april 2017 fentanyl slides for pharmacists · opioid receptors in the respiratory centre: at high...

Opioids, Overdose, and Naloxone

Fentanyls and Naloxone

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)


Commercial Support Disclosure

• This program has received no financial or in-kind support from any commercial or other organization


Outline:

Opioid refresher

Opioid overdose

Illicit fentanyls

Non-fentanyl illicit opioids

Potency, purity, product, administration, and analysis

Naloxone mechanism of action


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


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-160618124306/95/opioid-receptors-its-analgesics-23-638.jpg?cb=1466254016


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





http://images.medicaldaily.com/sites/medicaldaily.com/files/styles/headline/public/2015/12/18/heroin.jpg





https://upload.wikimedia.org/wikipedia/commons/f/f0/Occhi222.jpg


https://lh5.googleusercontent.com/x18Lx7tc3BDy



- 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


https://lh5.googleusercontent.com/x18Lx7tc3BDy


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


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


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


https://www.google.ca/url?sa=i&rct=j&q=&esrc=s&source=images&cd


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


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


Opioid Effective Dose*(pure product) Lethal Dose*

Morphine 10 mg 200 mg

Fentanyl 0.1 mg 2 mg

Carfentanil 0.001 mg 0.02 mg

*in an opioid-naive patient, i.e. no tolerance


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:FentanylHeroinCounterfeit pharmaceutical opioids (demerol, percocet, oxycontin)

Has appeared in:CocaineMethamphetamineMDMA


Routes of administration:

OralTransdermalSublingualBuccalInsufflationInhalationIntravenousRectal

It is unclear whether there are differences between fentanyls with respect to their bioavailability


Fentanyl detection:

Testing for fentanyl (point of care urine, lab analysis) was designed for pharmaceutical-grade 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)


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)

morphinenaloxone


Opioid overdose:

Lots of opioid over-activating the opioid receptors


Naloxone reverses the overdose:

By competing for opioid receptors and kicking off the opioid


Naloxone doesn’t last long:

Naloxone is metabolized faster than opioid agonists


Naloxone metabolism:

As naloxone levels fall, but the opioid remains, the overdoes could return


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


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?


Contact information:

Michael BeazelyAssociate ProfessorSchool of Pharmacy, University of [email protected] x21310


april 2017 fentanyl slides for pharmacists · opioid receptors in the respiratory centre: at high...

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