drinking and using drugs. His wife has left him several times, but when he quits, he  finds he cannot stay sober. She is getting a divorce. He has tried “controlled drinking” several times, but finds  that he drinks more than he plans to. Whenever he starts drinking, he finds that he starts using  cocaine again He constantly thinks about drinking and using drugs.  Diagnosis: Chemical Dependence = ADDICTION  Dawn Farm Education Series Oct 25, 2007 26
27. Slide 27: Tommy… Tommy is seen for his yearly checkup.   His BP is 160/100, his face is puffy.  He had an episode of severe right sided pain last month after a “weekend at Bernie’s” and he thought he looked yellow for the rest of the week, had a fever and was throwing up.  His cholesterol tests come back abnormal. Dawn Farm Education Series Oct 25, 2007 27
28. Slide 28: Consequences: Medical Hypertension: the most common cause of  “essential” (unexplained) hypertension is alcohol.  Diabetes: damage to the pancreas (temporary or permanent)  Cholesterol: LDL (bad cholesterol) goes up, triglycerides (fat) goes up. Dawn Farm Education Series Oct 25, 2007 28
29. Slide 29: Consequences? The Liver Fatty liver: from drinking; body uses  alcohol rather than fat. Fat accumulates.  Alcoholic Hepatitis: inflammation of the liver; fever, jaundice, pain, nausea and vomiting.  Viral Hepatitis: usually hepatitis C, from sharing needles, straws (cocaine), sex.  Cirrhosis: more to be revealed Dawn Farm Education Series Oct 25, 2007 29
30. Slide 30: The (keen) Alcoholic Mind When you see him today, he denies that  he has a problem, but says that he needs to \"take a break\". His wife left him, he says, because of his mother in law.  On the way out the door, he says: “I’m worried about you Dr. Are you getting any exercise?” Dawn Farm Education Series Oct 25, 2007 30
31. Slide 31: The (keen) Alcoholic Mind As you discuss his situation, you are  amazed by his ability to: – Minimalize -Rationalize – Deny -Deflect – Project He appears to have no insight about his  worsening drinking problem. Dawn Farm Education Series Oct 25, 2007 31
32. Slide 32: Cognition and Addiction  Recovering addicts make bad decisions Ex: 3 weeks into recovery, a man decides  to make a trip to……  Amsterdam?  Q: what does an alcoholic bring on a 2nd date?  A: a U haul. Dawn Farm Education Series Oct 25, 2007 32
33. Slide 33: “Biopsychosocial (?)” Dawn Farm Education Series Oct 25, 2007 33
34. Slide 34: Treatment of Addiction I A “biopsychosocial” disease:  – The body/brain – The person (mind, soul) – The environment You are not just removing a drug, you are  treating a chronic, progressive, relapsing disease Treatment for chronic diseases must be chronic:  diabetes, hypertension, obesity: “quick fixes lead to quick problems” Dawn Farm Education Series Oct 25, 2007 34
35. Slide 35: Treatment of Addiction II Abstinence: removes the drug, doesn’t treat the  disease (Hogback Hilton) Pharmacology: see later  Cognitive Behavioral Therapy: thoughts  emotionsbehavior (relaspe) Motivational Enhancement Therapy: variation of  Motivational Interviewing (MI): enhance’s the patient’s motivation to change Dawn Farm Education Series Oct 25, 2007 35
36. Slide 36: Alcoholics Anonymous: Cult, Threat or Menace? Dawn Farm Education Series Oct 25, 2007 36
37. Slide 37: CBT vs. AA Therapist:  Sponsor:  Dawn Farm Education Series Oct 25, 2007 37
38. Slide 38: CBT vs. AA Therapist:  – “you need closure with your family” Sponsor:  – “you need to closure mouth and go to meetings” Dawn Farm Education Series Oct 25, 2007 38
