1. Opioid Abuse and Dependence
Maritza Lagos, M.D.
Michigan State University
Kalamazoo Center for Medical Studies

2. Why Important? Non-medical use of Rx opioids:
↑ in US
12th graders:
1991  1%
2006  4 %
Lack of education (< 40 % of MDs trained)
MTF DATA
IN CONTRAST, SURVEYS OF THE NATIONAL CTR ON ADDICTION AND SUBSATNCE ABUSE @ COLUMBIA UNIVERSITY REPORT…..
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3. Opioids: Double-edged sword
Cornerstone of pain management
Mood altering properties
SUBJECTED SERIOUS SIDE EFFECTS: SEDATION, RESP Dep, tolerance, OD LEADING TO INC Physi liability

4. Physicians’ Dilemma and Challenge
To prescribe
Not to prescribe
Opiophobia vs generous prescriber
HOW TO BALANCE SO BENEFITS OUTWEIGH HARMS
Know, monitor, and balance use
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5. This Lecture Will Cover:
Classifications
Pharmacology
Use of Opioids
Assessment & Treatment
© AMSP

6. History Morphine: early 1800’s Heroin: late 1800’s
Sumerians and Egyptians
Medicinal value
Morphine: early 1800’s
Heroin: late 1800’s
Methadone: prior to WW II
ISOLATED
DEVELOPED IN GERMANY AND BY DRS DOLE & NYSWANDER
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7. Opiates Semi- synthetics morphine heroin codeine oxycodone hydrocodone
thebaine
buprenorphine
naloxone
Natural alkaloids
Semi-
synthetics
DERIVED FROM EXTRACTS OF THE JUICE OF THE POPPY PLANT
PREPARATIONS OF THESE NATURAL ALCALOIDS OR SEMI SYN DERIVATIVES
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8. Bind to opioid receptors
OPIOIDS
fully synthetic
OPIATES
Bind to opioid receptors
Morphine-like action
DSM-IV: OPIOIDS
FULLY SYNTHETIC CHEMICALS
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9. Opioid Classification
Full agonists:
morphine
oxycodone
Partial agonist:
butorphanol
CMATOSE PT WITH DEPRESSED RESPIRATION: ESTABLISH A PATENT AIRWAY AND VENTILATE
Antagonists:
naloxone
naltrexone
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10. Opioids FULL Pure agonists Antagonists Mixed agonists/ antagonists
morphine
oxycodone
fentanyl
PARTIAL
butorphanol
pentazocine
Antagonists
PURE
naloxone
naltrexone
Mixed agonists/
antagonists
buprenorphine
nalbuphine
others
tramadol
THIS IS JUST TO EXPAND ON THE PREVIOUS CLASSIFICATION
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11. Opioid Abuse/Dependence
Classifications
Pharmacology
Use of Opioids
Assessment & Treatment
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12. Opioid Receptors µ (mu):
Activated by morphine: analgesia
Primary action site of all opioids
Distribution: CNS and GI
Linked to abuse/dependence
κ (kappa): analgesia, endocrine changes and dysphoria
δ (delta): for endogenous peptides
OUT OF 17 RECEP DESCRIBED IN THE LITERATURE
MU: ANALGESIA BECAUSE EUPHORIC EFFECTS AND + REINF
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13. Binding Sites © AMSP Localization of opiate binding sites
When a person injects heroin or morphine travels quickly to the brain and concentrate in: VTA, nucleus accumbens, caudate nucleus and thalamus are highlighted. The opiates bind to opiate receptors that are concentrated in areas within the reward system. The action of opiates in the thalamus contributes to their ability to produce analgesia.
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14. opiate binding in nucleus accumbens and activation of the reward pathway
The big picture: As a result of opiate actions in the nucleus accumbens (the sprinkles of opiates), there are increased impulses leaving the nucleus accumbens to activate the reward system (the frontal cortex). As with cocaine, continued use of opiates makes the body rely on the presence of the drug to maintain rewarding feelings and other normal behaviors. The person is no longer able to feel the benefits of natural rewards (food, water, sex) and can't function normally without the drug present.
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15. Pharmacodynamics: CNS
Desirable:
Analgesia
Cough suppression
Undesirable:
Euphoria
Respiration
Sedation
Endocrine effects
EUPHORIA & REWARD CONDUCIVE TO ABUSE AND DEPENDENCE
RESPIR: DOSE DEPENDENT AND MOST SERIOUS
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16. Pharmacodynamics: GI Desirable: Undesirable: Nausea, vomiting
Antidiarrheal
Inhibit peristalsis
NAUSEA & VOMITING: CHMORECEPTOR TRIGGER ZONE
Undesirable:
Nausea, vomiting
Constipation
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17. Pharmacokinetics Absorption: GI tract Distribution: protein binding
Biotransformation: liver
Excretion: kidney and GI (bile)
Differs by age, gender
LIPID SOLUBLE: NASAL AND BUCCAL MUCOSA AND THE SKIN
FIRST-PASS RATE
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18. Pharmacokinetics ~3 hr 24 hr ~5 hr ~6 hr Limited Significant 6/1 2/1
OPIOID
MORPHINE
METHADONE
Plasma ½ life
~3 hr
24 hr
Duration - analgesia
~5 hr
~6 hr
Stored in body
Limited
Significant
IM/oral potency
6/1
2/1
Elimination
Kidney>>Gut
Kidney=Gut
Stored=accumulation
© AMSP
© AMSP 18

