Ms. Alvarez is a 45 year old Latin-American female with a history of multiple episodes of alcoholic pancreatitis. She presents to the ER complaining of epigastric abdominal pain and nausea for 2 days. The ER physician picks up her chart, rolls his eyes

1

• Ms. Alvarez is a 45 year old Latin-American
  female with a history of multiple episodes of
  alcoholic pancreatitis. She presents to the ER
  complaining of epigastric abdominal pain and
  nausea for 2 days. The ER physician picks up her
  chart, rolls his eyes after recognizing her name,
  and mumbles to himself in disgust, Why in the
  hell is she here again? What do you want me to
  dowhy doesnt she just stop drinking?

2

• He barges into her room, says a few words,
  smashes on her abdomen until she screams, and
  rushes out of the room. He orders a CBC, chem-14
  and lipase, and starts IVF. The lipase is only
  mildly elevated, but she is admitted with a
  diagnosis of pancreatitis. She tells the
  hospitalist that she quit drinking 9 months ago,
  but he does not believe her. She is made NPO,
  and given IVF and morphine prn.

3

• Overnight, her abdominal pain worsens, and she
  continues to ask for more pain medicine. Her
  nurse reluctantly gives her more morphine. At
  the nursing station, she is referred to as the
  alcoholic lady in 742, and the nurses talk about
  how many times they have taken care of her. When
  her admitting physician makes rounds the next
  morning, her nurse is annoyed and comments,
  This one kept me up all night.

4

• He examines the patient, and notes that her
  abdomen is much more tender, and she now has
  rebound tenderness. Her temperature is 101º and
  her WBC is 22K. He obtains a CT of the abdomen
  and a surgical consult. The CT shows an inflamed
  gallbladder with a surrounding fluid collection.
  She develops obvious peritoneal signs, and she is
  taken to the operating room. The surgeon finds a
  perforated gallbladder.

5
Points to Ponder.

• All of us have admitted patients with poorly
  controlled diabetes mellitus. We pardon their
  morbid obesity, poor dietary habits, and
  noncompliance, and we continue to treat them with
  respect. So, why do we excuse noncompliant
  diabetics BUT we stigmatize noncompliant or
  relapsing patients with substance abuse
  disorders?
• How often do we treat the medical complications
  but never address the underlying substance abuse
  disorder? If it were that simple, writing stop
  drinking on the discharge sheets would actually
  work.

6
Update on Substance Abuse Disorders

• Nilam J. Soni, MD

7
Overview

• Epidemiology
• Neurobiology of Addiction
• Definitions
• Screening for Substance Abuse
• Brief Interventions and Motivational Interviewing
• Alcohol
• Inpatient Management
• Outpatient Management
• Opioids
• Inpatient Management
• Outpatient Management
• Resources

8
Epidemiology
9
Epidemiology

• In 2002, approximately 19.5 million Americans, or
  8.3 of the population ages 12 or older, were
  current illicit drug users 2002 National Survey
  on Drug Use and Health (NSDUH), SAMHSA
• 53 of students have tried an illicit drug by the
  time they finish high school
• In 2003, 4.5 of 12th graders used Oxycontin in
  the past year and 10.5 used Vicodin-making
  Vicodin the second-ranked drug after marijuana
  (University of Michigan, 2003 Monitoring the
  Future Study)

10
Any Illicit Drug Including Inhalants Trends in
Lifetime Use(8th, 10th, and 12th Graders)

Percent Who Ever Used








Source Monitoring the Future Study, 2003, NIDA
11

• Mr. and Mrs. Smith come to see you in the clinic.
  Mrs. Smith is very angry about her husbands
  drinking, but he doesnt feel like he has a
  problem. His father was an alcoholic, but Mr.
  Smith adamantly says, There is no way that I
  am. Mrs. Smith says, I think that he is just
  weak, mentally that is, and he just needs to
  strengthen his will power. After all, isnt
  alcoholism just a matter of will power.
• How would you respond to her?

