Dextromethorphan Abuse in Adolescence: A Rising Trend Ilene B. Anderson, Pharm. D Clinical Professor; UCSF School of Pharmacy Senior Toxicologist California Poison Control System - SF
Conflicts of Interest u The speaker has no conflicts of interest to disclose regarding this topic. California Poison Control System
Overview u Case Studies – u u 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? u CPCS - California Poison Control System – – – 1 800 222 -1222 OR 1 800 876 -4766 24 hour Emergency Telephone Hotline www. calpoison. org u Advice to health care professionals/public u Over 300, 000 consultations a year – 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 – One Tonic Clonic seizure soon after ED arrival California Poison Control System
Ingested Product Active Ingredients: Dextromethorphan 30 mg Chlorpheniramine 4 mg California Poison Control System
Case Study - Outcome u Patient – Ativan • – was observed for 9 hours No repeat seizures All symptoms resolved u Toxicology – screen results Positive for phencyclidine (PCP) u Patient discharged home California Poison Control System
Dextromethorphan Pharmacology and Toxicology
Dextro-rotatary Isomers Levorphanol Dextromethorphan California Poison Control System
Pharmacology Dextromethorphan CYP 2 D 6 Dextrorphan (active metabolite) California Poison Control System
Dextromethorphan; Dextrorphan u u Do Not bind to classic opiate receptors Inhibits NMDA Receptor – – u u (N-methyl-d-aspartate receptor) Same site of action as ketamine, phencyclidine • Dissociative hallucinogens Inhibits reuptake of serotonin DXM substrate for and inhibitor of CYP 2 D 6 California Poison Control System
Genetic polymorphisms of CYP 2 D 6 u Poor • • metabolizers (PMs) Produce less Dextrorphan Experience higher incidence of side effects – • Nausea, Vomiting, Dysphoria Less likely to abuse DXM u Extensive • • • metabolizers (EMs) Produce more Dextrorphan Experience more of the euphoric, “desired” mind altering effects More likely to abuse DXM California Poison Control System
Clinical Effects (“Plateaus”) u 1 st Plateau: 1. 5 -2. 5 mg/kg Mild alcohol-marijuana-like intoxication, GI sxs u 2 nd Plateau: 2. 5 -7. 5 mg/kg – u 3 rd Plateau: 7. 5 -15 mg/kg – u ‘Enjoyed the best by most’ ‘CEV’ lethargy or agitation, ataxia, nystagmus, tachycardia, HTN Variable, often dysphoric, psychosis, disorientation, altered judgment may be severe 4 th Plateau: > 15 -30 mg/kg Fully dissociative, seizures, hyperthermia, aspiration California Poison Control System
Hidden Ingredients Do they pose a risk?
Case Study 2 u. A 14 yo 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. California Poison Control System
Case study 2; continued u Later – – that evening he started vomiting Mother called the Poison Center Patient referred into the ED u Acetaminophen – – – poisoning Dose (16 tabs x 500 mg = 8, 000 mg) Risk of liver Damage Symptoms are delayed about 10 hours. California Poison Control System
Product ingested Ingredients: Acetaminophen 500 mg Chlorpheniramine 2 mg Dextromethorphan 15 mg California Poison Control System
Case Study 2; Outcome u Laboratory – – Acetaminophen 65 mg/L at 13 hours Elevated liver enzymes by 30 hours u Patient – findings hospitalized for 3 days Treated with N-acetylcysteine (antidote) u Liver injury resolved u Patient discharged on Day 4 California Poison Control System
DXM and the Laboratory u Dextromethorphan – DXM may cause a false positive on the Phencyclidine (PCP) assay u Rule – – out acetaminophen Common in many OTC cough/cold preps Delayed hepatic toxicity California Poison Control System
Chronic Abuse Scant case reports ……
Psychosis-Vicks Formula 44 -D u 25 yr F ingested 800 ml x 1. 5 yrs (DXM, PPA, GG). Patient had a long hx of OTC abuse; No hx alcohol / Dof. A – – u u u 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 u 66 yr F hx of heavy alcohol use x 30 yrs since her teens. Abstinent for a few years & switched to DXM Cough Syrup 4 oz > 16 oz/d (no Et. OH) for > 10 years. – u Sxs: abdominal pain, N/V, tremor, dysphoric, depressed, insomnia – u 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 Interactions u Do they pose a serious risk? California Poison Control System
Selected Drug Interactions w/ DXM u SSRIs -- Eg: fluoxetine, paroxetine – SSRIs inhibit CYP 2 D 6 • • u MDMA “Ecstasy” – Reuptake of serotonin is inhibited • u Risk - Serotonin syndrome AMS, seizure, rigidity, hyperthermia, arrhythmias, HTN Risk - Serotonin syndrome Monoamine oxidase inhibitors – Catecholamine uptake/metabolism is altered • Risk: Increased sympathomimetic effects and Serotonin syndrome California Poison Control System
Why are teenagers abusing DXM ? u u Euphoria and hallucinations Commonly available over-the-counter – – u u 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 u The 3 rd Plateau: Beginner’s Guide to DXM – u Guide to Using Cough Syrup as DXM Source – u http: //www. third-plateau. org/knowledgebase/beginners. shtml http: //www. totse. com/en/drugs/otc/guidetousingco 169940. html Dextromethorphan Extraction http: //nepenthes. lycaeum. org/Drugs/DXM/extract. html u You. Tube – u www. youtube. com My Space, Face. Book California Poison Control System
Evaluating the Problem California Poison Control System
CPCS DXM Abuse Study 1999 -2004 u Retrospective review - All DXM abuse calls to the CPCS were reviewed over 6 years (1999 -2004) – Excluded: < 10 yrs, information, sxs unrelated to DXM u Charts evaluated for demographic & clinical data u 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, Mac. Dougall C, Anderson I. Arch Pediatr Adolesc Med. Dec 2006; 160: 1217 -1222. California Poison Control System
CPCS Results u u A total of 1382 Patients were included 74% involved minors < 18 years of age – u u 60% Male 93% involved minor/moderate outcome – – u 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 -- CPCS total human exposure call volume only increased 1. 5% ** Data from 2005 -2006 from CPCS surveillance California Poison Control System
Age Distribution California Poison Control System
Most Common DXM Products
National Trends of DXM Abuse (DAWN and AAPCC) * In 2004, DAWN reported 5, 581 DXM related ED visits (1, 791, minors) California Poison Control System
National DXM Statistics u NIDA 2006 Monitoring the Future – – – u 4. 3% of 8 th graders 5. 3% of 10 th graders 6. 9% of 12 th 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 Mt. F California Poison Control System
DXM Containing Products California Poison Control System
Poison Center Calls u u 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 Dof. A vs. Established Dof. A California Poison Control System
Slang Terms u Triple C’s, CCC u Robo’ing, Robotripping u Skittles, Skittling u DXM, Dexing California Poison Control System
What is Currently Being Done to Curb the Abuse? u Pharmacy Store Chains / Pharmacists – – u DXM products stored behind the counter Selected pharmacies - Birthdate prompt at sale Consumer Healthcare Products Association and The Partnership for a Drug-Free America • • u 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. California Poison Control System
Take Home Messages u Dextromethorphan – – Many OTC products contain DXM Beware hidden ingredients (APAP) u Reasons – – Abuse for DXMF Teenage Abuse Euphoria, legal, cheap, easily accessible, easy to fool parents. Many Internet websites promote DXMF California Poison Control System
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