48 th Annual Meeting. Synthetic Drugs of Abuse. Monitoring the Future Study. Disclosure. Objectives 7/19/2014. Why is this even a concern?

Transcription

1 48 th Annual Meeting Synthetic Drugs of Abuse Why is this even a concern? Dawn R. Sollee, Pharm.D., DABAT Assistant Director Florida/USVI Poison Information Center- Jacksonville Navigating the Oceans of Opportunity Disclosure Monitoring the Future Study I do not have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation Percentage MDMA = 3,4-methylenedioxy methamphetamine LSD = lysergic acid diethylamide Objectives By the end of the presentation, the audience will be able to: Describe complications associated with the utilization of synthetic drugs of abuse Identify commonly used synthetic drugs of abuse in adult and in pediatric patients Discuss key principles in the management of patients intoxicated with synthetic drugs of abuse DEA News: Huge Synthetic Drug Takedown Project Synergy Phase II continues attack on drug networks, sources of supply, global money flow 29 states involved More than 150 individuals arrested More than $20 million in cash and assets seized Targeted synthetic cannabinoids and cathinones Drug Enforcement Administration, May 7,

2 Discussion Topics Synthetic Cannabinoids Cannabinoid receptor homologs Synthetic cathinones Molly Kratom Pharmaceutical and research companies in search of agonists 1960 s Emerging use in USA 2010 Federal Legislation November 10, 2010 May 2013 January 2014 Recognized drug of abuse in Europe Early 2000 s State Legislation March 18, 2010 Synthetic Cannabinoids Background Agents work at cannabinoid receptors Chemicals placed into a solvent Sprayed onto plants/herbal blends Can be smoked or ingested Still able to be purchased Photo: FPIC/Jax FPIC Network Data In the Media Synthetic Cannabinoid Exposures Largest Synthetic Marijuana K2 Bust in Marion County To Date - Ocala Post, Sept 17, Jan Feb Mar April May June July Aug Sept Oct Nov Dec FPICN Query Builder 800 Packages of Synthetic Marijuana Confiscated in Seminole County Raids WFTV.com, Jan 14,

3 Major Structural Groups Mechanism of Action Adamantoylindoles Naphthoylindoles JWH-018, JWH-073 Naphthylmethylindoles Cannabinoid receptor agonists CB1 brain, the spinal cord, and PNS CB2 peripheral tissues (spleen and immune cells) Tetramethylcyclopropylindoles Cyclohexylphenols Naphythoylpyrroles Benzoylindoles Naphthylmethylindenes Phenylacetylindoles Classical Presley BC, et al. Forensic Sci Rev Thornton MD, Baum CR. Pediatr Emer Care Newer Products Presentation APINACA, AB-FUBINACA, ADB-FUBINACA, AB- PINACA, ADB-PINACA Newer products QUPIC and QUCHCI No pharmacological data Seizures Agitation Paranoia Tachycardia Chest Pain Hypertension Nausea Vomiting UR-144, XLR-11, APINACA, QUPIC, 5F-PB-22, AB- FUBINACA, ADB-PINACA Scheduled in 2013, 2014 Acute Kidney Injury Mydriasis Hyperthermia Myocardial Infarction Monte AA et al. NEJM 2014;370: Fed Register. 2013: Fed Register. 2014: Harris CR, Brown A. J EM Properties Lipid soluble Quicker onset Variable duration of action Active metabolites Potency is 4 to 100 X that of delta-9-thc Withdrawal Nightmares Sweating Tremor Headache Hypertension Tachycardia Nelson ME, et al. Emerg Med Clin N Am Zimmerman et al. Dtsch Arztebl Int

