Download POTENTIAL DRUG ABUSE - Canadian Society of Addiction Medicine

POTENTIAL DRUG ABUSE
« When doctor rhymes with pusher…»
Marie-Eve Morin, MD
Clinique OPUS
MdM,Projet Montréal
CSAM-SMCA 2014
17 Octobre 17, 2014
Disclosure of potential conflicts of interest
Dr. Marie-Eve Morin has received honoraria, research grants and
partial or total financial compensation as a presenter, consultant or
advisory committees for participation in symposia sponsored by
pharmaceutical companies and for the following companies:
Abbott inc.,
Astra-Zeneca,
Boerhinger Ingleheim,
Bristol-Myers Squibb Canada Inc.,
Glaxo-SmithKline,
Gilead inc.,
Hoffman LaRoche inc.,
Janssen-Ortho,
Eli-Lilly Canada,
Merck-Frost canada,
Pfizer Canada,
Reckittbenkiser Canada,
Schering Plough Canada (Merck),
Valeant Canada limitée,
Wyeth Canada Inc.
©MEMorin2014
PRESENTATION OBJECTIVES:
-
Why worry about drug abuse potential?
Diversion of legal psychotropic drugs
Psychotropic drugs: a brief history
Categories, indications and effects of
pharmacological psychotropic drugs
- Mixtures "at your own risk"
- Prevention: Do we have the necessary tools?
- Time for questions and discussions.
©MEMorin2014
WHY WORRY ABOUT
POTENTIAL DRUG ABUSE?
©MEMorin2014
WHY WORRY ABOUT POTENTIAL DRUG ABUSE?
Extent of the phenomenon since 2000:
• Canadians were among the biggest users of psychotropic drugs in the
world:
- In 2002, Canada ranked 4th for use per capita of prescription
opiates and 2nd for use of sedative-hypnotics (including BZ);
- 2002: Canada was already among the 15 countries where
amphetamines were most often prescribed.
• According to a study by CAMH Toronto, 11% of admissions to
detoxification centers concerned abuse of prescription
drugs in 99-2000.
©MEMorin2014
WHY WORRY ABOUT POTENTIAL DRUG ABUSE?
Pre-2000, USA vs Canada:
In USA, between 1995 and 2005, among
students, there was:
- a 450% abuse of tranquilizers
(opiates);
- a 225% abuse of anxiolytics
(BZ);
- a 95% abuse of stimulants
prescribed for ADHD (Ritalin
and Adderall).
- VS 110% for THC and 53% for
cocaine and heroin combined.
In Canada, there was still no study on
the abuse of prescription stimulants, but
from 97 to 2003, the requirements of the
Rx in children have 44.9% in Manitoba
and 14% in British Columbia.
©MEMorin2014
WHY WORRY ABOUT POTENTIAL DRUG ABUSE?
∙
∙
∙
ALMOST 10 YEARS AGO
According to an OPICAN 2006 study in 7 Canadian cities, prescription opiates
were already replacing heroin more and more :
●
Only 30% of participants consumed heroin against 37% for Dilaudid;
A very lucrative black market:
●
Hydromorph-Contin 30mg: P= 1,50$/R= 25$
●
MSContin 60mg: P= 1,70$/R= 35$
●
Hydromorphone 4mg: P= 0,35$/ R= 5 à 8$
●
Hydromorphone 8mg: P= 0,70$/ R= 10$
©MEMorin2014
WHY WORRY ABOUT POTENTIAL DRUG ABUSE?
4 drugs most frequently identified by toxicology labs
* NFLIS 2000-2005
2000
2001
2002
2003
2004
40%
2005
Is there a real
decrease of
opiate
consumption?
35%
30%
25%
20%
15%
10%
5%
0%
Methamphetamine Cannabis
Cocaine
Heroin
*National Forensic Laboratory Information System (NFLIS), USA
©MEMorin2014
Why Worry About Potential Drug Abuse?
Over 6.3 million Americans admitted current use of Rx prescriptions for nonmedical purposes in 2004
©MEMorin2014
WHAT ABOUT TODAY?
