Transcript San Francisco Designer Drug that was supposed to mimic heroin

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sensory event of both PNS and CNS
emotional component
cognitive component
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acute pain
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chronic pain
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pain can be modulated, enhanced or
diminished by both central and peripheral
mechanisms
◦ peripheral aspect – non steroidal antiinflammatory
drugs
◦ central aspects – opioid analgesics
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Roxicet, Tylox (acetaminophen and
oxycodone)
Percocet – (oxycodone with paracetamol)
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opium extracted from opium poppy
◦ used for thousands of years to produce euphoria,
analgesia, sleep and relief from diarrhea and cough
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ancient times – primarily for constipating
effects
Homer, Hippocrates, et
◦ sleep producing effects
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Early 1800’s – morphine isolated from opium
as its active ingredient
◦ treating severe pain
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1856- invention of the hypodermic syringe
◦ Civil War – “soldiers disease”
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1910 – concern about dangers of opioids and
dependence
1914- Harrison Narcotic Act
◦ use of most opioids strictly controlled
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1970 –
◦ established current schedules of drugs
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opium – juice or sap from the poppy
opiate – drug extracted from the sap
morphine
codeine
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opioid – any exogenous drug (natural,
semisynthetic or synthetic) that binds to an
opiate receptor and produces agonist or
morphine-like effects
endorphin – endogenous substance that
exhibits pharmacological properties like
morphine
3 familes of endogenous opioid peptides
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enkephalins
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dynorphins
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beta endorphins
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opioids occur in nature in 2 places
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the juice of the poppy
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in our bodies……
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all other opioids are either prepared from
morphine (semisynthetic opioids like heroin)
or synthesized from other precursors
(synthetic opioids such as fentanyl)
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analgesic potency of the agonist correlates
with affinity of agonist for opioid receptor
at least 3 types of opioid receptors
◦ mu◦ kappa
◦ delta
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some areas have all 3 types of opioid
receptors
◦ (spinal cord)
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some have predominantly one type of
receptor
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brain, sc, and periphery
morphine – mu agonist
◦ exerts effects in thalamus and striatum
◦ brain stem (affects respiration)
◦ spinal cord (analgesic effects)
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PAG, brain stem, nucleus accumbens,
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may modulate mu receptors
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minor analgesic effects;
pinpoint pupils
modest analgesia
no addiction potential
dysphoria
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pure agonists –
mu agonists
◦ produces analgesia, reward, respiratory depression
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morphine
codeine
heroin
meperidine (Demerol)
methadone (Dolophine)
oxymorphone (Numorphan)
hydromorphone (Dilaudid)
fentanyl (Sublimaze)
oxycodone
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produces agonist effects at one receptor and
antagonist at another
clinically useful mixed drugs – kappa agonist
and weak mu antagonist
useful for moderate pain
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not good if someone is dependent on opiates
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binds to opioid receptors but has low intrinsic
activity (low efficacy)
can produce analgesia – but ceiling lower
than pure agonist
buprenorphine (Suboxone)
binds to all 3 receptors
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block opiate receptors
naloxone, naltrexone
depot injections of naltrexone
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pure agonist
more potent and represents about 10% of
crude sap
codeine much less potent
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usually administered via injection although
rectal or oral is possible
intranasal system under development
absorption from GI slow and incomplete
compared to other routes
morphine crosses bbb fairly slowly (more H20
soluble than lipid soluble)
◦ heroin, fentanyl – cross bbb much more quickly
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liver metabolizes morphine; one metabolite is
actually 10 – 20X more potent than morphine
for analgesia
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analgesia
euphoria
respiratory depression
cough suppression
pupillary constriction
nausea and vomiting
GI symptoms
endocrine symptoms
immune system effects
histamine release
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codeine –
◦ one of the most commonly prescribed opioid
◦ usually combined with aspirin or acetaminophen for
relief of mild to moderate pain
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heroin
◦ (diacetylmorphine)
◦ 3X more potent than morphine
◦ produced by a slight modification of morphine
structure
◦ increased lipid solubility
◦ metabolized to monoacetylmorphine and morphine
◦ legally available in Great Britain
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(Percodan, OxyContin)- semisynthetic opioid
percodan short-acting; oxycontin – longacting
current abuse high;
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hydromorphone (Dilaudid), oxymorphone
(Numorphan)
both structurally related to morphine
as effective but 6 – 10X more potent
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meperidine (Demerol)
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◦ structurally different from morphine – different side
effect profile
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rate at which tolerance develops can vary
widely; pattern of use plays a role
cross-tolerance
physical dependence can develop
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many of the effects observed are opposite of
opiate
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Opiate withdrawal:
◦ Acute symptoms: restlessness, lacrimation, runny nose,
yawning, perspiration, goose flesh ("cold turkey"), restless
sleep and dilated pupils during the first 24 hours (onset
usually 8 to 12 hours after a reduction in dose or
cessation of use)
◦ 5 – 7 days into withdrawal;
 symptoms can become more severe
 can be characterized by twitching and
spasms of muscles; kicking movements
(“kicking the habit”), severe aches in the
back, abdomen, and legs; abdominal and
muscle cramps; hot and cold flashes;
insomnia; nausea, vomiting, and
diarrhea; sneezing; fever
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Jittery, high pitched cry, hyperactive reflexes,
restlessness, GI upset, etc.
heroin withdrawal occurs within 48-72 hours
in 50-80% of infants
Methadone withdrawal may be delayed up to
6 days after birth
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1935 - first federal
"narcotics farm" (U.S.
Public Health Prison
Hospital) opens in
Lexington, Kentucky
Role of cues
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substitution therapy
What are the advantages of substitution
therapy?
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methadone –
◦ synthetic mu agonist
◦ 2 primary legitimate users
 substitution for opiate dependent heroin users
 long acting analgesic for chronic pain syndromes
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Physicians who are not in licensed methadone
programs cannot prescribe methadone for
opioid dependence
methadone clinics locations
diversion
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Oral administration – reaches peak levels in ~
2 hrs;
Half life – the amount of time necessary for ½
of the drug to be metabolized in the body;
for methadone – very variable but for most
people ~ 24-25 hours
◦ When used for treating addiction – 1/day
◦ For pain management – more likely 3 – 4 times/day
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levo-alpha acetylmethadol
approved in mid 1993 for clinical
management of opioid dependence
longer ½ life
not currently available because of possible
serious cardiac complications
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Subutex –
advantages – longer ½ life
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Suboxonebuprenorphine/naloxone
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advantages of buprenorphine
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naloxone (Narcan)
◦ treating overdose
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what happens in opiate dependent
individuals?
◦ must be given by injection- short ½ life
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naltrexone (Trexan, ReVia)
◦ longer duration of action and can be taken orally
◦ downside to naltexone
How was it discovered--1982 – San Francisco
Designer Drug that was
supposed to mimic heroin
Seven heroin addicts at ER
All showed signs of severe
Parkinsons like Disease
First human cohort of MPTPinduced parkinsonism
Found that the drug had been
contaminated with a toxin
called MPTP
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Vanguard
◦ “The Oxycontin Express”
◦ Can be found on Hulu
June 2010
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July 1, 2001, nationwide law in Portugal
decriminalized all drugs, including cocaine
and heroin
◦ drugs were "decriminalized," not "legalized.”
◦ drug possession for personal use and drug usage
itself are still legally prohibited
 FINES BUT NOT JAIL
◦ trafficking still a criminal offense