4 Synthetic Cathinones Synthetic Cathinones First synthetic cathinone (methcathinone) 1928 Schedule I substance Cathinone 1993 Mephedrone in USA market 2009 Outbreaks in USA in Europe 1990 s Mephedrone use in Australia and Europe 2007 Federal Legislation September 2011 March 2014 Photo: FPIC/Jax Thornton MD, Baum CR. Pediatr Emer Care FPIC Network Data 10 Synthetics Into Schedule I Synthetic Cathinone Exposures 4-methyl-N-ethylcathinone (4-MEC) Alpha-pyrrolidinopentiophenone (alpha- PVP) 2-(methylamino)-1-phenylpentan-1-one (pentedrone) 4-fluoro-N-methylcathinone (4-FMC) 1-(naphthalene-2-yl)-2-(pyrrolidin-1- yl)pentan-1-one (naphyrone) 4-methyl-alphapyrrolidinopropiophenone (4-MePPP) 1-(1,3-benzodioxol-5-yl)-2- (methylamino)butan-1-one (butylone) 1-(1,3-benzodioxol-5-yl)-2- (methylamino)pentan-1-one (pentylone) 3-fluoro-N-methylcathinone (3-FMC) Alpha-pyrrolidinobutiophenone (alpha- PBP) 0 Jan Feb Mar April May June July Aug Sept Oct Nov Dec FPICN Query Builder Fed Regist In the Media Man sentenced to prison for drugs after several overdosed on bath salts Orlando Sentinel, Feb 19, 2014 To be able to start a beautiful organic garden you must need to commit to it, and the best way to do this is by using plant fertilizers. Plant fertilizers, such as 4mec, which you can easily buy online, are a key to achieve a garden that everyone envies. Spreading 4mec helps maintain a neutral PH, which means it helps to hold on to more nutrients for the plant to feed on and be able to grow. Plant Feed Shop is a leading plant feed supplier offering wide range of plant food products including Mephedrone, 4- methylmethcathinone, 4-MMC, MCAT, Bubbles and many such products 4

5 Background Presentation Chewing the khat plant (Catha edulis) Routes of exposure Snorting, orally IV, IM, rectal Sold as bath salts, plant food, stain remover powders, glass cleaner, pipe cleaner, lady bug attractant, shoe deodorizer Hypertension Tachycardia Hyperthermia Agitation Headache Chest Pain Tremors Bruxism Insomnia Paranoia Delusions Mydriasis Acute Renal Failure Diaphoresis Rhabdomyolysis Nausea German CL et al. Life Sciences Mechanism of Action Molly Inhibit reuptake of dopamine, serotonin, and norepinephrine Increase presynaptic release Sympathomimetic Used to be a pure form of MDMA Versions have contained 1-(3-trifluoromethyphenyl) piperazine (TFMPP) 4-methylmethcathinone (4-MMC) 4-methyl-n-ethylcathinone (4-MEC) MDPV Methylone Pharmacokinetics Kratom Methylone, mephedrone mg orally has onset of min and duration of 2-5 hours Metabolism by phase I pathways MDPV mg orally has onset of15-30 min and duration of 2-7 hours CYPs (1A2, 2D6, 2C19) involved in demethylation Kratominformation.blogspot.com Rosenbaum CD et al. J. Med Toxicol Nelson ME, et al. Emerg Med Clin N Am

6 In the Media Need a Pick-Me-Up? Is Kratom quickly becoming a legal addiction? DEA, FDLE investigating new drug popular with teens - Click Orlando, Feb 7, 2013 Ingredients L-tryptophan Kratom Caffeine Background 4X100 Available in multiple forms Chewed, pills, tea, cocktails Mitragyna speciosa contains 25 alkaloids Mitragynine is the main focus On the DEA s list of Drugs and Chemicals of Concern Components Kratom Caffeinated soft drink Cough syrup Codeine or diphenhydramine Ice Antidepressant or analgesic Hassan Z, et al. Neuroscience and Behavioral Reviews Hassan Z, et al. Neuroscience and Behavioral Reviews Krypton Mechanism of Action Contains kratom leaves infused with o-desmethyltramadol Still available on the internet Stimulant effects at low doses Opiate effects at high doses Has high affinity at mu opioid receptors More than 10X the potency of morphine Blocks neuronal Ca 2+ channels Rosenbaum CD et al. J. Med Toxicol Arndt et al. Forensic Science International Hassan Z, et al. Neuroscience and Behavioral Reviews

7 Pharmacokinetics Management Onset of 5 minutes Duration of 1 hour Inhibits the activity of 3 CYP450 s 2C9, 2D6, 3A4 ABC s Supportive care Agitation, seizures, tachycardia, hypertension Benzodiazepines Persistent hypertension Vasodilators Hyperthermia Cooling measures Naloxone may be an option for Kratom exposures Presentation Monitoring Low Dose Tremors Euphoria Giddiness Talkativeness High Dose Sedation Nausea Vomiting Dizziness Vital signs, including temperature Electrocardiogram and cardiac monitoring Potential laboratory evaluation Cardiac enzymes Renal function tests Electrolytes Creatinine kinase Nelson ME, et al. Emerg Med Clin N Am Withdrawal Take Home Message Hostility Aggression Excessive tearing Aching muscles/bones Jerky limb movements Anxiety Tremor Sweating These products are readily available Lack of product information and testing We re playing catch up No specific antidote Talk to your adolescents about the dangers! Rosenbaum CD et al. J. Med Toxicol Singh et al. Drug and Alcohol Dependence

