Molly, are these your bath salts? A look at contemporary drug abuse Midwest Pediatric Trauma Conference May 2, 2014

Transcription

1 Molly, are these your bath salts? A look at contemporary drug abuse 2014 Midwest Pediatric Trauma Conference May 2,

2 Disclosures I have no relevant financial relationships to disclose. Thanks for asking. Rebecca L. Tominack MD Medical Director, Missouri Poison Center Adjunct Professor, Saint Louis University School of Medicine and College for Public Health and Social Justice 2

3 In 2011, 1.25 million ED visits related to illicit drugs & 1.24 million for nonmedical use of pharmaceutical 1 Cocaine 505,224 2 Marijuana 455,668 3 Heroin 258,482 4 Amphetamine /meth 159,840 5 PCP 75,538 6 Synthetic cannabinoids 28,531 7 MDMA (Ecstasy) 22,498 8 Bath Salts 22,904 9 Diphenhydramine 19, Dextromethorphan 14,684 3

4 Treatment priorities for bath salts/k2 Calm the agitated patient Benzodiazepine: lorazepam, diazepam, midazolam. Add haloperidol or a 2 nd generation antipsychotic such as olanzapine (Zyprexa), ziprasidone (Geodon) or risperidone If serotonin toxicity is suspected, can add cyproheptadine or chlorpromazine Pulse ox, basic serum labs, CK, urine for myoglobin Supportive care including cooling, hydration, electrolytes, oxygen, etc. 4

5 Designer drugs Designer drugs --Intentional, rational chemical synthesis Known structure-activity relationships to incorporate desired mechanisms of action Changing the molecular structure renders the new molecule legal China is the main source 5

6 Synthetic cannabinoids Research compounds, to characterize the newly discovered cannabinoid receptors Examples: JWH-018, CP-47,497, HU210, AM2201, resurrected by illicit drug manufacturers Supported by unprecedented internet marketing, user forums, and bold exploitation of loopholes in the drug control laws 6

7 Structure-activity THC relationship of synthetic cannabinoids JWH x more potent HU x more potent Also an NMDA antagonist 7

8 First seen as brands K2 and Spice as herbal products or incense blends Active agent Sprayed on unidentified vegetable matter 8

9 Legal highs sold in gas stations, convenience stores, head shops. Target teens and young adults 9

10 Note the reasonable price of $

11 Synthetic cannabinoid presentation Significant psychotoxicity: Paranoia, thought disorder, disorganized behavior (ie, psychosis) Anxious and depressed Perhaps with intense suicidal thoughts or behavior. 11

12 Long duration of psychiatric features Abnormalities linger for days to weeks If K2-agent presentation includes psychotic features, the duration of hospitalization is 13 days vs 4-5 days Variations in the agent can cause variable presenting symptoms Example: one K2 agent - and only one so far - is specifically toxic to kidneys 12

13 Crazy Clown toxicity in 22 patients Brunswick, GA Aug 22 - Sept 9, 2013 Nausea, vomiting (n = 8; 36%) Tachycardia (n = 13; 59%) Hyperglycemia (n = 13; 59%) Hypokalemia (n = 9; 41%) Acidosis (n=7; 32%) Confusion (n = 7; 32%) Aggression (n = 7 32%) Coma (n = 7; 32%) Seizures (n = 3; 14%) 2 pneumonia, 1 rhabdo, 1 MI ADB-PINACA (N-(1-amino-3,3-dimethy-1-oxobutan-2-yl)- 1-pentyl-1H-indazole-3-carboxamide), a previously unrecognized synthetic cannabinoid related to indole compounds recently identified in Europe and Japan 13

14 Bath salts Not your mother s bath salts Hallucinogenic amphetamines -- designer chemistry and modern marketing 14

15 Marketing & advertising of bath salts Packaged as innocuous household products: bath salts, fertilizer/ plant food, stain remover, etc True nature is passed by word of mouth, and via the internet May also be sold as research chemicals Either way, labeled Not for human consumption to try to escape the drug laws to control 15

16 Khat: the origin of bath salt chemistry A flowering shrub native to Ethiopia/Somalia region of Africa and Arabian peninsula, chewed as mild stimulant 16

17 Tender new shoots and leaves 17

18 Must be used fresh to preserve potency 18

19 WHO considers khat mild-moderately habituating, not seriously addicting 19

20 Cathinone (Khat) CH 3 Amphetamine Cathinone More lipid soluble so more CNS effects 20

21 What can be done to enhance lipid solubility and CNS action? Add a methyl group Amphetamine Methamphetamine 21

22 Add a methyl group to cathinone CH 3 CH 3 CH 3 Cathinone Methcathinone 22

23 Add yet another methyl group! 4-methyl methcathinone meow- meow Mephadrone Internet available in 2007, spread throughout Europe by

