Heroin,Fentanyl and other

Opioids

Steve Hanson

Heroin/Opioids

142Americans

192

Neurotransmitter Action

ReuptakeRelease of NT

Receptor

Brain Changes

This is Your Brain on Drugs

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Opiates Increase DA Release

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Time After Morphine

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MORPHINE

Source: Di Chiara and Imperato

HEROIN

What Drugs Do

Agonists

• Increase NT activity

• Produce more NT

• Block Reuptake

• Mimic NT’s

Antagonists

• Decrease NT activity

• Block NT’s

• Decrease NT’s

Mixed• Ceiling effect

Opiates

• Dates to 4,000 BC

• Mimics endorphin activity

• Natural - Opium, morphine, codeine

• Semi-synthetic- Heroin, Dilaudid

• Synthetics - Darvon, Demerol, Fentanyl

Modern History• Off and on use through until the 60’s

• “Man with the Golden Arm”

• Vietnam war – soldiers using heroin

• 1970’s – increased prevalence – urban areas

• Treatment programs – Methadone Maintenance / Therapeutic Communities

• 1980’s Hard to find – substitutes

• 1990’s – resurgence

• 2010’s – “epidemic”

Opiates

•Heroin more potent -60-80% - <10% in ‘70’s

•Younger age group - High School

•Users start with snorting - IV within 12 months

•Withdrawal painful - not deadly

NATURAL OPIATES

MorphineCodeineThebaine

OPIUM

Semi-synthetics

Heroin Dilaudid

Morphine

Synthetics

• Demerol

• Fentanyl

• Methadone

• Darvon

Opiates

• Fat solubility – Heroin – high – rush

• Morphine – lower – longer onset

• Heroin metabolized into morphine

• Morphine metabolized by the liver

• Metabolite is 10-20X more powerful

• Detectable in urine for 2-4 days

The Action ofHeroin(Morphine)

Tolerance

• Rapid tolerance with continued use

• Initial dose of 50mg/day can go to 500mg/day in as little as 10 days

• Cell sensitivity thought to be the tolerance mechanism.

Opiates & Reward Pathway

Opiates Increase DA Release

Agonists, Mixed and Antagonists

Heroin

Effects

• Analgesia - change in pain perception

• Euphoria - intense• Sedation - “on the nod”• Respiratory depression• Cough suppression• Nausea/vomiting• Constipation

Withdrawal

• Pain• Depression• Alert• Rapid breathing• Coughing• Nausea/vomiting• Diarrhea• 3-5 days

Addiction/Dependency Cycle

•Opioids trigger reward system – euphoria – leads to continued use – addiction

•Withdrawal symptoms are significant – regular use to avoid withdrawal - dependence

Addiction vs. Dependency

Natural History of Opioid Dependence

Potency Factors by Weight

• Morphine 1

• Heroin 3

• Codeine 0.1

• Dilaudid 8

• Demerol 0.05

• Fentanyl 300 - 1000

Heroin usage patterns

•Highly addictive and dependence producing

•Significant tolerance up to 35X

• Increased cost

•Tolerance management (Tx, jail, etc.)

•Mixing with other opiates and other drugs (speedballing/cocaine)

OxyContin

• Oxycodone – synthesized from thebaine (part of opium)

• OxyContin – 1995• Crush the tablet for quicker high

• Oral, snort, inject

• Percocet – oxycodone & acetaminophen

• Percodan – oxycodone & aspirin

Vicodin

•Hydrocodone and acetaminophen

• Lorcet, Lortab

•Schedule III – high psychological/medium physical

•Pain and post-surgical use (pain)

Fentanyl

• Synthetic Opiate

• Very powerful formulas

• Extensive Medical Use

• Sold as heroin

• High overdose risk

Potency

NIDA

Overdose amount

Treatment

• Traditional Recovery Based/NA

• Naltrexone - Antagonist/Blocker

• Opiate Maintenance Tx – withdrawal management• Methadone- daily

• Buprenorphine/Suboxone

• Methadone to abstinence models

PharmacotherapyMethadone

Buprenorphine

Naltrexone

Psychosocial Interventions

CBT, MI, CM

Recovery SupportAA, NA, SMART Recovery

Recovery Coaches

What is effective treatment?

Detox

• Detox: Medical risk with opioid withdrawal is low, while discomfort is very high • Inpatient • Outpatient

• Only recommended during 2nd trimester of pregnancy if mother is invested

• Otherwise methadone stabilization is in best interest of mother and fetus

Levels of Care

• Inpatient rehabilitation• 5-21 days length of stay• Focus on medical/psychiatric stabilization• May initiate Suboxone for opiates

• Community residence (halfway houses)• Supportive living environment• 3-12 months

Levels of Care

• Intensive Residential

▪ Supportive environment – therapeutic community

▪ Longer term stays 6-24 months

▪ Focus on rehabilitation/sober living skills

• Outpatient

▪ Intensive outpatient

Does Treatment Work?

• Medications +psychosocial therapy bothbenefit brain function and recovery.

• Each affects different partsof brain and inopposite ways.

PET scans adapted and retouched from Goldapple et al. 2004

Pharmacological Approaches

Goals – Provide:• relief from withdrawal symptoms,

• prevent drugs from working,

• reduce craving,

• aversive reactions

These actions are helpful in

reducing relapse and increasing

retention in programs

Pharmacological Approaches

Methadone – Opiate addiction – reduces craving, mediates withdrawal symptoms, helps restore normal functioning

Buprenorphine (Suboxone) – similar to methadone, may be prescribed by an MD with special training)

Naltrexone (Vivitrol) – stops opiates from working, changes alcohol action for some – reduction in relapse – 30 day dose.

Pharmacology of Treatments

Patient Needs

Diabetes

• Some can control with diet

• Some can control with medication

• Some are insulin dependent

• Without adequate treatment -many will die

Opiod Addicts

• Some can quit on own

• Some can remain abstinent with “regular” treatment

• Some need ORT

• Without adequate treatment -many will die

Buprenorphine Maintenance75% retained in treatment75% abstinent by toxicology

Detoxification0% retained in treatment20% died

Kakko et al. Lancet. 2003 Feb 22;361(9358):662-8

Buprenorphine is Effective at Retaining Patients in Treatment & Preventing Relapse

Methadone EffectivenessGunne & Gronbladh, 1984

H H HH

H H HH

H H HH

H H HH

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H H HH

H H HH

H H HH

H H HH

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Methadone Regular Outpatient Rx.

Baseline

Methadone EffectivenessGunne & Gronbladh, 1984

After 2 Years

1- Sepsis & endocarditis

2- Leg amputation

3- Sepsis

P H HH

H

P HP

H H HH

H H HH

H H H

Methadone No Methadone1

32

D

D

Methadone EffectivenessGunne & Gronbladh, 1984

P H H

H

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Methadone No Methadone

After 5 Years

P P D

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Centers for Disease Control (2011)

Retention in treatmentHeilig, Lancet 2003

BuprenorphineA tragic appendix: Mortality

Heilig, Lancet 2003

Placebo BPN

Dead 4/20 (20%) 0/20 (0%)

Vivitrol•Long Acting

Injectable

•Helps with compliance

•Non-Addicting

Is Vivitrol “THE ANSWER”?

2015 Vermont Review

• Research is limited. FDA approval based on a single 6 month trial in Russia.

• Health Risk – Liver toxicity, Death (51 from 2006-2010)

• Overdose Risk upon termination

• Effective for Some – still to be defined

NARCAN - Overdose Reversal Kits

7/9/2019 52

Alive is Good!