8 Any Questions? Arndt T, Claussen U, Gussregen B, et al. Kratom alokaloids and O-desmethyltramadol in urine of a Kryton herbal mixture consumer. Forensic Science International. 2011;208: CDC. Notes from the field: Severe illness associated with reported use of synthetic marijuana- Colorado, August-September MMWR Weekly. 2013;62: DEA. Schedule of controlled substances: Temporary placement of 10 synthetic cathinones into Schedule I. Final order. Fed Regist. 2014;79: DEA. Schedules of controlled substances: Temporary placement of four synthetic cannabinoids into Schedule 1. Fed Regist. 2014;79: DEA. Schedules of controlled substances: Temporary placement of three synthetic cannabinoids into Schedule 1. Fed Regist. 2013;78: Editorial Staff: THC Homologs (Management/Treatment Protocol). In: Klasco RK (Ed): POISINDEX System. Truven Health Analytics, Greenwood Village, Colorado (Edition expires 6/2014). Editorial Staff: Synthetic Cathinone Derivatives (Management/Treatment Protocol). In: Klasco RK (Ed): POISINDEX System. Truven Health Analytics, Greenwood Village, Colorado (Edition expires 6/2014). ElSohly MA, Gul W, Wanas AS, et al. Synthetic cannabinoids: analysis and metabolites. Life Sciences. 2014;97: German CL, Fleckenstein AE, Hanson GR. Bath salts and synthetic cathinones: An emerging designer drug phenomenon. Life Sciences. 2014;97:2-8. Gunderson EW, Kirkpatrick MG, Willing LM, et al. Substituted cathinone products: A new trend in bath salts and other designer stimulant drug use. J Addict Med. 2013;7: Harris CR and Brown A. Synthetic cannabinoid intoxication: A case series and review. JEM. 2013; 44: Hassan Z, Muzaimi M, Navaratnam V, et al. From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction. Neuroscience and Behavioral Reviews. 2013;37: Hill SL and Thomas SHL. Clinical toxicology of newer recreational drugs. Clinical Toxicology. 2011;29: Johnston, L. D., O'Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (December 18, 2013). "American teens more cautious about using synthetic drugs." University of Michigan News Service: Ann Arbor, MI. Retrieved 04/04/2014 from Levin M, Levitan R, Skolnik A. Compartment syndrome after bath salts use: A case series. Ann Emerg Med. 2013;61: Lewin AH, Seltzman HH, Carroll FI, et al. Emergence and properties of spice and bath salts: A medicinal chemistry perspective. Life Sciences. 2014;97:9-19. Nelson ME, Bryant SM, Aks SE. Emerging drugs of abuse. Emerg Med Clin N Am. 2014;32:1-28. Presley BC, Jansen-Varnum SA, Logan BK. Analysis of synthetic cannabinoids in botanical material: A review of analytical methods and findings. Forensic Science Review. 2013;25:27-46, Prosser JM and Nelson LS. The toxicology of bath salts: A review of synthetic cathinones. J. Med Toxicol. 2012;8: Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow and back again? A review of herbal marijuana alternatives, synthetic cathinones, salvia divinorum, methoxetamine, and piperazines. J. Med. Tox. 2012;8:15-32 Singh D, Muller CP, Vicknasingam BK. Kratom dependence, withdrawal symptoms and craving in regular users. Dug and Alcohol Dependence. 2014;139: Thornton MD and Baum CR. Bath salts and other emerging toxins. Pediatr Emer Care. 2014;30: Wiley JL, Marusich JA, Huffman JW. Moving around the molecule: Relationship between chemical structure and in vivo activity of synthetic cannabinoids. Life Sciences. 2014;97: Zimmermann US, Winkelmann PR, Pilhatsch M, et al: Withdrawal phenomena and dependence syndrome after the consumption of "spice gold". Dtsch Arztebl Int. 2009; 106: