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 The speaker has no conflicts of interest to disclose regarding this topic. California Poison Control System 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? California Poison Control System 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 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 30mg Chlorpheniramine 4mg California Poison Control System Case Study - Outcome Patient was observed for 9 hours – Ativan • – All symptoms resolved Toxicology screen results – 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 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 California Poison Control System 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 California Poison Control System Clinical Effects (“Plateaus”) 1st Plateau: 1.5-2.5mg/kg Mild alcohol-marijuana-like intoxication, GI sxs 2nd Plateau: 2.5-7.5mg/kg – 3rd Plateau: 7.5-15mg/kg – ‘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 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. California Poison Control System 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. California Poison Control System Product ingested Ingredients: Acetaminophen 500mg Chlorpheniramine 2mg Dextromethorphan 15mg California Poison Control System 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 California Poison Control System 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 California Poison Control System 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. California Poison Control System 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. – Sxs: abdominal pain, N/V, tremor, dysphoric, depressed, insomnia – 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 Do they pose a serious risk? California Poison Control System Selected Drug Interactions w/ DXM SSRIs -- Eg: fluoxetine, paroxetine – SSRIs inhibit CYP2D6 • • MDMA “Ecstasy” – Reuptake of serotonin is inhibited • 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 ? 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 California Poison Control System DXM Abuse on the Internet The 3rd Plateau: Beginner’s Guide to DXM – Guide to Using Cough Syrup as DXM Source – 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 YouTube – www.youtube.com My Space, FaceBook California Poison Control System Evaluating the Problem California Poison Control System CPCS DXM Abuse Study 1999-2004 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. California Poison Control System CPCS Results A total of 1382 Patients were included 74% involved minors < 18 years of age – 60% Male 93% involved minor/moderate outcome – – 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) 200 100 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 300 2500 250 2000 200 1500 150 1000 100 500 50 0 0 < 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 > 10 25 # 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 0 200 400 600 800 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 0 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 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 DXMcontaining OTC cough medicines to get high. – …. 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 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 Triple C’s, CCC Robo’ing, Robotripping Skittles, Skittling DXM, Dex, Dexing California Poison Control System 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. California Poison Control System 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 California Poison Control System