Download Session A3

A Brief History of Heroin Use in the United
States:
Evolving Impact on Prescription Drug Abuse
By Phil Walls, RPh
©2016 myMatrixx. All Rights Reserved
Learning Objectives
At the conclusion of today’s webinar, the audience will:
• Be able to trace the use of heroin from its introduction as a treatment for
morphine withdrawal, use as a cough syrup, designation as a dangerous drug and
today as a substitute for prescription opioids in iatrogenic opioid addicts
• Understand that heroin is an opioid, and that all opioids produce similar effects
• Recognize that the chemical structure of heroin is very similar to prescription
opioids
• Understand the schedule of controlled substances and the differences between
schedule 1 and the other schedules
• Know efforts to prevent addiction
©2016 myMatrixx. All Rights Reserved
Why Focus on Heroin?
©2016 myMatrixx. All Rights Reserved
Prescription Drug Abuse, Misuse and Diversion
• $177 billion – annual cost of prescription drug abuse to the US healthcare
system
• The Drug Enforcement Administration (DEA) estimates that diversion is a
$25 billion-a-year industry
• $8.5 billion – annual cost of hospital admissions for people who do not
take their medications as prescribed
How did this happen?
©2016 myMatrixx. All Rights Reserved
Review of Definitions
• Tolerance is a state of adaptation in which exposure to a drug induces changes that
result in a diminution of one or more of the drug's effects over time. Tolerance
develops at different rates, in different people, to different effects.
• Physical dependence is a state of adaptation that is manifested by a drug class-specific
withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction,
decreasing blood level of the drug, and/or administration of an antagonist.
• Addiction is a primary, chronic neurobiological disease with genetic, psychosocial and
environmental factors influencing its development and manifestation
• Diversion is the use of a legitimately prescribed medication for illicit or illegitimate
purposes—perhaps with the intent to sell or distribute
©2016 myMatrixx. All Rights Reserved
Addictive Behaviors
• Addictive behaviors include one or more of the following:
• Impaired control over drug use
• Compulsive use
• Continued use despite harm (physical,
mental, and/or social)
• Craving
©2016 myMatrixx. All Rights Reserved
Timeline to Discovery of Heroin
• 1806 – morphine isolated from opium poppy – named after
Morpheus, the Greek god of dreams
• Heinrick Emanuel Merck – converted pharmacy into a full-time
producer of morphine – Engel-Apotheke or The Angel
Pharmacy
• Today known as Merck and Company
• 1853 – invention of the hypodermic syringe and first
injection of morphine
• Co-invented by Alexander Wood and Charles Pravaz
• Woods’ wife was the first fatality of an injected overdose of
morphine
©2016 myMatrixx. All Rights Reserved
Alexander Wood
(1817 – 1884)
Timeline to Discovery of Heroin
• Dr. Woods’ discovery preceded the American Civil War by almost a decade
• Approximately 400,000 soldiers became addicted to morphine
• Characterized as “old soldiers’ disease”
• One of these veteran’s was Colonel John Pemberton
•
•
•
•
A pharmacist by training
Mixed cocaine and the kola nut in an elixir to treat morphine withdrawal
Branded as Coca Cola in 1886
Original formula with cocaine available until 1905
• 1874 - Diacetylmorphine is first synthesized
©2016 myMatrixx. All Rights Reserved
Timeline to Discovery of Heroin
Between 1878 and 1885 however opium addiction
became much more widespread among middle- to
upper-class white women.
©2016 myMatrixx. All Rights Reserved
Timeline to Discovery of Heroin
• Diacetylmorphine is “re-discovered” by chemists working for Friedrich
Bayer in the mid-1880’s through a process known as acetylation
• Morphine → diacetylmorphine
• Acetylsalicylic acid → aspirin
• Bayer named this drug heroin after the German word heros meaning
hero.
Morphine
Heroin
©2016 myMatrixx. All Rights Reserved
The two drugs differ
by the addition of
two acetyl groups
Metabolism of Opioids
codeine
morphine
6-MAM†
hydrocodone
hydromorphone
oxycodone
oxymorphone
heroin
*Not comprehensive pathways, but may explain the presence of
apparently unprescribed drugs
†6-MAM=6-monoacetylmorphine, an intermediate metabolite
Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004
©2016 myMatrixx. All Rights Reserved
Timeline to Discovery of Heroin
• Aspirin was first synthesized a year later – ironically
aspirin required a prescription whereas heroin did
not
• Bayer and Merck had launched the start of the
modern day pharmaceutical industry with the
development of three of the world’s most popular
analgesics: morphine, heroin and aspirin
©2016 myMatrixx. All Rights Reserved
Trial Treatment – Free of Charge!
