Transcript Document

Pharmacology of Opiates
Steve Hanson
Associate Commissioner
July 16, 2015
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Neurotransmitter-receptor interactions
To transmit instructions to
cells, neurotransmitters
interact with their receptors.
receptor
neurotransmitters
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Neurotransmitter Action
Reuptake
Release of NT
Receptor
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ENDORPHINS
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Endogenous Morphine
Response to Pain
Morphine Receptor sites
Enkephalins – found in tears
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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
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Opiates
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Dates to 4,000 BC
Mimics endorphin activity
Natural - Opium, morphine, codeine
Semi-synthetic- Heroin, Dilaudid
Synthetics - Darvon, Demerol, Fentanyl
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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”
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“Heroin Chic”
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Why would people
use Heroin?
“Take the best orgasm
you’ve ever had…
Multiply it by a thousand.
And you’re still nowhere
near it.”
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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
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N
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Semi-synthetics
Morphine
Heroin
Dilaudid
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Synthetics
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Demerol
Fentanyl
Methadone
Darvon
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Opiates
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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
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The Action of
Heroin
(Morphine)
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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.
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Addiction/Dependency
• Opioids trigger reward system – euphoria
– leads to continued use – addiction
• Withdrawal symptoms are significant –
regular use to avoid withdrawal dependence
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Opiates & Reward Pathway
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Opiates Increase DA Release
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Heroin
Effects
• Analgesia - change in
pain perception
• Euphoria - intense
• Sedation - “on the nod”
• Respiratory depression
• Cough suppression
• Nausea/vomiting
• Constipation
Withdrawal
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Pain
Depression
Alert
Rapid breathing
Coughing
Nausea/vomiting
Diarrhea
3-5 days
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Addiction vs. Dependency
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Potency Factors by Weight
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Morphine
Heroin
Codeine
Dilaudid
Demerol
Fentanyl
1
3
0.1
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0.05
300 - 1000
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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)
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OxyContin
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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
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Vicodin
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Vicodin
• Hydrocodone and acetaminophen
• Lorcet, Lortab
• Schedule III – high psychological/medium
physical
• Pain and post-surgical use (pain)
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Trends in Substance Abuse Admissions
• Heroin/Opioid admissions increasing
• Cocaine admissions decreasing
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Primary Opioid Admissions
2005-2013
60,000
50,000
40,000
30,000
20,000
10,000
0
2004
2005
2006
2007
Heroin
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2008
2009
2010
2011
2012
Other Opiates
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2013
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National Overdose Deaths
Heroin/RX Opioids
2000-2013
16,235
Rx Opiates
CDC/NCHS Data Brief – 3/15
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Heroin
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2013
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
2001
8,257
2000
20,000
15,000
10,000
5,000
0
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Treatment
• Traditional Recovery Based/NA
• Naltrexone - Antagonist/Blocker
• Opiate Maintenance Tx – withdrawal
management
– Methadone- daily
– Buprenorphine/Suboxone
– Methadone to abstinence models
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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
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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
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Levels of Care
• Intensive Residential
 Supportive environment – therapeutic community
 Longer term stays 6-24 months
 Focus on rehabilitation/sober living skills
• Outpatient
 Intensive outpatient
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Proposed Residential Redesign
• 3 levels of Residential:
– Stabilization
– Rehabilitation
– Community Reintegration
• Enhanced medical/nursing/clinical staffing
• Medicaid reimbursement for clinical/medical portion of services
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Pharmacological Approaches
Goals – Provide:
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relief from withdrawal symptoms,
prevent drugs from working,
reduce craving,
aversive reactions
These actions are helpful in
reducing relapse and increasing
retention in programs
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Does Treatment Work?
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Medications +
psychosocial
therapy both
benefit brain
function and
recovery.
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Each affects
different parts
of brain and in
opposite
ways.
PET scans adapted and retouched from Goldapple et al. 2004
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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)
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Pharmacological Approaches
Naltrexone (Vivitrol) – stops opiates from
working, changes alcohol action for some
– reduction in relapse
Baclofen – possible reduction in cocaine
cravings
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Patient Needs
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Diabetes
Some can control with diet
Some can control with
medication
Some are insulin dependent
Without adequate treatment many will die
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Opiod Addicts
Some can quit on own
Some can remain abstinent
with “regular” treatment
Some need ORT
Without adequate treatment many will die
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Methadone Effectiveness
Gunne & Gronbladh, 1984
Baseline
Methadone
H H H H
Regular Outpatient Rx.
H H H H
H H H H
H H H H
H H H H
H H H H
H H H H
H H H H
H
H
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Methadone Effectiveness
Gunne & Gronbladh, 1984
After 2 Years
Methadone
No Methadone
P P H 1
H H 2H 3H
H H H H
P H H H
H
H H H D
D
1- Sepsis & endocarditis
2- Leg amputation
3- Sepsis
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Methadone Effectiveness
Gunne & Gronbladh, 1984
After 5 Years
Methadone
No Methadone
P P D
D
D
P H H
P D
H
D
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Retention in treatment
Heilig, Lancet 2003
Centers for Disease Control (2011)
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Buprenorphine
A tragic appendix: Mortality
Heilig, Lancet 2003
Placebo
Dead
BPN
4/20 (20%) 0/20 (0%)
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NARCAN - Overdose Reversal Kits
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AMYGDALAR CONNECTIVITY during brief .5 sec Cocaine
Cues
Placebo
Drug 2
amyg conx
(n=7)
Baclofen blunts AMYGDALAR CONNECTIVITY
Baclofen
Source: Childress, et al, unpublished
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Past Month and Past Year Heroin Use among Persons
Aged 12 or Older: 2002-2012 (National)
Substance Abuse and Mental Health Services Administration (2013)
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Johnston, L.D., O’Malley, P.M., Bachman, J.G., & Schulenberg, J.E.
(2012)
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Past Month Non-medical Use of Types of Psychotherapeutic
Drugs among Persons Aged 12 or Older: 2002-2012
Substance Abuse and Mental Health Services Administration (2013)
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Monitoring the Future (2013)
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Centers for Disease Control (2011)