39. Slide 39: Tommy Cont’d Tommy completes his IOP.   He declines attendance at AA, says that it is a “cult”.  He feels he has everything under control.  His wife, now attending Alanon, declines to return.  He is lost to follow up. Dawn Farm Education Series Oct 25, 2007 39
40. Slide 40: Tommy Cont’d He returns to see you 2 years later and  has relapsed.  He reveals that he has had continual craving for drugs and found that when he started using them again he could not quit.  He says he had use just to feel \"normal\". Dawn Farm Education Series Oct 25, 2007 40
41. Slide 41: Tommy Cont’d He has been drinking heavily.  He was admitted to detox but had to be  sent to the hospital for DTs. Dawn Farm Education Series Oct 25, 2007 41
42. Slide 42: Drug Withdrawal I Withdrawal: what happens when the drug  is removed  Typically the opposite effect for which the drug is taken  A physiologic response that depends on where the drug acts  Not a cause/result of addiction Dawn Farm Education Series Oct 25, 2007 42
43. Slide 43: Drug Withdrawal: types of withdrawal Sedative withdrawal  – Brain has been tranquilized, now goes into “overdrive” – May result in seizures Stimulant withdrawal  – Brain has been in overdrive, now goes to “sleep” – Not physically dangerous – Patient will complain of dysphoria/craving when awake Dawn Farm Education Series Oct 25, 2007 43
44. Slide 44: Sedative Withdrawal I Alcohol, Benzos and Barbituates   Bind to the GABA receptor: – Causes sedation Inhibits the NMDA receptor:  – Prevents excitation Now stop the sedative and……  Dawn Farm Education Series Oct 25, 2007 44
45. Slide 45: Dawn Farm Education Series Oct 25, 2007 45
46. Slide 46: Sedative Withdrawal II Brain becomes over-excited, “disinhibited”  “Angry Grey Planet”  Stimulates the autonomic nervous system  Dawn Farm Education Series Oct 25, 2007 46
47. Slide 47: Drug Withdrawal: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 47
48. Slide 48: Alcohol Withdrawal: Stage I A “bad hangover”: increased pulse, blood  pressure, stimulation, “everything hurts” – Treatment: eye of the dog – SEIZURES MAY OCCUR DURING THIS TIME – SEIZURES ARE MORE LIKELY ONCE YOU HAVE HAD ONE (“kindling”) – ANYONE WITH A HISTORY OF ALCOHOL WITHDRAWAL SEIZURES SHOULD BE MEDICALLY DETOXED (benzos, phenobarb) Dawn Farm Education Series Oct 25, 2007 48
49. Slide 49: Alcohol Withdrawal: Stage II Alcoholic Hallucinosis   The “string sign”  Should be admitted to hospital  Visual hallucinations are often friendly (“pink elephant”) Dawn Farm Education Series Oct 25, 2007 49
50. Slide 50: Alcohol Withdrawal: Stage III Delerium Tremens   Brain is in overdrive  Agitation, audio and visual hallucinations; delirium (acute confusion)  Mortality used to be up to 35%!!  MUST be admitted and heavily sedated  “Helicopter sign” Dawn Farm Education Series Oct 25, 2007 50
51. Slide 51: Alcohol Withdrawal: Stage IV Prolonged withdrawal   Anxiety, insomnia, headache  “Restless, irritable and discontent”  Post Acute Withdrawal Syndrome: PAWS  Recommended treatment: AA/meds  Most COMMON treatment: alcohol Dawn Farm Education Series Oct 25, 2007 51
52. Slide 52: Pharmacotherapy? His new addiction doctor, Dr. Uptha Creek, has  put him on disulfiram (Antabuse), naltrexone (Rivea®), acamprosate (Campral®), lorazepam (Ativan®), fluoxetine (Prozac®), and zolpidem (Ambien®). No spiritual treatment is recommended.  He wants to sell his house* to pay for a Prometa  treatment.  *already gone! Dawn Farm Education Series Oct 25, 2007 52
53. Slide 53: Alcohol Metabolism and Disulfiram Ethanol------Acetaldehyde----------- C02 (1) (2) 1: alcohol dehydrogenase: – M>W; younger>older; protective – metabolizes 1 drink/hour 2: aldehyde dehydrogenase: – Detoxifies acetaldehyde – Inhibited by Disulfiram (Antabuse) Dawn Farm Education Series Oct 25, 2007 53
