Transcript Fentanyl - Spirit of Healing: Alberta First Nations Conquering

Fentanyl
Fentanyl
Fentanyl is one of the most potent opioids used in medicine and is a
being used as a street drug with sometimes fatal consequences.
Pharmaceutical fentanyl is an analgesic (pain-killer) opiate 80-100 times
more potent than morphine.
Drug traffickers are using illicit fentanyl products as a cut in heroin and
as the primary psychoactive ingredient in imitation Oxycodone pills,
commonly sold as ‘Oxy 80’s’.
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Fentanyl is an Opioid
Fentanyl is a synthetic opioid (also known as an opiate). This means it is
chemically manufactured.
An opioid is any drug compound that binds to opiate receptors (protein
molecules located on the membranes of some nerve cells) found in the
brain, spinal cord and digestive tract.
Opioids are drugs derived naturally, synthetically, or semi-synthetically
from opium in the poppy plant.
Opioids including Fentanyl are legally designated as narcotics.
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How Do Opioids Work?
Our bodies naturally make opioids called “endogenous opioids”.
“Endogenous” simply means that it is produced within the body.
An example of a specific kind of endogenous opioid would be
endorphins, which are produced naturally in the body when we
exercise.
Morphine is also produced in small amounts naturally in the body.
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How Do Opioids Work?
“Opioid receptors” are specific receptors that attach only to opioids,
which then cause pain relief.
Opioid receptors are located in the brain, spinal cord, and digestive
tract.
When a person takes an opioid, such as Fentanyl or heroin, the opioids
attach to the body’s opioid receptors in a lock and key manner.
Once the opioids are attached to the opioid receptors, the effects of the
opioid take place (pain relief, drowsiness, confusion, nausea, etc.).
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Pleasure Effect of Fentanyl
Opioids such as Fentanyl attach to receptors in the brain.
When opiate drugs attach themselves to the body’s opioid receptors,
they cause an increase in dopamine levels in the brain’s reward areas.
Since dopamine is responsible for pleasure reward, attention, sleep, and
mood, the body reacts by feeling euphoric, relaxed, and drowsy.
Fentanyl produces a number of effects very similar to other opioid drugs
(such as heroin, morphine).
The main effect is euphoria (intense pleasure), and explains why it is
popular as a street drug.
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Fentanyl is an Analgesic
Fentanyl belongs to a class of drugs known as analgesics.
Analgesia means relief from pain. An analgesic or painkiller is a drug
used to relieve pain.
Analgesic drugs act in various ways on the peripheral and central
nervous systems.
Analgesics work in the brain to change how the body feels and responds
to pain. Fentanyl is used to help relieve severe ongoing pain.
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History of Pharmaceutical Fentanyl
Fentanyl was first synthesized by Janssen Pharmaceutical (Belgium) in
the late 1950s, as an alternative form of anesthesia.
At the time, morphine-oxygen anesthesia was most commonly used for
medical purposes, but it posed some issues:
◦ Incomplete amnesia
◦ Occasional histamine-related reaction
◦ Marked increases in respiratory depression
Fentanyl was introduced into medical practice in the 1960s.
Illicit use of Fentanyl first appeared in the 1970s within the medical
community.
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How is Fentanyl Used?
Fentanyl is most commonly used intravenously, intramuscularly, via
epidural injection, or transdermal patch (72-hour period).
In powder form, Fentanyl can also be smoked, inhaled, and snorted.
When pressed into pill form, Fentanyl can be swallowed and absorbed
through the gastrointestinal tract.
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Pharmaceutical Fentanyl Products
Fentanyl is produced through chemical synthesis by the pharmaceutical
industry.
It is a synthetic (man-made) opioid sold under trade names including:
◦ Sublimaze® (injectable fentanyl citrate)
◦ Duragesic® (transdermal [skin] patch)
◦ Oralet® or Actiq® (buccal lozenge). Fentanyl lozenges (often called lollipops)
sold as Oralet® deliver the drug transmucosally (through the membranes of
the mouth). Note fentanyl lozenges are not available in Canada.
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Fentanyl Patch
Fentanyl is easily absorbed through
the skin (transdermal absorption).
Fentanyl patches work by releasing
fentanyl into body fats, which then
slowly release the drug into the
blood stream over 72 hours,
allowing for long lasting relief from
pain.
◦ Takes 12 hours for onset of analgesia
(pain relief)
◦ Need adequate subcutaneous tissue
for absorption
◦ Takes 24 hours to reach maximum
effect.
◦ Suitable for stable pain only
◦ Has a half-life of about 17 hours after
removal
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Onset of Effects of Fentanyl
When injected intravenously, the effects of Fentanyl occur almost
immediately.
◦ Analgesic effects last 30 to 60 minutes (100mcg)
When injected intramuscularly, the effects of Fentanyl occur after
approximately 8 minutes
◦ Analgesic effects last up to 2 hours (100mcg)
When used as a transdermal patch, Fentanyl is slowly delivered for up
to 72 hours (pain management)
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Medical Use of Fentanyl
Fentanyl provides short-duration pain relief during anesthesia as a presurgical medication, inducing anesthesia and managing pain for those
patients requiring continuous opioid analgesia for chronic persistent
pain relief (such as for cancer patients). It can be also used for sedation
in procedures such as colonoscopies.
It is often used in the operating room and intensive care unit. Fentanyl
has a rapid onset and very short half-life – it needs to be delivered
intravenously or in transdermal patch for constant analgesia (pain
relief).
Fentanyl causes similar effects as other opioids, but is less likely to
cause vomiting
Fentanyl is odourless and tasteless.
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What Does Fentanyl Look Like?
Fentanyl citrate comes in the form of a white crystalline powder, which
is soluble in water and slightly soluble in alcohol.
The transdermal (absorbed through the skin) delivery system (Fentanyl
patch) is composed of four layers:
1.
2.
3.
4.
Backing layer
Gel layer (containing Fentanyl)
Membrane layer (controlling drug release)
Adhesive layer
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Potency of Fentanyl
Fentanyl is extremely potent with as
little as two milligrams of fentanyl
enough to cause overdose and
death.
Fentanyl is approximately 80 - 100
times more potent than morphine.
A 100 mcg dose of fentanyl has the
potency equivalent to approximately
10 mg of morphine.
1 mcg = 0.001mg. This means a tiny
amount of fentanyl is very potent.
That amount is as small as 2 grains
of salt.
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Potency Comparison
Comparison of potency of fentanyl and other prescription opioid
drugs to morphine
Fentanyl
100:1
Oxycodone (Percocet®, OxyContin®)
2:1
Hydromorphone (Dilaudid®)
5:1
Codeine
1:10
Methadone
10:1
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Short-term Effects of Fentanyl Use
(low dose)
The following are some of the
possible short-term effects of
Fentanyl (low doses):
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Euphoria
Muscle rigidity
Respiratory depression
Pain relief
Anxiety
Depression
Drowsiness
Confusion
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Dizziness
Weakness
Pupillary constriction
Suppression of cough reflex
Reduction in blood pressure
Fainting
Nausea and vomiting
Constipation
Slowing of breathing
Constriction of bronchi and
impairment of ventilation
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Short-term Effects of Fentanyl Use
(high dose)
The following are some of the possible short-term effects of Fentanyl
(high doses):
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Loss of consciousness
Cessation of breathing
Respiratory depression
Chest muscle paralysis
Increase in blood pressure
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Effects of Long-Term Use
With long-term use of Fentanyl, users are at risk of developing a
tolerance to the drug, as well as a cross-tolerance to other opioids.
When discontinuing use of Fentanyl, doses should be gradually reduced
in order to avoid serious withdrawal symptoms.
Long-term use of Fentanyl may result in the slowing of respiration,
although this may occur at any time during use.
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Adverse Effects on Respiration
The most concerning adverse effect of Fentanyl is its effect on
respiration.
Adverse effects include:
◦ Respiratory depression - (slowed breathing). Even low doses can cause
respiratory depression. The respiratory depressant effect lasts longer than
the pain killing effects.
◦ Respiratory cessation (in other words the user stops breathing). The risk for
respiratory cessation is higher than for other opioid drugs (like morphine and
heroin).
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Withdrawal Symptoms
Withdrawal effects from Fentanyl
can be very strong and unpleasant.
Symptoms may include:
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Extreme restlessness
Yawning
Sweating
Muscle and bone pain
Anxiety
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Irritability
Weakness
Stomach cramps
Insomnia
Nausea and vomiting
High blood pressure
Watery eyes and runny nose
Chills
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Lethality
The risk for death is greater than for morphine and heroin.
Fentanyl overdose deaths are usually as a result of inadequate oxygen
supply associated with the combined respiratory depressant effects of
the drug and paralysis of the chest muscles.
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Death can be immediate (while the needle is still in the user’s arm).
Even one small dose of fentanyl can be fatal.
Symptoms of overdose include extreme drowsiness and sedation.
Large doses of the drug naloxone are needed to reverse overdose effects of
fentanyl.
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Overdosing
Overdose from Fentanyl requires higher doses of opioid receptor
antagonists than other opioids, however, overdose from Fentanyl shares
the same characteristics as other opioid overdoses, making it very
difficult to identify whether a person is overdosing from Fentanyl, or
whether they are overdosing from a milder opioid.
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Potential for Abuse
Dependence liability:
◦ As great as that of heroin
◦ Rapid onset of action after intravenous use increases Fentanyl’s dependence
liability
Inherent harmfulness:
◦ As great as heroin and morphine, but higher risk of breathing cessation
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Signs of Abuse
The signs and symptoms of Fentanyl abuse will vary depending on the
person, the amount they are using, and whether or not they are mixing
Fentanyl with any other drugs.
The signs and symptoms of Fentanyl abuse may be similar to the signs
and symptoms of heroin abuse.
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Signs of Abuse
Some possible signs and symptoms of Fentanyl abuse may include:
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Sudden change in behavior
Mood swings
Withdrawal from family members
Careless about personal grooming
Loss of interest in hobbies, sports and other favorite activities
Changed sleeping pattern; up at night and sleeping during the day
Red or glassy eyes
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Signs of Abuse
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Sniffling or runny nose
Tiny pupils
Slow breathing
Flushed skin
Tendency to nod off
Scratching
Slurred speech
Complaints of constipation
Complaints of nausea
Change in appetite (not eating)
Covering arms with long sleeves (hiding needle marks)
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Illicit Fentanyl
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Illicit Fentanyl Products
There has been a lot of focus in the international, national and local
news lately on illegal Fentanyl products sold on the street and causing
fatal overdoses.
Illicit fentanyl products include powdered fentanyl marketed as such or
combined with illicit drugs (e.g. heroin); and illicit synthetic drug tablets
manufactured in domestic clandestine labs, notably those produced to
resemble OxyContin (fake Oxy-80’) and more recently fake Percocets.
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Illicit Fentanyl Market
Fentanyl is finding its way to the Canadian illicit drug market via three
means:
1.
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3.
Diversion of pharmaceutical fentanyl products (primarily transdermal
patches) medicines from legitimate sources (e.g. buying/stealing from
people legitimately prescribed Fentanyl, stealing from hospitals,
pharmacies etc.).
Importation or smuggling of pharmaceutical-grade fentanyl into Canada
from abroad, notably China.
Illicit production, most commonly in a clandestine laboratory. A
clandestine laboratory, also referred to commonly as a ‘lab’, is a place
where illegal drugs are made, often by organized crime groups.
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Potency of Illicit Fentanyl
Only a small amount of Fentanyl is required for the desired effect, for
example .1 mg - .2 mg can be used to turn one (1) ounce of heroin into
two (2) ounces of ‘fentanyl heroin’ with sometimes-fatal consequences.
Also, one (1) gram of Fentanyl can be mixed with filler and other
substances, such as caffeine, to make 1000 of imitation ‘Oxy 80’s’.
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Powder Fentanyl Use in Street Drugs
Powdered fentanyl is often sold as
‘synthetic heroin’, or mixed with heroin
to increase the heroin's potency or to
compensate for poor quality heroin.
The powder is dissolved and injected. It
can also be smoked or inhaled.
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Fentanyl Patches in Street Drug Use
Users may heat the contents of a new
or used patch (in a container such as
a pipe or on foil) and inhale the
fentanyl.
