dextromethorphan abuse in adolescence: a rising trend ilene b. anderson, pharmd clinical professor;...

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.


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?


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


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


Ingested Product

Active Ingredients:

Dextromethorphan 30mg

Chlorpheniramine 4mg


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

DextromethorphanPharmacology and Toxicology


Dextro-rotatary Isomers

Levorphanol Dextromethorphan


Pharmacology

CYP 2D6

Dextromethorphan

Dextrorphan (active metabolite)


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


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


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

Hidden Ingredients

Do they pose a risk?


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.


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.


Product ingested

Ingredients:

Acetaminophen 500mg

Chlorpheniramine 2mg

Dextromethorphan 15mg


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


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

Chronic Abuse

Scant case reports ……


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.


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.


Drug Drug Interactions

Do they pose a serious risk?


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


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


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


Evaluating the Problem


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.


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


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


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


Most Common DXM Products

0 200 400 600 800 1000

Coricidin HBP CCCRobitussin

Other CoricidinNyquilSlang Other


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)


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


DXM Containing Products


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


Slang Terms

Triple C’s, CCC

Robo’ing, Robotripping

Skittles, Skittling

DXM, Dex, Dexing


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.


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

dextromethorphan abuse in adolescence: a rising trend ilene b. anderson, pharmd clinical professor;...

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