A classroom presentation on opioid dependence and management

1. OPIOID
DEPENDENCE
Presented By
Dr. Nashid Islam
Dr. Jheelam Biswas
Resident , Palliative medicine
BSMMU

2. WHAT ARE OPIOIDS? (A QUICK
REVIEW!)
 Opioids are a class of drugs that act
primarily on the body’s opioid
receptors.
 Opioids are often referred to as
narcotics.
 They act by blocking μ, κ, σ and possibly
δ receptor classes.
 Most opioid receptors are found in the
central nervous system and in the
gastrointestinal tract.
Morphine

3. ADDICTION, DEPENDENCE AND
TOLERANCE
 Drug addiction: is a condition in which an individual has lost
the power of self-control with reference to a drug and
abuses the drug to such an extent that the individual,
society, or both are harmed.
 Dependence: refers to a state resulting from habitual use of
a drug, where negative physical withdrawal symptoms result
from abrupt discontinuation.
 Tolerance: describes the need for a drug user to administer
larger and larger doses of the drug to achieve the same
psychoactive effect.

4. MECHANISM OF DEPENDENCE
AND ADDICTION
a) Negative Reinforcement Models:
• Physical dependence (withdrawal) theory
–driven largely by opiates, barbiturates, alcohol
–based largely on tolerance and physical
dependence
• Self-Medication Hypothesis
b) Positive Reinforcement Models:
• Positive incentive (reward) theory
–driven largely by cocaine, amphetamine, nicotine
–based largely on reward and reinforcement

5. PHYSICAL DEPENDENCE THEORY
•Take drug -> nasty withdrawal goes away
•So by this theory, if we treat withdrawal (or wait for it to go
away), we treat addiction.
•Note that this theory assumes addiction = dependence

6. POSITIVE INCENTIVE THEORY
• Positive reinforcement - response that is followed by
pleasant consequences likely to be repeated
• Take drug to get euphoria or drug "high"
• Can account for addictiveness (most to least):
Amphetamine > Heroin = Cocaine >Morphine

7. •Initial exposure to a drug of abuse may produce effects
which are interpreted by the individual as “desirable” or
“pleasurable”, i.e. “rewarding”.
• These effects may lead to “craving” or “hunger” for the
drug, with resultant spontaneous activity or work for drug
acquisition and self-administration.
REINFORCING OR “REWARD”
EFFECTS
Kreek, 1987; 2005

8. RELATIONSHIP BETWEEN
DEPENDENCE AND ADDICTION

9. NEURO CHEMICAL MEDIATORS
OF “REWARDING” OR
“REINFORCING”
 Dopamine
 Mu opioid receptor agonists (e.g., beta-endorphin and
enkephlins)
 CRF and ACTH (e.g., cocaine and alcoholism)
 +/- serotonin,
 +/- norepinephrine
Kreek, 2003; 2007

10. MECHANISM OF TOLERANCE
Two factors have been isolated
1. Receptor Downregulation: Opioid receptors in the
body are actively reduced due to overexposure to
opioids. This can also have an effect on regular
functioning of endorphins.
2. Antiopiates: Chemicals like neuropeptide, orphanin,
nociceptin, have all been found to block the function of
opioids.

11. DSM-IV CRITERIA OF
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

12. DSM IV CRITERIA OF ABUSE
 1 in 12 months:
Failure to fulfill role
Use in hazardous situations
Legal problems
Use despite problems

13. SYMPTOMS OF OPIOID
OVERDOSE
 Euphoria + + +
 Unconsciousness
 Respiratory depression
 Pulmonary edema
 Seizures
 Hypothermia
 Death

14. SYMPTOMS OF OPIOID WITHDRAWAL
 After quit or ↓chronic use or use of opioid antagonist
 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

15. OPIOID ABSTINENCE
SYNDROME
 Lacrimation
 Yawning
 Chills
 Gooseflesh
 Hyperventilation
 Diarrhea
 Insomnia
 Hostility
 Hyperthermia
 Mydriasis
 Muscle aches
 Vomiting