54. Slide 54: Naltrexone Blocks the opiate (µ) receptor  Prevents you from using opiates  Also blocks your endogenous (own) opiates:  endorphins Opiate receptors may be partly responsible for  alcohol craving Has been shown to reduce drinking ONCE YOU  HAVE ALEADY STOPPED Available as an injection (Vivitrol®)  Dawn Farm Education Series Oct 25, 2007 54
55. Slide 55: Dawn Farm Education Series Oct 25, 2007 55
56. Slide 56: Dawn Farm Education Series Oct 25, 2007 56
57. Slide 57: The Reward Pathway: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 57
58. Slide 58: Acamprosate (Campral®) Thought that it worked through GABA  (where alcohol works)  Not known how it works  May decrease “number of drinking days”  May reduce craving  Often being used by patients being admitted to detox units. Dawn Farm Education Series Oct 25, 2007 58
59. Slide 59: Benzodiazepines Analogues: Ativan (lorazepam)   Valium (diazepam)  Xanax (alprazolam) Ambien (Zolpidem)   Klonopin Lunesta   (clonazepam) Restoril  Produce amnesia!  (temazepam) Dawn Farm Education Series Oct 25, 2007 59
60. Slide 60: Benzodiazepines Work through the same receptor as  alcohol (GABA)  Prevent alcohol withdrawal  The original pharmacotherapy for alcoholism – Valium  Often results in “cross addiction”  Dangerous combination in relapse Dawn Farm Education Series Oct 25, 2007 60
61. Slide 61: Antidepressants: SSRIs 85% of patients admitted to rehab will  have a diagnosis of clinical depression  Only 15% will have that diagnosis on discharge  Patients are often prescribed SSRIs while using Dawn Farm Education Series Oct 25, 2007 61
62. Slide 62: Suboxone® (buprenorphine) Binds to the opiate receptor (µ)   Reduces craving and withdrawal  Safer than methadone  Doesn’t require a methadone clinic (DEA)  Primarily for withdrawal/detox; cravings  DOESN’T treat the disease of addiction Dawn Farm Education Series Oct 25, 2007 62
63. Slide 63: Dawn Farm Education Series Oct 25, 2007 63
64. Slide 64: Prometa®?? Combination of three drugs:  Flumazenil: a benzodiazepine antagonist:   Gabapentin (Neurontin®): an antiepileptic drug:  Hydroxizine (Atarax®):  Cost: $15,000+  Controlled studies now in progress Dawn Farm Education Series Oct 25, 2007 64
65. Slide 65: He is now smoking crack, drinking 1 pint  to 1/5 per day, using marijuana daily, abusing his Ativan, and has lost his job. He continues to take Vicodin with his Suboxone.  However, he says that he is \"doing okay\" and feels that he is \"on the right track\".  He declines your recommendation for residential therapy. Dawn Farm Education Series Oct 25, 2007 65
66. Slide 66: Consequences: brain You are asked to see him in the hospital  several years later.  He says he knows you, but cannot remember your name.  You ask him who the president is, he replies “Who cares? They’re all crooks”.  He walks with a shuffling broad-based gait and has to hold his hand on the wall to keep his balance. Dawn Farm Education Series Oct 25, 2007 66
67. Slide 67: Wernike-Korsakoff Syndrome Immediately after stopping drinking:  Wernike’s encephalopathy (brain disease)  Caused by thiamine (B1) deficiency – Eye muscles are paralyzed – Ataxia (can’t walk straight) – Encephalopathy: confusion, agitation, restlessness Dawn Farm Education Series Oct 25, 2007 67
68. Slide 68: Korsakoff’s psychosis Confabulation: make things up   Retrograde amnesia: can’t remember what happened in the past  Antegrade amnesia: can’t remember info you are given (remember these 3 objects…)  Polyneuropathy: periperhal nerve damage Dawn Farm Education Series Oct 25, 2007 68