©2016 myMatrixx. All Rights Reserved
The Solution for Coughs
©2016 myMatrixx. All Rights Reserved
©2016 myMatrixx. All Rights Reserved
Early Attempts at Regulation
• 1906 – Pure Food and Drug Act – Coca Cola was one of few products
that survived this legislation
• 1914 – Harrison Narcotic Act
• 1919 – ruling by the Supreme Court that it was unconstitutional to
stop physicians from prescribing narcotics for addicts, but then the
court later reversed that decision
• The case of Alexander Ameris – characterized as a “dope fiend”
©2016 myMatrixx. All Rights Reserved
Prevailing Attitude Early to Mid-Century
1900
• “…save our people from the clutches of this hydra-headed monster which
stalks the civilized world, wrecking lives and happy homes, filling our jails and
lunatic asylums…”
Witherspoon JA. A protest against some of the evils in the profession of medicine. JAMA.
1900;34 :1589– 1592
1941
• “The use of narcotics in the terminal cancer patient is to be condemned …
due to undesirable side effects … dominant in the list of these … is addiction”
Lee LE Jr. Medication in the control of pain in terminal cancer. JAMA 1941;116:216-219
©2016 myMatrixx. All Rights Reserved
The Vietnam War Era
• Represented a turbulent time in American history
• Janis Joplin dies of a heroin overdose on October 4, 1970
• The following May, Congressmen Steele and Murphy conducted an official visit to
Vietnam
• Their message upon returning: 15% of US servicemen in Vietnam were addicted to
heroin
• The timing coincided with the implementation of the Comprehensive Drug Abuse
Prevention and Control Act of 1970
• On June 17th of 1971, President Richard Nixon characterized drug abuse as “a
national emergency” - He asked Congress to amend the Narcotic Addict
Rehabilitation Act of 1966 to increase access to methadone maintenance programs
©2016 myMatrixx. All Rights Reserved
America’s War on Drugs
• President Nixon’s legacy includes creation of the Drug Enforcement
Administration in 1973
• 1975: the Ford administration names marijuana a low-priority drug
• 1976: Carter campaigns for de-criminalization of marijuana
• 1978: the Comprehensive Drug Abuse Prevention and Control Act is
amended to allow law enforcement to seize “all things of value”
involved in and exchange for controlled substances
• 1981 – 1982: rise of the Medellin Cartel in Columbia and creation of
a bilateral extradition treaty between the governments of Colombia
and the United States
©2016 myMatrixx. All Rights Reserved
America’s War on Drugs
• 1984: Nancy Reagan launches her “Just Say No” campaign, which becomes
a focal point of President Reagan’s anti-drug campaign
• 1989: President Bush creates the Office of National Drug Control Policy
(ONDCP) and campaigns to “make drug abuse socially unacceptable”.
Spending for treatment and law enforcement increase under the ONDCP,
but the budget for treatment is less than one-third that of law
enforcement.
• 1993: President Clinton signs the North American Free Trade Agreement
(NAFTA). This agreement results in a significant increase in legitimate trade
shipments across the Mexican-US border, but has the unintended
consequence of making it difficult for US Customs agents to find
contraband narcotics in these shipments.
• 2000: President Clinton commits $1.3 billion in aid to Colombia to fight
drug trafficking.
©2016 myMatrixx. All Rights Reserved
America’s War on Drugs
It is important to note in the War
on Drugs that the DEA announced
just this past May the most
successful enforcement action in
its history: known as Operation
Pilluted, this operation resulted in
280 arrests including 22 doctors
and pharmacists; resulted in the
seizure of $11,651,565 US currency
and $6,745,800 in real property.
©2016 myMatrixx. All Rights Reserved
Controlled Substance Schedules
Schedule
I
II
III
IV
V
Description
Restrictions
Examples
High potential for abuse.
No currently accepted medical use in the U.S.
Lack of accepted safety for use of the drug.
No legal use.
heroin, LSD, marijuana, crystal
meth
High potential for abuse.
Prescription cannot be refilled.
Currently accepted medical use in the U.S.
Abuse may lead to severe psychological or
physical dependence.
Potential for abuse less than Schedule I and II.
Requires an original signed order
from the prescriber.
morphine, oxycodone, fentanyl,
cocaine,
amphetamine
Currently accepted medical use in the U.S.
Refills limited to 6 times within
Abuse may lead to moderate or low physical
dependence or high psychological dependence.
6 months from the date of the Rx.
Lower potential for abuse than Schedule III.
Currently accepted medical use in the U.S.
