nora volkow final edits
Post on 18-Nov-2014
2.588 Views
Preview:
DESCRIPTION
TRANSCRIPT
Dr. Nora D. Volkow, MD, Director, National Institute on Drug Abuse (NIDA) National
Institute of Health
April 10-12, 2012 Walt Disney World Swan Resort
Prescription Drug Abuse: It’s Not What the Doctor Ordered
Nora D. Volkow, M.D. Director
National Institute on Drug Abuse
Learning Objectives Attendance at this presentation will give participants a better understanding of:
• Recent increasing trends in the misuse and abuse of prescription drugs as well as the growing number of opioid and stimulant prescriptions being dispensed by retail pharmacies in the U.S.
• The ways in which the most commonly abused prescription drug classes affect the brain and body and the possible deleterious consequences that can result from such use and abuse.
• Strategies being developed and implemented that will increase awareness of the growing problem, and research aimed at identifying tools and interventions to most effectively prevent and treat prescription drug abuse.
Disclosure Statement
Presenter has nothing to disclose
Pharmaceutical Drug Abuse is a Major Problem in the US
Past Month Use (Among Persons Aged 12 or Older) in Millions
Source: 2010 National Survey on Drug Use and Health, SAMHSA, 2011.
Prevalence of Past Year Drug Use Among 12th graders 2011 Monitoring the Future Study
* Nonmedical use
Drug Prev. Drug Prev. Alcohol 63.5 OxyContin* 4.9 Marijuana/Hashish 36.4 Sedatives* 4.3 Synthetic Marijuana 11.4 Hall other than LSD 4.3 Amphetamines* 8.2 Inhalants 3.2 Vicodin* 8.1 Cocaine (any form) 2.9 Adderall* 6.5 LSD 2.7 Salvia 5.9 Ritalin* 2.6 Tranquilizers* 5.6 Ketamine 1.7 Cough Medicine* 5.3 Provigil 1.5 MDMA (Ecstasy) 5.3 GHB 1.4 Hallucinogens 5.2 Methamphetamine 1.4
Categories not mutually exclusive
Past Year Initiates of Specific Illicit Drugs Among Persons Aged 12 or Older: 2010
Num
bers
in T
hous
ands
Source: 2010 National Survey on Drug Use and Health, SAMHSA, 2011.
Number of Opioid Prescriptions Dispensed by U.S. Retail Pharmacies, Years 1991-2011
76 78 80 86 91 96 100 109
120 131
139 144 151 158
169 180
192 201 202
210 219
0
50
100
150
200
250 91
92
93
94
95
96
97
98
99
20
00
01
02
03
04
05
06
07
08
09
10
11
Pres
crip
tions
(mill
ions
)
IMS’s Source Prescription Audit (SPA) & Vector One®: National (VONA)
Opioids Hydrocodone Oxycodone
Dentists and Emergency Medicine Physicians were the main prescribers for patients 5-29 years of age
0
100
200
300
400
500
600
700
800
900
0-‐4 5-‐9 10-‐14 15-‐19 20-‐24 25-‐29 30-‐39 40-‐59 60+
Rate per 10,000 pe
rson
s
Age Group
GP/FM/DO
IM
DENT
ORTH SURG
EM
5.5 million prescrip8ons were prescribed to children and teens (19 years and under) in 2009
Eight-Fold Deaths from Drug Overdoses 1971-2007
Source: CDC, Unintentional Drug Poisoning in the US, National Vital Statistics System, 2010
Trends in ED Visits Involving the Nonmedical Use of Narcotic Pain Relievers
Num
ber o
f ED
Visi
ts
Source: 2008 (8/2009 update) SAMHSA DAWN
Number of Stimulant Prescriptions Dispensed by U.S. Retail Pharmacies, Years 1991-2011
The use of stimulant medications among healthy individuals for cognitive enhancement is increasing, raising questions not only about safety but also its efficacy across cognitive tasks and individuals
Source: 2010 National Survey on Drug Use and Health, SAMHSA 2011.
Source of Prescription Drugs (how they obtained the drugs they most recently used nonmedically)
Rates averaged across 2009 and 2010
Perc
ent
0 100 200 300 400 500 600 700 800 900
1000 1100
0 1 2 3 4 5 hr Time After Amphetamine
% o
f Bas
al R
elea
se
AMPHETAMINE
0
50
100
150
200
0 60 120 180 Time (min)
% o
f Bas
al R
elea
se
Empty Box Feeding
Di Chiara et al.
