prescription drug abuse and addiction, spf-rx• vicodin $1/mg • vyvance $8/40mg • klonopin...
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Raj Masih, MD, MPHRegional Coordinator
WV Strategic Prevent ion Framework for Prescr ipt ion Drugs
WV Region 2
PRESCRIPTION DRUG ABUSE & ADDICTION:
SPF-RX
No financial conflict of interest
DISCLOSURE
23 million Americans have Substance Use Disorder (CDC, 2016)
SCOPE OF THE PROBLEM
There is a massive black market for diverted prescription drugs:
$72 BILLION( D E A , 2 0 1 6 )
FINANCIAL CONSIDERATIONS
Ford Motor Company
Annual sales in 2013:
$11.8 BILLION
FINANCIAL CONSIDERATIONS
Purdue Pharma
Annual sales of OxyContin in 2013:
$10.3 BILLION
( p u r d u e p h a r m a . o r g 2 0 1 4 )
FINANCIAL CONSIDERATIONS
Endo Pharmaceuticals
Annual sales of Endocet in 2013:
$1.6 BILLION
( e n d o . o r g 2 0 1 4 )
FINANCIAL CONSIDERATIONS
Street values:
FINANCIAL CONSIDERATIONS
• Oxycodone $1/mg• Hydrocodone $5/mg• Oxycontin $90/80mg• Opana $50/40mg• Dilaudid 4mg $4/20mg• Adderall 10mg $1.69• Adderall 30mg $5• Percocet $9/10mg• Tramadol $5/100mg• Vicodin $1/mg
• Vyvance $8/40mg• Klonopin $2/2mg• Methadone $5/10mg• Ativan $30/mg• Xanax $4/mg• Ritalin $25/20mg• Codeine Syrup $200/pint• Demerol $10/dose• Fentanyl $100/patch• Morphine $60/100mg• Suboxone $25/strip
(streetrx 2017, justice.gov 2017)
DEFINITIONS
Neonate: an infant less than four weeks old
Addiction: a chronic brain disease characterized by inability to consistently abstain, craving, impairment in behavioral control, and diminished recognition of significant problems related to substance use disorder (ASAM).
Dependence: an adaptive state that develops from repeated drug administration, and which results in withdrawal upon cessation of drug use
DEFINITIONS
WHICH DRUGS ARE ABUSED?
Opioids Heroin OxyContin Oxycodone Oxymorphone Hydrocodone Hydromorphone Morphine Fentanyl Methadone Suboxone Codeine
CNS Stimulants
Amphetamines
Methamphetamines
Cocaine
Crack
Ritalin
SPECIFIC DRUGS OF ABUSE
CNS Depressants
Alcohol
Marijuana
Benzodiazepines
Barbiturates
Sedative - Hypnotics
Methaqualone
Chloral Hydrate
SPECIFIC DRUGS OF ABUSE
Hallucinogens
LSD
Ecstasy
MDA
MMDA
Inhalants
Nitrous Oxide
Paint
Glue
Paint thinner
SPECIFIC DRUGS OF ABUSE
EPIDEMIOLOGY
160 deaths per day in the United States from opioids (USDOJ, 2017)
WV has the highest drug overdose death rate: 51.1/100000 people (CDC, 2016)
WV has the highest rate of Neonatal Abstinence Syndrome (NAS) 44.3/1000 live births (CDC, 2016)
SCOPE OF THE PROBLEM
In 2016 54,000 Americans died from opioid overdoses (CDC, 2017).
BACKGROUND
30,000 people in WV are in Substance Use Disorder treatment (CDC, 2017)
SCOPE OF THE PROBLEM
2007-2013
WV HEALTHCARE AUTHORITY UNIFORM BILLING DATA
119,605 newborn admissions
1974 NAS diagnoses
WV HEALTHCARE AUTHORITY UNIFORM BILLING DATA
2007 NAS Incidence Rate
7.74 per 1000 live births
2013 NAS Incidence Rate
31.56 per 1000 live births
WV HEALTHCARE AUTHORITY UNIFORM BILLING DATA
In 2013 the southeastern part of West Virginia had the highest incidence rate of NAS:
48.76 per 1000 live births
WV HEALTHCARE AUTHORITY UNIFORM BILLING DATA
Reported
Unreported
UNREPORTED NAS BIRTHS PROBLEM IS UNDEFINED AND ALARMING
WHY DRUG ABUSE?