12
Neurobiology of Addiction

• (National Institute on Drug Abuse)

13
Advances in science have revolutionized our
fundamental views of drug abuse and addiction
14
This is your brain on drugs..
YELLOW shows areas of brain stimulated by cocaine
(striatum)
15
Disease Model for Drug Addiction

• Genes
• CYP 2A6 levels and tobacco dependence
• Mu-receptor and heroin addiction
• Environment
• Early physical/sexual abuse
• Witnessing violence
• Stress
• Drug availability
• Dopamine and Serotonin Pathways

16
Dopamine Receptor Levels and Response to
Methamphetamine
Subjects with low dopamine receptor levels found
methamphetamine pleasant while those with high
dopamine receptor levels found methamphetamine
unpleasant Thus, drugs have variable effects on
the brain which determine a pleasant from an
unpleasant response.
2.5
unpleasant response
0
pleasant response
17
Dopamine Pathways
Serotonin Pathways

• Functions
• mood
• memory
• processing
• sleep
• cognition

• Functions
• reward (motivation)
• pleasure, euphoria
• motor function
• compulsion
• perseveration

18
Effects of Drugs on Dopamine Release
Source Di Chiara and Imperato
19
Development of Addiction

• Genetic Predisposition
• ?
• Environmental Stress
• ?
• Drug Abuse
• (Initiation of drug use, pleasurable experiences,
  hazardous use)
• ?
• Drug Addiction
• (Neurochemical brain changes, uncontrollable drug
  use)

20
Amygdala
Nature Video
Cocaine Video
Anterior Cingulate
Prolonged drug use? development of pathways that
cause craving
21
Cocaine CravingPopulation (cocaine addicts vs.
controls) x Films (cocaine, erotic)
Cingulate
Ant Cing
Signal Intensity (AU)
IFC
Controls Cocaine Addicts
Garavan et al A .J. Psych 2000
22

C-11d-threo-methylphenidate
Effects of Abstinence

• Abstinence from methamphetamine for 24 months
  demonstrated some recovery, but not complete
  normalization.
• Therefore, addicts are always at risk for relapse.

Normal Control
Methamphetamine Abuser (1 month detoxification)
Methamphetamine Abuser (24 month abstinent)
Volkow, N.D. et al., Journal of Neuroscience,
21(23), pp. 9414-9418, December 1, 2001.
23
Summary

• Normal
• (at risk) Drug Use Addiction Treatment

24
Definitions
25
Spectrum of Substance Use
Substance Use Disorders
heavy
severe
Dependent
Abuse
consumption
Hazardous
consequences
Low Risk
Abstinence
none
none
26
Drug AbuseDSM IV Criteria

• 1 or more adverse effects over 12 months
• Recurrent use resulting in failure to fulfill
  major role obligations
• Recurrent use in hazardous situations
• Recurrent substance-related legal problems
• Continued use despite interpersonal or social
  problems related to use

27
Drug DependenceDSM IV Criteria

• 3 or more in 12 months
• Tolerance
• Withdrawal
• Much time obtaining, using, recovering
• Activities given up or reduced
• More or longer than intended
• Unable to cut down or control
• Use despite knowledge of health consequences
• (Preoccupation and compulsion addressed in 3-7)

28
What is Addiction?

• Compulsive substance use without medical purpose
  in the face of negative consequences
• A different neurobiological state the addicted
  brain is different from the non-addicted brain
• A condition involving activation of the brains
  mesolimbic dopamine system a common denominator
  in the acute effects of drugs of abuse

Leshner AI. Science-based views of drug
addiction and its treatment. JAMA.
19992821314-1316.
29
Alcohol Use in Primary Care SettingAdults gt 18
Hazardous Drinkers 9
Alcohol Abuse 8
Alcohol Dependent 5
Low-risk Drinkers 38
Abstainers 40
Manwell, et al, 1997
30
Case

• A 36 year old white male presents to your clinic
  for the first time. He reveals that he smoked
  marijuana occasionally in high school.
  Currently, he drinks socially and does not use
  any drugs. You investigate his drinking further.
  He reports drinking a 6-pack with friends on
  Friday night and 6-pack while watching sports on
  Saturday or Sunday. His drinking has never
  interfered with his daily activities.
• Are his drinking habits consistent with hazardous
  drinking, alcohol abuse, or alcohol dependence,
  OR is his drinking of no concern?

