Fentanyls and Naloxone. Opioids, Overdose, and Naloxone
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1 Opioids, Overdose, and Naloxone
2 Presenter Disclosure Presenter s Name: Michael Beazely I have no current or past relationships with commercial entities Speaking Fees for current program: I have received a speaker s fee from McKesson for this learning activity (not personally, but to the University of Waterloo)
3 Commercial Support Disclosure This program has received no financial or in-kind support from any commercial or other organization
4 Outline: Opioid refresher Opioid overdose Illicit fentanyls Non-fentanyl illicit opioids Potency, purity, product, administration, and analysis Naloxone mechanism of action
5 What is an opioid?: Any chemical that activates opioid receptors can be described as an opioid: - chemicals produced in the human brain - chemicals found in nature, - modified versions of natural opioids - fully synthetic chemicals
6 What is an opioid receptor?: A protein found in many cell types, including brain cells, that interacts with opioids and mediates their effects The three main types of opioid receptors are: μ Mu δ Delta κ Kappa image.slidesharecdn.com/opioidreceptorsopioidanalgesics /95/opioid-receptors-its-analgesics jpg?cb=
7 What do opioids do?: Activation of opioid receptors leads to: - relief of pain and altered pain perception - sedation and anesthesia - cough suppression - constipation/treatment of diarrhea - miosis (small pupils) - euphoria - tolerance, dependence, addiction - nausea and vomiting - sweating - respiratory depression
8 What do opioids do?: Activation of opioid receptors leads to: - relief of pain and altered pain perception - sedation and anesthesia - cough suppression - constipation/treatment of diarrhea - miosis (small pupils) - euphoria - tolerance, dependence, addiction - nausea and vomiting - sweating - respiratory depression
9 What do opioids do?: Activation of opioid receptors leads to: - relief of pain and altered pain perception - sedation and anesthesia - cough suppression - constipation/treatment of diarrhea - miosis (small pupils) - euphoria - tolerance, dependence, addiction - nausea and vomiting - sweating - respiratory depression
10 Fentanyls and Naloxone What do opioids do?: Activation of opioid receptors leads to: - relief of pain and altered pain perception - sedation and anesthesia - cough suppression - constipation/treatment of diarrhea - miosis (small pupils) - euphoria - tolerance, dependence, addiction - nausea and vomiting - sweating - respiratory depression
11 What do opioids do?: Activation of opioid receptors leads to: - relief of pain and altered pain perception - sedation and anesthesia - cough suppression - constipation/treatment of diarrhea - miosis (small pupils) - euphoria - tolerance, dependence, addiction - nausea and vomiting - sweating - respiratory depression
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13 Respiratory centre: The respiratory centre controls breathing without conscious control When oxygen levels fall (and carbon dioxide levels start to rise) the respiratory centre causes you to breath more and rapidly When oxygen and CO2 levels normalize breathing slows
14 Opioid receptors in the respiratory centre: At high doses, opioids interfere with respiratory centre function Over-activation of opioid receptors make the respiratory centre less and less sensitive to rising carbon dioxide levels in the blood Breathing becomes less frequent, more shallow, and ultimately stops during an opioid overdose
15 Illicit fentanyls: Fentanyl is a potent opioid, used in anesthesia, for pain, chronic pain, pain in end of life care Typically administered as a patch placed on the skin Illicit fentanyls ( bootleg ) include fentanyl itself, and up to 35 chemically-related, but distinct fentanyl analogues
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17 Illicit fentanyls in Canada/US: fentanyl, acrylfentanyl, beta-hydroxythiofentanyl, thenylfentanyl, 3-methylfentanyl, acetylfentanyl, butyrfentanyl, furanfentanyl, carfentanil What we know: - variability in potency, all have opioid activity What we don t know: - definitive human potency, duration of action, metabolism, metabolite activities, unique actions and toxicities
18 Non-fentanyl illicit opioids in Canada/US: U-47700, AH-7921, MT-45 (confirmed) What we know: - these were drugs in the pharma pipeline, we know a considerable amount about their preclinical info - slightly more potent than therapeutic opioids, less potent than fentanyls What we don t know: - definitive human potency, duration of action, metabolism, metabolite activities, unique actions and toxicities
19 Opioid Effective Dose* (pure product) Lethal Dose* Morphine 10 mg 200 mg Fentanyl 0.1 mg 2 mg Carfentanil mg 0.02 mg *in an opioid-naive patient, i.e. no tolerance
20 Purity and product: Imported pure fentanyl is diluted, typically to 2-3% or less of a bulk powder, sold as powder or pressed into pills It is sold as: Fentanyl Heroin Counterfeit pharmaceutical opioids (demerol, percocet, oxycontin) Has appeared in: Cocaine Methamphetamine MDMA
21 Routes of administration: Oral Transdermal Sublingual Buccal Insufflation Inhalation Intravenous Rectal It is unclear whether there are differences between fentanyls with respect to their bioavailability
22 Fentanyls and Naloxone Fentanyl detection: Testing for fentanyl (point of care urine, lab analysis) was designed for pharmaceuticalgrade fentanyl These tests may, or may not, cross-react with fentanyl analogues These test may, or may not, be sensitive enough to detect very low amounts (e.g. carfentanil)
23 Overdose reversal by naloxone: All opioids are opioid receptor AGONISTS (binds and activates the receptor) Naloxone is opioid receptor ANTAGONIST (binds, but does not activate the receptor) naloxone morphine
24 Opioid overdose: Lots of opioid over-activating the opioid receptors
25 Naloxone reverses the overdose: By competing for opioid receptors and kicking off the opioid
26 Naloxone doesn t last long: Naloxone is metabolized faster than opioid agonists
27 Naloxone metabolism: As naloxone levels fall, but the opioid remains, the overdoes could return
28 Affinity and concentration: Receptor affinities for opioids and naloxone are similar carfentanil > fentanyl = naloxone > morphine > oxycodone (Depending on the concentration!), you would predict that more naloxone would be required to reverse a carfentanil vs. fentanyl vs. morphine overdose
29 Unanswered questions: Is intranasal naloxone more effective than IM injections in the field How likely are intranasal naloxone or high-dose IM injections to cause severe withdrawal, including agitation and possible aggression, compared to standard IM doses? How can we distribute the right naloxone product and dose to the right patient?
30 Contact information: Michael Beazely Associate Professor School of Pharmacy, University of Waterloo x21310
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