Opiates: History and Treatment Options

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Opiates History and Treatment Options

• West Virginia UniversitySchool of Medicine Ehab
  S. Abdallah M.D

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General Terms

• Narcotics A general term technically referring
  to an opiate - related or opiate -derived drugs.
  It is often mistakenly used to include several
  other illicit drug categories as well.
• Opium An analgesic and euphoriant drug acquired
  from the dried juice of the opium poppy.
• Opiates Any ingredients of opium or chemical
  derivatives of these ingredients. Opiate
  generally refer to opium, morphine, codeine,
  thebaine and Heroin.

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• Synthetic opiates Synthetic drugs unrelated to
  morphine that produce opiate like effects.
• Codeine One of the three active ingredients in
  opium, used primarily to treat coughing.
• Morphine One of the three major active
  ingredients in opium.
• Thebaine One of the three major active
  ingredients in opium.
• Heroin A chemical derivative of morphine. It
  is approximately three times as potent as
  morphine and a major drug of abuse

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Opium
Opiates
Morphine
Codeine
Thebaine
Opiate Derivatives
Heroin
Hydromor- phone (Dilaudid)
Oxymorphine (Numorphan)
Oxycodone (Percondan)
Etorphine
Synthetic Opiates
Methadone
Meperidine (Demerol)
Propoxy- phene (Darvon)
LAAM (Orlaam)
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Opium in History

• The source is the opium poppy. Known by its
  potential name as papaver somniferum (literally
  the poppy that brings sleep.)
• Opium is harvested by a small shallow incision in
  the capsules allowing a milky white juice to ooze
  out.
• Opium was first described in specific detail in
  the third century B.C. but we can be fairly sure
  that it was used for at least a thousand years
  before that.

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• Egyptians were knowledgeable about the medicinal
  value of opium evidence of this was found in the
  Ebers Papyrus writings.
• In the second century A.D., Claudius Galen, the
  famous Greek physician and surgeon to Roman
  gladiators recommended opium for everything.
• Western Europe was introduced to opium in the
  eleventh and twelfth centuries from returning
  crusaders who learned of it from the Arabs.
• In 1520, a physician named Paracelsus introduced
  a medicinal drink containing opium, wine and an
  assortment of spices. He called the mixture
  Laudanum (Derived from Latin meaning something
  to be praised) .

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• In 1680, the English physician Thomas Sydenham,
  considered the father of clinical medicine,
  introduced a highly popular version of an opium
  drink called Syndenhams Laudanum.
• For the next 200 years or so, the acceptable form
  of taking opium among Europeans and Americans
  would be in the form of a drink, either
  Sydenhams recipe or variations.

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The Opium War

• Sometime in the eighteenth century, China
  invented a novel form of opium use, opium
  smoking, which eventually became synonymous in
  the Western mind with China itself.
• In the eighteenth century the British people had
  fallen in love with Chinese tea.
• British merchants wanted to buy tea and send it
  home, but what could they sell to the Chinese in
  exchange?
• The problem was that there were few, if any,
  commodities that China really wanted from the
  outside.
• In Chinese eyes, the rest of the world was
  populated by barbarians with inferior cultures
  offering nothing or little the Chinese people
  needed.
• The answer was the opium. In 1773 British forces
  has conquered Bengal province in India and
  suddenly had a monopoly on raw opium.
• It was now easy to introduce opium to China as a
  major item of trade

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• Opium was successfully smuggled into China
  through local British and Portuguese merchants,
  allowing the British government and its official
  trade representative, the East India Company, to
  carry off the public image of not being directly
  involved in opium trade.
• Opium, flooding into the country from its
  southern part of Canton, found a ready market,
  opium dependence soon became a major Chinese
  problem.
• Despite repeated efforts by the Chinese emperor
  to reduce the use of opium within China or to cut
  the supply line from India, the monster
  flourished.
• By 1839, the tension had reached a peak. In a
  historic act of defiance against the European
  powers, including Britain, an imperial
  commissioner appointed by the Chinese emperor to
  deal with the opium problem once and for all
  confiscated a huge quantity of opium and burned
  it publicly in Canton.
• Events escalated shortly after this until open
  fighting between Chinese and British soldiers
  broke out. The opium war had begun.