31
Screening for Substance Abuse
32
Screening for Alcohol Abuse
Alcohol Use
None
Light
Moderate
Heavy
Hazardous
Abuse
Dependent
Low Risk
Severe
Moderate
Small
None
Alcohol Problems
33
NIAAA Guidelines

• Low risk drinking
• Men lt 14 drinks/wk lt 4 drinks/occ
• Womenlt 7 drinks/wk lt 3 drinks/occ
• No use in risky situations
• Hazardous (at risk) drinking
• Men gt14 drinks/wk gt4 drinks/occ
• Women over 65
• gt7 drinks/wk gt3 drinks/occ
• National Institute on Alcohol Abuse and
  Alcoholism. Physicians Guide to Helping People
  with Alcohol Problems, 1995,2003

34
What is a Standard Drink?
1 can of ordinary beer or ale 12 oz.
single shot of spirits, gin, whiskey, vodka,
etc.. 1.5 oz.
small glass of sherry 4 oz.
glass of wine 5 oz.
small glass of liqueur or aperitif 4 oz.
35
Screening Instruments

• Common in Practice
• Quantity frequency
• CAGE
• AUDIT-C
• Piccinelli 97, Bradley 98, 03, Reid 99,
  Knight 01, Isaacson 94, Brown 95

• Other Screens
• MAST (25 items)
• S-MAST
• AUDIT (10 items)
• TWEAK (pregnancy)
• T-ACE (pregnancy)
• CRAFFT (adolescent)
• POSIT (adolescent)
• CAGE-AID (drugs)

36
CAGE Questions

• Cut down on your drinking?
• Annoyed at others criticism of your drinking?
• Guilty about something that happened when you
  were drinking?
• Eye-opener (drink 1st thing in the morning)
• Cut- off point gt 2 positive
• Mayfield, et al Am J Psychiatry
  1311121-1123, 1974

37
CAGE gt 2 Positive Responses

• Sensitivity 77 - 94
• Specificity 76 - 96
• Positive predictive value 55-75, assuming 20
  prevalence

• Limitations
• Lifetime use
• More reliable for alcohol abuse and dependence
• Not as sensitive for
• women
• elderly
• African-Americans

38
Summary of Screening
39
Summary of Screening
Monitor patient progress
40
Detection Time in Urine

• 1-3 days
• marijuana, heroin, cocaine, codeine, morphine
• 2-4 days
• Amphetamine, methamphetamine, short-acting
  barbiturates, methadone
• Up to 30 days
• chronic marijuana or PCP use
• long-acting benzodiazepines

41
Case

• A 36 year old white male present to your clinic
  for the first time. He reveals that he smoked
  marijuana occasionally in high school.
  Currently, he drinks socially and does not use
  any drugs. You investigate his drinking further.
  He reports drinking a 6-pack with friends on
  Friday night and a 6-pack while watching sports
  on Saturday or Sunday. His drinking has never
  interfered with his daily activities.
• Are his drinking habits consistent with hazardous
  drinking, alcohol abuse, or alcohol dependence,
  OR is his drinking of no concern?