69. Slide 69: Consequences: liver You see him one more time, several years later.  He has been readmitted for vomiting blood, jaundice, and encephalopathy. He is given multiple transfusions. He has  esophageal varices from his cirrhosis. He is jaundiced. He says that he is asking  his sister to pay for a liver transplant. When he are speaking to him, his hands will  occasionally flap. Dawn Farm Education Series Oct 25, 2007 69
70. Slide 70: Alcoholic Cirrhosis Hardening of the liver (scar tissue)   Causes blood to back up in the veins feeding the liver: – Esophageal varices: vomit blood – Hemorrhoids: rectal bleeding Can’t metabolize toxins: encephalopathy   Can’t make proteins: – bleeding (coagulopathy) – Can’t hold fluids: ascites Dawn Farm Education Series Oct 25, 2007 70
71. Slide 71: Cirrhosis Dawn Farm Education Series Oct 25, 2007 71
72. Slide 72: Ascites/Jaundice Dawn Farm Education Series Oct 25, 2007 72
73. Slide 73: “Caput Medusae” Dawn Farm Education Series Oct 25, 2007 73
74. Slide 74: Esophageal Varices Dawn Farm Education Series Oct 25, 2007 74
75. Slide 75: He dies several weeks later of liver failure.  “Jails, institutions, and death”   Narcotics Anonymous Dawn Farm Education Series Oct 25, 2007 75
76. Slide 76: Dawn Farm Education Series Oct 25, 2007 76
77. Slide 77: The Brain and Addiction Dopamine is the chemical involved in  reward  The more dopamine receptors you have, the more “normal” you (may) feel  Addicts have lower levels of dopamine receptors – Must increase their levels of dopamine to feel “normal”? Dawn Farm Education Series Oct 25, 2007 77
78. Slide 78: Dawn Farm Education Series Oct 25, 2007 78
79. Slide 79: Dawn Farm Education Series Oct 25, 2007 79
80. Slide 80: The Reward Pathway: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 80
81. Slide 81: Withdrawal Pathways: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 81
82. Slide 82: RELAPSE Drug triggered: “I thought I could have  just one drink” Stress triggered: “I’m going through too  much right now” Cue triggered: “Wet faces and wet places”  Dawn Farm Education Series Oct 25, 2007 82
83. Slide 83: Drug Triggered Relapse: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 83
84. Slide 84: Stress Triggered Relapse: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 84
85. Slide 85: Cue Triggered Relapse: Gardner 2006 Dawn Farm Education Series Oct 25, 2007 85
86. Slide 86: Brain Scans
87. Slide 87: Effect of Alcohol on Brain Function Dawn Farm Education Series Oct 25, 2007 87
88. Slide 88: Ventricles Non-alcoholic Alcoholic Dawn Farm Education Series Oct 25, 2007 88
89. Slide 89: Volume Recovery 2 Years Later During Treatment Dawn Farm Education Series Oct 25, 2007 89
90. Slide 90: Stimulants & Blood Flow High blood flow Low Cocaine-dependent Healthy Control blood flow Gottschalk, 2001, Am J Psychiatry Dawn Farm Education Series Oct 25, 2007 90
91. Slide 91: Blood Flow Recovery High blood flow Non users Cocaine users, 10 days sober Low blood flow Cocaine Users, 100 days sober Dawn Farm Education Series Oct 25, 2007 91
92. Slide 92: Dawn Farm Education Series Oct 25, 2007 92
93. Slide 93: Who in the room has the lowest hedonic tone?????? Dawn Farm Education Series Oct 25, 2007 93
94. Slide 94: Salsitz 2006: Hedonic Tone Dawn Farm Education Series Oct 25, 2007 94
95. Slide 95: Volkow, Am J Psychiatry 2001; 158:377-382 Dawn Farm Education Series Oct 25, 2007 95
96. Slide 96: Abnormal response to Ritalin is due to abnormal brain chemistry Dawn Farm Education Series Oct 25, 2007 96
97. Slide 97: Obese subjects have decreased DA Dawn Farm Education Series Oct 25, 2007 97
98. Slide 98: Dawn Farm Education Series Oct 25, 2007 98