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Anderson, PharmD Clinical Professor; UCSF School of Pharmacy Senior Toxicologist California Poison Control System - SF Conflicts of Interest: Conflicts of Interest The speaker has no conflicts of interest to disclose regarding this topic.Overview: 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?: 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 voluntaryCase Study : 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 arrivalIngested Product: Ingested Product Active Ingredients: Dextromethorphan 30mg Chlorpheniramine 4mgCase Study - Outcome: 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 homeDextromethorphanPharmacology and Toxicology: Dextromethorphan Pharmacology and ToxicologyDextro-rotatary Isomers: Dextro-rotatary Isomers Levorphanol DextromethorphanPharmacology: Pharmacology CYP 2D6 Dextromethorphan Dextrorphan (active metabolite)Dextromethorphan; Dextrorphan: 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: 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 DXMClinical Effects (“Plateaus”): 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: Hidden Ingredients Do they pose a risk?Case Study 2: 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 : 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: Product ingested Ingredients: Acetaminophen 500mg Chlorpheniramine 2mg Dextromethorphan 15mgCase Study 2; Outcome: 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: 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: Chronic Abuse Scant case reports …… Psychosis-Vicks Formula 44-D: 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: 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: Drug Drug Interactions Do they pose a serious risk?Selected Drug Interactions w/ DXM: 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 ?: 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 InternetDXM Abuse 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 Extraction http://nepenthes.lycaeum.org/Drugs/DXM/extract.html YouTube www.youtube.com My Space, FaceBookEvaluating the Problem: Evaluating the ProblemCPCS DXM Abuse Study1999-2004: 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. CPCS Results: 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 --: Dextromethorphan Abuse -- Reported to the CPCS -- CPCS total human exposure call volume only increased 1.5% ** Data from 2005-2006 from CPCS surveillanceAge Distribution: Age Distribution Most Common DXM Products: Most Common DXM ProductsNational Trends of DXM Abuse(DAWN and AAPCC): National Trends of DXM Abuse (DAWN and AAPCC) * In 2004, DAWN reported 5,581 DXM related ED visits (1,791, minors)National DXM Statistics: 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: DXM Containing ProductsPoison Center Calls: 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: Slang Terms Triple C’s, CCC Robo’ing, Robotripping Skittles, Skittling DXM, Dex, Dexing What is Currently Being Done to Curb the Abuse?: 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: 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 You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.