billie bartel, pharmd sanford aberdeen medical center aberdeen, sd
TRANSCRIPT
Designer DrugsToxicity Management and Impact on South Dakota
Billie Bartel, PharmDSanford Aberdeen Medical CenterAberdeen, SD
Disclosures
I have had no financial relationship over the past 12 months with any commercial sponsor with a vested interest in this presentation.
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
New Designer Drugs
“Synthetic drugs”
“Legal highs”
Modified molecular structure of existing drugs
Created for recreational use to evade legislation
Accessibility
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!
National Association of Poison ControlsDesigner Drug Calls
Marketing geared toward young consumers
Social media involvement
New Designer Drugs
Synthetic Cannabinoids
Synthetic Cathinones
Synthetic Hallucinogens
Synthetic Cannabinoids
K2 Spice SCs Krypton Aztec Fire Bombay Blue Fake Weed Yucatan Fire No More Mr. Nice Guy Mr. Smiley Eclipse Black Mamba
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”
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”
Reported Use of 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
American Association of Poison Control Centers:Number of calls regarding human exposures to synthetic cannabinoids
Reported Use of Synthetic Cannabinoids 2015
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
Desired Effects
Alteration in mood Dissociative state
Timing: Onset: 10 mins Duration: 2-6 hours
Adverse Effects
Anxiety/agitation Psychosis
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
Treatment
Supportive care Monitor vitals Protection, limit stimuli Fluids Antiemetics Benzodiazepines Diphenhydramine
Clinical effects last < 8 hours in most users
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…”
Synthetic Cathinones
Bath salts Ivory Wave, Vanilla
Sky M-cat Meow-meow
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 300-500mg package < 10mg considered
normal “dose” Cost: 1gm = $50
Reported Use of Synthetic Cathinones
Year Number of Calls
2009 0
2010 3.2
2011 6,138
2012 2691
2013 995
2014 582
2015 (as of August 31) 377
American Association of Poison Control Centers:Number of calls regarding human exposures to synthetic cathinones
Molecular Structure
Bupropion
MDMA (Ecstasy)
Mechanism of Action
Increase brain levels of stimulatory neurotransmitters Serotonin: elevate mood and cause
calming effect Norepinephrine: increase alertness,
concentration, motivation Dopamine: increases pleasure
Desired Effects
Euphoric high with rush Similar to cocaine,
ecstasy or methamphetamine
Increased: Energy Concentration Sociability Libido Sense of well-being
Timing: Onset: 5-20 mins Peak: 45-90 mins Duration: 2-4 hours ▪ Then decrease over
6-12 hours
Adverse Effects
Agitation* Psychosis:
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
Treatment
Supportive care Monitor vitals Protection, limit stimuli Fluids Benzodiazepines Diphenhydramine Vasodilators
Ensure staff and patient safety
Identification of Ingestion
No cross-reactivity with amphetamines
Labs can compare substances with references Cathinone Methcathinone MDPV Mephadrone
Synthetic Hallucinogens
N-Bomb 25I-NBOMe 2C-I-NBOMEe 25I Smiles Wizard Solaris Dots Legal acid N-boom Hoffman Cimbi-5
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?
50-1500 mcg or “cap” dosing
Mechanism of Action
Serotonin receptor agonist High affinity
25I-NBOMe
Desired Effects
Euphoria Physical and
mental stimulation Increased
empathy Hallucinations Depersonalization
Timing: Onset: rapid Peak: 20 mins Duration: 3-13
hours
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
Treatment
Supportive care IV fluids Correct metabolic abnormalities Benzodiazepines Antipsychotics Diphenhydramine Dialysis
Clinical effects last 4-10 hours After-effects last 1-7 days
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?
Designer Drug Clinical Signs/Symptoms
Body System Finding Drug(s)
General Hyperthermia Cathinones, hallucinogens
Head & neck Bruxism Cathinones
Cardiac TachycardiaHypertensionChest pain
All classesAll classesCannabinoids, cathinones
Renal Acute kidney injury
Cannabinoids
Gastrointestinal Nausea/vomitingAcute hepatitis
CannabinoidsAll classes
Musculoskeletal
Muscle spasmsRhabdomyolysis
Cathinones (cannabinoids less)Cathinones, hallucinogens
Skin DiaphoresisEcchymosis
CathinonesHallucinogens
Neurologic ClonusSeizures
HallucinogensAll classes
Psychiatric AgitationHallucinationsPsychosis
All classesAll classesAll classes
Desomorphine
Krokodil Crocodile Zoombie Drug Russian Magic
Desomorphine
Morphine derivative Greater addictive
potential
Route of ingestion: IV
Timing: Onset: seconds Duration: 2-3 hours
1 mg = 10 mg morphine
$10-30 per gram
Desomorphine Effects
Desired: Sedation Analgesia Euphoria
Adverse: Nausea/vomiting Constipation Respiratory
depression Seizures Phlebitis Skin ulceration Gangrene Dependence
Treatment
Supportive care Naloxone Antibiotics if indicated
Average survival from first use of desomorphine is ~2 years
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
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
Operation Log Jam
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
Drug Testing Challenges
Widespread standardized designer drug testing is not yet available
Challenges: Heterogeneity of products contents Rapid evolution of products
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