• According to the Ontario Student
Drug Use and Health Survey
(OSDUHS)*
• One out of eight teenager
admits having used
prescription drugs to get high;
• 70% of them have taken it at
home, in the family pharmacy
*Center for Addiction and Mental Health
©MEMorin2008
Recent figures are concerning…
• In 2010, Canada became the
world's second largest
consumer per person for
prescription opioids after the
United States (source:
International Narcotics Control
Board)
• In 2011, opioids had become
the third preferred abused
substance among youths in
Canada (source: OSDUHS)
©MEMorin2008
Even more recently…
- Only 25% of opiate addicts are currently
participating in a methadone program
(source: Peter Selby, CAMH, 2012)
- A systematic review reveals a
prevalence of non-medical use of
psychostimulants from 5 to 35% among
teens and young adults in North
America (FCTC, 2014)
©MEMorin2008
Abuse of Sedative and Benzos
- Among First Nations population aged over
18 years old and living on reserves or in
northern Canada, nearly 6% reported use of
sedatives without prescription from 2008 to
2010 (source: CCSA report, 2013)
- One study estimates that the number of
elderly people who need treatment for drug
addiction in the U.S. could increase from 1.7
million in 2000 to 4.4 million in 2020 (source:
Gfroerer et al, Drug and Alcohol
Dependence. , # 69, 127-135, 2003)
©MEMorin2008
How The Diversion Of Licit
Psychotropic Drugs Is Done
©MEMorin2014
How And Why Diversion Of Prescription (Rx)
Drugs Occur
- Obtaining of multiple prescriptions from
various doctors;
- Prescription "pads" theft and prescription
forgery;
- Sale of forged prescriptions by doctors;
- Purchase from re-salers, parents, friends
who were prescribed Rx legitimately.
Elderly = opiates / BZ +++;
©MEMorin2014
How And Why Diversion Of Prescription (Rx)
Drugs Occur
- Diversion of Rx in rehab centers (methadone);
- Diversion from stocks Rx for patients in
hospitals;
- Breaking into and theft from homes, doctors'
offices, pharmacies, manufacturers, courier
services, clinics and hospitals;
- Purchase of Rx on Internet. ***
©MEMorin2008
Several users physically or chemically alter Rx to increase the
effect and accelerate the speed at which Rx begins to take effect:
∙
Change the form to
allow other ways of Use
●
∙
E.g. "sniffing" or injecting
Dilaudid and Ritalin;
Extract the active
substance formulations
at high doses
●
©MEMorin2014
E.g. removing the gel in a
"patch" of fentanyl using a
syringe or with various
solvents;
Several users physically or chemically alter Rx to increase the
effect and accelerate the speed at which Rx begins to take effect:
∙
Separating opiates of unwanted
or inactive ingredients in the
tablets
●
∙
E.g. separate acetaminophen,
ibuprofen or aspirin codeine,
hydrocodone, oxycodone or
pseudoephedrine contained in a
tablet using acid solutions.
Modifying sustained release
formulations
●
©MEMorin2014
E.g. crush Oxycontin tablets for
immediate effect in consuming
content.
BRIEF HISTORY OF
PSYCHOTROPHES
©MEMorin2014
WHAT IS A PSYCHOTROPE?
«"Some foreign substances
provide immediate and
pleasurable sensations,
while at the same time
changing our sensitivity to
render us incapable of
feeling unpleasant
sensations. These properties
are the danger and
harmfulness of these
substances."
©MEMorin2014
Sigmund Freud
Civilization and its discontents, 1930
WHAT IS A PSYCHOTROPE?
PSYCHOTROPE (or psychoactive drug)*:
Substance that acts on the psyche of an individual changing his mental
functioning. It can cause changes in perception, mood, consciousness,
behavior, and various psychological functions.
It is the kind of medicinal products most commonly used in the world.
By definition, all illegal drugs are psychotropic, but all drugs are not
psychotropic (e.g. antibiotics, antihypersensives ...)
*From «Les psychotropes; Pharmacologie et toxicomanie », L. Léonard et M. Ben Amar
©MEMorin2014
WHAT IS A PSYCHOTROPE?
Brief history...
1803:
Serturner isolated morphine from opium;
1860:
Niemann extracted cocaine from coca leaves;
1880-1900: Cocaine was proclaimed "wonder of the
therapeutic arsenal"
1887:
Amphetamines became synthetic;
1888:
Cocaine was part of the original formula for
Coca-Cola, but was removed from the drink
around 1902;
1898:
Dreser synthesized heroin from morphine.
