1. Designer Drugs Toxicity Management and Impact on South Dakota
Billie Bartel, PharmD
Sanford Aberdeen Medical Center
Aberdeen, SD

2. Disclosures
I have had no financial relationship over the past 12 months with any commercial sponsor with a vested interest in this presentation.

3. Objectives
Describe the mechanism of action and toxicity profile of designer drugs
Identify treatment approaches to adverse reactions to designer drugs
Describe the impact of designer drug use in South Dakota

4. New Designer Drugs “Synthetic drugs” “Legal highs”
Modified molecular structure of existing drugs
Created for recreational use to evade legislation

5. Accessibility

6. Why do we need to know about this?
Use is widespread
Recognize and manage the intoxication syndromes
Educate patients about their potential dangers
May be more dangerous that substances they want to imitate!

7. National Association of Poison Controls Designer Drug Calls
Marketing geared toward young consumers
Social media involvement

8. New Designer Drugs Synthetic Cannabinoids Synthetic Cathinones
Synthetic Hallucinogens

9. Synthetic CannabinoidsK2
Spice
SCs
Krypton
Aztec
Fire
Bombay Blue
Fake Weed
Yucatan Fire
No More Mr. Nice Guy
Mr. Smiley
Eclipse
Black Mamba

10. Synthetic Cannabinoids
Marketed as “legal marijuana”
Chemical sprayed on plant material
Route of ingestion:
Inhalation (smoke)
Ingestion (food, tea)
Available in 1, 3, 9, 30 gm packages
1 gm = 3 “servings” or rolled joints
1 gm = $20
Discount for buying in “bulk”

11. Appearance
Chemicals usually in powder form and dissolved into solvents then sprayed onto dried plant material
Imprecise methods of manufacturing results in variable potencies
Risk of “hot spots”

12. Reported Use of Synthetic Cannabinoids
American Association of Poison Control Centers:
Number of calls regarding human exposures to synthetic cannabinoids
Year
Number of Calls
2010
2,906
2011
6,959
2012
5,225
2013
2,668
2014
3,680
2015 (as of September 23)
6,189

13. Reported Use of Synthetic Cannabinoids 2015

14. Mechanism of Action
Bind to same receptors in the brain as tetrahydrocannabinol (THC)
Full agonist to cannabinoid (CB)-1 and CB-2 receptors
No ceiling of dose effect

15. Desired Effects Alteration in mood Dissociative state Timing:
Onset: 10 mins
Duration: 2-6 hours

16. Adverse Effects Anxiety/agitation Psychosis Depression
Paranoia
Hallucinations
Delusions
Depression
Suicidal thoughts/actions
Seizures
Loss of consciousness
Nausea/vomiting
Tachycardia
Hypertension
Diaphoresis
Muscle spasms
Tremors
AKI
Long term effects of use not known
Risk of withdrawal effects

17. Treatment Supportive care
Monitor vitals
Protection, limit stimuli
Fluids
Antiemetics
Benzodiazepines
Diphenhydramine
Clinical effects last < 8 hours in most users

18. Identification of Ingestion
Not as important as treating symptoms
Does not cross-react with THC on standard urine drug screen
Some private and reference labs have capacity to compare tests with some reference compounds
For example: “Substance consistent with…”

19. Synthetic Cathinones Bath salts M-cat Meow-meow
Ivory Wave, Vanilla Sky
M-cat
Meow-meow

20. Synthetic Cathinones Designer stimulant
Synthetic derivatives of cathinone
Leaves of the Khat Plant
Mephedrone
Methylene-dioxypyrovalerone (MDPV)
Methylone
Supplied as a powder and compressed into crystals
Route of ingestion:
Nasal
Oral
IV or IM injection
Sold in mg package
< 10mg considered normal “dose”
Cost: 1gm = $50

21. Reported Use of Synthetic Cathinones
American Association of Poison Control Centers:
Number of calls regarding human exposures to synthetic cathinones
Year
Number of Calls
2009
2010
3.2
2011
6,138
2012
2691
2013
995
2014
582
2015 (as of August 31)
377

22. Molecular Structure
Bupropion
MDMA (Ecstasy)

23. Mechanism of Action
Increase brain levels of stimulatory neurotransmitters
Serotonin: elevate mood and cause calming effect
Norepinephrine: increase alertness, concentration, motivation
Dopamine: increases pleasure

24. Desired Effects Euphoric high with rush Increased: Timing:
Similar to cocaine, ecstasy or methamphetamine
Increased:
Energy
Concentration
Sociability
Libido
Sense of well-being
Timing:
Onset: 5-20 mins
Peak: mins
Duration: 2-4 hours
Then decrease over 6-12 hours

25. Adverse Effects Agitation* Psychosis: Seizures
Paranoia
Hallucinations
Delusions
Seizures
Long term effects unknown
Risk of tolerance, dependence, withdrawal effects
Hyperthermia
Diaphoresis
Muscle spasms
Bruxism
Palpitations
Tachycardia
Hypertension
Arrhythmias/myocarditis
Hyponatremia
Rhabdomyolysis

