Drug Abuse and Overdose Trends: What’s Still Out There and What’s New? Ernest Stremski, MD, MBA Children’s Hospital of WI – ED Trauma Medical College of WI – Pediatrics Concordia University School of Pharmacy and Physician Assistant Program

No Financial Disclosures

Today, Fond du Lac EMS will be responding to:

Apnea Arymo

Seizure from MDMA

Smoking “spice”

Bath salts

Skittles

1-800-222-1222

Some easy Neuropharmacology: How drugs affect the brain

Cerebral Cortex

Limbic System

MESOLIMBIC & VTA

Multi-divergent pathways of the CNS are projections from the Brainstem & Midbrain, into the Cerebral Cortex and Limbic System

Series of stimulating and inhibiting messages via chemical neurotransmitters These chemical neurotransmitters mediate: Mood , Appetite, Sleep – Wake Cycles, Motivation, Pain Perception, Cognition, Sex drive, Behavioral, Reward, Pleasure Drugs (be it prescription or illicit) affect the actions of these neurotransmitters: Xanax – Gamma amino butyric acid Cocaine – Dopamine Adderall – Norepinephrine MDMA – Serotonin

NOREPINEPHRINE

DOPAMINE

SEROTONIN

ANANDAMIDE

Stimulant

Dissociative

Euphoria

Sedation & Anxiolytic

So many ways to get “High”

Many are provided by Mother Nature

Many neurotransmitters & receptors can mediate dissociative effects

Heroin & Opioids

Lysergol

Dextromethorphan

Psylocibin

Peyote

Salvinorin A

Muscimol

Scopolamine

MDMA MME 2C-B Ketamine

Myristicin

Synthetic Cannabinoid

Cathoniones

PCP

LSD

GHB

THC

Our first group of drugs, stimulants (AKA: Psychostimulants) Naturally occurring & synthetic forms Enhance effects of catecholamines

Used to: Keep Partying (stay up and going), Performance enhancing (sports & sex)

Tachycardia (SVT), Hypertension / Vasoconstriction (MI, CVA, Ischemia) Agitation & Violence, Seizures, Diaphoresis & Dehydration

AMPHETAMNES, PHENYLETHYL AMINES, CATHINONES, METHYL XANTINES, TROPANE ALKALOIDS

Historical use of Amphetamines in the USA Increase work & productivity Treat Depression Weight loss / Appetite suppressant

Recreational Pharmaceutical Mood Elevator ADD / ADHD Arousal / Energy Narcolepsy Sexual stamina Weight loss Sport enhance Decongestant Should NOT be prescribing amphetamines for Depression, Chronic Fatigue, Asthma

5mg Methamphetamine

Military Weight Loss

Depression

Normally, we have a baseline amount of catecholamine stimulation of the brain Example: Water going into the sink (Epi releasing into the brain)

Keeps EPI in the brain for longer duration

Enhances amount of EPI released to the brain

Enhances and prolongs EPI in the brain

The “bath salts” (again, nothing to do with a relaxing spa)

Typically are synthetic cathinone products (Khat – natural source of Cathus edulis)

Mephedrone, Methylone, Methylenedioxypyrovalerone (MDPV)

Approach with Caution: CV & Neuro Support Benzodiazepines Cool Hydrate Not detected in standard drug screens

Another groups of synthetic psychostimulants – Phenethylamines MDMA, MME, 2C-B – names include XTC, E, Molly, Hug Drug, Foxy, Dragonfly, …)

Dissociative effects are based on enhancement of Serotonin

Manage as per other stimulant drugs, special focus on cooling & hydration

Methylene dioxymethylmethamphetamine Bromo dimethoxyphenethylamine Bromo aminopropylbenzodifuran

XTC 2C-B B-DFLY

Weed versus Synthetic Pot

Each are a form of a Cannabinoid

We have 2 cannabinoid neurotransmitters They both act like THC (active component of marijuana) Anandamide and Arachadonyl glycerol There action is mediated at a receptor known as CB1

Marijuana (Sacred grass) – effects written B.C. Marijuana widely available OTC – pre 1910 Marijuana warnings – Refer Madness 1930s Marijuana Hippies – 1960s Marijuana – isolated THC as component 1964 Marijuana – discovered site of action at CB1 1992 Marijuana – medical & dispensaries begin 1998 New targets for CB1 – JWH compounds 2000s Marijuana – legalized recreational use ____ & ____ 2014

Where is the legitimate medicinal use of THC? Reduce intra-ocular pressure in certain forms of glaucoma Effective anti-emetic during chemotherapy Reduce pain of Multiple Sclerosis & peripheral neuropathy Minimize seizures in certain forms of refractory Epilepsy Appetite enhancing effects in HIV wasting Roles in: Cancer? Auto Immune Suppression? PTSD? ….. Is marijuana a “stepping stone” to drug abuse and Heroin? Would you rather have your kid doing marijuana versus ______? Are the motor & long term effects of THC less problematic than ETOH?