24 Mephedrone, as shown on previous slide May also be sold as research chemicals 24

25 Meow-meow mephedrone Nasal: Onset minutes; peak 30 min, lasts 2-3 hrs Euphoria, mood elevation, better mental function, mydriasis, mild sexual stimulation similar to cocaine, amphetamine, or Ecstasy Bruxism, tachycardia, sweating, poor concentration and short term memory, hallucinations, delusions, anxiety, paranoia esp if high dose or prolonged/repeated use 25

26 What else can be done with the basic cathinone structure? Make it a catechol like epinephrine, NE, dopamine Norepinephrine Dopamine Like NE except missing OH 26

27 What does mother nature suggest? Methoxy groups on natural hallucinogens a combination of hydroxyl (such as on dopamine) plus a methyl group for lipid solubility and enhanced CNS effects CH 2 Mescaline in peyote Myristicin in nutmeg 27

28 Methylene dioxy methamphetamine CH 3 CH 3 methamphetamine 28

29 Methylene dioxy methamphetamine MDMA Ecstasy Molly CH 3 CH 3 Methylene dioxy methamphetamine 29

30 Ecstasy effects Releases serotonin, NE, DA and oxytocin - hormone that facilitates bonding and trust, released during birthing & lactation Unique effect - empathogen - feelings of empathy, love, security, emotional closeness Adverse effects: poor concentration, bruxism, anorexia, dry mouth and thirst; dehydration, hyponatremia 30

31 Ecstasy overdose: serotonin toxicity and/or stimulant psychosis with amphetamine-like cardiovascular effects Hyperactivity, hyperthermia, hyperreflexia, muscle rigidity, rhabdomyolysis Confusion, agitation, paranoia, delusions, hallucinations, amnesia, coma Tachycardia, hypertension, stroke, angina, MI, dyspnea 31

32 Serotonin 5-HT; 5-hydroxy tryptamine Note the mixed-ring indole It has many actions, which it carries out mainly by modulating the effects of *other* neurotransmitters; eg, enhances dopamine release 32

33 The serotonin-dopamine connection is seen in serotonergic psychedelics Excess dopamine activity induces hallucinations & other features of psychosis. Certain serotonin-like agents induce dopamine release so *they* cause hallucinations. examples: Psilocybin, LSD 33

34 Psilocybin magic mushrooms 4 position CH 3 N CH3 Psilocin 5 position Serotonin 34

35 Lysergic acid diethylamide (LSD) Serotonin 35

36 PCP; phencyclidine Phenyl Cyclohexyl Piperidine Dissociative anesthetic, sigma agonist & NMDA receptor antagonist, blocking glutamate action Detachment from immediate surroundings and experiences; no pain registers Hallucinations, disordered thoughts, catatonia very close clinically to schizophrenia Also seen in ketamine, dextromethorphan, and HU-211, a synthetic cannabinoid 36

37 Dextromethorphan PCP 37

38 To understand the possible effects of a drug, consider all relevant receptors that a drug interacts with of From Drugs, Brains and Behavior by C. R. Timmons & L. W. Hamilton

39 N-BOMe derivatives ( N-Bomb ) Hallucinogenic empathogen 2,5 I-NBOMe [2-(4-iodo-2,5- dimethoxyphenyl) - N-[(2-methoxyphenyl)methyl]ethanamine] CH 3 CH 3 CH 3 Basically a double up on 2CI: 2,5-dimethoxy-4- iodophenethylamine; also come in chloro and fluoro flavors 39

40 The clinical bottom line on the current trend in designer drugs Structures & mechanisms of action are being mixed and matched so that distinctions between types of agents are clinically irrelevant Novel & untested agents, by-products from uncontrolled synthesis, adulterants, coingestants, underlying psychiatric conditions, size of dose, frequency, route, chronicity, etc. Treat the patient, not the poison. 40

41 Menu of possible effects Psychosis including hallucinations, extreme agitation, disorganized thinking, paranoia, compulsion for violence and/or self-harm, which may not resolve quickly or completely Serotonin toxicity including clonus, hyper-reflexia, agitation, diaphoresis, tremor, fever Adrenergic overload including hypertension, tachycardia, arrhythmia, fever, restlessness, tremor, hyperglycemia, hypokalemia Misc Catatonia, muscle rigidity, rhabdomyolysis, seizures, secondary trauma, direct renal toxicity, etc Contributions from co-ingestants 41

42 Treatment priorities for bath salts/k2 Calm the agitated patient Benzodiazepine: lorazepam, diazepam, midazolam. Add haloperidol or a 2 nd generation antipsychotic such as Olanzapine (Zyprexa), ziprasidone (Geodon) or risperidone If serotonin toxicity is suspected, can add cyproheptadine or chlorpromazine Pulse ox, basic serum labs, CK, urine for myoglobin Supportive care including cooling, hydration, electrolytes, oxygen, etc. 42