Opioid Abuse and Dependence

Maritza Lagos, M.D. Michigan State University

Kalamazoo Center for Medical Studies

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Why Important?

• Non-medical use of Rx opioids:

– ↑ in US

– 12th graders:

• 1991 1%

• 2006 4 %

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

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Opioids: Double-edged sword

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Physicians’ Dilemma and Challenge

Know, monitor, and balance use

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This Lecture Will Cover:

1.Classifications

2. Pharmacology

3. Use of Opioids

4. Assessment & Treatment

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History

• Sumerians and Egyptians

– Medicinal value

• Morphine: early 1800’s

• Heroin: late 1800’s

• Methadone: prior to WW II

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Opiates

Semi-synthetics

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OPIOIDSfully synthetic

OPIATES

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Opioid Classification

Full agonists:•morphine•oxycodone

Partial agonist:•butorphanol

Antagonists:•naloxone•naltrexone

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Opioids

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Opioid Abuse/Dependence

Classifications

Pharmacology

Use of Opioids

Assessment & Treatment

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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

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Binding Sites

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Pharmacodynamics: CNS

Undesirable:• EuphoriaRespiration• Sedation• Endocrine effects

Desirable:• Analgesia• Cough suppression

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Pharmacodynamics: GI

Undesirable:• Nausea, vomiting • Constipation

Desirable:• Antidiarrheal• Inhibit peristalsis

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Pharmacokinetics

• Absorption: GI tract

• Distribution: protein binding

• Biotransformation: liver

• Excretion: kidney and GI (bile)

• Differs by age, gender

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Pharmacokinetics

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

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Opioid Abuse/Dependence

Classifications

Pharmacology

Use of Opioids

Assessment & Treatment

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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

Rx Opioids

Misuse

• Incorrect use– By patient

• Mismanaged– By physicians

• D ated• D uped• D isabled• D ishonest

Non-medical

• Illegal use– Not prescribed – Took for euphoria

• Most commonly used

• In US, age 12 +:– Past month 2%– Lifetime: 14%

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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

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Abuse

• Not if dependent

• 1 in 12 months:

– Failure to fulfill role

– Use in hazardous situations

– Legal problems

– Use despite problems

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Abuse/DependenceAnnual Prevalence

0 0.5 1 1.5 2

Heroin

Rx opioids

Cocaine

THC

NSDUH 2006

1.7%

0.7%

0.7%

0.1%

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Opioid Tolerance

• With repeated use

• Need ↑ doses to maintain effect

• Can see in pain patients

• Adaptation of receptors

• Different rates for each effect

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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

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Opioid Overdose

• Recent use

• Life threatening

• Constricted pupils

• 1+:– Drowsiness or coma

– Slurred speech

– Poor attention and memory

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Opioid Abuse/Dependence

Classifications

Pharmacology

Use of Opioids

Assessment & Treatment

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Treatment Goals• ↓ or eliminate use

• ↓ risks: – Overdose– IV use– Dependence

• Address:– Co-morbid conditions – Psychosocial outcomes – Somatic needs

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

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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

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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

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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

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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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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