Abuse may lead to limited psychological or physical
dependence relative to Schedule III substances.
Prescription can be phoned or faxed.
Refills limited to 6 times within 6
months from the date of the Rx.
lorazepam, alprazolam,
carisoprodol, tramadol
Low potential for abuse relative to Schedule IV drugs.
Currently accepted medical use in the U.S.
Abuse may lead to limited psychological and physical
dependence relative to Schedule IV substances.
Exempt narcotics
codeine containing cough syrups,
diphenoxylate
Prescription can be phoned or faxed.
©2016 myMatrixx. All Rights Reserved
buprenorphine, Marinol®
Seminal Event in the 1990’s
• American Pain Society “Pain is the Fifth Vital Sign”
• Launch of “I Got My Life Back” video by Purdue Pharma
©2016 myMatrixx. All Rights Reserved
OxyContin Video
• In 1998, Purdue Pharma distributed a promotional video to 15,000
doctors telling how OxyContin improved seven patient’s lives.
©2016 myMatrixx. All Rights Reserved
By the Early 21st Century in Workers’
Compensation
“The abuse of prescription opioids has become a
grave personal risk to injured workers, a
disruptive force in the lives of those close to
claimants harmed by abuse, and a cost concern
to other stakeholders in the United States
workers’ compensation system.”
Joint statement of ACOEM and IAIABC
©2016 myMatrixx. All Rights Reserved
Workers’ Compensation Statistics
• Temporary disability payments are 3.5 times higher when
opioids are prescribed.
• A study of 17 states found that many physicians who
prescribed narcotics to injured workers were not using
recommended tools to monitor use, abuse and diversion.
©2016 myMatrixx. All Rights Reserved
Turning Point in 21st Century
• Confession of Dr. Russell Portenoy – December 2012 WSJ
• Development of FDA REMS program
• Ultra-short acting opioids
• Long-acting opioids
• Creation of state Prescription Drug Monitoring Programs (PDMPs)
©2016 myMatrixx. All Rights Reserved
Decrease in Use of Rx Opioids
©2016 myMatrixx. All Rights Reserved
Unintended Consequences?
• Abuse-deterrent formulations of long-acting opioids, i.e., OxyContin and Opana ER,
have successfully decreased abuse of prescription opioids— but may not be actually
decreasing opioid abuse
• Heroin use has nearly doubled— easier to use, less expensive and readily available
*Cicero, TJ, et al. Effect of Abuse-Deterrent Formulation of OxyContin, N Engl J Med
2012, 367: 187-189, July 12, 2012
However, Cicero’s letter did not acknowledge that heroin use was already trending up
1 to 2 years prior to re-formulation of opioids
©2016 myMatrixx. All Rights Reserved
Drug Use Statistics – In Hindsight
• 80% of the world’s supply of opioids is consumed in the US.
• 99% of the world’s supply of hydrocodone is consumed in the
US.
• 2/3 of the world’s supply of illicit substances are consumed in
the US.
Manchikanti, L. National Drug Control Policy and Prescription Drug Abuse: Facts
and Fallacies. Pain Physician. 10:399-424, 2007.
©2016 myMatrixx. All Rights Reserved
Statistics: Through 2007
Prescription opioid overdose was the second
leading cause of accidental death in the U.S.,
killing more people than heroin and cocaine
combined.
©2016 myMatrixx. All Rights Reserved
2011:
Use of Rx Opioids
©2016 myMatrixx. All Rights Reserved
Heroin Related Hospital Admissions
©2016 myMatrixx. All Rights Reserved
Red Flags In Screening/Early Therapy
• Little or no relief using opioid therapy in acute/sub-acute phases
• Diagnosis identified as one that hasn’t been shown to have good success using
opioids, i.e. unidentifiable pain or pain associated with physiological factors
• Patient request of opioid medication, with inconsistencies in history,
presentation, behaviors or physical findings
• Inappropriate use of opioids within first 30 days of therapy
©2016 myMatrixx. All Rights Reserved
Daily Equivalent Morphine Dosage (MED)
• Computed utilizing dosages of all opioid and opioid-containing
medication taken during a 24-hour period
• 120 mg MED threshold as an indicator of risk
• Patients receiving 100 mg or more per day MED had a 9-fold increase
in overdose risk – most were medically serious, 12% were fatal
©2016 myMatrixx. All Rights Reserved
When to Stop Treatment
• Indicators should be well documented and include:
• Level of function – if no overall improvement, stop therapy
• Continuing pain with intolerable adverse effects – side effects may outweigh
benefits
• Serious non-adherence in the way the patient takes medication or in the
manner it’s obtained
• Evidence of diversion, forgery, stealing or motor vehicle accident related to
opioids or other illicit drugs
• Repeated violations of medication contract or evidence of abuse/addiction
©2016 myMatrixx. All Rights Reserved
Resurgence of Heroin Use
Although prescriptions for
opioids have tripled over the
past 25 years, the number of
“past-year heroin users”
doubled in just 7 years from
approximately 380,000 in 2007
to 670,000 in 2012.