FOOD
VTA/SN nucleus accumbens
frontal cortex
These prescription drugs, like other drugs of abuse (cocaine, heroin, marijuana) raise brain dopamine levels
Dopamine Neurotransmission
Why Do People Abuse Prescription Drugs?
BUT dopamine is also elevated by natural reinforcers
Opioid Peptides
Nicotine Alcohol Opiates
VTA Interneuron
Alcohol
DA
Glutamate inputs (e.g., from cortex)
+
?
DA
GABA
-
?
+
Stimulants
Cannabinoids
Opiates -
-
-
Alcohol PCP
+
Nicotine
Glutamate inputs (e.g., from amygdala PPT/LDT)
Drugs of Abuse Act on the Reward & Ancillary Circuits Through Different Mechanisms…But All Lead to Similar Dopaminergic Effects in the VTA & NAc
Adapted from Nestler 2005.
`
+
Similarities Between Illicit & Prescription Drugs
Opioids
Attach to opioid receptors in the brain and spinal cord, blocking the transmission of pain messages and causing an increase in the activity of dopamine
Examples: OxyContin, Vicodin How They Work…
• Postsurgical pain relief • Management of acute or chronic pain • Relief of coughs and diarrhea
Opioids are Generally Prescribed for:
Activate Opiate Receptors, which Modulate Pain & Reward
Opiate Receptors Activate Dopamine Cells
Amydala (reward)
NAc (reward)
Thalamus (pain)
Methamphetamine
Adderall
Similarities Between Illicit & Prescription Drugs
Stimulants
Enhance brain activity by increasing the activity of brain excitatory chemical messengers, such as norepinephrine and dopamine, leading to mental stimulation
Example: Ritalin How They Work…
• ADHD • Narcolepsy • Depression that does not
respond to other treatments • Asthma that does not
respond to other treatment
Stimulants Are Generally Prescribed For:
CNS Depressants
Cause an increase in gamma-aminobutyric acid (GABA), an inhibitory chemical messenger leading
to a decrease in brain activity
Examples: Valium, Xanax How They Work…
CNS Depressants are Generally Prescribed for: • Anxiety • Tension • Panic attacks • Acute stress reactions • Sleep disorders • Anesthesia (at high doses)
Sedatives
Activate the Same Receptor as Alcohol Brain areas where activity is increased by
sedative drugs and by alcohol
Sedative Drug Alcohol
Examples: Valium, Xanax, Librium
• Expectation of Drug Effects Expectation of clinical benefits vs euphoria “high”
• Context of Administration School, clinic, home vs bar,
discotheque
• Dose and Frequency of Dosing Lower, fixed regimes vs higher, escalating use
• Route of Administration Oral vs injection, smoking, snorting
What is the Difference Between Therapeutic Use and Abuse?
*
cocaine d-methamphetamine MDMA
methylphenidate modafinil amphetamine
Psychostimulant Drugs
Pharmacokinetics in Human Brain [11C]Cocaine [11C]Methylphenidate
"High" "High" 0
20
40
60
80
100
0
20
40
60
80
100
0 10 20 30 40 50 60 70 80
% P
eak
[11C]Cocaine
Time (min)
[11C]Methylphenidate
0 10 20 30 40 50 60 70 80
Effects Depend on the Drug Pharmacokinetics— How fast it gets into the Brain
When Used Therapeutically Drugs are Given Orally which Results in Slow Brain Uptake When Abused Drugs are Snorted or Injected which Results n Fast Brain Uptake
0 0.01 0.02 0.03 0.04 0.05 0.06
0 20 40 60 80 100 120 Upt
ake
in S
tria
tum
(%/c
c)
Time (minutes)
Upt
ake
in S
tria
tum
(nC
i/cc) iv Ritalin
Fast!!!
0
0.0005
0.001
0.0015
0.002
0.0025
0.003
0.0035
0 20 40 60 80 100 120 Time (minutes)
oral Ritalin
Slow!!!
• Expectation of Drug Effects Expectation of clinical benefits vs euphoria “high”
• Context of Administration School, clinic, home vs bar,
discotheque
• Dose and Frequency of Dosing Lower, fixed regimes vs higher, escalating use
• Route of Administration Oral vs injection, smoking, snorting
What is the Difference Between Therapeutic Use and Abuse?