GENERAL MECHANISM OF REWARD
Activation of specific neural pathways that originate in the pons and midbrain and project to the pleasure center in the forebrain
VentralTegmental
Area
Nucleus AccumbensVentral PallidumMedial Pre-frontal CortexAmygdala
ANALGESIC MECHANISMS
Dopamine is in neurotransmitter in the central nervous system and an adrenergic agonist in the peripheral nervous system (Blum, 2011).
WHAT IS DOPAMINE?
Dopamine produces psychotropic effects including mood elevation, euphoria, satisfaction and empathy in physiologic doses (Blum, 2011).
WHAT IS DOPAMINE?
Dopamine is synthesized from the amino acids L-tyrosine and phenylalanine by the enzyme amino acid decarboxylase (AADC), in the presence of pyridoxal 5-phosphate, ionic zinc and magnesium (Blum, 2011).
WHAT IS DOPAMINE?
Adequate levels of bioavailable substrate (L-tyrosine) and phenylalanine are needed to synthesize dopamine in the central nervous system.
WHAT IS DOPAMINE?
Director of NIDA
DR. NORAVOLKOW
The decreased metabolism of dopamine in the D2 receptors of the nucleus accumbens and the amygdala results in a decreased dopaminergic reward in response to normal pleasurable stimuli (Volkow, 2007). This condition is known as dopamine deficiency syndrome or reward deficiency syndrome.
BACKGROUND
Individuals with DDS have been shown to have reduced dopamine release (in the physiological “pleasure centers” of the brain
DOPAMINE DEFICIENCY SYNDROME IN ADDICTIONS
Children with DDS may exhibit maladaptive behaviors such as overeating, binge-eating, consuming and craving large quantities of sugary foods and sugary beverages (Volkow, 2007)
DOPAMINE DEFICIENCY SYNDROME IN ADDICTIONS
Later in life if these susceptible individuals with the genotypes for DDS are exposed to alcohol or other drugs such as marijuana, opioids, cocaine, or methamphetamine, the neuroplastic and neuro-adaptive changes in the mesolimbic system and pre-frontal cortex become attenuated leading to a pattern of craving and recurrent misuse.
DOPAMINE DEFICIENCY SYNDROME IN ADDICTIONS
GENERAL MECHANISM OF REWARD
Drugs of abuse such as heroin, opioids, and cocaine increase the release of dopamine at the nucleus accumbens which has a rewarding/reinforcing effect on upper centers in the brain
Chronic opiate use induces neuroadaptations (brain expects it)
RELAPSE
PET SCAN IMAGING
DETERMINING AN ACE SCORE
While you were growing up, during your f irst 18 years of life:
1. Did a parent or other adult in the household often or very often, swear at you, insult you, put you down, or humiliate you or act in a way that made you afraid that you might be physically hurt?If yes enter 1___
2. Did a parent or other adult in the household often or very often, push, grab, slap, or throw something at you or ever hit you so hard that you had marks or were injured? If yes, enter 1___
DETERMINING AN ACE SCORE
While you were growing up, during your f irst 18 years of life:
3. Did an adult person at least 5 years older than you ever touch or fondle you or have you touch their body in a sexual way, attempt or actually have oral, anal, or vaginal intercourse with you?If yes enter 1 ___
4. Did you often or very often feel that no one in your family loved you or thought you were important or special, or your family didn’t look out for each other, feel close to each other, or support each other? If yes enter 1 ___
DETERMINING AN ACE SCORE
While you were growing up, during your f irst 18 years of life:
5. Did you often or very often feel that you didn’t have enough to eat, had to wear dirty clothes, and had no one to protect you, or your parents were too drunk or high to take care of you or take you to the doctor if you needed it? If yes enter 1 ___
6. Were your parents ever separated or divorced? If yes enter 1 ___
DETERMINING AN ACE SCORE
While you were growing up, during your f irst 18 years of life:
7. Was your mother or stepmother often or very often pushed, grabbed, slapped, or had something thrown at her, or sometimes, often, or very often kicked, bitten, hit with a fist, or hit with something hard, or ever repeatedly hit at least a few minutes or threatened with a gun or knife? If yes enter 1 ___
8. Did you live with anyone who was a problem drinker or alcoholic or who used street drugs? If yes enter 1 ___
DETERMINING AN ACE SCORE
While you were growing up, during your f irst 18 years of life:
9. Was a household member depressed or mentally ill , or did a household member attempt suicide? If yes enter 1 ___
10. Did a household member go to prison? If yes enter 1 ___
Now add up your “Yes” answers: ___ This is your ACE Score.
WHAT IS AN ADVERSE CHILDHOOD
EXPERIENCE / ACE?