19. Opioid Abuse/Dependence
Classifications
Pharmacology
Use of Opioids
Assessment & Treatment
© AMSP

20. Medical Use of Opioids Analgesia Severe diarrhea Cough suppressant
Maintenance tx of opioid dependence
Methadone & buprenorphine / naloxone
Long-term administration
Blocks effects of opioids  ↓illicit use
BEFORE TALKING ABOUT ABUSE AND DEPENDENCE
ANALGESIA; MORPHIN, POWERFUL, LOCAL, PCA , GENERAL ANESTHE
METHDONE BLOCKS EFFECTS OF OPIOIDS AND REDUCES ILLICIT OPIOID USE
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21. Rx Opioids Incorrect use Mismanaged Illegal use Most commonly used
Misuse
Non-medical
Incorrect use
By patient
Mismanaged
By physicians
D ated
D uped
D isabled
D ishonest
Illegal use
Not prescribed
Took for euphoria
Most commonly used
In US, age 12 +:
Past month 2%
Lifetime: 14%
ELDERLY, ILLITERATE, CONFUSED
PHYSICIANS MAY BE CLASSIFIED IN ONE OF THESE CATEGORIES
OPIOIDS ARE THE MOST COMMON CLASS
RESULTS OF THE 2006 NATIONAL SURVEY ON DRUG USE AND HEALTH
© AMSP

22. Dependence 3+ in same 12 months Tolerance Withdrawal
Larger & longer use than intended
Can’t quit
Much time obtaining, using, or recovering
↓ activities
Continued use despite problems
CATASTROPHIC
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23. Abuse Not if dependent 1 in 12 months: Failure to fulfill role
Use in hazardous situations
Legal problems
Use despite problems
PATTERN OF REPETITIVE AND MALADAPTIVE
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24. Abuse/Dependence Annual Prevalence
NSDUH 2006
1.7%
0.7%
0.7%
RESULTS OF THE 2006 NATIONAL SURVEY ON DRUG USE AND HEALTH
0.1%
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25. Opioid Tolerance With repeated use Need ↑ doses to maintain effect
Can see in pain patients
Adaptation of receptors
Different rates for each effect
PHENOMENON THAT DEVELOPS WITH CERTAIN SUBSTANCES
EXAMPLE
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26. Opioid Withdrawal After quit or ↓chronic use or antagonist
Opposite to agonist effects
DSM-IV criteria: 3+ (minutes to days):
Unhappy mood
Muscle aches
Tearing/runny nose
Pupillary dilation
Goose bumps or sweating
Nausea/Vomiting
Diarrhea – Fever - Yawning
TOP TO BOTTOM
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27. Opioid Overdose Recent use Life threatening Constricted pupils 1+:
Drowsiness or coma
Slurred speech
Poor attention and memory
Can not allow yourself to take a break
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28. Opioid Abuse/Dependence
Classifications
Pharmacology
Use of Opioids
Assessment & Treatment
© AMSP

29. Treatment Goals ↓ or eliminate use ↓ risks: Address: Overdose IV use
Dependence
Address:
Co-morbid conditions
Psychosocial outcomes
Somatic needs
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30. Treatment Diagnosis: DSM-IV Lab tests
Direct , empathic, non-judgmental
Lab tests
Urine, blood, others
12-36 hrs after use
Targeted to morphine and most opiates
Methadone: GC/MS
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31. Acute Intervention Overdose Withdrawal Emergency Support vital signs
Naloxone: 0.4 mg q 2-3 min. SC/IV
Withdrawal
Rating scales: CINA, COWS
Opioid substitution with gradual ↓
Symptomatic treatment
CINA: Clinical Institute Narcotic Assessment. Adapted from Peachey, J.E., and Lei, H. Assessment of opioid dependence with naloxone. British Journal of Addiction 83(2):193–201, 1988.
COWS - Clinical Opiate Withdrawal Scale. Wesson et al
; 11 ITEMS RATED BY THE CLINICIAN 5-36
NOR ADRENERGIC HYPERACTIVITY IN THE LOC C
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32. Maintenance Treatment
When chronic & relapsing condition
Most studies for heroin dependence
Goals:
Achieve a stable dose that
Suppresses withdrawal
↓ craving
Block effects of illicit opioids
Facilitate and promote rehabilitation
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33. Pharmacological Treatment
Methadone
Full µ agonists
Once/day dosed
40-60 mg/d: sufficient to block withdrawal sx.
Buprenorphine/Naloxone
µ Receptor partial agonist
Kappa receptor partial antagonist
12-16 mg/d
Combination ↓ risk of diversion
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34. Psychosocial Treatment
Specialized programs
Cognitive behavioral therapy
Behavioral therapy
Psychodynamic/interpersonal
Recovery-oriented therapies
Group and Family therapy
Self-help groups: NA, Al-Anon
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35. Summary Pain relief, but … misuse/dependence
Can’t separate misuse & therapeutic use
Tolerance, abuse and dependence
Learn to use it
Monitor effectiveness and side effects
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