Dextromethorphan Abuse in Adolescence: A Rising Trend

1
Dextromethorphan Abuse in Adolescence A Rising
Trend

• Ilene B. Anderson, PharmD
• Clinical Professor UCSF School of Pharmacy
• Senior Toxicologist
• California Poison Control System - SF

2
Conflicts of Interest

• The speaker has no conflicts of interest to
  disclose regarding this topic.

3
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?

4
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

5
Case Study

• 14 year female took 24 Skittles during a
  sleep-over at her friends 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

6
Ingested Product
Active Ingredients Dextromethorphan
30mg Chlorpheniramine 4mg
7
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

8
DextromethorphanPharmacology and Toxicology
9
Dextro-rotatary Isomers
Levorphanol
Dextromethorphan
10
Pharmacology
Dextromethorphan
CYP 2D6
Dextrorphan (active metabolite)
11
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

12
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

13
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 gt 15-30mg/kg
• Fully dissociative, seizures, hyperthermia,
  aspiration

14
Hidden Ingredients

• Do they pose a risk?

15
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.

16
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.

17
Product ingested
Ingredients Acetaminophen 500mg Chlorpheniramine
2mg Dextromethorphan 15mg
18
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

19
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

20
Chronic Abuse

• Scant case reports

21
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.

22
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 gt 16oz/d (no EtOH) for gt 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 200619(3)320-322.

23
Drug Drug Interactions

• Do they pose a serious risk?

24
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

25
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

26
DXM Abuse on the Internet

• The 3rd Plateau Beginners Guide to DXM
• http//www.third-plateau.org/knowledgebase/beginne
  rs.shtml
• Guide to Using Cough Syrup as DXM Source
• http//www.totse.com/en/drugs/otc/guidetousingco16
  9940.html
• Dextromethorphan Extraction
• http//nepenthes.lycaeum.org/Drugs/DXM/extract.htm
  l
• YouTube
• www.youtube.com
• My Space, FaceBook

27
Evaluating the Problem
28
CPCS DXM Abuse Study1999-2004

• Retrospective review - All DXM abuse calls to the
  CPCS were reviewed over 6 years (1999-2004)
• Excluded lt 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
  20061601217-1222.

29
CPCS Results

• A total of 1382 Patients were included
• 74 involved minors lt 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

30
Dextromethorphan Abuse -- Reported to the CPCS --
CPCS total human exposure call volume only
increased 1.5 Data from 2005-2006 from CPCS
surveillance
31
Age Distribution
32
Most Common DXM Products
33
National Trends of DXM Abuse(DAWN and AAPCC)
In 2004, DAWN reported 5,581 DXM related ED
visits (1,791, minors)
34
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

35
DXM Containing Products
36
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

37
Slang Terms

• Triple Cs, CCC
• Roboing, Robotripping
• Skittles, Skittling
• DXM, Dex, Dexing

38
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.

39
Take Home Messages

• Dextromethorphan Abuse
• Many OTC products contain DXM
• Beware hidden ingredients (APAP)
• Reasons for DXMF Teenage Abuse
• Euphoria, legal, cheap, easily accessible, easy
  to fool parents.
• Many Internet websites promote DXMF