Fentanyl and Meth

WB PALATNICK, MD, FRCPC UNIVERSITY OF MANITOBA

Disclosures

I provide on-call Toxicology consultations

for which I am paid a stipend.

ED Presentation: Drugs of Abuse

comatose

agitated

Comatose Partygoer

18 yo male found unresponsive at a “crack house”

BP 90/60 HR 60 RR 8 T 37C

localizes to pain

received 1.2 mg of naloxone by EMS

Management?

Differential Diagnosis?

Resuscitation

Airway

Breathing

Circulation

D: altered mental status? bedside glucose

D50W prn

more naloxone?

Toxicologic Differential Diagnosis opioids

benzodiazepines

gamma hydroxy butyrate (GHB)

ethanol

barbiturates

baclofen

antidepressants

antipsychotics

others

Clinical Presentation of Opioid Toxicity

CNS depression

respiratory depression

pinpoint pupils

other effects:

hypotension

seizures

non-cardiogenic pulmonary edema

Management of Opioid Overdose

ABCs

naloxone

dose: variable

route of administration

onset: seconds to minutes

duration: 45-90 minutes

continuous infusion sometimes required

admit to ICU

Boyer NEJM 2012

Adverse Effects of Naloxone

• precipitation of opioid withdrawal

• especially if opioid dependent

• catecholamine excess

• hypertension, tachycardia,

• ventricular stiffness + pulmonary capillary permeability, → naloxone-associated pulm edema

• nausea + vomiting → aspiration

Adverse Effects of Naloxone

• behavioral disturbance: • agitation, anxiety, or aggression

• danger to staff or patient

• elopement following a transient naloxone induced improvement in LOC followed by recurrent opioid

toxicity due to the limited duration of action of

naloxone

• I would have to talk with them!

Table 5. Complications seen before or after naloxone administration (or patients may have never received naloxone) for acute

intoxication with heroin or heroin mixtures (n = 538) [Osterwalder, 1996].

Published in: Daniel P. Wermeling; Therapeutic Advances in Drug Safety 6, 20-31.

Copyright © 2015 SAGE Publications

Naloxone: Palatnick Approach

• BVM and support respirations

• naloxone dose 0.4 mg IV/IM/IO/etc

• may repeat once at 0.4 mg

• may give an additional 0.8 mg

• if patient responds: observe

• if requires further dosing: consider a naloxone infusion

• if no meaningful response: intubate

Advantages of Intubation

• patient will not die of respiratory failure

• I do not need to talk to them

• avoid the adverse effects of naloxone administration

• Did I mention: I do not need to talk to them?

Disadvantages:

• potential adverse effects of intubation and ventilation

• have to talk to ICU

Opioids

interact with opioid receptors

agonist, partial agonist, antagonist

classification:

naturally occurring

semi-synthetic

synthetic

Naturally Occurring Opioids

• opium

• morphine

• codeine

• thebaine

Semi-synthetic Opioids

• heroin

• hydromorphone (dilaudid)

• hydrocodone

• oxycodone (percocet/percodan, oxycontin)

Synthetic Opioids

meperidine (demerol)

methadone

pentacozine (talwin)

diphenoxylate (lomotil)

fentanyl and congeners

Heroin

“epidemic” on the West coast 3,5 diacetyl morphine

10X more potent than morphine

intense euphoria

purity: variable

route of administration:

IV, IM, SC (skin popping)

smoked (chasing the dragon)

Oxycontin/Oxy Neo

time release formulation of oxycodone

indication: moderate to severe pain

available: 10, 20, 40, 80 mg tablets

Street names: Hillbilly Heroin, oxy, OC, oxycotton, killer, kicker

mode of use:

chewed,

smoking crushed tablet,

IV (dissolved tablets)

.