42
Brief Interventions and Motivational Interviewing
43
Readiness to Change Model

• Precontemplation

Contemplation
Relapse
Determination
Maintenance
Action
44
Motivational InterviewingMotivational
interviewing is a directive, client-centered
counseling style for eliciting behavior change by
helping clients explore and resolve ambivalence.
Stephen Rollnick, William R. Miller, 1995
Rollnick, S., Miller, W. R. What is
motivational interviewing? Behavioral and
Cognitive Psychotherapy. 199523325-334.
45
Motivational Interviewing Techniques

• Develop discrepancy
• Avoid argumentation
• Role with Resistance
• Express Empathy
• Support Self-efficacy

Miller WR, Rollnick S, Conforti K. Motivational
Interviewing, Second Edition Preparing People
for Change. New York Guilford Press 2002.
46
Brief Intervention

• 5-15 minute counseling session
• Four components
• State your concerns about patients use of
  alcohol/drugs
• Make explicit recommendation for change in
  behavior
• Discuss patients reaction
• Review treatment options negotiate plan

47
Case

• A 42 year old Navajo male is brought by EMS to
  the ER with altered mental status. He ended a
  7-day alcohol binge 1 day ago. His blood alcohol
  level is negligible, and he is admitted for
  alcohol withdrawal. He is given 4mg of lorazepam
  IV in the ER followed by 2mg upon arrival to the
  floor. He receives scheduled lorazepam, 2mg IV
  every 6 hours. Over the next 12-16 hours, he
  becomes progressively more agitated. His nurse
  calls you, and you give him a booster of
  lorazepam 4mg IV.

48
Case

• She calls you back in 1 hr and tells you that he
  is still very agitated with a pulse of 140 bpm
  and BP of 185/100. You give him an additional
  4mg of lorazepam. The nurse calls you after
  30min and says that he is out-of-control. He
  is pulling fiercely at his restraints, screaming,
  and complaining of insects on the wall, and his
  BP and pulse are still elevated. You give him
  4mg more of lorazepam, but he does not improve.
• What should you do next?

49
Management of Alcohol Abuse

• Inpatient and Outpatient Management

50
Alcohol Withdrawal

• Onset 5-10 hrs, peak 2-3 days, resolve 4-5 days
• Signs and symptoms ( 2 by DSM IV criteria)
• Autonomic hyperactivity (sweating, tachycardia, ?
  BP)
• Tremor
• Nausea/vomiting
• Anxiety
• Psychomotor agitation
• Anxiety
• Grand mal seizures
• Hallucinations (tactile, visual, auditory)

51
Management of Alcohol WithdrawalASAM Guidelines

• Symptom-triggered (q1h when severe)
• Chlordiazepoxide 50-100 mg
• Diazepam 10-20 mg
• Lorazepam 2-4 mg
• Fixed Schedule (q6h for 4/8 doses prn)
• Chlordiazepoxide 50mg/25mg
• Diazepam 10mg/5mg
• Lorazepam 2mg/1mg

Mayo-Smith and ASAM working group JAMA
1997278144-51 Saitz and OMalley Med Clin N A
199781881-907
52
Management of Alcohol Abuse or Addiction
(Inpatient or Outpatient)

1. Detoxification (inpatient vs. outpatient)
2. Social Services (psychological, medical,
   employment, and legal problems)
3. Removal from drinking environment
4. Mutual/self-help groups (AA, NA, cocaine
   anonymous, etc.)
5. Counseling (cognitive-behavioral, family,
   psychotherapy,etc.)
6. Pharmacotherapy

53
Disulfiram

• Relevant mechanism
• Inhibits ALDH allowing acetaldehyde to
  accumulate
• Desired effects (take qd or before risky
  situation)
• Flushing, tachycardia, nausea, vomiting,
  hypotension, blurred vision, confusion, dizziness
  (30 minutes)
• Side effects
• Lethargy, neuropathy, liver toxicity, psychosis,
  HTN

54
Disulfiram (DS)

• Multicenter RCT, 12 month follow-up, N605
• DS 250 mg, 1 mg, or none
• More abstinence in those adherent to DS (43 vs.
  8, plt0.001)
• Fewer drinking days in the 162 who were assigned
  to DS, adhered, and completed follow-up, compared
  with the other 2 groups (p0.05)
• Need supervised administration and involvement
  of counselor