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• By 1842, British artillery and warships had
  overwhelmed a nation unprepared to deal with
  European firepower. In a humiliating treaty,
  China was forced to sign over to Britain the
  island of Hong Kong and its harbor (until the
  distant year of 1997), granting to British
  merchants exclusive trading rights in major
  Chinese ports, and pay a large amount of money to
  the British losses during the war.
• Despite these agreements, fighting broke out
  again between 1858 and 1860 this time British
  soldiers were joined by the French and Americans.
• Finally in a treaty signed in 1860, China was
  required to legalize opium within its borders.
• The opium war had succeeded in opening up the
  gates of China, much against its will, to the
  rest of the world.
• (The Opium War from the Chinese perspective.)

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Opium in Britain

• The acceptable form of opium use in Victorian
  England was opium drinking in the form of
  laudanum.
• The Oriental practice of opium smoking was
  identified by the British with vice and
  degradation and associated with the very lowest
  fringes of society.
• Opium in the mid-1800s was the aspirin of its
  day. There was no negative public opinion and
  seldom any trouble with the police.

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• Any opium addict, as long as there were no signs
  of opium smoking, was considered no worse than a
  drunkard.
• Dozens of laudanum based medicines, with
  appealing names like
• A penny worth of peace
• Mrs. Winslows Soothing Syrup,
• Were used to dull teething pain or colic, or to
  keep children quiet.
• In 1821, Thomas DeQuincey published his book,
  Confessions of an English Opium Eater, that
  created a new cultural phenomenon for
  recreational opium use.

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Opium in the United States

• Opium consumption in the U.S. paralleled its
  widespread use in Britain.
• Opium poppies were cultivated in Vermont and New
  Hampshire, in Florida and Louisiana, and later in
  California and Arizona.
• Women outnumbered men in opium use during the
  1800s by as much as three to one.
• Alcohol drinking was not an acceptable behavior
  for females but laudanum was. The consequence
  was that husbands drank alcohol in the saloons
  wives took opium at home.

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• Opium was advertised as a treatment of alcohol
  addiction, white star secret liquor cure was
  designed to be added to a gentlemens
  after-dinner coffee.
• 1850s-1860s
• Thousands of Chinese men and boys were brought to
  the West to build the railroads.
• Most of the Chinese workers were recruited from
  the Canton area where opium traffic was
  particularly intense.
• The practice of opium smoking was well known to
  them.

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• In 1875 San Francisco outlawed opium smoking, a
  federal law forbidding opium smoking soon
  followed.
• The Harrison Act of 1914 required that physicians
  registered with the Internal Revenue Service the
  opiate drugs that were being prescribed to their
  patients and pay a small fee for the right to
  prescribe such drugs.
• In the 1920s, the U.S. Supreme Court interpreted
  the Harrison Act more widely. Under the Courts
  new interpretation of the Harrison Act, no
  physician was permitted to prescribe opiate drugs
  for non-medical use.

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• In 1803, a German clerk named Friedrick Serturner
  First isolated a yellowish-white substance in raw
  opium turned to be its primary active ingredient.
  He called it morphium, later changed to
  morphine, in honor of Morpheus, the Greek god of
  dreams.
• In 1898, heroin was introduced into the market by
  the Bayer Company in Germany as a new pain
  killer. It is the same company that had been
  successful in the development of aspirin.

