Billie Bartel, PharmD Sanford Aberdeen Medical Center Aberdeen, SD.

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

Synthetic Drugs are Not Safe!