Beyond Opiates and Heroin: The New Designer Drugs of Abuse. Megan J. Ehret, PharmD, MS, BCPP Associate Professor University of Connecticut

Transcription

1 Beyond Opiates and Heroin: The New Designer Drugs of Abuse Megan J. Ehret, PharmD, MS, BCPP Associate Professor University of Connecticut Disclosures O I serve as a faculty member on Project ECHO Buprenorphine for Weitzman Institute 1

2 Off Label O Off label indications for medications will be discussed during this presentation Objectives O Identify current trends and new treatment options in the battle of opiates and heroin addiction O Describe the current laws regarding synthetic drugs O Explain the presentation, adverse effects, and treatment of synthetic cannabinoids, cathinones, 2-C agents, and piperazine derivatives O Identify new designer drugs hitting the streets 2

3 How Did We Get Here? O 1986: Opioid analgesics in non-malignant pain: 38 Cases by Portenoy and Foley O Late 1990s: Untreated pain epidemic: State medical boards lift restrictions, expanded use of opioids encouraged by guidelines O 2000: Fifth vital sign O 2007: Opioid sales increase 7-fold over 10 year period O 2010: Opioid related deaths increase 313% over 10 year period O Today: Opioid Epidemic Manchikanti et al. Pain Physician 2014;7:E1-10 What is Being Done? O Prescription Drug Monitoring Programs O High risk patients and high volume prescribers O Securing the supply O In the home, proper disposal, drug take-back O Expanding access to substance abuse treatment O Buprenorphine and methadone O New laws, regulations, policies, guidelines O Providing take-home naloxone 3

4 Take Home Naloxone Take Home Naloxone 4

5 What is Take Home Naloxone? O First aid for an opioid overdose O Bystander administered like epinephrine or glucagon O Dispensed and distributed at overdose prevention programs, in the field, in-office, or from community pharmacies Does it Work? O Efficacy outside of the hospital O 94% response (Glasgow >14 or RR >10 in 5 minutes) when IM or IV administered by paramedics O Response time (RR> 10) O 6 minute for IM O 8 minute for nasal Sporer et al. Acad Emerg Med 1996;3:660-7 Kelly et al. Med J Aust 2005;182:

6 How does it work? O Mechanism: μ opioid antagonist, no clinical effects in the absence of opioid agonists O Onset: 6-13 minutes O Duration: minutes O Bioavailability: <1% oral, 4% nasal, 36% IM O Metabolism: hepatic O Excretion: renal Kelley et al. MJA 2005;182:24-7 Naloxone Formulations Intramuscular 0.4 mg/ml O All components available at community pharmacies O Third party reimbursement possible O Pain patients may not be comfortable with needles Intranasal 2 mg/ml O No needles or risks of needle sticks O Not as easy to assemble O Confusion in the prescribing process O Atomizer availability and reimbursement 6

7 Intramuscular O Naloxone 0.4 mg/ml single dose vial O SIG: Inject 1ml IM upon signs of opioid overdose. Call 911. May repeat x1 in 3 minutes O Syringe 3ml 22G x 1 ½ #2; Use as directed for naloxone administration Intranasal O Naloxone 2mg/ml prefilled syringe #2 O SIG: Spray ½ of syringe into each nostril upon signs of opioid overdose. Call 911. May repeat x1 in 3 minutes O Atomizer #2 O SIG: Use as directed for naloxone administration 7

8 Does Connecticut Have Good Samaritan Laws? O A: Yes O B: No CT Laws O Naloxone- available through CT prescribers O Good Samaritan laws 8

9 Designer Drugs Designer Psychoactive Substances 18 SOURCE: forum.com. 9

10 Why People Use Psychoactive Substances Why Start? Experimental Peer Pressure Medical Why Continue? Relieve stress/pain Function better Have fun/relax Cope with mental health disorders SOURCE: NIDA. (2010). Drugs, Brains, and Behavior: The Science of Addiction. 19 Laws regarding Synthetic Drugs O Mid-80s: Federal controlled substance analogue Enforcement Act O Illegal to manufacture, sell, or possess chemicals that are substantially similar in chemistry and pharmacology to substances with psychoactive properties similar to schedule 1 or 2 substances O Intended for human consumption Title 21 United States Code Controlled Substances Act. Section 813 Treatment of Controlled substance analogues. US: Office of Diversion Control,