16. WHO ARE IN THE RISK OF
ADDICTION
 Rates of abuse and/or addiction in chronic pain
populations are 3-19%
 Known risk factors for addiction are-
-Past cocaine use,
-History of alcohol or cannabis use,
-Lifetime history of substance use disorder
-Family history of substance abuse,
-Tobacco use
- History of severe depression or anxiety

17. OPIOID ADDICTION TREATMENT
OUTLINE
The three most prevalent approaches:
•Drug Substitution Treatment, which is also called “medication-
assisted treatment”
•Abstinence-Based Treatment, in which total abstinence
following a brief detoxification
•Psychosocial and Behavioral Treatments

18. TRADITIONAL DRUG BASED
TREATMENTS
 The primary method of treating and managing opioid
addiction and dependence has been with the use of other
opioid drugs.
 These drugs are-
-Methadone
-Buprenorphine
 These replacement drugs function to essentially wean the
user off of opioid use in case of chronic relapsing
dependence.

19. METHADONE
 Properties:
 u opioid receptor agonist
 produces the typical morphine like effect.
 Methadone suppresses opioid withdrawal effects
 Doses:
 starting dose 20-30 mg, with 5 to 10 mg increases every other
day as tolerated.
 Target dose 50 mg/day, highest dose 100 mg/day

20. METHADONE BENEFITS
Methadone Maintenance Therapy (MMT) is widely used
because-
 reduces illicit drug use;
 Reduces relapse, improves psychological factors
 advances personal, academic and workplace functionality;
 increases treatment retention;
 and reduces chances of accidental overdose
 Can be used for a long time

21. BUPRENORPHINE
 Properties
 Partial µ agonist activity with ceiling
 Long half life
 Decreased risk of respiratory, CNS depression
 “Combo” tablet with naloxone limits abuse
 Doses:
 Starting dose- 4/1 mg buprenorphine/ naloxone .
 Maintaince dose- 12/3 to 16/4 mg per day
 Three times weekly dosing as generally recommended

22. BUPRENORPHINE SAFETY
 No alteration of cognitive functioning
feel “normal”
 No organ damage
Early concern of hepatic toxicity unconfirmed
No evidence of QT prolongation
 No clinically significant interactions with other drugs

23. METHADONE VS. BUPRENORPHINE
Methadone Buprenorphine
• Criteria:
Withdrawal symp
>12 months use
• Criteria:
DSM IV of abuse
No time criteria
• Age > 18 • Age > 16
Duration of treatment is still debatable, but most addiction
clinics continue these drugs indefinitely.

24. OPIOID ANTAGONIST
PHARMACOTHERAPY
Naltrexone
 Properties:
 Competitive opioid antagonist
 Orally effective and
 can block opioid effects for 24 hours
 Doses:
 Initial dose of 25 mg or 50 mg, the following dose schedules
have been used for naltrexone :(1) 50 mg daily (2) 100 mg every
other day

25.  Criteria for Naltrexone use:
 To minimize the precipitations of opioid withdrawal,
naltrexone treatment should not be initiated until the patient
is opioid free for 7 to 10 days
 Recommended for acute opioid intoxication, but it does not
reduce opioid curving, so not recommended for long time use.

26. ABSTINENCE-BASED TREATMENT
 Quitting opioid use abruptly and completely is the cheapest
method.
 Significant withdrawal symptoms occurs.
 The symptoms increase in severity over two to three days.
 Within a week to 10 days the illness is over.
 But not very much recommended because of the withdrawal
symptoms and tendency to relapse.

27. OPIOID TAPERING
 It is not wise to quit opioid abruptly in out patient setting. So
tapering of opioid is advised.
 Katrina Disaster Working Group Suggested Tapering
Regimens [AAPM 2005]
 Reduction of daily dose by 10% each day, or…
 Reduction of daily dose by 20% every 3-5 days, or…
 Reduction of daily dose by 25% each week.

28. VA CLINICAL GUIDELINE
TAPERING REGIMENS
 Short-Acting Opioids [2003]
 Decrease dose by 10% every 3-7 days, or…
 Decrease dose by 20%-50% per day until lowest available
dosage form is reached
 Then increase the dosing interval, eliminating one dose every
2-5 days.