Bayer marketed heroin and switched to "overthe-counter";
1911:
Cocaine was prohibited in Canada for the first
time.
©MEMorin2014
WHAT IS A PSYCHOTROPE?
Brief history...
1912:
1923:
1939:
1940:
1960:
1960:
2005:
.
©MEMorin2014
Placed on the market, phenobarbital,
was the first barbiturate;
Heroin was banned in Canada;
First reported use of steroids in
humans;
German chemists synthesized
Adolphine, renamed methadone in 1946;
Placed on the market (Librax)
chlordiazepoxide, the first BZ;
Amphetamines ceased to be legally
available without a prescription
Methamphetamine was declared illegal in
Canada.
STREET PHARMACY?
Abuse of Psychotropic Drugs
©MEMorin2014
BENZODIAZEPINES
©MEMorin2008
Abuse of Psychotropic Drugs
BENZODIAZEPINES
MEDICAL INDICATIONS FOR
USAGE:
- Contextual anxiety (E.g. before
surgery)
- Psychiatry: chronic anxiety
disorder (e.g. panic disorder)
- Insomnia (e.g. elderly)
- Alcohol withdrawal (to prevent
withdrawal convulsions and
deliriums)
- Seizures (e.g. emergency)
©MEMorin2014
Ativan 1 mg
Abuse of Psychotropic Drugs
BENZODIAZEPINES
13 BZ marketed in Canada:
Alprazolam/ XANAX
0,25 / 0,5 / 1 / 2mg I-I
Bromazepam/LECTOPAM
3 / 6 mg I-I
Chlordiazepoxide / LIBRAX
5mg I-L
Clorazepate / TRANXENE
3,75 / 7,5 / 15 mg R-L
Diazepam / VALIUM
2 / 5 / 10 mg R-L
©MEMorin2014
BENZODIAZEPINES
13 BZ marketed in Canada …con’t:
Clonazepam / RIVOTRIL 0,25/0,5/1 mg I-L
Lorazepam / ATIVAN 0,5 / 1 / 2 mg I-I
Oxazepam / SERAX 10 / 15 / 30 mg L-I
Flurazepam / DALMANE 15 / 30 mg R-L
Midazolam / VERSED I-V only in 2 / 5 / 10 ml vials
Nitrazepam / MOGADON 5 / 10 mg I-L
Témazepam / RESTORIL 15 / 30 mg I-I
Triazolam / HALCION* 0,125 / 0,25 mg R-C
** Due to severe toxic effects as anterograde amnesia,
suicidal tendencies and crimes committed under its
effect, tablets 0.5 mg were removed
©MEMorin2014
BENZODIAZEPINES
Desired Effect By The User:
- Reducing anxiety and pain
- Facilitating the "crash" of psychostimulants (eg cocaine)
- Maximizing the effect of alcohol, GHB and opiates
- Generating an overall sense of well-being;
Sale: $1 to $2 per tablet on the street
(VS <$ 0,20 / co)
©MEMorin2014
BENZODIAZEPINES
RISKS OF ABUSE:
- Decrease of inhibitions = risk in behavior;
- Decrease in FC and blood pressure;
- Low concentration and confusion;
- Marked tiredness;
- Loss of coordination, impaired memory and judgment;
- Respiratory depression or respiratory arrest in case of overdose;
- + + high risk of dependence (the worst: alprazolam);
- Necessary caution if mixed with alcohol and/or opiates and/or GHB
- Withdrawal can be dangerous + + + (convulsion, arrhythmia ...)
©MEMorin2014
PRESCRIPTION OPIATES
•
©MEMorin2014
Abuse of Psychotropic Drugs
OPIATES
MEDICAL INDICATIONS:
- Relief of acute physical pain e.g. bone fracture,
appendicitis after surgery …
- Relief of chronic pain when
other Rx are ineffective - e.g.
chronic back pain, cancer …
- Relief of irritant cough (syrup /
codeine)
©MEMorin2014
OPIATES
What are « Addicts » looking for?
EFFECTS EXPERIENCED:
∙
« RIDING THE HORSE»
/ « CHASING THE DRAGON »:
pain relief, euphoria, mental
numbness, wellness and relaxation
...