Some users cut up patches into pieces
and suck on them or swallow them.
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‘Oxy-80’s’
Fentanyl is the drug in counterfeit
OxyContin® (oxycodone) pills sold
as ‘Oxy-80’s’. They are made in
clandestine drug labs most often
by organized crime groups.
Fake Oxy 80s contain no
OxyContin®. OxyContin® is no
longer manufactured.
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’Oxy-80’s’ Street Names
Street names for ‘Oxy 80s’ include:
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Green beans
Beans
Green apples
Apples
Eighties
Fake Oxy
Shady eighties
Hulks
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Manufacturing ‘Oxy-80s’
Fentanyl is mixed with other
ingredients – most commonly
caffeine and glucose in clandestine
[illegal] drug labs and pressed into
pills.
The pills are often dyed green and
stamped to look the legitimate
pills (e.g. as fake Oxy 80s they will
have '80' pressed on one side and
'CDN' pressed on the other).
The pills may also be stamped with
other logos or made in other
colours.
Photo source: Pill press
http://www.cbc.ca/news/canada/calgary/calgarykelowna-fentanyl-operation-1.3493932
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Concentration
Due to uneven mixing in blenders
and Magic Bullets in illicit labs, the
percentage of fentanyl in each
tablet cannot be controlled.
Consequently some tablets may
contain very little fentanyl and
others can contain deadly
amounts.
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Cross-Contamination
Cross-contamination from
equipment such as scales can
cause fentanyl to be transferred to
other drugs such as marijuana,
meth amphetamine and cocaine.
In other words, drug dealers are
not necessarily deliberately
‘lacing’ other drugs with fentanyl –
rather, fentanyl is easily absorbed
into other drugs in the same
location.
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Legal implications
Fentanyl is considered a Schedule 1 Controlled Substance.
Without a legitimate prescription, possession of Fentanyl is illegal and
could result in financial penalties, and/or jail or prison sentence.
Buying and selling of Fentanyl on the street is illegal and could also
result in either financial penalties, or jail/prison sentence.
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Fentanyl Use Is Not Always Known
In a recent study conducted by the B.C. Centre for Disease Control,
clients at 17 participating harm reduction sites were asked to complete
an anonymous questionnaire describing what drugs they used within
the last three days and provide a urine sample to test for fentanyl.
Nearly 30% of participants tested positive for fentanyl even though 73%
did not report using it.
This study indicates users are not always aware they have taken
Fentanyl.
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Fentanyl Related Deaths: Canada
The following is a summary of Fentanyl related deaths in Canada (CCSA):
◦ Between 2009 and 2014: 655 deaths
◦ Between 2009 and 2014: 1019 drug poisoning deaths with presence of
Fentanyl in toxicology screening (more than 50% of these were between
2013 and 2014)
These numbers are likely underestimated due to unreported instances,
or unknown Fentanyl related deaths.
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Alberta
Statistics
Overdose Deaths
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Alberta Fentanyl Deaths: 2011-2014
Between 2011
and 2014 there
were a total of
162 fentanyldetected and 61
fentanylimplicated deaths
in Alberta.
The number of
fentanyl-detected
deaths for 2014
was 120.
Source: Office of the Chief Medical Examiner
of Alberta
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Alberta Fentanyl Deaths: 2015
From January to December, 2015, there were 272 Albertan deaths
associated with fentanyl:
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90 in the Calgary Zone
75 in the Edmonton Zone
57 in the North Zone
35 in the Central Zone
15 in the South Zone
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2015 Emergency/Urgent Visits
From January 1, 2015 to September 30, 2015 there were:
• 1,173 Emergency Department and Urgent Care visits in Alberta, due to
“poisoning by other opioid”
• 250 visits due to “poisoning by heroin”
• 350 visits due to “poisoning by synthetic narcotic”
These data categories include, but are not limited to, fentanyl.
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Fentanyl
Analogues
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Fentanyl Analogues
New fentanyl drug analogues are appearing on the illicit drug market,
some of which are far more dangerous than Fentanyl.
A drug analogue is one whose physical structure is related to that of
another drug.
