Dextromethorphan Abuse in Adolescence: A Rising
Trend
Ilene B. Anderson, PharmDClinical Professor; UCSF School of
PharmacySenior Toxicologist
California Poison Control System - SF
California Poison Control System
Conflicts of Interest
The speaker has no conflicts of interest to disclose regarding this topic.
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Overview
Case Studies– 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?
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What is the CPCS?
CPCS - California Poison Control System– 1 800 222-1222 OR 1 800 876-4766– 24 hour Emergency Telephone Hotline– www.calpoison.org
Advice to health care professionals/public
Over 300,000 consultations a year– Calls to the CPCS are voluntary
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Case Study
14 year female took #24 ‘Skittles’ during a sleep-over 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– One Tonic Clonic seizure soon after ED arrival
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Ingested Product
Active Ingredients:
Dextromethorphan 30mg
Chlorpheniramine 4mg
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Case Study - Outcome
Patient was observed for 9 hours– Ativan
• No repeat seizures
– All symptoms resolved Toxicology screen results
– Positive for phencyclidine (PCP) Patient discharged home
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Pharmacology
CYP 2D6
Dextromethorphan
Dextrorphan (active metabolite)
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Dextromethorphan; Dextrorphan
Do Not bind to classic opiate receptors Inhibits NMDA Receptor
– (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
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Genetic polymorphisms of CYP 2D6
Poor metabolizers (PMs)• Produce less Dextrorphan• Experience higher incidence of side effects
– Nausea, Vomiting, Dysphoria • Less likely to abuse DXM
Extensive metabolizers (EMs)• Produce more Dextrorphan• Experience more of the euphoric, “desired”
mind altering effects• More likely to abuse DXM
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Clinical Effects (“Plateaus”)
1st Plateau: 1.5-2.5mg/kg Mild alcohol-marijuana-like intoxication, GI sxs
2nd Plateau: 2.5-7.5mg/kg – ‘Enjoyed the best by most’ ‘CEV’ lethargy or
agitation, ataxia, nystagmus, tachycardia, HTN 3rd Plateau: 7.5-15mg/kg
– Variable, often dysphoric, psychosis, disorientation, altered judgment may be severe
4th Plateau: > 15-30mg/kg Fully dissociative, seizures, hyperthermia, aspiration
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Case Study 2
A 14yo M skipped school with friends and took 16 Coricidin HBP Maximum Strength Flu tablets to get high.
– Friends claim he was acting goofy, slept for a while, but seemed okay.
– Skipped dinner and went to sleep early.
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Case study 2; continued
Later that evening he started vomiting– Mother called the Poison Center– Patient referred into the ED
Acetaminophen poisoning– Dose (16 tabs x 500mg = 8,000mg)– Risk of liver Damage– Symptoms are delayed about 10 hours.
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Product ingested
Ingredients:
Acetaminophen 500mg
Chlorpheniramine 2mg
Dextromethorphan 15mg
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Case Study 2; Outcome
Laboratory findings– Acetaminophen 65 mg/L at 13 hours– Elevated liver enzymes by 30 hours
Patient hospitalized for 3 days– Treated with N-acetylcysteine (antidote)
Liver injury resolved Patient discharged on Day 4
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DXM and the Laboratory
Dextromethorphan– DXM may cause a false positive on the
Phencyclidine (PCP) assay
Rule out acetaminophen– Common in many OTC cough/cold preps– Delayed hepatic toxicity
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Psychosis-Vicks Formula 44-D
25yr F ingested 800ml x 1.5 yrs (DXM, PPA, GG). Patient had a long hx of OTC abuse; No hx alcohol / DofA– 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.
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DXM Withdrawal Syndrome
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.– Last dose: 3 days prior to ED
Sxs: abdominal pain, N/V, tremor, dysphoric, depressed, insomnia– 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.
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Selected Drug Interactions w/ DXM
SSRIs -- Eg: fluoxetine, paroxetine– SSRIs inhibit CYP2D6
• Risk - Serotonin syndrome• AMS, seizure, rigidity, hyperthermia, arrhythmias, HTN
MDMA “Ecstasy”– Reuptake of serotonin is inhibited
• Risk - Serotonin syndrome Monoamine oxidase inhibitors
– Catecholamine uptake/metabolism is altered• Risk: Increased sympathomimetic effects and
Serotonin syndrome
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Why are teenagers abusing DXM ?
Euphoria and hallucinations Commonly available over-the-
counter– 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
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DXM Abuse on the Internet
The 3rd Plateau: Beginner’s Guide to DXM– http://www.third-plateau.org/knowledgebase/beginners.shtml
Guide to Using Cough Syrup as DXM Source
– http://www.totse.com/en/drugs/otc/guidetousingco169940.html
Dextromethorphan Extractionhttp://nepenthes.lycaeum.org/Drugs/DXM/extract.html
YouTube– www.youtube.com
My Space, FaceBook
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CPCS DXM Abuse Study1999-2004
Retrospective review - All DXM abuse calls to the CPCS were reviewed over 6 years (1999-2004)
– Excluded: < 10 yrs, information, sxs unrelated to DXM
Charts evaluated for demographic & clinical data
CPCS Data was compared to national trends– 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.
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CPCS Results
A total of 1382 Patients were included 74% involved minors < 18 years of age
– 15 and 16 year olds were the most common age
60% Male 93% involved minor/moderate outcome
– 0.5% involved major outcomes– no deaths reported
64% of subjects treated in a health care facility
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Dextromethorphan Abuse -- Reported to the CPCS --
0
100
200
300
400
500
600
1999 2000 2001 2002 2003 2004 2005 2006
Age 9-17 y(>15 fold)
All Ages (>10 fold)
CPCS total human exposure call volume only increased 1.5%
** Data from 2005-2006 from CPCS surveillance
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Age Distribution
0
500
1000
1500
2000
2500
3000
<10
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 >25
U
Age
# D
XM
Cas
es R
epor
ted
to A
AP
CC
0
50
100
150
200
250
300
# of
DX
M C
ases
Rep
oted
to C
PC
S
AAPCC
CPCS
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Most Common DXM Products
0 200 400 600 800 1000
Coricidin HBP CCCRobitussin
Other CoricidinNyquilSlang Other
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National Trends of DXM Abuse
(DAWN and AAPCC)
0
500
1000
1500
2000
2500
3000
3500
4000
4500
1999 2000 2001 2002 2003 2004
Year
# o
f R
ep
ort
s
DAWN
AAPCC(All ages)
AAPCC(Ages 9-17 years)
* In 2004, DAWN reported 5,581 DXM related ED visits (1,791, minors)
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National DXM Statistics
NIDA 2006 Monitoring the Future– 4.3% of 8th graders– 5.3% of 10th graders– 6.9% of 12th graders
Partnership Attitude Tracking Study– 10% of teens admitted abusing DXM-containing
OTC cough medicines to get high.
– …. 2006 was the first year DXM abuse was tracked by MtF
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Poison Center Calls
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
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Slang Terms
Triple C’s, CCC
Robo’ing, Robotripping
Skittles, Skittling
DXM, Dex, Dexing
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What is Currently Being Done to Curb the Abuse?
Pharmacy Store Chains / Pharmacists– DXM products stored behind the counter– Selected pharmacies - Birthdate prompt at sale
Consumer Healthcare Products Association and The Partnership for a Drug-Free America
• Awareness campaign, Educational commercial• Drugfree.org and dxmstories.com
Legislation to limit sale of DXM to minors:– ND, CA, NY, VA– US House of Representatives: H.R. 5280
• DXM Distribution Act -- 109/110 Congress.