OVERDOSE / OD:
∙
Drowsiness, nausea, constipation,
stop urinating, "pin-point Pupils",
confusion, cold and bluish skin,
respiratory slowing, coma, death.
©MEMorin2014
*When to talk about
dependence .. When
stopping the consumption
causes WITHDRAWAL
∙
+ + + Anxiety, insomnia,
sweating + + +, abdominal
cramps, dilated pupils,
muscle spasms, chills,
tremors ...
Opioid Consumption Map
Morphine Equivalents, mg/capita, 2010
Treatment Profe
Policy Makers
Pharmaceutica
Patients
http://ppsg-production.heroku.com/. Accessed October 23, 2013.
©MEMorin2014
Total Pharmaceutical Opioid Consumption
1980 – 2010, Morphine Equivalents per capita
©MEMorin2014
http://ppsg-production.heroku.com/chart
Oxycodone-Related Deaths in
Canada
©MEMorin2014
Dhalla, et al. CMAJ , 2009
May 2014,
Montreal:
15 deaths in a
month due to
overdose of
Fentanyl
©MEMorin2014
Prescription Opioid Deaths
England and Wales Drug Related Deaths 2001 - 2011
Source: RADARS® System, Denver Health and Hospitals
©MEMorin2014
Giraudon et al. Br J Clin Pharm 2013
Death By Overdose Of Opiates,
San Francisco Bay Area
©MEMorin2014
More Drug Production = More Drug Abuse
But the Slope Varies by Drug
©MEMorin2014
Dasgupta N et al. Drug Alcohol Depend. 2006;82(2):135-142.
OPIATES
CODEINE, trade name:
- Codeine (short-acting) 15/30 mg = ± 4 hrs
-
Codeine-Contin (controlled release) 50/100/150/200 mg = ± 12 hrs
- Users puncture capsules to inject product and get an immediate
effect; overdose risks are then higher, but still less than morphine
-
Several combined formulations:
Tylenol # 1-5: contain between 8 and 60 mg of codeine per tablet
Empracet 30: same as Tylenol # 3 and 4, ie. containing 30 or 60 mg
of codeine
"222" / Fiorinal: contains ASA-caffeine-codeine
Risks associated with other ingredients (e.g. Tylenol / liver, Aspirin /
bleeding ...)
©MEMorin2014
OPIATES
MORPHINE, trade name:
-
± 10 X more potent than codeine;
-
Less present on the streets in Montreal;
-
Statex co. 5/10/25/50 mg suppositories or 5/10/20/30 mg = ± 4
hrs effect;
-
M-Eslon co. 10/15/30/60/100/200 mg = ± 12 hrs effect;
-
MS-Contin co.15/30/60/100/200 mg or suppositories
30/60/100/200 mg = ± 12 hrs effect; **The only opioid LA
available in supp.
- Kadian co. 20/50/100 mg ** can last up to 24 hours
©MEMorin2014
OPIATES
HYDROMORPHONE, trade name:
- 50 X more potent than codeine and 5-6 X
stronger than morphine!
- This is the most popular legal opiate on the black
market in Montreal;
- Dilaudid 1/2(2,50$)/4(5$ )/8(10$ ) mg = ± 4-6
hrs effect;
- Hydromorph-Contin
3(2,50$)/6(5$)/12(10$)/24(20$)/30(25$) mg = ±
12 hrs effect but users puncture capsules to
inject the product and get an immediate effect ...
higher OD risk!
©MEMorin2014
OPIATES
OXYCODONE, trade name:
• 3-4 X less potent than Dilaudid, but 10X more
potent than morphine and 20X more than
codeine;
• It is the most popular legal opiate on the black
market in USA, and the number of fatal OD is in
constant increase since '99 (see NIDA);
Supeudol co. 5/10 mg or supp. 10/20 mg = ± 4 hrs
effect;
Percocet co. 5 mg + 325 mg acetaminophen
OxyContin 10/20/40/80 mg and OxyIR 5/10/20 mg =
± 12 hrs effect, but tablets are also often injected
to have an immediate effect …
©MEMorin2014
OPIATES
PETHIDINE (Demerol), trade name:
- 50 mg tablets only; 4 to 6 hrs effect;
- Available in injectable solution at
Emergency or during surgery;
- Increasingly popular on the black market
to replace heroin (the tablets are
dissolved to be injected).
