Transcript Dextromethorphan Abuse in Adolescence: A Rising Trend

Dextromethorphan Abuse in
Adolescence: A Rising Trend
Ilene B. Anderson, PharmD
Clinical Professor; UCSF School of Pharmacy
Senior Toxicologist
California Poison Control System - SF
Conflicts of Interest
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The speaker has no conflicts of
interest to disclose regarding this
topic.
California Poison Control System
Overview
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Case Studies
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Clinical presentation (OD, chronic abuse), Management
Pharmacology
Selected Drug Interactions with DXM
Incidence of Teenage DXM Abuse
What is being done to curb the abuse?
California Poison Control System
What is the CPCS?
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CPCS - California Poison Control System
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1 800 222-1222 OR 1 800 876-4766
24 hour Emergency Telephone Hotline
www.calpoison.org
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Advice to health care professionals/public
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Over 300,000 consultations a year
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Calls to the CPCS are voluntary
California Poison Control System
Case Study
14 year female took #24 ‘Skittles’ during a sleepover at her friend’s house. Her friends became
alarmed when she became agitated and started
hallucinating. EMS called.
Vital Signs: HR 150, BP 157/92, T 100
– pupils dilated, nystagmus
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One Tonic Clonic seizure soon after ED arrival
California Poison Control System
Ingested Product
Active Ingredients:
Dextromethorphan 30mg
Chlorpheniramine 4mg
California Poison Control System
Case Study - Outcome
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Patient was observed for 9 hours
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Ativan
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All symptoms resolved
Toxicology screen results
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No repeat seizures
Positive for phencyclidine (PCP)
Patient discharged home
California Poison Control System
Dextromethorphan
Pharmacology and Toxicology
Dextro-rotatary Isomers
Levorphanol
Dextromethorphan
California Poison Control System
Pharmacology
Dextromethorphan
CYP 2D6
Dextrorphan
(active metabolite)
California Poison Control System
Dextromethorphan; Dextrorphan
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Do Not bind to classic opiate receptors
Inhibits NMDA Receptor
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(N-methyl-d-aspartate receptor)
Same site of action as ketamine, phencyclidine
• Dissociative hallucinogens
Inhibits reuptake of serotonin
DXM substrate for and inhibitor of CYP2D6
California Poison Control System
Genetic polymorphisms of CYP 2D6
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Poor metabolizers (PMs)
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Produce less Dextrorphan
Experience higher incidence of side effects
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Nausea, Vomiting, Dysphoria
Less likely to abuse DXM
Extensive metabolizers (EMs)
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Produce more Dextrorphan
Experience more of the euphoric, “desired”
mind altering effects
More likely to abuse DXM
California Poison Control System
Clinical Effects (“Plateaus”)
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1st Plateau: 1.5-2.5mg/kg
Mild alcohol-marijuana-like intoxication, GI sxs
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2nd Plateau: 2.5-7.5mg/kg
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3rd Plateau: 7.5-15mg/kg
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‘Enjoyed the best by most’ ‘CEV’ lethargy or
agitation, ataxia, nystagmus, tachycardia, HTN
Variable, often dysphoric, psychosis, disorientation,
altered judgment may be severe
4th Plateau: > 15-30mg/kg
Fully dissociative, seizures, hyperthermia, aspiration
California Poison Control System
Hidden Ingredients
Do they pose a risk?
Case Study 2
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A 14yo M skipped school with friends
and took 16 Coricidin HBP Maximum
Strength Flu tablets to get high.
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Friends claim he was acting goofy, slept
for a while, but seemed okay.
Skipped dinner and went to sleep early.
California Poison Control System
Case study 2; continued
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Later that evening he started vomiting
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Mother called the Poison Center
Patient referred into the ED
Acetaminophen poisoning
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Dose (16 tabs x 500mg = 8,000mg)
Risk of liver Damage
Symptoms are delayed about 10 hours.
California Poison Control System
Product ingested
Ingredients:
Acetaminophen 500mg
Chlorpheniramine 2mg
Dextromethorphan 15mg
California Poison Control System
Case Study 2; Outcome
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Laboratory findings
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Acetaminophen 65 mg/L at 13 hours
Elevated liver enzymes by 30 hours
Patient hospitalized for 3 days
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Treated with N-acetylcysteine (antidote)
Liver injury resolved
 Patient discharged on Day 4
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California Poison Control System
DXM and the Laboratory
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Dextromethorphan
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DXM may cause a false positive on the
Phencyclidine (PCP) assay
Rule out acetaminophen
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Common in many OTC cough/cold preps
Delayed hepatic toxicity
California Poison Control System
Chronic Abuse
Scant case reports ……
Psychosis-Vicks Formula 44-D
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25yr F ingested 800ml x 1.5 yrs (DXM, PPA, GG).
Patient had a long hx of OTC abuse; No hx
alcohol / DofA
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Dishevelled, tangential speech, delusional (US
hostage in Lebanon), hyperreflexic, nystagmus
HR 140, BP 148/102
Supportive Care - no meds given.
No withdrawal syndrome
Resolution in 3 days
Craig DF. Can Med Assoc J 1992; 146(7): 1199-1200.
California Poison Control System
DXM Withdrawal Syndrome
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66yr F hx of heavy alcohol use x 30yrs since
her teens. Abstinent for a few years &
switched to DXM Cough Syrup 4oz > 16oz/d
(no EtOH) for > 10 years.
