Opioid Abuse and

Dependence

Mr. Raghavendra Kumar Gunda

Assistant professor
MAM College of Pharmacy
 Why Important?
• Non-medical use of Rx opioids:
– ↑ in US

– 12th graders:

• 1991  1%

• 2006  4 %

• Lack of education (< 40 % of MDs trained)

© AMSP 2
Opioids: Double-edged sword

Cornerstone
of pain
management Mood altering
properties

3
Physicians’ Dilemma and Challenge

To prescribe

Not to
prescribe

Know, monitor, and balance use

© AMSP 4
 This Lecture Will Cover:

1.Classifications

2. Pharmacology

3. Use of Opioids

4. Assessment & Treatment

© AMSP 5
 History
• Sumerians and Egyptians
– Medicinal value

• Morphine: early 1800’s

• Heroin: late 1800’s
• Methadone: prior to WW II

© AMSP 6
 Opiates

Natural Semi-
alkaloids synthetics

morphine heroin

oxycodone
codeine

hydrocodone

thebaine buprenorphine
naloxone
© AMSP 7
 OPIOIDS OPIATES
fully synthetic

Bind to opioid receptors

Morphine-like action

DSM-IV: OPIOIDS
© AMSP 8
 Opioid Classification

Full agonists:
•morphine
•oxycodone

Partial agonist:
•butorphanol

Antagonists:
•naloxone
•naltrexone
© AMSP 9
 Opioids
Pure Antagonists Mixed others
agonists agonists/
PURE antagonists
naloxone
FULL
• morphine tramadol
• oxycodone naltrexone
• fentanyl

buprenorphine
PARTIAL
butorphanol
nalbuphine
pentazocine
© AMSP 10
 Opioid Abuse/Dependence

 Classifications

 Pharmacology

 Use of Opioids

 Assessment & Treatment

© AMSP 11
 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
© AMSP 12
 Binding Sites

© AMSP 13
© AMSP 14
 Pharmacodynamics: CNS

Desirable:
• Analgesia
• Cough suppression

Undesirable:
• Euphoria
• Respiration
• Sedation
• Endocrine effects
© AMSP 15
 Pharmacodynamics: GI

Desirable:
• Antidiarrheal
• Inhibit peristalsis

Undesirable:
• Nausea, vomiting
• Constipation

© AMSP 16
 Pharmacokinetics
• Absorption: GI tract

• Distribution: protein binding

• Biotransformation: liver

• Excretion: kidney and GI (bile)

• Differs by age, gender

© AMSP 17
 Pharmacokinetics
OPIOID MORPHINE METHADONE

Plasma ½ life ~3 hr 24 hr
Duration - ~5 hr ~6 hr
analgesia
Stored in body Limited Significant
IM/oral 6/1 2/1
potency
Elimination Kidney>>Gut Kidney=Gut
© AMSP 18
 Opioid Abuse/Dependence

 Classifications

 Pharmacology

 Use of Opioids

 Assessment & Treatment

© AMSP 19
 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

© AMSP 20
 Rx Opioids
Misuse Non-medical
• Incorrect use • Illegal use
– By patient – Not prescribed
• Mismanaged – Took for euphoria
– By physicians • Most commonly
• D ated used
• D uped • In US, age 12 +:
• D isabled – Past month 2%
• D ishonest – Lifetime: 14%

© AMSP 21
 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

© AMSP 22
 Abuse
• Not if dependent
• 1 in 12 months:
– Failure to fulfill role
– Use in hazardous situations
– Legal problems
– Use despite problems

© AMSP 23
 Abuse/Dependence
Annual Prevalence
NSDUH 2006

THC
1.7%

Cocaine 0.7%

Rx opioids 0.7%

Heroin 0.1%

0 0.5 1 1.5 2

24
© AMSP
 Opioid Tolerance
• With repeated use
• Need ↑ doses to maintain effect
• Can see in pain patients
• Adaptation of receptors
• Different rates for each effect

© AMSP 25
 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
© AMSP 26
 Opioid Overdose
• Recent use
• Life threatening
• Constricted pupils
• 1+:
– Drowsiness or coma
– Slurred speech
– Poor attention and memory

© AMSP 27
 Opioid Abuse/Dependence

 Classifications

 Pharmacology

 Use of Opioids

 Assessment & Treatment

© AMSP 28
 Treatment Goals
• ↓ or eliminate use
• ↓ risks:
– Overdose
– IV use
– Dependence
• Address:
– Co-morbid conditions
– Psychosocial outcomes
– Somatic needs
© AMSP 29
 Treatment
• Diagnosis: DSM-IV
– Direct , empathic, non-judgmental

• Lab tests
– Urine, blood, others
– 12-36 hrs after use
– Targeted to morphine and most opiates
– Methadone: GC/MS

© AMSP 30
 Acute Intervention
• Overdose
– 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
© AMSP 31
 Maintenance Treatment
• When chronic & relapsing condition
• Most studies for heroin dependence
• Goals:
1. Achieve a stable dose that
 Suppresses withdrawal
 ↓ craving
 Block effects of illicit opioids
2. Facilitate and promote rehabilitation

© AMSP 32
 Pharmacological Treatment

1. Methadone
 Full µ agonists
 Once/day dosed
 40-60 mg/d: sufficient to block withdrawal sx.
2. Buprenorphine/Naloxone
 µ Receptor partial agonist
 Kappa receptor partial antagonist
 12-16 mg/d
 Combination ↓ risk of diversion

© AMSP 33
 Psychosocial Treatment
• Specialized programs
• Cognitive behavioral therapy
• Behavioral therapy
• Psychodynamic/interpersonal
• Recovery-oriented therapies
• Group and Family therapy
• Self-help groups: NA, Al-Anon

© AMSP 34
 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

© AMSP 35