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2018 Heroin Lecture (undergrad)

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Samantha Bauer

on 22 June 2018

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Transcript of 2018 Heroin Lecture (undergrad)

What does heroin do to the body?
Heroin Terms:

Big H, H, Brown Sugar,
Hell Dust,
Nose Drops, Smack,
Dragon, White Snuff,
Black Pearl
Physiology
Samantha Bauer, M.S.
What Are Opioids?
U.S. Drug Schedules
Drug Enforcement Administration
Schedule I
(e.g., heroin, cannabis, ecstasy, LSD)
No currently accepted medical use, High potential for abuse

Schedule II
(e.g., Vicodin, adderall, fentanyl, methadone, cocaine)
High potential for abuse, May lead to severe dependence
Schedule III
(e.g, anabolic steroids, ketamine, testosterone)
Lower abuse potential than Schedule I & II but more than IV, Moderate-Low potential for dependence
Schedule IV
(e.g, Xanax, Valium, Ambien, Ativan)
Low potential for abuse, Low risk of dependence
Schedule V
(e.g., cough preparations < 200mg of codeine/100 mL = Robitussin AC)
Lower potential for abuse than Schedule IV
Heroin Use Epidemiology
EPI 390 Disease in Society
Opium Poppy, Papaver Somniferum, "Flower of Joy"

Grow in warm,
dry climates
After the poppies bloom, the petals fall away
Seed pod is exposed, which contains a milky, opaque sap
Opium in its crudest form
In the body:
Administering Heroin
Notes from
'Drugs of Abuse: Uses and Effects' Chart:
Physical dependence: High

Psychological dependence: Very high

Tolerance: Yes
Defintion: "The reduced effectiveness of a drug after repeated administration."
Possible Health Effects
Euphoria, drowsiness, dizziness, double vision, slowed respiration, nausea, vomiting, constipation
Effects of Overdose
Slow & shallow breathing, clammy skin, constricted pupils, coma, possible death
Withdrawal Syndrome
Watery eyes, runny nose, yawning, loss of appetite, tremors, panic, chills, sweating, cramps, nausea
Help from YouTube
A Few Take Aways
1. Surge of dopamine

2. Prefrontal cortex
Decision making & judgement
3. Amygdala
Motivation
4. Locus ceruleus
Motivation, Focus, Energy
5. Hippocampus
Memory (e.g., visual, visceral, emotive)
On the Street
Usually sold in the form of white or brown powder or as a black sticky substance.
Often cut with other drugs or substances or (e.g., sugar, starch, powdered milk, fentanyl).

Terminology
Opioid: a drug derived from opium or a synthetic drugs that produce opiate-like effects (active ingredients are made via chemical synthesis).

Opiate: drugs derived from the naturally-occurring alkaloids in the opium poppy.

Medically, both bind to opioid receptors = referred to as opioids.

All opiates are opioids, but not all opioids are opiates.
Descriptive Epidemiology
Abuse/Dependence Potential
Disease Burden
FYI
*Drug poisoning deaths included are those with ICD-10 underlying cause code X40-X44, X60-X64, X85, and Y10-Y14. Heroin-related deaths are those with ICD-10 related cause code T40.1
In 2013, more than 1 in 4 (26.6%) drug poisoning deaths were related to heroin use.
Michigan: Stratifying by Age
When estimating disease burden, if medical examiners
incorrectly
determine cause of death to be
overdose due to morphine rather than heroin
, what does this do to our estimated incidence of mortality?
Incidence will be underestimated.
Can change public health initiatives.
Incidence:
The number of
new
health-realted events in a defined populaiton 'at risk' for having the event within a specified period of time.
Mode of Transmission
Descriptive Epidemiology
Mode of transmission:
How an infectious agent is spread from the natural reservoir to a susceptible host.

Although, heroin use/dependence/overdose, is NOT an infectious disease, mode of transmission can be useful way to think about how incident heroin use occurs.

Incident heroin use primarily occurs through person to person transmission of the drug.

Some heroin users can be thought of as "spreaders", who initiate new users to heroin.