- Cost on the street =??? ...
©MEMorin2014
OPIATES…
Alternatives ...on The Street
METHADONE:
©MEMorin2014
-
At least 10X more potent than morphine;
-
Dissolved in juice, so difficult to inject;
-
Available in tablets for treatment of chronic
pain (Metadol co. 1/5/10/25 mg )
-
Sold for about $1 /mg on black market (40 mg
= $ 40);
-
Risk of OD + + + if taken with other opioids at
the same time;
-
24 to 48 hrs and + duration of action
OPIATES…
Alternatives ...on The Street
SUBOXONE (Buprenorphine/naloxone)
- Available in Canada since Nov.2007
- Also contains naloxone (Narcan) to counter the
injection and / or abuse;
- If injected, can trigger violent withdrawal
symptoms if the person is still under the
influence of heroin or methadone;
- Anecdotal cases of abuse in Montreal, no
reported deaths related to buprenorphine
or naloxone
- Cost on the street: ?..
©MEMorin2014
PSYCHOSTIMULANTS
©MEMorin2014
Médicaments psychotropes d’abus
LES PSYCHOSTIMULANTS
MEDICAL INDICATIONS:
- Treatment of attention
deficit disorder (ADHD) in
children and adults;
- Narcolepsy;
- Rarely to treat obesity
©MEMorin2014
Several stimulants sold over
the counter:
- "Wake-Up pills" = caffeine;
- Energy drinks;
- Ephedrine is easily found in
the gym ...
- Pseudoephedrine is still
found in Canada in oral
decongestants
PSYCHOSTIMULANTS:
Why are they so affordable?
EPHEDRINE
H
H
C
C
OH
CH3
H
N
CH3
METHAMPHETAMINE
©MEMorin2014
H
H
C
C
H
CH3
H
N
CH3
Since 2008, Quebec =
“Ritalin Champion"
Quebec accounts for 23% of the use of Ritalin in Canadian population
- Accounts for 44% of prescriptions for methylphenidate;
- Accounts for 35% of methylphenidate tablets sold
The number of tablets sold each month is increasing:
- 2009: 2,522,419 tablets sold;
- 2008: 2,198,052 tablets sold;
The number of orders issued each month is increasing:
- 2009: 70,284 prescriptions each month
- 2008: 58,309 prescriptions each month
©MEMorin2014
LES PSYCHOSTIMULANTS
DESIRED EFFECTS:
●
Euphoria and stimulation;
●
Prolonged wakefulness;
●
Sexual disinhibition;
●
Diminution of
embarrassment;
●
Increase in alertness;
●
Appetite suppressant
** Very common in
adolescents;
●
Improvement of athletic or
academic performance
©MEMorin2014
PSYCHOSTIMULANTS:
What Are The Associated Risks?
IF ABUSE OR OVERDOSE:
heart rate and blood pressure = risk
of arrhythmias, stroke and heart
attack;
- Irritability and aggressiveness;
- Anxiety, panic attacks, paranoia,
psychosis
IN CASE OF PROLONGED USE
- Memory and Learning Disorders;
- Loss of appetite and weight;
- Depressive mood with long term use.
©MEMorin2014
PSYCHOSTIMULANTS
DRUGS INVOLVED:
- Dexedrine ( dexamphetamine )
IR forme: 5/10 mg, 4 hrs effect
SR forme: 5/10/15 mg, 8hrs
effect
- Vyvanse: prodrug, little or no risk of
abuse, duration beyond 12 hours.
- Biphentin (methylphenidate
hydrochloride)
Multiples dosing: 10-15-20-3040-50-60-80 mg
Short half-life of 2.4 hrs
©MEMorin2014
PSYCHOSTIMULANTS
DRUGS INVOLVED:
- Ritalin ( methylphenidate )
- IR forme: 10/20 mg, 4 hrs
effect
- SR forme: 20 mg, 8-10 hrs
effects
- Adderall XR ( 4 amphetamine
salts)
- 5/10/15/20/25/30mg, 8-10
hrs effects
- Concerta ( methylphenidate
Oros )
- 18/27/36/54 mg, 8-10 hrs
effects
©MEMorin2014
ANTIPSYCHOTICS:
Newcomers to the "black market"
MEDICAL INDICATIONS:
• Schizophrenia;
• Bipolar disorder;
• Major depression with
psychotic features;
• Toxic psychosis;
• Dementia with psychotic
symptoms;
• Delusional disorder;
• Agitation and / or severe
irritability during a detox.