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Sxs: abdominal pain, N/V, tremor, dysphoric,
depressed, insomnia
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Last dose: 3 days prior to ED
VS: HR 96, BP 183/91, T 99.
Tx: Librium, counseling. Resolved 2-5 days
Desai S, et al JABFM. May-June 2006;19(3):320-322.
California Poison Control System
Drug Drug Interactions
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Do they pose a serious risk?
California Poison Control System
Selected Drug Interactions w/ DXM
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SSRIs -- Eg: fluoxetine, paroxetine
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SSRIs inhibit CYP2D6
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MDMA “Ecstasy”
– Reuptake of serotonin is inhibited
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Risk - Serotonin syndrome
AMS, seizure, rigidity, hyperthermia, arrhythmias, HTN
Risk - Serotonin syndrome
Monoamine oxidase inhibitors
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Catecholamine uptake/metabolism is altered
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Risk: Increased sympathomimetic effects and
Serotonin syndrome
California Poison Control System
Why are teenagers abusing DXM ?
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Euphoria and hallucinations
Commonly available over-the-counter
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Legal
Relatively inexpensive
Easy to fool parents
Lacks the stigma of a ‘drug of abuse’
False perception that use is safe
Widely advertised on the Internet
California Poison Control System
DXM Abuse on the Internet
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The 3rd Plateau: Beginner’s Guide to DXM
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Guide to Using Cough Syrup as DXM Source
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http://www.third-plateau.org/knowledgebase/beginners.shtml
http://www.totse.com/en/drugs/otc/guidetousingco169940.html
Dextromethorphan Extraction
http://nepenthes.lycaeum.org/Drugs/DXM/extract.html
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YouTube
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www.youtube.com
My Space, FaceBook
California Poison Control System
Evaluating the Problem
California Poison Control System
CPCS DXM Abuse Study
1999-2004
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Retrospective review - All DXM abuse calls to the
CPCS were reviewed over 6 years (1999-2004)
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Excluded: < 10 yrs, information, sxs unrelated to DXM
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Charts evaluated for demographic & clinical data
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CPCS Data was compared to national trends
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AAPCC = American Assoc of Poison Control Centers
DAWN = Drug Abuse Warning Network
Bryner J, Wang U, Hui J, Bedodo M, MacDougall C, Anderson I.
Arch Pediatr Adolesc Med. Dec 2006;160:1217-1222.
California Poison Control System
CPCS Results
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A total of 1382 Patients were included
74% involved minors < 18 years of age
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60% Male
93% involved minor/moderate outcome
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15 and 16 year olds were the most common age
0.5% involved major outcomes
no deaths reported
64% of subjects treated in a health care facility
California Poison Control System
Dextromethorphan Abuse
-- Reported to the CPCS -600
500
400
Age 9-17 y
(>15 fold)
300
All Ages
(>10 fold)
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100
0
1999
2000
2001
2002
2003
2004
2005
2006
CPCS total human exposure call volume only increased 1.5%
** Data from 2005-2006 from CPCS surveillance
California Poison Control System
3000
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2500
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1500
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1000
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500
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< 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 >
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# of DXM Cases Repoted to CPCS
# DXM Cases Reported to AAPCC
Age Distribution
U
Age
California Poison Control System
AAPCC
CPCS
Most Common DXM Products
Coricidin HBP CCC
Robitussin
Other Coricidin
Nyquil
Slang
Other
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200
400
600
800
1000
California Poison Control System
National Trends of DXM Abuse
(DAWN and AAPCC)
4500
4000
# of Reports
3500
DAWN
3000
2500
AAPCC
(All ages)
2000
1500
1000
AAPCC
(Ages 917 years)
500
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1999
2000
2001
2002
2003
2004
Year
* In 2004, DAWN reported 5,581 DXM related ED visits (1,791, minors)
California Poison Control System
National DXM Statistics
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NIDA 2006 Monitoring the Future
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4.3% of 8th graders
5.3% of 10th graders
6.9% of 12th graders
Partnership Attitude Tracking Study
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10% of teens admitted abusing DXMcontaining OTC cough medicines to get high.
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…. 2006 was the first year DXM abuse was
tracked by MtF
California Poison Control System
DXM Containing Products
California Poison Control System
Poison Center Calls
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Voluntary
Calls regarding ‘drugs of abuse’ are
usually triggered by a serious adverse
reaction
No study linking incidence of CPCS calls
to general use in the population
Emerging DofA vs. Established DofA
California Poison Control System
Slang Terms
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Triple C’s, CCC
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Robo’ing, Robotripping
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Skittles, Skittling
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DXM, Dex, Dexing
California Poison Control System
What is Currently Being Done
to Curb the Abuse?
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Pharmacy Store Chains / Pharmacists
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DXM products stored behind the counter
Selected pharmacies - Birthdate prompt at sale
Consumer Healthcare Products Association and
The Partnership for a Drug-Free America
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Awareness campaign, Educational commercial
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Drugfree.org and dxmstories.com
Legislation to limit sale of DXM to minors:
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ND, CA, NY, VA
US House of Representatives: H.R. 5280
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DXM Distribution Act -- 109/110 Congress.
California Poison Control System
Take Home Messages
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Dextromethorphan Abuse
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Many OTC products contain DXM
Beware hidden ingredients (APAP)
Reasons for DXMF Teenage Abuse
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Euphoria, legal, cheap, easily
accessible, easy to fool parents.
Many Internet websites promote DXMF
California Poison Control System