Although they have similar physical properties, analogues can have very
different chemical and biological properties.
Fentanyl analogues are synthetic opioid drugs that are like fentanyl
‘cousins’.
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W-Series Compounds
The “W-series” compounds are a class of opioids discovered at the
University of Alberta in 1982.
There are 32 compounds, denoted W-1 to W-32. They have never been
used clinically. The most toxic are W-18 (100 times the potency of
fentanyl/10,000 times the potency of morphine), W-19 (10x fentanyl)
and W-11(1.5 x fentanyl) while some are many times less toxic than
fentanyl.
These compounds are not currently regulated under the Controlled
Drug and Substances Act and as such can be manufactured and
transacted freely.
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W-18
Full name: W-18 - 1-(4-Nitrophenylethyl) piperidylidene-2-(4chlorophenyl) sulfonamide
W-18 is very potent opioid that is roughly 10,000 times the potency of
morphine and 100 times more toxic than fentanyl.
It is usually used as an anesthesia for large animals.
The Canadian Community Epidemiology Network on Drug Use
(CCENDU) issued an Advisory on the new drug (W-18) that is similar to,
but much more toxic than fentanyl. Health Canada laboratories
identified this new drug in tablets that looked like fentanyl seized by
Calgary law enforcement in 2016.
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MT-45
Another synthetic drug on the illicit drug market horizon is MT-45.
It has properties similar to morphine and is attributed to overdose
deaths in the United States and Sweden in the last 2 years.
It is reported to be 400 – 6000 times more powerful than fentanyl.
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Other W-series compounds
3-Methylfentanyl (3-MF): Estimated to be between 400-6000 times stronger than
morphine. Street names: 3-MF, China White
Acetyl-Fentanyl: 40 times more potent than heroin, 80 times more potent than
morphine, and 15 times less potent than fentanyl. Street names: a-f, China White,
Apache, Goodfella, Jackpot, TNT, Murder 8 and Tango and Cash
W-15: A potent opioid that is 5.4x more potent than Morphine.
MT-45: Roughly 80% potency of morphine
AH-7921: Approximately 80% the potency of morphine
U-47700: 7.5 more potent than morphine
Butyr-fentanyl: ¼ the potency of fentanyl. Street name: b-f
Parafluorobutyrfentanyl: Similar effects to fentanyl which include itching nausea and
potentially serious respiratory depression which can be life-threatening
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Naloxone & W-Series Compounds
The mixed agonist-antagonist effect and varying toxicity makes the
administration of naloxone challenging as it is unlikely that the identity of
the specific compound will be known.
When tested with mice, Naloxone successfully reversed the analgesic (painkilling) effects of W-3. Reversal of respiratory depression, the means by
which opioid overdose causes death, was not assessed.
While reversal has never been tested in humans, naloxone should
theoretically be effective, with two stipulations:
1.
2.
Given the high toxicity of some of the W-compounds, high doses of
naloxone may be required.
Second, the agonist-antagonist effects of W-20 to W-32 mean that effects
of naloxone would be difficult to predict. Thus, it is important that the
naloxone dose be titrated to reverse of respiratory depression during
overdose – in other words, more than one dose may be given based on the
response to each dose.
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References
Brands, B., Sproule, B., & Marshman, J. (eds) (1998). Drugs & drug abuse (3rd ed.).
Canada: Centre for Addiction and Mental Health
BC Centre for Disease Control www.towardtheheart.com
Canadian Centre on Substance Abuse. (2015) CCENDU Bulletin: Deaths Involving
Fentanyl in Canada, 2009-2014.
Center for Substance Abuse Research. (Dec. 7 2015). NDEWS Special Report: Fentanyl
and Fentanyl Analogs.
http://www.ndews.org/sites/ndews.umd.edu/files/NDEWSSpecialReportFentanyl120
72015.pdf
Narcanon. http://www.narconon.org/drug-abuse/signs-symptoms-heroin-use.html
O’Neille, N. (2013). Pharmacy Intro Opioids and other drugs we use on palliative
care. http://slideplayer.com/slide/735151/
The National Alliance of Advocates for Buprenorphine Treatment
https://www.naabt.org
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