Fuller RK et al. JAMA 2561449, 1986
55
Supervised Disulfiram randomized studies
 Length of follow-up was as follows Gerrein
1973 8 weeks Azrin 1976 2 years, Azrin 1982
6 months Liebson 1978 6 months.  Thirty-day
abstinence at 6-months
56
Naltrexone

• Relevant mechanism
• Blocks endogenous opioids release due to dopamine
  release in reward center
• Desired Effects
• Less pleasurable effect of alcohol, reinforcement
• Side Effects
• Nausea, dizziness, hepatotoxicity, difficult pain
  management
• Contraindications
• Opiate dependence, pregnancy, active liver disease

57
Naltrexone for Alcohol Dependence
Combined analysis from Volpicelli (1992) and
OMalleys (1992) studies, N186. Taken
from O'Brien CP, McLellan AT. Lancet
1996347237-240.
58
Naltrexone Initial and Maintenance Treatment
STUDY 1 Initial Naltrexone Treatment Randomized
(n 197) 10 weeks
Received CBT NTX (n 97)
Received PCM NTX (n 93)
STUDY 2. CBT Naltrexone Maintenance Responders
randomized (n 60) 24 weeks
STUDY 3. PCM Naltrexone Maintenance Responders
randomized (n 53) 24 weeks
Received CBT NTX (n 30)
Received CBT PLA (n 30)
Received PCM NX (n 26)
Received PCM PLA (n 27)
59
Naltrexone Initial and Maintenance Treatment
CBT
PCM (n97) (n93) Primary
Outcomes Responder (n, ) 77 (79.4) 74
(79.6) Percentage of days abstinent 79.9
31.4 77.9 30.9 Secondary Outcomes Drinks per
drinking day 3.3 5.6 3.3 4.7 No relapse
to heavy drinking 60 (61.9) 52
(55.9) Continuous Abstinence (n, ) 43
(44.3) 31 (33.3) GGT end point change
from baseline (mean SD) -43.1 75.3 -37.9
65.7 OCDS total score Therapy (mean SD)
8.0 5.4 8.2 5.8
60
Acamprosate

• Relevant mechanism unclear GABA analogue
• Desired effects unclear
• Side effects diarrhea
• Increased abstinence, decreased drinking days
• Not available (yet) in the US

61
Management of Opioid Abuse and Addiction

• Inpatient and Outpatient Management

62
Opioids
Natural (opiates), Semisynthetic, and synthetic
63
Opioid Intoxication

• Altered level of consciousness
• Respiratory rate lt12 breaths per minute
• Direct effect on brainstem respiratory center
• Reduction of responsiveness to CO2
• Miotic pupils
• Response to naloxone

64
Opioid Overdose Treatment

• Adequate ventilation
• Observation until normal level of consciousness
• Inadequate ventilation
• Ventilate with 100 O2
• Naloxone 0.2-0.4 mg IV, SQ, or IM, repeat with
  1-2 mg if no improvement in 5-7 minutes
• Observe for 2-3 hours for complications or
  re-sedation
• 3-7 complicated by pneumonia, pulm edema
• No prospective clinical trials comparing IV vs IM
  vs. SQ or different doses

65
Opioid Overdose Treatment

• Higher doses may be required for semi-synthetic
  oral opioids
• Small rate (6 of 453 patients) of complications
  with naloxone treatment
• Seizure, arrhythmias, pulmonary edema and severe
  agitation with violent behavior
• All complications occurred within 10 minutes
• Complication rate similar to flumazenil treatment
  for benzodiazepine overdose
• Osterwalder JJ. J Toxicol Clin Tox 1996

66
Naloxone

• Opioid antagonist at mu, kappa and delta
  receptors
• No agonist activity
• Absorbed IV, IM, SQ and endotracheal
• Rapid onset IV but offset by time to place IV
• Orally inactivated by hepatic metabolism
• Highly lipid soluble
• Onset of action 1-2 minutes
• Peak Action 15 minutes
• Duration of action 45-90 minutes