Methadone

synthetic opioid

chronic pain

opioid maintenance therapy

long half life

dosing

overdose

prolonged QT

torsades de pointe/sudden death

Risk factors for prolonged QT with

Methadone

• high doses of methadone

• female gender

• concomitant admin of CYP3A4 inhibitors

• hypokalemia

• hepatic failure

• administration of other QT prolonging drugs

• pre-existing heart disease • including congenital Long QT syndromes

Medscape

grapefruit

Opioid Epidemic:

How did we get there?

• 1990’s approval of oxycontin

• heavily marketed by Purdue

• sold as “non-addictive” •“pain as the 5th vital sign” • hospitals judged by management of pain

• “pts with chronic pain do not get addicted”

Opioid Epidemic:

How did we get there?

• 2011: landmark report from CDC

• similar stats from Canada

• 2012 oxycontin replaced by Oxyneo

• “crackdown” on opioid prescribing • →illicit opioids resulting in “epidemic” of deaths

• heroin

• fentanyl, carfentanil from China

November 2011

Number of unintentional drug overdose deaths

involving opioid analgesics, cocaine, and heroin — United States, 1999–2007

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6101a3.htm#fig1

NY Times

Fentanyl and Carfentanil

• synthetic opioids

• fentanyl: 50-100 X more potent than morphine

• carfentanil: 10,000 X more potent than morphine

• T 1/2 : 5-6 hours

• furanyl fentanyl

• U47700

Fentanyl profits

Macleans

Winnipeg Experience: Deaths

• October 2016 to May 2017

• Number of post-mortem screen positives

• Carfentanil positive: 29

• Furanyl fentanyl: 3

• U47700: 3

• January: approx 4 deaths/week

• Now: approx 1 every 2 weeks

Curtis Oleschuk (DSM)

CTV News May 10 2017

2015 Manitoba Overdose Deaths

Opioid Overdose Surveillance

Winnipeg Health Region, 2016

• In 2016, there were 715 Naloxone administrations by the WFPS in the City of Winnipeg

• the majority of Naloxone occurred in the 20-39 year age group

• The number of naloxone administrations began to rise in March 2016 and peaked in November 2016

• Just over half (57%) of naloxone administrations occurred in the Downtown and Point Douglas

Community Areas

• The majority of victims (51%) live in the urban suburbs, outside of the Downtown and Point Douglas

Community Areas

https://www.canada.ca/en/public-health/services/publications/healthy-living/apparent-

opioid-related-deaths-report-2016-2017-december.html

https://www.canada.ca/en/public-health/services/publications/healthy-living/national-

report-apparent-opioid-related-deaths-released-june-2018.html

http://www.ccdus.ca/Eng/Opioids/issue/Pages/default.aspx

“So far in 2018, 224 people have been treated with naloxone, compared to 371 patients during

the same period last year”

Agitated Partygoer

18 yo male was at a social

drinking ++

police called due to aggressive behaviour

screaming and running into traffic

BP 180/110 HR 120 RR 12 T 38C

Management?

Differential Diagnosis?

Management

ABCs

bedside glucose

physical restraints

positional asphyxia

chemical restraints

haloperidol

lorazepam

? ketamine

Toxicologic Differential Diagnosis cocaine

methamphetamine

ethanol

phencyclidine

other amphetamines

“bath salts” ecstasy

synthetic cannaniboids (K2, Spice)

others

Methamphetamine

methyl substitution of amphetamine

cheaper and longer lasting than cocaine

CMAJ June 03, 2008 178 (12) 1537-1539

Global News Feb 8 2018

• While other regions of Canada are dealing with an opioid crisis, crystal meth has become

the drug of choice in Manitoba.

• The Addictions Foundation of Manitoba says meth use increased by more than 100 per

cent in adults and nearly 50 per cent in youth

since 2014.

The province’s chief medical

Medical Examiner says meth was

involved in 35 overdose deaths in 2017,

up from 19 the year before.

In contrast, fentanyl was involved in 14

fatal overdoses and carfentanil, was

involved in 32.