Source: Volkow, ND et al., Journal of Neuroscience, 23, pp. 11461-11468, December 2003.
Glucose Metabolism Was Greatly Increased By the Expectation of the Drug
Unexpected MP 70
0 µmol/100g/min
Expected MP
Increases in Metabolism Were About 50% Larger When MP Was Expected Than Unexpected
0 5
10 15 20 25 30
% C
hang
e
Une
xpec
ted
MP
Expe
cted
MP
Expe
cted
MP
Got
Pla
cebo
• Expectation of Drug Effects Expectation of clinical benefits vs euphoria “high”
• Context of Administration School, clinic, home vs bar,
discotheque
• Dose and Frequency of Dosing Lower, fixed regimes vs higher, escalating use
• Route of Administration Oral vs injection, smoking, snorting
What is the Difference Between Therapeutic Use and Abuse?
signal! signal!
low DA cell firing! high DA cell firing!
DA"
DAT"
DA D2-R"
MP"
MP ability to increase DA is affected by the rate of DA release; which makes its effects
Context Dependent
0
5
10
15
20
MP Neutral Context
MP Salient Context
MP-
indu
ced
chan
ge in
DA
P < 0.05
Four-Fold Substance Use Disorder TX Admissions Pain Relievers: 1998-2008
Source: SAMHSA Treatment Episode Data Set (TEDS), 1998 and 2008.
Treatment of Prescription Medications
Full and Partial Agonists vs Antagonists Treatment Strategies for Opioid Addiction
effect no effect
agonist antagonist
an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same
effect
an antagonist drug is close enough in shape to bind to the receptor but not close
enough to produce an effect. It also takes up receptor space and so
prevents the endogenous ligand from binding
Opi
oid
Effe
ct
Full Agonist (Methadone)
Partial Agonist (Buprenorphine)
Antagonist (Naloxone)
Log Dose
Subutex® -- Monotherapy product Suboxone® -- Buprenorphine/Naloxone
Buprenorphine for the Treatment of Addiction to Opioid Medication
Currently 19,000 physicians are certified to prescribe buprenorphine (Source: CSAT Buprenorphine Information Center) Related to morphine (partial agonist)
Uses same receptors as morphine but does not produce the same high
Long-lasting, less likely to cause respiratory depression
Can be abused, but combining with naloxone decreases abuse potential
Normal Control
Methadone Maintained Patient
Source: Kling et al., JPET, 2000.
Specific Binding [18F]cyclofoxy (µ ligand)
30-35 % receptor occupancy for methadone doses > 80 mg a day
Specific Binding [11C]carfentail (µ ligand)
Greenwald, MK et al., Neuropsychoph, 2003.
Medications to Treat Those Addicted
27-47 % occupancy for 2mg Bup 85-92% occupancy for 16 mg Bup 94-98% occupancy for 32 mg Bup
Need for New Medications
• Develop medications with lower abuse potential including drugs that don’t cross BBB (i.e., CbR2 agonist)
• Develop slow release formulations (low dose and long duration)
• Develop novel formulations to reduce abuse liability including mixture formulations (e.g., naloxone and buprenorphine)
0 0.0005 0.001 0.0015 0.002
0.0025 0.003
0.0035
0 20 40 60 80 100 120
Upt
ake
in S
tria
tum
(nC
i/cc)
Time (minutes) Slow!!!
How to Minimize the Diversion and Abuse of Prescription Medications
Prevention Strategies - Training & Education
• Enhance clinical training for physicians, nurses, dentists and pharmacists in the areas of pain management, opioid pharmacology and abuse and addiction
Prevention Strategies – Public Education
• Increase patient, lay public, and policy makers’ awareness of the potential risks for abuse inherent in all opioid analgesics
Take Back Programs Maine model
– Postage paid medicine return envelopes distributed across the state
– Disposal in compliance with state and federal laws and sound environmental practices
– 3850 envelopes returned (85% prescription drugs)
– Psychotherapeutics made up 31% of returns for individuals ages 50 and under
Prescription Monitoring Programs
• Statewide electronic database collects data on substances dispensed in the state.
• Through the database, physicians and pharmacies can identify patients who are seeking multiple prescriptions.
• As of the summer of 2010, 34 states had operational programs.
Revised Dec 2011
Revised Jan 2012
Published Dec 2011 Revised Oct 2011
www.drugabuse.gov
top related