Growing up experiencing any of the following conditions in the household prior to age 18: 1. Recurrent physical abuse
2. Recurrent emotional abuse
3. Contact sexual abuse
4. An alcohol and/or drug abuser in the household
5. An incarcerated household member
6. Family member who is chronically depressed, mentally ill, institutionalized, or suicidal
7. Mother is treated violently
8. One or no parents
9. Physical neglect
10. Emotional neglect
RELAPSE
Changes in reward circuitry can become permanent, leading to an inability to experience pleasure through any event
This is the set up for relapse
Coupling of reward circuitry with visual cortex and memory pathways can cause craving by simply viewing images of drugs
GENETICS OF ADDICTION
OPRM-1 gene Codes for opioid addiction
1189 variant codes for alcoholism
OPRD-1 gene Codes for heroin addiction
Brain imaging studies have confirmed that individuals with OPRD-1 and OPRM-1 genotypes are predisposed to not only dopamine deficiency in the limbic system and nucleus accumbens of the brain, but are also susceptible to opioid and alcohol addiction (Volkow, 2007).
DOPAMINE DEFICIENCY SYNDROME IN ADDICTIONS
DNA swab that determines genetic susceptibility to addiction High
Intermediate
Low
PROOVE TEST
CRAVINGS“I HAVE TO TAKE A LEAK”
-DR. NORA VOLKOW
NEUROPHYSIOLOGY OF CRAVING
Release of dopamine in the ventral tegmental area (VTA), and the nucleus accumbens (NA) leads to profound euphoria
Animal studies show stimulation of the dopamine system, by a lever press, leads to ignoring water, food and rest
The dopamine system stimulation leads to changes in reward circuitry
PATHOPHYSIOLOGY
Diagnosis
Heritability
Etiology
Course
Pathophysiology
CHARACTERISTICS OF CHRONIC DISEASES
According to the DSM V, addiction must have three or more of seven criteria
Must have tolerance and withdrawal
Compulsive desire, despite serious consequences
DIAGNOSIS
Most treatment strategies view drug addiction as a curable acute condition rather than a chronic disease
Treatment models need to be the same for Type II Diabetes, hypertension and asthma
FALSE TREATMENT MODEL
Twin studies of Hypertension range from 0.25 to 0.50
Twin studies of Diabetes range from 0.30 to 0.55
Twin studies of Asthma range from 0.36 to 0.70
Twin studies of Heroin Addiction range from 0.34 to 0.55
GENETIC HERITABILITY
Less than 60% of patients with Diabetes II adhere to their medication
Less than 30% of patients with Diabetes II adhere to their diet and behavioral changes
Less than 40% of patients with Hypertension and Asthma adhere to their medication
Less than 30% of these patients adhere to their diet and behavioral changes
COMPARISON WITH OTHER CHRONIC DISEASES
Since the use of any drug is voluntary, behavioral control is important
Does the voluntary initiation of the disease process set drug dependence apart from other medical illnesses?
ROLE OF PERSONAL RESPONSIBILITY
Voluntary choice affects initiation of disease, especially when these choices interact with genetic and cultural factors
Salt sensitivity among males
Obesity
Role of inactivity in Hypertension
Role of diet in Diabetes II
PERSONAL RESPONSIBILITY IN OTHER CHRONIC DISEASES
Many substance use disorder treatment models deliver treatment in a manner that is more appropriate for acute care disorders
Many patients receive detox only
Many patients are admitted to specialized treatment programs where the goal is to rehabilitate them much as a surgical patient is rehabilitated following a joint replacement
PARADOX OF ACUTE ILLNESS MODEL
Hypertensive patients would be admitted to a 28 day hypertension rehabilitation program
Patients would receive group and individual counseling regarding behavioral control of diet, exercise, and lifestyle
Very few would be prescribed medications
Discharged patients would follow up with community resources without medical follow-up
APPLYING THIS TREATMENT MODEL TO HYPERTENSION
Evaluation at 6-12 months
Success of the program would be measured by how many patients have normal blood pressure during the entire post-discharge period
APPLYING THIS TREATMENT MODEL TO HYPERTENSION
MEDICATION ASSISTED TREATMENT (MAT)
Methadone
Suboxone
Subutex
Naltrexone
Probuphine
WHAT DRUGS ARE USED IN MAT?
Changes in reward circuitry can become permanent, leading to an inability to experience pleasure through any event
This is the set up for relapse
Coupling of reward circuitry with visual cortex and memory pathways can cause craving by simply viewing images of drugs
WHY MAT MAKES SENSE
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