©MEMorin2014
ANTIPSYCHOTICS
Effects and risks associated with the use
THERAPHEUTIC EFFECTS:
• Reduces hallucinations,
delusions and thought
disturbances;
•
•
•
Desired effects for the user:
• Calming obsessions from consumption;
• Appease the "crash" post-consumption
(eg cocaine).
Reduces aggression and
Side effects and risks:
agitation;
• Little risk of fatal OD;
In early use: somnolence
• Stimulates appetite + +;
(temporary if taken regularly);
• Drowsiness + + +;
• Uncontrollable shaking (* akathisia)
Mood stabilization (medium
and long term).
• Acute dystonia (rare);
• Convulsions if PCP or stimulants.
©MEMorin2014
ANTIPSYCHOTIC DRUGS
TRADE NAMES:
∙
Olanzapine /zyprexa
−
co. 2,5/5/7,5/10 mg
∙
∙
Quetiapine / seroquel
−
co. 25/100/200/300 mg
Risperidone / risperdal;
−
co. 0,25/0,5/1/2/3/4 mg
Several others less used
(Haldol, Nozinan... )
©MEMorin2014
Drugs Abused WITHOUT Psychotropic
Effect
ERECTILE DYSFUNCTION:
- Sildenafil 25/50/100 mg
- Tadalafil 5/10/20 mg
- Vardénafil 2,5/5/10/20 mg
** Risk of priapism
STEROIDS AND HORMONES:
- Testosterone undecanoate
40mg/co (Andriol)
**Risk of aggression
- Oestradiol, Progesterone...
©MEMorin2014
« NEUROBIOLOGY 101 »
Link Between Drugs And Rx Abuse
In the brain, psychotropics, licit or
illicit, mainly act as a "booster" of
DOPAMINE AND SEROTONIN, two
important neurotransmitters in:
● Proper functioning of the central
nervous system;
● Emotional and mental balance.
● Most of all: « REWARDSYSTEM »
©MEMorin2014
Cocktails of Psychotropic Drugs:
ABUSE AT YOUR OWN RISK!!!
©MEMorin2014
Cocktails of Psychotropic Drugs:
ABUSE AT YOUR OWN RISK!!!
Some mixtures are much
riskier:
OPIATES +
BENZODIAZEPINES:
●
BZ the effect of Opiates =
risk of fatal OD.
BENZODIAZEPINES +
ALCOHOL:
●
Cumulative effect sedative
= severe risk of quickly
being impaired = risk of
aspiration ± of alcoholic
coma.
Cocktails of Psychotropic Drugs:
ABUSE AT YOUR OWN RISK!!!
Some mixtures are much
riskier:
∙
∙
PSYCHOSTIMULANTS +
COCAINE/SPEED:
●
Risk a/n cardiac + Risk
toxic psychosis.
PCP+ ANTIPSYCHOTICS:
●
Risk of severe agitation +
risk of seizures.
©MEMorin2014
PRESCRIPTION DRUG ABUSE:
Are There Any Solutions?
©MEMorin2014
PRESCRIPTION DRUG ABUSE:
Are There Any
- Alert system
- Vigilance + + + of
physicians with "pad"
prescriptions
- Increasingly, use of
electronic prescriptions
- Centralized Provincial
Registry for prescriptions
©MEMorin2014
solutions?
PRESCRIPTION DRUG ABUSE:
Are There Any
- Written patientphysician contract
- Drugs given by single
dose or weekly
- Counting tablets when
visiting doctor
- EDUCATION!
©MEMorin2014
solutions?
In closing ... THANK YOU!
- Luc Beaucage, Drugs and Organized Crime
Awareness Service (DOCAS)
- Pénélope and Sarika, street nurses from
Projet-Montréal;
- CSAM for their invitation
- Each of my patients with a substance abuse
problem: they are my best teachers ...
©MEMorin2014
QUESTIONS? COMMENTS?
©MEMorin2014