Fentanyl and Meth - CSHP Manitoba...Methamphetamine: Synthesis ³HSKHGULQHUHGXFWLRQ´...
Transcript of Fentanyl and Meth - CSHP Manitoba...Methamphetamine: Synthesis ³HSKHGULQHUHGXFWLRQ´...
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Fentanyl and Meth
WB PALATNICK, MD, FRCPC UNIVERSITY OF MANITOBA
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Disclosures
I provide on-call Toxicology consultations
for which I am paid a stipend.
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ED Presentation: Drugs of Abuse
comatose
agitated
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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?
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Resuscitation
Airway
Breathing
Circulation
D: altered mental status? bedside glucose
D50W prn
more naloxone?
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Toxicologic Differential Diagnosis opioids
benzodiazepines
gamma hydroxy butyrate (GHB)
ethanol
barbiturates
baclofen
antidepressants
antipsychotics
others
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Clinical Presentation of Opioid Toxicity
CNS depression
respiratory depression
pinpoint pupils
other effects:
hypotension
seizures
non-cardiogenic pulmonary edema
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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
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Boyer NEJM 2012
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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
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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!
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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
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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
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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
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Opioids
interact with opioid receptors
agonist, partial agonist, antagonist
classification:
naturally occurring
semi-synthetic
synthetic
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Naturally Occurring Opioids
• opium
• morphine
• codeine
• thebaine
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Semi-synthetic Opioids
• heroin
• hydromorphone (dilaudid)
• hydrocodone
• oxycodone (percocet/percodan, oxycontin)
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Synthetic Opioids
meperidine (demerol)
methadone
pentacozine (talwin)
diphenoxylate (lomotil)
fentanyl and congeners
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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)
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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)
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Methadone
synthetic opioid
chronic pain
opioid maintenance therapy
long half life
dosing
overdose
prolonged QT
torsades de pointe/sudden death
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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
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Medscape
grapefruit
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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”
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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
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November 2011
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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
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NY Times
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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
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Fentanyl profits
Macleans
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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)
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CTV News May 10 2017
2015 Manitoba Overdose Deaths
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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
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https://www.canada.ca/en/public-health/services/publications/healthy-living/apparent-
opioid-related-deaths-report-2016-2017-december.html
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https://www.canada.ca/en/public-health/services/publications/healthy-living/national-
report-apparent-opioid-related-deaths-released-june-2018.html
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http://www.ccdus.ca/Eng/Opioids/issue/Pages/default.aspx
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“So far in 2018, 224 people have been treated with naloxone, compared to 371 patients during
the same period last year”
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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?
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Management
ABCs
bedside glucose
physical restraints
positional asphyxia
chemical restraints
haloperidol
lorazepam
? ketamine
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Toxicologic Differential Diagnosis cocaine
methamphetamine
ethanol
phencyclidine
other amphetamines
“bath salts” ecstasy
synthetic cannaniboids (K2, Spice)
others
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Methamphetamine
methyl substitution of amphetamine
cheaper and longer lasting than cocaine
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CMAJ June 03, 2008 178 (12) 1537-1539
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Global News Feb 8 2018
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• 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.
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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.
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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
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• western Canada:
2.8-4%
• Manitoba:
3% (33,400)
Used/tried Meth
Source: Addictions Foundation of Manitoba
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Methamphetamine: Abuse
Patterns
low intensity abuse
not psychologically addicted
casual user
binge abuse
high intensity abuse
“speed freaks”
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Acute Methamphetamine “Overdose”
• agitation • anxiety • hallucinations • psychosis • delirium • seizures • hypertension • tachycardia • dysrhythmias • hyperpyrexia
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Medical Consequences of Chronic
Methamphetamine Abuse
• cardiovascular
• neurologic
• renal • rhabdomyolysis
• infectious disease • increased use among MSM
• HIV risk
• dental • “meth mouth”
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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
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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
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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
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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.
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www.loni.ucla.edu
www.loni.ucla.edu
www.loni.ucla.edu
www.loni.ucla.edu
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https://www.accsa.co.za/single-
post/2017/05/14/Methamphetamine-and-Psychosis
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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)
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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”
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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
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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
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“Dark Web”
CBC
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Questions?