67
Opioid Withdrawal
Hours after use
4-6
6
8-12
12-72
68
Short-term Treatment

• Methadone
• or buprenorphine (more expensive)
• Other
• Clonidine (hyperadrenergic state)
• NSAIDS (muscle cramps and pain)
• Benzodiazepines (insomnia)
• Dicyclomine (abdominal cramps)
• Bismuth subsalicylate (Diarrhea)

69
Heroin versus Methadone
70
Methadone Hydrochloride

• Full opioid agonist available in tablets, oral
  solution, parenteral
• PO onset of action 30-60 minutes
• Duration of action
• 24-36 hours to prevent opioid withdrawal
• 6-8 hours analgesia
• Proper dosing
• Acute withdrawal 20-40 mg
• Chronic withdrawal gt80 mg

71
Inpatient Methadone Dosing Guidelines

• Start with 20 mg of methadone
• Reassess q 2-3 hours, give additional 5-10 mg
  until withdrawal signs abate
• Do not exceed 40 mg in 24 hours
• Monitor for CNS and respiratory depression

72
Inpatient Methadone Dosing Guidelines

• On following day, give total dose QD
• 20 - 40mg QD
• 10 - 20 mg q12
• Goal is to alleviate acute withdrawal
• Patient will continue to crave heroin
• Referral for long-term substance abuse
  treatment
• Allows 24-36 hour withdrawal-free period after
  discharge

73
Long-term Goals

• Detoxification Program (lt15 success)
• Medically supervised withdrawal, a tapering of an
  approved drug to a medication-free state.
• Maintenance Program
• Sustained administration of an approved opioid
  medication at stable doses
• Residential Program
• Outpatient counseling
• Narcotics Anonymous (NA)

74
Maintenance Programs

1. Methadone Maintenance Program
2. Buprenorphine and Buprenorphine/Naloxone
   Treatment Program
3. Naltrexone

75
Methadone Maintenance Treatment

• Daily methadone dosing
• Daily nursing assessment
• Weekly individual and/or group counseling
• Random supervised toxicology screens
• Psychiatric services
• Medical services
• Acupuncture

76
Methadone Effect

• Methadone 20-40 mg
• Treats acute withdrawal
• Methadone gt80 mg
• Treats chronic withdrawal (craving, insomnia)
• Blocks effects of other opioids (e.g. heroin)

77
Methadone Dose Response
Acute w/d
Chronic w/d
78
MMT Decrease Drug Use Over Time
79
MMT Relapse After Leaving Treatment
80
Methadone Maintenance Treatment The Gold
Standard

• In a Comprehensive Rehabilitation Program
• Improves overall survival
• Increases retention in treatment
• Decreases illicit opioid use
• Decreases seroconversion of hepatitis and HIV
• Decreases criminal activity
• Increases employment
• Improves birth outcomes

81
Buprenorphine Treatment Program

• Partial agonist
• Ceiling effect on respiratory and CNS depression
• Antagonizes effect to full agonists

82
Buprenorphine Treatment Program

• Retention rates comparable to methadone
• Efficacy comparable to methadone (80mg)
• Milder withdrawal syndrome
• Very low risk for overdose
• Decreased risk of abuse and diversion
  (Buprenorphine/Naloxone)
• Available in Primary Care Settings

83
Buprenorphine Precipitated Withdrawal

• Displaces a full agonist off the mu receptors
• Buprenorphine only partially activates receptors
• Net decrease in activation occurs and withdrawal
  develops (must be in withdrawal to start)

84
Naltrexone

• Opioid antagonist
• Low interest among street addicts
• No better than placebo except in highly motivated
  patients
• Impaired physicians gt 80 abstinence at 18 months

85
Resources
86
Resources
87
Resources

• National Institute on Drug Abuse
• www.nida.nih.gov
• www.drugabuse.gov
• Presbyterian Hospital MHMR
• Inpatient and outpatient treatment programs
• Pat Tally [phone]
• Greater Dallas Council on Drug and Alcohol Abuse
• [phone]