Download Drugs for the Treatment of Heroin Addiction

Drugs for the Treatment
of Heroin Addiction
Karina Garrett
CHEM 5398
April 6, 2006
What is heroin?
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Heroin is an opioid, derived from the opium
poppy
Chemical name: diacetylmorphine
Morphine, the active ingredient in opium, is
substituted with two acetyl units
morphine
diacetylmorphine
Effects of heroin

“Positive” effects
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Heroin's main effect is a sense of euphoria
Also, flushing of the skin and heavy extremities
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The onset of these effects differs based on the method of
administration
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Smoked/snorted = 10-15 min
Injected = 7-10 seconds
The sense of euphoria lasts for several hours
Negative effects
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Drowsiness and mental cloudiness
Nausea and vomitting
Itchy skin
Slowed breathing and cardiac function
History of heroin
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Originally created by the Bayer company in 1895 as
an alternative to morphine
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It had the same effects as morphine without the negative
side effects of morphine, and was thought to be much safer
It was used as a step-down drug for morphine addicts
By 1905, heroin addiction had risen to alarming rates
In 1923, it became illegal to sell narcotics
The Heroin Act was passed in 1924, making it illegal
to manufacture or produce heroin
How heroin works
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Because of the two acetyl groups, heroin is
less polar than morphine
This allows heroin to cross the blood-brain
barrier with much greater effeciency
Once in the brain, heroin is converted to
morphine, and becomes “trapped” by the
barrier
The morphine interacts with receptors and
causes the effects.
How heroin works

Three analgesic receptors where morphine interacts (as an
agonist)
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Receptors located non-uniformly throughout Central Nervous
System
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µ-receptor
κ-receptor
δ-receptor
Cerebral cortex has most
Spinal cord has significantly less
Morphine reacts differently at each receptor site
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At µ-receptor, morphine binds most strongly – causes euphoria and
negative side effects – causes addiction!
At κ-receptor, morphine binds less strongly – cause sedation and
analgesic effect without negative side effects
At δ-receptor, morphine binds strongly – causes analgesic effect
Receptors

µ-receptor - changes shape
after morphine
binds, opens up a
K+ ion channel
Receptors
κ-receptor –
changes shape after morphine binds,
closes Ca2+ ion channel
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Receptors
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δ-receptor –
G-protein-linked –
when morphine
binds, causes
fragmentation of Gprotein, no cAMP
produced (necessary
for pain
transmission)
How users become addicted

The body cannot completely eradicate drugs.
It metabolizes them, and the metabolites get
stored in fatty tissue. When the fatty tissue is
broken down, the metabolites are released and
act on the brain again, causing a craving.
Drugs used in the United States
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Methadone
Levo-alpha-acetyl-methadol (LAAM)
buprenorphine
naltrexone
Methadone
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History
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Created during World War II in Germany as a
morphine substitute
In 1960’s Dr.’s Nyswander and Cole carried out
clinical trials for methadone treatment for heroin
addiction
Ten years of studies showed that methadone
eliminated withdrawal symptoms and cravings
Approved by the FDA for heroin addiction
maitenance treatment in 1972
Methadone
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How it works
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Methadone is broken down in the liver and stored
When the brain opiate receptors are ready,
methadone is mobilized and fills the receptors
Methadone is an agonist, so it works similar to
heroin, but does not produce the extreme highs and
lows
If patients are on blockade doses (70 mg), they can
go 2 days between doses
Methadone
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Methadone is folded to
fit into the opioid receptor