11 Synthetic Drug Abuse Prevention Act 2012 O Permanently places 26 synthetic cathinones, hallucinogenic phenethylamines, and synthetic cannabinoids into schedule 1 substances Food and Drug Administration Safety and Innovation Act. Scheduling Update. Microgram Bulletin, Synthetic Cannabinoids 11

12 Synthetic Cannabinoids O Developed to maximize the analgesic & antiinflammatory properties of Δ9-THC while eliminating psychotropic effects O K2 or spice: composed of herbal blends with mixture of plant matter and chemical grade synthetic cannabinoids Rosenbaum CD, et al. J Med Toxicol 2012 Street Names O Spice O K2 O White rabbit O Black mamba O Banana Cream Nuke O Happy tiger incense O Crazy clown Rosenbaum CD, et al. J Med Toxicol

13 Herbals blends O Baybean, beach bean, Indian warrior, blue lotus, dog rose or rosehip, lion's ear or tail, wild dogga, lousewort, dwarf skullcap, maconha brava, blue or sacred lotus, pink lotus, white and blue water lily, marshmallow, red clover, rose, Siberian motherwort or honeyweed, vanilla, and honey. Rosenbaum CD, et al. J Med Toxicol 2012 Synthetic Cannabinoid Data 13

14 CB Receptors O O O 7 categories of synthetic cannabinoids based on structure O Lack similarity to Δ9-THC CB1 receptors: CNSbasal ganglia, cerebellum, hippocampus, and cortex O Psychoactive effects CB2 receptors: blood cells, immune tissues, spleen Thakur GA, et al. Mini Rev Med Chem 2005 Case Report O 29 yo, mildly obese veteran O + ETHO and marijuana O Sertraline 100 mg QD- MDD w/o ψ features O Panic attack; episode of agitation X 15 minutes O Choking, palpiatations, dizziness, SOB, abdominal pain O 110 bpm O Urine drug screen: negative Prim Care Companion CNS Disord. 2013; 15(2): PCC.12l

15 Treatment for Case O Benzodiazepines Adverse Effects O Anxiety O Paranoia O Avoidance of eye contact O Agitation O Delusions O Tachycardia O Diaphoresis O N/V O Xerostomia O Psychosis O Acute kidney injury O Seizures O HTN O Hypotension O Palpitations O Hyperthermia O Rhabdomyolysis Rosenbaum CD, et al. J Med Toxicol

16 Drug Screens O Can you use routine drug screens to detect? O A. Yes O B. No Diagnosis O Routine urine drug screens: do not cross react O Development of rapid toxicologic screening procedures in development O History, acute clinical signs and symptoms 16

17 Treatment O Supportive care O Parenteral benzodiazepines O Seizures, agitation, or anxiety Synthetic Cathinones 17

18 Synthetic Cathinones O Evergreen shrub native to East Africa and the Middle East O Leaves and twigs contain cathinone O Chewed: amphetamine-like euphoric effects O Bath salts, bath crystals, plant food, screen cleaner, insect repellant, and herbal incense Fass JA, et al. Ann Pharmacother 2012 Common Brand Names O Blue Silk O Charge+ O Green Monster O Ivory Snow O Ivory Wave O Ocean Burst O Pure Ivory O Purple Wave O Snow Leopard O Stardust O Vanilla Sky O White Knight O White Lightening Fass JA Ann Pharmacother

19 Pharmacology O Structurally similar to amphetamines and pharmacologically comparable to methamphetamine and MDMA O Inhibit 5-HT, dopamine, and norepinephrine O Increase presynaptic release of monoamines Prosser JM, et al. J Med Toxicol 2012 Bath Salt Data 19

20 Bombing and Keying O Bombing: powder is wrapped in cigarette powder and swallowed O Keying: dipping a key into powder and then insufflating Prosser JM, et al. J Med Toxicol 2012 Case Presentation O 33 yo; no significant medical history O Few hours of chest discomfort and muscle aches O + Visual hallucinations O CPK: 6600 U/L and Creatinine 1.32 mg/dl O Tachycardia J Emerg Med Sep;45(3):