29. LONG ACTING OPIOIDS
 Methadone
 Decrease dose by 20%-50% per day to 30 mg/day, then…
 Decrease by 5 mg/day every 3-5 days to 10 mg/day, then...
 Decrease by 2.5 mg/day every 3-5 days.
 Morphine CR (controlled-release)
 Decrease dose by 20%-50% per day to 45 mg/day, then…
 Decrease by 15 mg/day every 2-5 days.

30.  Oxycodone CR (controlled-release)
 Decrease by 20%-50% per day to 30 mg/day, then…
 Decrease by 10 mg/day every 2-5 days.
 Fentanyl
 first rotate to another opioid, such as morphine CR or
methadone, then tapering done according to previous
guideline.

31. DETOXIFICATION
 It is the management of withdrawal.
 Categorized according to their duration :
 long term (typically 180 days),
 short term (upto 30 days),
 rapid (typically 3-10 days), and
 ultra-rapid (1-2 days)
 Long term and short term detoxification are practically
applied.

32.  The Pharmacologic agents used during detoxification-
 Methadone , 10-40mg/24 hrs, tapered after control of
abstinence symptoms
 Buprenorphine , 2-4 mg/day sublingually, well tolerated and
effective for withdrawal symps.
 Naloxone/Naltrexone, used in rapid detoxification
 Clonidine, used with Naloxone
 Benzodiazepines, for muscle cramp

33. PSYCHOSOCIAL TREATMENTS
 5 modalities of treatment-
 Cognitive Behavioral Therapies
 Behavioral Therapies
 Group and Family Therapy
 Psychodynamic Psychotherapies
 Self-Help Groups

34. POST ACUTE WITHDRAWAL
SYNDROME
Starts after acute withdrawal ends. This syndrome often lasts
for several months.
Symptoms include difficulty with…
 Thinking clearly
 Remembering
 Stress management
 Emotion management
 Sleeping restfully
 Physical coordination

35. MANAGEMENT
Some things that are helpful for management of including-
 Having a structured lifestyle
 Getting enough rest
 Healthy diet and eating habits
 Regular exercise
 Social support
 Deep-breathing relaxation skills
 Emotion management skills
 Conflict management skills
 H.A.L.T. – Don’t get too Hungry, Angry, Lonely or Tired.

36. ADDICTIVE PREOCCUPATION
 A type of delusional thinking associated with-
 Euphoric recall (recalling only the positives about using)
 “Awfulizing” sobriety (focusing on only the negatives
about sobriety)
 Magical thinking about future use (thinking using will
somehow make things better)
 Left unattended, this becomes obsession, compulsion and
craving.

37. MANAGEMENT
 Euphoric recall
Force yourself to remember specific negative experiences
involving using.
 “Awfulizing” sobriety
Force yourself to consider positive things about recovery.
 Magical thinking about future use
Force yourself to consider what would actually happen if you
used.

38. RECOVERY
 There are 6 stages of recovery-
1. Transition-
The person is still using, but gradually motivated to give up
using.
2. Stabilization-
physically recover from acute withdrawal and learn to manage
post acute withdrawal.

39. 3. Early recovery-
the person becomes fully conscious recognition of addictive
disease
Learns non-chemical coping skills
4. Middle recovery-
The person faces and resolves the demoralization crisis
Repairing addiction-caused social damage.

40. 5. Late recovery
Recognizing the effects problems on sobriety
Change in lifestyle
6. Maintenance Stage:
Balanced living and continued day to day coping

41. SPECIAL CONSIDERATIONS IN
TREATING
OPIATE ADDICTS
After stopping using, opiate addicts commonly experience…
 Discomfort of body, mind and spirit
 Vivid using dreams, drug cravings
 Depression and anxiety
 Strong urge to abort treatment due to discomfort of early
abstinence
So we need to approach them with empathic listening and
attempt to understand their distress throughout the
treatment .

42. CONCLUSIONS
 Opioid dependence is a serious issue that must be given
more thought than at present.
 Current treatments are only partially successful in
breaking the hold of addiction and dependence on the
addict.

43. THANK YOUTHANK YOU