NOTE: Once underway, a heroin epidemic may not be self-limiting and will continue until proactive intervention strategies are implemented.
Risk Factors
Analytical Epidemiology
Figure 1 - Opioid Prescriptions Dispensed by US Retail Pharmacies IMS Health, Vector One: National, years 1991-1996, Data Extracted 2011. IMS Health, National Prescription Audit, years 1997-2013, Data Extracted 2014.
Jones, C.M., Logan, J., Gladden, R. M., & Bohm, M.K. (2015) "Vital signs: demographic and substance use trends among heroin users- United States, 2002-2013"
Morbidity and Mortality Weekly Report
64(26): 719-725.
Exposure Variable:
Demographic or Substance
Characteristic
Outcome:
Past Year
Heroin Abuse or Dependence
Causal Model:
Rules to Remember:
1. Measures of association (OR, RR, HR)
> 1 : increases risk
< 1 : decreases risk
Amount away from 1 is the
percentage
increase or decrease in risk. If 2 or greater, stated as how many
times
increased or decreased risk.
2. Controls/Reference Group
1.0
The only group we can compare increased or decreased risk to.
3. We can look for overall relationships (i.e.,
dose responses).
4. We cannot disaggregate a listed exposure
variable (e.g., We cannot infer beer's
effect on heroin abuse/dependence based
on the OR for alcohol.).
One Example Interpretation:

Those who have an annual household income of $20,000-$49,000, compared to those who have an annual household income of <$20,000, have a statistically significant 50% decreased risk of meeting the DSM-IV criteria for past year heroin use or dependence.
Treatment & Public Health
What can we do about this problem?
Thank you

Feel free to contact me with questions or comments at: sbauer@epi.msu.edu

Treatment for Heroin Dependence

1. Agonists
2. Partial Agonists
3. Antagonists
Activate opioid receptors
Methadone (Dolophine, Methadose)
Slow-acting
Oral adminstration: less subjective "high feeling" compared to other routes
Prevents withdrawal symptoms
Available through approved outpatient treatment programs
Given daily
Used since 1960s
Activates opioid receptors, but produces a smaller response
Buprenorphine (Subutex):
Relieves cravings without subjective "high" or side effects
Prescription (eliminates visits)
Suboxone: Formulation of buprenorphine & contains naloxone
Oral adminstration
If individual were to inject Suboxone, nalaxone would induce
withdrawal symptoms (which would be avoided if taken orally).
Block opioid receptor & interfere with rewarding effects
Naltrexone (Depade, Revia, Vivitrol):
Does not result in dependence
Longer-acting Vivitrol (once a month injection) has shown to have better compliance than daily doses of Depade or Revia
(Plus Behavioral Therapy)
In the case of overdose:
Naloxone

opioid antagonist
reverse & block effects of other opioids
slowed or stopped respiration is quickly restored
Good Samaritan
Good Samaritan Law provides...
immunity from arrest, charge, or prosecution for certain controlled substance possessions when
someone is experiencing an opiate-related overdoes
or
someone is observing on and calls 911 or seeks medical attention.
Must be reported in "good faith"
Drug overdose immunity and good samaritan laws,
National Conference of State Legislatures
(2017) http://www.ncsl.org/research/civil-and-criminal-justice/drug-overdose-immunity-good-samaritan-laws.aspx
Heroin: What are the treatments for heroin addiction? (2014)
National Institute on Drug Abuse: Advancing Addiction Science,
https://www.drugabuse.gov/publications/research-reports/heroin/what-are-treatments-heroin-addiction

Naloxone: what is naloxone? (2016)
National Institute of Drug Abuse: Advancing Addiction Science,
https://www.drugabuse.gov/related-topics/naloxone
Hart, C.L. & Ksir, C. (2008) "Drugs, Society, & Human Behavior: 15th edition"
McGraw Hill.
Additional References
"Opioid overdose: drug overdose death data" (2016) Centers for Disease Control and Prevention" https://www.cdc.gov/drugoverdose/data/statedeaths.html

Lipari, R.N., & Hughes, A. (2015) "Trends in heroin use in the United States 2002 to 2013", Substance Abuse and Mental Health Services Administration, The CBHSQ Report.

Volkow, N. presentation (2014) "America's addiction to opioids: heroin and prescription drug abuse" National Institute on Drug Abuse: Advancing Addiction Science.