Medical marijuana legislation In February 2017, Sen. John Erpenbach and Rep. Chris Taylor introduced S 38/A 75, which would create a state-regulated program allowing access to medical cannabis for patients with serious medical conditions and their doctors’ recommendations. Meanwhile, two other proposals — SJR 10/ AJR 7 — would call for an advisory referendum on whether Wisconsin should create a medical marijuana program. Unfortunately, no action has been taken since the bills were referred to committee. However, there has been modest progress on improving Wisconsin’s CBD-focused medical cannabis law. On April 17, 2017, Gov. Scott Walker signed Act 4, which expands the state’s existing limited medical cannabis law, Lydia’s law, enacted in 2014. The original law allowed patients with documentation of a seizure disorder to possess CBD treatments, but it did not legalize the production of CBD products in the state. Act 4 expands the program to protect all patients who possess CBD and have a letter from their physician. Unfortunately, it remains illegal to produce or distribute CBD products. Sen. Chris Larson and Rep. Jimmy P. Anderson introduced legislation (S 104/A 158) that would allow state-licensed businesses to produce and dispense CBD treatment products.

delta 9, tetrahydrocannabinol (THC)

JWH 018 - 1-pentyl-3-(1-naphthoyl)indole

POT and SYNTHETIC POT are both activators of CB1 The synthetic forms are more profound in their ability to act on CB1 and other sites Leads to exaggerated effects (CV)

“pure THC” user “synthetic pot” user Tachycardic & Hypertensive Agitated Unresponsive Seizures

Careful, today there are many hybrids of the cannabis plant with varying growing and extraction techniques THC concentrations vary

Endogenous: Anandamide & 2, AG

Botanical: Tetrahydrocannabinol

Synthetic: Many, JWH compounds

While synthetic pot activates CB1, it is also more potent & dirty, no standardization practices Experience more profound neuro & cardiovascular effects

What did they take? Unresponsive, minimal to zero respiratory effort, pinpoint pupils, hypotonia

Crushed and insufflated tablets Ingested oral tablets Injected a powder

The Journal of the Pharmacy Society of Wisconsin, 2014: Volume 17

Prescription drug abuse affects > 6,000,000 US Citizens As many as 50 deaths / day due to Opioid Analgesic Overdose 80 % of heroin abusers have previously used Opioid analgesic medications

Opioid Analgesic Drugs Natural source is the opium poppy (Papaver somniferum)

Up to 10 % dry weight is Morphine

Actions of Opioid Drugs (Stimulate Mu, Kappa, Delta receptors of CNS) Stimulation of these 3 receptors blocks neural processing Primary effect on spinal cord / brain is to stop pain processing Problems: Slows and can fully inhibit respiratory processing Enhances Dopamine release in the Mesolimbic system Relaxes smooth muscle (drops BP, stops labor, slows peristalsis) Release histamine (warm flushed, pruritic, red skin)

Katzung, Basic and Clinical Pharmacology, 2012, 13th Ed.

Heroin

0.01 0.01

Are we only dying due to heroin and fentanyl products?

It’s ALL the Opioid Analgesic drugs: Morphine, Hydromorphone, Oxycodone, Hydrocodone, Codeine

Long acting opioid analgesic drugs, some of these are “newer”

Arymo

Avinza

Embeda

Kadian

Exalgo Palladone

Oxycodone

Oxymorphone Tapentadol Hydrocodone

Hydromorphone ?

Old OxyContin

ABUSE – DETERRANT TABLET TECHNOLOGY

New OxyContin

Agonist Antagonist

Remember the duration of Narcan is almost always shorter than that of the opioid

DXM looks like an opioid but has almost zero opioid effect. A metabolite (DXO) has Dissociative effects via Serotonin and NMDA SKITTLES – not going to be Narcan-reversible, let it wear off

Today, Fond du Lac EMS rescued:

Morphine

Phenethylamine

Smoking “JWH Compounds”

Cathinone stimulants

Dextromethorphan

1-800-222-1222

BENZO

BENZO BENZO

NARCAN

NO NARCAN

Questions? Comments ?

Ernest.Stremski@cuw.edu