26. Treatment Supportive care Ensure staff and patient safety
Monitor vitals
Protection, limit stimuli
Fluids
Benzodiazepines
Diphenhydramine
Vasodilators
Ensure staff and patient safety

27. Identification of Ingestion
No cross-reactivity with amphetamines
Labs can compare substances with references
Cathinone
Methcathinone
MDPV
Mephadrone

28. Synthetic Hallucinogens
N-Bomb
25I-NBOMe
2C-I-NBOMEe
25I
Smiles
Wizard
Solaris
Dots
Legal acid
N-boom
Hoffman
Cimbi-5

29. Synthetic Hallucinogens
2C phenethylamine derivative
Similar to LSD
Supplied as a blotter, powder, or spray
Route of ingestion:
Nasal
Buccal/SL
IV injection
Inhalation of vapor
Orally active?
mcg or “cap” dosing

30. Mechanism of Action
Serotonin receptor agonist
High affinity
25I-NBOMe

31. Desired Effects Euphoria Physical and mental stimulation
Increased empathy
Hallucinations
Depersonalization
Timing:
Onset: rapid
Peak: 20 mins
Duration: 3-13 hours

32. Adverse Effects Agitation/aggression Confusion Hallucinations Delirium
Paranoia
Violence
Seizures
Hyperthermia
Mydriasis
Hyperreflexia/clonus
Tachycardia
Hypertension
Metabolic acidosis
Rhabdomyolysis
Acute kidney injury
High risk of overdose

33. Treatment Supportive care Clinical effects last 4-10 hours IV fluids
Correct metabolic abnormalities
Benzodiazepines
Antipsychotics
Diphenhydramine
Dialysis
Clinical effects last 4-10 hours
After-effects last 1-7 days

34. Designer Drug Toxicity Work-up
EKG
Labs:
CBC
CMP
Serial cardiac enzymes
CK level
Pregnancy test
Assess for co-ingestions:
Urine Toxicology
Ethanol
APAP and salicylate levels
Other prescription medications?

35. Designer Drug Clinical Signs/Symptoms
Body System
Finding
Drug(s)
General
Hyperthermia
Cathinones, hallucinogens
Head & neck
Bruxism
Cathinones
Cardiac
Tachycardia
Hypertension
Chest pain
All classes
Cannabinoids, cathinones
Renal
Acute kidney injury
Cannabinoids
Gastrointestinal
Nausea/vomiting
Acute hepatitis
Musculoskeletal
Muscle spasms
Rhabdomyolysis
Cathinones (cannabinoids less)
Skin
Diaphoresis
Ecchymosis
Hallucinogens
Neurologic
Clonus
Seizures
Psychiatric
Agitation
Hallucinations
Psychosis
Designer Drug Clinical Signs/Symptoms

36. Desomorphine
Krokodil
Crocodile
Zoombie Drug
Russian Magic

37. Desomorphine Morphine derivative Route of ingestion: Timing:
Greater addictive potential
Route of ingestion: IV
Timing:
Onset: seconds
Duration: 2-3 hours
1 mg = 10 mg morphine
$10-30 per gram

38. Desomorphine Effects Desired: Adverse: Sedation Analgesia Euphoria
Nausea/vomiting
Constipation
Respiratory depression
Seizures
Phlebitis
Skin ulceration
Gangrene
Dependence

39. Treatment Supportive care Naloxone Antibiotics if indicated
Average survival from first use of desomorphine is ~2 years

40. Designer Drug Legislation
Synthetic Drug Abuse Prevention Act of 2012
Adds 31 compounds to the FDA Schedule 1 class
9 Cathinone-based compounds
20 Cannabinoid-based compounds

41. South Dakota Legislation
2012: Synthetic designer drugs added to list of controlled substances prohibiting the unauthorized manufacture, distribution, counterfeiting or possession of substances with high potential for abuse as a felony
2014: Annual bill to update list of substances on the controlled substance schedule

42. Operation Log Jam

43. Operation Log Jam Nationwide synthetic drug takedown in July 2012
91 individuals arrested
4.8 million packets of synthetic cannabinoids seized
Plus products to produce 13.6 million more
167,000 packets of synthetic cathinones seized
Plus products to produce 392,000 more
Sioux Falls, SD:
3 tobacco shops closed temporarily

44. Drug Testing Challenges
Widespread standardized designer drug testing is not yet available
Challenges:
Heterogeneity of products contents
Rapid evolution of products

45. Drug testing in SD
May 2012: South Dakota Public Health Laboratory received grant to improve ability to test for suspected illegal synthetic drugs
Compare case samples to drug test standards that contain known characteristics of banned compounds
Money from drug control fund

46. Synthetic Drugs are Not Safe!