"Heroin-related mortality among Michigan residents" Michigan Department of Community Health. https://www.michigan.gov/documents/mdch/Heroin-Related_Mortality_Fact_Sheet_Age_Group_2_483955_7.pdf

"In Michigan heroin epidemic, deciding whose lives are worth saving" (2015) Bridge: News and AnalysisThe Center of Michigan http://www.bridgemi.com/public-sector/michigan-heroin-epidemic-deciding-whose-lives-are-worth-saving

http://www.pbs.org/wgbh/pages/frontline/shows/heroin/transform/

Robins, L. N. (1993) "Vietnam veterans' rapid recovery from heroin addiction: a fluke or normal expectation" Addiction, 88:1041-1054.

Hanzi, R. (1976) "Diffusion of heroin use" dissertation, Arizona State University

Concerns with Measures of Prevalence
Problems with a lifetime prevalence of heroin definition:

--- premature death
--- movement out of population to...
--- treatment
--- correctional institutions

Underestimation of prevalence
Palamar, J.J., Shearston, J.A., Dawson, E.W., Mateu-Gelabert, P., & Ompad, D.C. (2016) "Nonmedical opioid use and heroin use in a nationally representative sample of us high school seniors"
Drug and Alcohol Dependence
, 158:132-138.
Lifetime Opioid Use
Lifetime Heroin Use
In a sample of U.S. high school seniors...
Hart, C.L. & Ksir, C. (2008) "Drugs, Society, & Human Behavior: 15th edition"
McGraw Hill.
Jones, C.M., Logan, J., Gladden, R. M., & Bohm, M.K. (2015) "Vital signs: demographic and substance use trends among heroin users- United States, 2002-2013"
Morbidity and Mortality Weekly Report
64(26): 719-725.
"Vital signs: demographic and substance use trends among heroin users- United States, 2002-2013"
Palamar, J.J., Shearston, J.A., Dawson, E.W., Mateu-Gelabert, P., & Ompad, D.C. (2016) "Nonmedical opioid use and heroin use in a nationally representative sample of us high school seniors" Drug and Alcohol Dependence, 158:132-138.
"Nonmedical opioid use and heroin use in a nationally representative sample of us high school seniors"
Smoked
Snorted
Oral
Injected
The same dose will have
a greater effect.
More severe withdrawal symptoms & a greater risk of overdose.
Using Heroin Terms:

Chasing the dragon,
Give wings,
Jolly pop, Paper boy,
Do up, Dip and Dab,
Channel swimmer
http://www.bridgemi.com/public-sector/map-heroin-deaths-county-michigan
Bridge: News and analysis from The Center for Michigan
America's Opioid Crisis
Chronic Pain?
Physicians?

Over Prescribing?

Withdrawaling
Prescriptions?
Big Pharma?
Chemistry
Heroin's half-life = 2-6 minutes

Metabolizes to 6-Acetylmorphine

Acetylmorphine's half-life =
6-25 minutes

Metabolizes to Morphine

Think about it:

Why might we care about this information?

Morphine
Heroin
Ellis, A.D., McGwin, G., Davis, G.G., & Dye, D.W. (2016) "Identifying cases of heroin toxicity where 6-acetylmorphine (6-AM) is not detected by toxicological analyses",
Forensic Sci Med Pathol
, 12:243-247.
1. Sap from opium poppy is extracted. The sap becomes thick & dark, forming a brown-black gum.
2. Gum is packed together.
3. The opium (gum) enters the black market & is bought.
4. Refining to morphine:
a. Opium is mixed with lime in boiling water to form a white band of morphine on the surface.
c. A series of collecting, reheating, filtering & boiling steps occur until a brown paste is formed.
5. Morphine is further synthesized to heroin by a series of boiling steps with acetic anhydride.
From Opium to Heroin
Lachenmeier, D.W., Sproll, C., &Musshoff, F. (2010) "Poppy seed foods & opiate drug testing - where are we today?"
Therapeutic Drug Monitoring
, 32:11-18.
Potency?
Doctor Explains Synthetic Drugs
In testimony before the House Bipartisan Heroin Task Force, American Society of Addiction Chair Doctor Corey Waller explains synthetic drugs and their affects depending on an individual, depending on the dosage.

www.c-span.org/video/?c4655197/doctor-explains-synthetic-drugs


Drug Dependence Is A Disease

Waldhoer et al. (2004) "Opioid Receptors", Annu. Rev. Biochem


"Drugs, Society, & Human Behavior"
Euphoria
Focused on the United States
History
Early Opium
1500 BC:
Egyptian & Greek
Medical use

16th-18th Centuries:
Increased awareness of opium & its preparations
"Healing Art" of Opium
Opium in the 19th Century
Few moral restrictions regarding drug use

Opioids: pleasures & pain

1812: withdrawal & dependence
Morphine & Codeine
1806
Frederich Serturner
Morphium





Heroin
1874: Heroin

1898: Marketed by Bayer

1900: tolerance & dependence are only minor problems

A few years later...Powerful Effects
Harrison Act: Before & After
20th Century: At least 1% of US population dependent on opioids.