Furthermore, heroin related
deaths more than doubled in
just 2 years from 2011 to 2013,
with 8200 deaths in 2013
alone.
©2016 myMatrixx. All Rights Reserved
Possible Reasons for Increase
• Increased awareness among physicians and other prescribers that
opioids are indeed dangerous and highly addictive.
• Access to controlled substance prescribing data through various state
Prescription Drug Monitoring Databases (PDMPs). These databases
are now available to prescribers in 49 states, although their use is
mandated in only 10 states.
• Development of abuse-deterrent formulations for long-acting opioids.
This development is a key component of the FDA’s Risk Evaluation and
Mitigation Strategy (REMS) and in essence makes it more difficult for
an individual to intentionally misuse or abuse prescription opioids.
©2016 myMatrixx. All Rights Reserved
How to Respond
©2016 myMatrixx. All Rights Reserved
Prevention
Reduce the overprescribing of opioids. Monitor data for high risk
behavior:
• Excessive morphine equivalent (MED) doses
• Use of more than one long-acting opioid or more than a single long-acting
and a single short-acting opioid
• Using opioids for excessive periods of time
• Combining opioids with drugs such as Soma® (carisoprodol) and
benzodiazepines such as Xanax® (alprazolam)
• Early refills
• Seeing more than one physician for controlled substances
• Receiving controlled substances from more than one pharmacy
• Use of controlled substances with a past diagnosis of substance abuse
©2016 myMatrixx. All Rights Reserved
Reduce Addiction
• The CDC recommends that individuals addicted to heroin or prescription
opioids have access to medication assisted treatment, which combines
therapy with drugs like methadone, buprenorphine or naltrexone with
counseling and behavioral therapy.
• One of the first efforts was the passage of House Bill 1 in 2012 by the
Kentucky legislature. This legislation, designed to control pill mills and
overprescribing of opioids, achieved one goal: prescriptions for these
drugs declined. However, the legislation did not put similar restrictions on
prescriptions for buprenorphine prescriptions. Buprenorphine is the active
ingredient in drugs like Suboxone® and Subutex®. When used properly
these drugs can help an addict quit using heroin without going through
horrible withdrawal. However, one addict was quoted as saying: “it was
just a great substitute for heroin. It was like doing the same thing, really.
http://kbml.ky.gov/hb1/Pages/default.aspx
©2016 myMatrixx. All Rights Reserved
High Cost of a Proposed Cure
©2016 myMatrixx. All Rights Reserved
Reverse Heroin Overdose
• The CDC also recommends that the use of naloxone be expanded. Naloxone has the
ability to reverse the effects of an opioid overdose if it is administered in time.
• Naloxone was first discovered in the 1960’s, and it has been available under the brand
name Narcan® (naloxone) as an injectable drug and has been the mainstay treatment for
opioid overdose for over three decades. It has an AWP of $3.58 per vial
• Evzio® was introduced last year as an auto-injector version of naloxone to treat opioid
overdose. It is not intended to be a self-injector – therefore a family member or
caregiver must administer the injection
• It has an AWP of $862.50 for a kit containing two syringes
• Evzio has been recommended by the myMatrixx P&T Committee to be a non-formulary
drug for two reasons – one is price, but as a life-saving drug that is not the most
important factor; the other is the fact that Evzio will not be dispensed through a retail
pharmacy in an emergency situation – there is not enough time. Therefore patients at
risk of overdose must be identified by the physician and prescribed Evzio in advance.
Therefore, in a non-emergent situation, there is sufficient time for Evzio to go through
our clients’ authorization process
©2016 myMatrixx. All Rights Reserved
Conclusions
Unfortunately there is not magic bullet to solve either the prescription
drug abuse epidemic or the heroin crisis. Instead each patient must be
treated individually. Therefore the value of early recognition and
prevention cannot be emphasized enough.
• Be aware of the signs of potential drug abuse
• Take advantage of tools to identify at risk individuals
• Refer patients for a drug regimen review
• Engage a clinical pharmacist to consult with the treating physician
©2016 myMatrixx. All Rights Reserved
Thank You!
Thank You!
Questions?
©2016 myMatrixx. All Rights Reserved