21 Adverse Effects O Euphoria O Heightened alertness O Increased energy O Talkativeness O Openness O Increased sexual arousal O Aggressive and psychotic behavior Prosser JM, et al. J Med Toxicol 2012 Symptoms of Toxicity O Agitation O Tachycardia O Hallucinations O HTN O Hyperthermia O Dehydration O Headache O Chest pain O Trismus O Paranoia O Bruxism O Tremors O Palpitations O Psychomotor agitation O Mycocarditis Prosser JM, et al. J Med Toxicol

22 Dependence Development O Tachyphylaxis O Cravings O Dependence O Symptoms of withdrawal Detection O Urine screenings for amphetamines: negative results O Rely on patient history and clinical signs and symptoms to determine diagnosis 22

23 Treatment O Cardiac monitoring O Electrocardiogram O Serial temperature checks O Electrolytes O Creatine kinase levels O Renal and liver function tests O Cardiac enzyme levels Treatment O Supportive care O Intravenous fluid replacement O Liberal use of benzodiazepines: control agitation, anxiety, hyperthermia, and seizures O Haloperidol- after benzos O Anticholinergic: worsen hyperthermia and NMS 23

24 Treatment O Refractory Hypertension O Vasodilators: nitroglycerin or sodium nitroprusside O Aggressive cooling measures: hyperthermia O Excess heat generation and reduced dissipation: antipyretics are of no use 2 C Agents 24

25 2 C Agents O Phenethylaminebased structures; 2 carbons between the amino group and the benzene ring Musselman ME, et al. Pharmacotherapy 2014 Street Names O Solaris O Smiles O N-bomb O Pandora O Dime O C-Boom O Cimbi-5 Musselman ME, et al. Pharmacotherapy

26 Pharmacology O Affinity for 5-HT 2 and α-adrenergic receptors O Can be agonist or antagonist O MAO-A and MAO-B responsible for deamination Musselman ME, et al. Pharmacotherapy C Drugs Experiences O Enhanced visual, auditory, and tactile sensations O Unpleasant hallucinations O Tachycardia O Hyperthermia O Hypertension Musselman ME, et al. Pharmacotherapy

27 2C Intoxication O Hallucinations O Euphoria O Empathy O Nausea/Vomiting O Agitation O Tachycardia O Hypertension O Respiratory Depression O Seizures O Excited delirium: agitation to violence, hyperactivity, and hyperthermia Musselman ME, et al. Pharmacotherapy 2014 Treatment O Supportive Care O Fluid resuscitation O Sedation O Cooling measures O Continuous cardiac monitoring, baseline EKG O Neuroleptics- watch QTc prolongation 27

28 Piperazine Derivatives Piperazine Derivatives O Originially developed as anthelminthic drugs: management of intestinal roundworm and tapeworm O Potential antidepressants in70s and 80s: stopped b/c of abuse potential O Party pills or legal ecstasy Musselman ME, et al. Pharmacotherapy

29 Street Names O MDAI O Head Rush O XXX Strong as Hell O Exotic Super Strong Musselman ME, et al. Pharmacotherapy 2014 Pharmacology O Sympathomimetic agent with weak amphetamine-like effects O Stimulates release of dopamine O Inhibits the reuptake of dopamine, serotonin, and norepinephrine Musselman ME, et al. Pharmacotherapy

30 Symptoms and Diagnosis of Intoxication O Palpitations O Anxiety O Paranoia O Tremors O Insomnia O Diaphoresis O Headache O Vomiting O Sinus tachycardia O Hallucinations O QT-interval prolongation O Seizures O Risk of serotonin syndrome Musselman ME, et al. Pharmacotherapy 2014 Treatment O Acute stabilization O Baseline and serial EKGs O Benzodiazepines O IV Fluids O Aggressive cooling measures 30

31 New Designer Drugs Bromo DragonFLY O Phenylethylamine- effects lasting up to 3 days O α1-agonist and potent vasoconstrictor O Similar to LSD O Hallucinations, stimulation, and increase in mood Musselman ME, et al. Pharmacotherapy

32 Effects of Bromo DragonFLY O Published case reports: O Severe agitation O Hallucinations O Tonic-clonic seizures O Renal failure O Hepatic failure O Profound vasoconstriction: multiple digital amputations, death Musselman ME, et al. Pharmacotherapy 2014 Benzofurans O Analogues of 3,4- methylenedioxyamphetamine O Euphoria and stimulation O Potent 5-HT 2B and 5-HT 2C agonist O Triple monoamine reuptake inhibitor Musselman ME, et al. Pharmacotherapy

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