Few government regulations, self-medicate
Available, socially acceptable, relatively inexpensive, effective
Medical concerns grew due to increased opioid dependence.
It was believed that opioid use
initiated by physicians
was the primary cause of dependence .
The 1914 Harrison Act:
Regulated & taxed the production, importation, & distribution of opiates & coca products (along with their derivatives & preparations).

Required the drugs that those dependent obtained were to be secured from physicians registered under the act & that it be a matter of record.

Before 1914 the drugs were available for purchase in pharmacies.
Supreme court: Physicians could prescribe drugs to non-hospitalized users to maintain their dependence. Few physicians would do so.
The only source of opioids for non-hospitalized user was an illegal dealer.


Most potent opioid & easy to conceal: Dealers choice
Opioids through dealer ~ 30-50x cost
User's wanted the most 'bang for their buck": injection
American Troops in Vietnam
Due to availability, inexpensive price, & purity heroin use became prevalent among American troops in Vietnam.
1971: 10-15% were dependent on heroin
Urine screening & treatment before returning to the US
Follow up:
Most users didn't continue using upon return (1-2% after 8-12 months after return)
Heroin use & the potential for dependence are not inevitable among all users.

Under the right conditions (e.g., availability, low cost) recreational use of opioids can increase.
1970s Epidemic
1972:
Turkey was the major source
Turkey agreed to stop opium cultivation/prodcution in return for $35 million from US to make up for farmers' financial loss.
Reduced US supply

1975:
80% of U.S. supply was from Mexico
(Mexican Brown or Black Tar)
Drug Enforcement Administration works to eradicate opium in Mexico.
Cannot eliminate all production, but efforts were helpful.
OxyContin
1832 Codeine
Pierre Jean Robiquet
"Poppy Head"
Heroin
"I Like My Opioids"
Drugs: 1) acceptable medical use
2) potential for abuse or dependence
Lipari, R.N. and Hughes, A. How people obtain the prescription pain relievers they misuse. The CBHSQ Report: January 12, 2017. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, Rockville, MD.


Those obtaining opioids from a doctor generally are not the ones misusing the medication.
The Food & Drug Administration?
Info
for the Public

Careful Measurement
Concerns with Measures of Incidence
Also...
--- Lifetime case definitions do not tell us anything about current use, amount taken, frequency of use, or temporality in relation to outcomes.

Prevalence:
The number of cases health-realted events
present
in a defined populaiton 'at risk' for having the event within a specified period of time.
The United States
2016: 42,249 deaths due to opioid overdose
2016 higher heroin death rate
males aged 25-44 at 15.5/100,000
(a 17.4% increase from 2015)
23-38%
of newly incident heroin users will become dependent within 1-12 months of starting.
Santiago Rivera, O.J., Havens, J.R., Parker, M.A. & Anthony, J.C. (2018) "Becoming 'hooked' on heroin: What are the odds? Increased or stable?
JAMA
(in press)
Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period (Sun et al., 2016)
Hint hint!
Look at all the great tables to practice with!
1.
To distinguish between various opioid classifications (e.g., opiates).
2.
To understand the general history of opioids in the US and major events that have changed how opioids are perceived.
3.
To describe the various factors that may have contributed to the current epidemic, along with descpritive trends & risk factors.
(remember: heterogeneity, variation)
4.
To name major physiological responses to opioids and be able to describe drug dependence using appropriate terminology (e.g., disease, stigma).
5.
To think critically about measurement in relation to caseness and be able to interpret tables of measures of association (e.g., OR).
6.
To know public health responses to the opioid epidemic.

Learning Objectives
https://www.today.com/video/new-fda-commissioner-speaks-out-on-opioid-crisis-1143469635680
Pain as a Vital Sign?
Use post-recovery once detox has occurred.
Short-term opioid blocker
Surgery?
Pill Take Back Day
FYI
Full transcript