Controls cravings by keeping receptors active without
producing euphoria
Drugs used in the United States
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Methadone
Levo-alpha-acetyl-methadol (LAAM)
buprenorphine
naltrexone
Levo-alpha-acetyl-methadol
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Similar to methadone
Agonist
Controls cravings without producing a sense of
euphoria
Long-lasting
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Methadone =24-48 hours
LAAM = 72 hours
Levo-alpha-acetyl-methadol
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History
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First produced in 1948 as an analgesic
Studies from 1952 showed it was effective at suppressing
opiate withdrawal symptoms
Studies from the 70’s showed that LAAM is safe and
effective for heroin addiction treatment
After a decade of little research, the NIDA submitted for
FDA approval
After one final study, in addition to the studies from the
70’s, LAAM was approved by the FDA in 1993
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How it works
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Metabolized in liver to nor-LAAM and dinorLAAM
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Both have slower metabolism times than LAAM
Causes the long-lasting effect
Acts using the same mechanism as methadone
Levo-alpha-acetyl-methadol
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Problems and questions
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No travel dosage is allowed
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Methadone is given for emergency travel
Not enough information on the effect of using
LAAM during pregnancy
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Currently, the FDA suggests pregnant women switch to
methadone
Drugs used in the United States
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Methadone
Levo-alpha-acetyl-methadol (LAAM)
Buprenorphine
Naltrexone
Buprenorphine
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Partial agonist
Controls cravings
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Safer than heroin
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Not as addictive, little risk of overdose
Longer-lasting than methadone, not as long as LAAM
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Still some sense of euphoria
24-60 hours
Lowest category drug for treatment of heroin
addiction (cat. III)
Easier than methadone to escape dependency
Buprenorphine
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History
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In 1978, Dr. Donald Jasinski first suggested the possibility
of buprenorphine as a treatment for opiate addiction
Several studies over the next 15 years were conducted
A treatment plan was approved by the FDA in 2003
It included a buprenorphine pill during the initial tolerance phase
 The maintenance phase uses a different pill, containing
buprenorphine and naloxone
**Not all buprenorphine is approved for heroin addiction treatment!
Buprenorphine is not safe in an unsupervised setting!
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Buprenorphine
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How it works
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It is partial agonist, meaning it uses the same
mechanism as heroin, methadone, and LAAM
Metabolized in the liver to metabolites that are
more effective
The effects increase linearly, but only to a certain
dosage – after that, the effects plateau (the “ceiling
effect”)
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Prevents overdose
Helps lower addictiveness – not as high of a high
Buprenorphine
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Problems and Questions
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There is little information on the effect of
buprenorphine on pregnant women
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A few cases have showed no problems
The withdrawal effects are not completely masked
by buprenorphine
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They are much milder
Drugs used in the United States
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Methadone
Levo-alpha-acetyl-methadol (LAAM)
Buprenorphine
Naltrexone
Naltrexone
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Used mainly for alcoholism treatment
New method in other countries, currently
being researched in the United States
Opioid antagonist – blocks effect of opioids by
blocking receptors
Non-addictive
Naltrexone
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History
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Approved by the FDA in 1984 for opioid treatment
Approved by the FDA in the last five years for
alcoholism treatment
Naltrexone
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How it works
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Naltrexone is attached to the opioid receptors,
competitively inhibiting the attachment of opioids
to the receptors
Completely blocks euphoria feeling, but some still
feel nauseous
Naltrexone
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Problems and Questions
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Not used in pregnant women
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Why not?
No evidence showing harm to either mother or fetus
Studies have shown that patients taking naltrexone
rarely maintain the dosage prescribed by their
doctor
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High relapse numbers
Australia research
Naltrexone
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The Australian Medical Procedures Research
Foundation has started a new and
revolutionary treatment plan
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Starts with rapid de-tox
Naltrexone implants to maintain steady level
Rapid de-tox
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Rapid de-tox is a relatively new procedure
(began in 1997)
Patient is given some anesthesia and a drug
cocktail to rapidly remove all drugs from the
system
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Drugs include:
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Narcan – removes all opioids from receptors
Naltrexone – blocks receptors
Naltrexone implants
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Done to maintain natrexone levels over an
extended period of time
Naltrexone tablets are stacked in a
biodegradable tube
Inserted into the abdominal wall
Tablets dissolve slowly, exposing tablet
underneath
Usually three implants, which will last 12-18
months
Results
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The clinic statistics show that 95% of patients
remain opioid-free at the 6 month mark after
the treatment
This is significantly higher than with oral
naltrexone
Pregnancy is not an issue, and has been
showed to have many positive effects on the
baby
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No withdrawal post-natal
References
www.opioids.com
www.drugabuse.gov
www.health.org
buprenorphine.samhsa.gov
www.drugs.com