Drugs for the Treatment of Heroin Addiction

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Drugs for the Treatment of Heroin Addiction

• Karina Garrett
• CHEM 5398
• April 6, 2006

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What is heroin?

• Heroin is an opioid, derived from the opium poppy
• Chemical name diacetylmorphine
• Morphine, the active ingredient in opium, is
  substituted with two acetyl units

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Effects of heroin

• Positive effects
• Heroin's main effect is a sense of euphoria
• Also, flushing of the skin and heavy extremities
• The onset of these effects differs based on the
  method of administration
• Smoked/snorted 10-15 min
• Injected 7-10 seconds
• The sense of euphoria lasts for several hours
• Negative effects
• Drowsiness and mental cloudiness
• Nausea and vomitting
• Itchy skin
• Slowed breathing and cardiac function

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History of heroin

• Originally created by the Bayer company in 1895
  as an alternative to morphine
• 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

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How heroin works

• 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.

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How heroin works

• Three analgesic receptors where morphine
  interacts (as an agonist)
• µ-receptor
• ?-receptor
• d-receptor
• Receptors located non-uniformly throughout
  Central Nervous System
• Cerebral cortex has most
• Spinal cord has significantly less
• Morphine reacts differently at each receptor site
• At µ-receptor, morphine binds most strongly
  causes euphoria and negative side effects
  causes addiction!
• At ?-receptor, morphine binds less strongly
  cause sedation and analgesic effect without
  negative side effects
• At d-receptor, morphine binds strongly causes
  analgesic effect

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Receptors

• µ-receptor - changes shape after morphine
• binds, opens up a
• K ion channel

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Receptors

• ?-receptor
• changes shape after morphine binds, closes Ca2
  ion channel

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Receptors

• d-receptor
• G-protein-linked when morphine binds, causes
  fragmentation of G-protein, no cAMP produced
  (necessary for pain transmission)

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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.

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Drugs used in the United States

• Methadone
• Levo-alpha-acetyl-methadol (LAAM)
• buprenorphine
• naltrexone

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Methadone

• History
• Created during World War II in Germany as a
  morphine substitute
• In 1960s 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

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Methadone

• How it works
• 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

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Methadone

• Methadone is folded to
• fit into the opioid receptor
• Controls cravings by keeping receptors active
  without producing euphoria

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Drugs used in the United States

• Methadone
• Levo-alpha-acetyl-methadol (LAAM)
• buprenorphine
• naltrexone

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Levo-alpha-acetyl-methadol

• Similar to methadone
• Agonist
• Controls cravings without producing a sense of
  euphoria
• Long-lasting
• Methadone 24-48 hours
• LAAM 72 hours

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Levo-alpha-acetyl-methadol

• History
• First produced in 1948 as an analgesic
• Studies from 1952 showed it was effective at
  suppressing opiate withdrawal symptoms
• Studies from the 70s 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 70s, LAAM was approved by the FDA in
  1993

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• How it works
• Metabolized in liver to nor-LAAM and dinor-LAAM
• Both have slower metabolism times than LAAM
• Causes the long-lasting effect
• Acts using the same mechanism as methadone

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Levo-alpha-acetyl-methadol

• Problems and questions
• No travel dosage is allowed
• Methadone is given for emergency travel
• Not enough information on the effect of using
  LAAM during pregnancy
• Currently, the FDA suggests pregnant women switch
  to methadone

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Drugs used in the United States

• Methadone
• Levo-alpha-acetyl-methadol (LAAM)
• Buprenorphine
• Naltrexone

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Buprenorphine

• Partial agonist
• Controls cravings
• Still some sense of euphoria
• Safer than heroin
• Not as addictive, little risk of overdose
• Longer-lasting than methadone, not as long as
  LAAM
• 24-60 hours
• Lowest category drug for treatment of heroin
  addiction (cat. III)
• Easier than methadone to escape dependency

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Buprenorphine

• History
• 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

• How it works
• 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)
• Prevents overdose
• Helps lower addictiveness not as high of a high

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Buprenorphine

• Problems and Questions
• There is little information on the effect of
  buprenorphine on pregnant women
• A few cases have showed no problems
• The withdrawal effects are not completely masked
  by buprenorphine
• They are much milder

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Drugs used in the United States

• Methadone
• Levo-alpha-acetyl-methadol (LAAM)
• Buprenorphine
• Naltrexone

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Naltrexone

• 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

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Naltrexone

• History
• Approved by the FDA in 1984 for opioid treatment
• Approved by the FDA in the last five years for
  alcoholism treatment

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Naltrexone

• How it works
• 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

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Naltrexone

• Problems and Questions
• Not used in pregnant women
• 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
• High relapse numbers
• Australia research

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Naltrexone

• The Australian Medical Procedures Research
  Foundation has started a new and revolutionary
  treatment plan
• Starts with rapid de-tox
• Naltrexone implants to maintain steady level

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Rapid de-tox

• 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
• Drugs include
• Narcan removes all opioids from receptors
• Naltrexone blocks receptors

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Naltrexone implants

• 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

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Results

• 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
• No withdrawal post-natal

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References
www.opioids.com www.drugabuse.gov www.health.org b
uprenorphine.samhsa.gov www.drugs.com