Worldwide “Meth” Trends

• most widely used illicit drug other than THC • WHO 2004 data estimates:

• 42 million Meth users worldwide

• 15 M Heroin users

• 12 M Cocaine users

• Heavy use: Thailand, Phillipines. SE Asia, Eastern Europe, Russia, Japan, Western USA

• Increasing use: Canada, Europe, moving east in North America

• biker gangs

• western Canada:

2.8-4%

• Manitoba:

3% (33,400)

Used/tried Meth

Source: Addictions Foundation of Manitoba

Methamphetamine: Abuse

Patterns

low intensity abuse

not psychologically addicted

casual user

binge abuse

high intensity abuse

“speed freaks”

Acute Methamphetamine “Overdose”

• agitation • anxiety • hallucinations • psychosis • delirium • seizures • hypertension • tachycardia • dysrhythmias • hyperpyrexia

Medical Consequences of Chronic

Methamphetamine Abuse

• cardiovascular

• neurologic

• renal • rhabdomyolysis

• infectious disease • increased use among MSM

• HIV risk

• dental • “meth mouth”

Cardiovascular Effects

• acute MI and ACS Watts Amer J Emerg Med 2005

Furst et al NEJM 1990

Turnipseed et al J Emerg Med 2003

• cardiomyopathy Wijetunga et al J Tox Clin Tox 2003

Hong et al JAMA 1991

• dissecting thoracic aneurysm Davis et al J Forensic Sci 1994

Neurological Effects

• ischemic or hemorrhagic stroke

• etiology

• acute hypertension

• vasculitis

• pre-existing vascular abnormality

• vasoconstriction

Perez et al: J Emerg Med 1999

Inamasu et al: Neurol Med Chir(Tokyo) 2003

Moriya For Sci Int 2002

Rothrock et al Neurology 1988

Methamphetamine: chronic CNS effects

tolerance

loss of dopamine transporter activity

memory impairment

verbal learning impairment

psychomotor slowing

anxiety

psychosis Volkow et al Am J Psychiatry 2001

structural brain abnormalities Thompson et al J Neurosci 2004

PET Scan: Dopamine Transporter

Concentrations

www.loni.ucla.edu

www.loni.ucla.edu

www.loni.ucla.edu

Source: Volkow, N.D. et al, Am. J. Psychiatry, 158(3), pp. 377-382, 2001.

www.loni.ucla.edu

www.loni.ucla.edu

www.loni.ucla.edu

www.loni.ucla.edu

https://www.accsa.co.za/single-

post/2017/05/14/Methamphetamine-and-Psychosis

Methamphetamine Psychosis

up to 40% of users

associated with high doses/IV use

acute symptoms can include

agitation, violence, paranoid delusions

auditory and tactile hallucinations,

usually last 1-3 days→ weeks psychosis can recur and persist

may be difficult to distinguish from schizophrenia

Management: benzo’s, antipsychotics (olanzapine, quetiapine)

Methamphetamine: Synthesis

“ephedrine reduction”

“ take a pinch of red phosphorus, a smidgen of ephedrine, a dash of iodine and a skosh of lye. Add some distilled water and simmer for a few hours and hope it doesn’t explode and kill you ”

Excerpt from the “Betty Cranker Cookbook”

Meth Precursor Substances Acetone

Alcohol

Freon

Hydrogen Peroxide

Anhydrous Ammonia (fertilizer)

Hydrochloric Acid Ether = Engine Starter

Sodium Hydroxide = Lye

Sulfuric Acid = Drain Cleaner

Methanol = Gas line antifreeze

Toluene = Brake cleaner

Trichloroethane = Gun cleaner

Ephedrine

Pseudoephedrine

Phenylpropanolamine Kerosene

Lithium batteries

Sodium metal

Iodine (flakes or crystals)

Salt (table or rock)

Red Phosphorus = Road flares or matches

Ethylene glycol = Antifreeze

Methamphetamine Labs

• often in remote locations • hazards include:

• fires, explosions, toxic gases, toxic wastes

• approx 5-6 lbs of toxic waste per lb of Meth

“Dark Web”

CBC

Questions?