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Symptoms of administering heroin and of
withdrawing heroin

• Administering
• Lowered body temperature
• Decreased blood pressure
• Skin flushed and warm
• Papillary constriction
• Constipation
• Respiratory depression
• Decreased sex drive
• Muscular relaxation
• Nodding, stupor

• Withdrawing
• Elevated body temperature
• Increased blood pressure
• Piloerection (gooseflesh)
• Tearing, runny nose
• Diarrhea
• Yawning, panting, sneezing
• Spontaneous ejaculations and orgasms
• Restlessness, involuntary twitching and kicking
  movements
• Insomnia

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Street names for narcotic drugs

• Type of Narcotic
• Morphine
• White heroin
• Brown heroin (from Mexico)
• Heroin combined with amphetamines
• Heroin combined with cocaine
• Heroin combined with marijuana
• Heroin combined with cocaine and marijuana
• Heroin combined with cocaine and morphine
• Codeine combined with Doriden (a nonbarbiturate
  sedative-hypnotic)

• Street Name
• Big M, Miss Emma, white stuff, M, dope, hocus,
  unkie, stuff, morpho
• Junk,smack, horse, scag, H, hard stuff, dope,
  boy, boot, blow, jolt, spike, slam
• Black tar, tootsie roll, chapapote (Spanish for
  tar), Mexican mud, peanut butter, poison, black
  jack
• Bombitas
• Dynamite, speedball, whizbang, goofball
• Atom bomb, A-bomb
• Frisco special, Frisco speedball
• Cotton brothers
• Loads, four doors, hits

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Common Opiate Agents of Abuse

• Generic Name
• Morphine
• Heroin
• Codeine
• Methadone
• Meperidine
• Butorphanol
• Hydromorphone
• Nalbuphine

• Trade Name(s)
• Astromorph, PF, Duramorph, Epimorph, Kadian,
  Infumorph 200500, morphitec, M.O.S., MS Contin,
  MSIR, OMS Concentrate, Oramorph SR, RMS, Roxanol,
  Rescudose, Ultraject
• --------
• Codeine
• Dolophine, Methadose
• Demerol, Pathadol, Pethidine
• Stadol
• Dilaudid
• Nubain
• Darvon, Dolene, Novapropoxyn

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• Exogenous opiate drugs act on opiate receptors in
  the brain. Researchers theorize that these
  opiate receptors exist in order to facilitate the
  action of the bodys endogenous opiate like
  substances known as endorphine and enkaphalin
  (natural morphine).
• Exogenous opiate drugs function as agonist to the
  brain opiate receptors, turning on the natural
  analgesic pathway in the brain and producing the
  characteristic analgesia and euphoria sensation
  that in susceptible individuals reinforces drugs
  and propels the addiction.
• Habitual opiate use, while turning on the
  pain-suppression pathway, causes the normal
  endogenous opiate system to decrease the
  production of endorphin and enkephalin.

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• Repetitive use of exogenous opiates also produces
  adaptation of the opiate receptors, rendering
  them less sensitive to agonist actions.
• This Down-Regulation of the receptors requires
  larger amounts of the drug to produce similar
  effects, a phenomena called tolerance, and
  produces withdrawal symptoms when the receptors
  are not under agonist effect.

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Treatment Options

• Methadone
• Clonidine (Alpha-adrenergic receptor agonist)
• Ultra rapid detox
• Methadone maintenance
• LAMM (Levo-alpha-acetylmethadol).

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Rapid Detox

• Substance abuse and dependency is a major public
  health concern in the United States because of
  the economic and human costs.
• Current drug abuse treatment approaches,
  developed primarily during the 1960s and
  1970s, have changed very little since their
  inception. The changes that have occurred in
  treatment in the last decade have been primarily
  structural and have been propelled by the tide of
  managed care reforms rather than the emergency of
  treatment models.

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• Managed care and cost-containment polices have
  affected substance abuse treatment by decreasing
  the type and intensity of services, shifting
  treatment from in-patient and residential care to
  out-patient settings.
• Eighty-seven percent of patients are now treated
  in out-patient programs (substance abuse and
  Mental Health Services Administration, 1996).

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The Development of New Models of Treatment

• Substantive advancements have occurred in our
  understanding of the genetic and biochemical
  basis of substance abuse and addiction in the
  last 10 years. Yet little of this information has
  been translated into alternative treatment models
  for the addicted patient.
• Abstinence remains the goal of traditional
  addiction treatment.
• Sudden cessation of opioid use causes predictable
  cascade of symptoms collectively referred as
  withdrawal symptoms as previously mentioned.

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• Medically supervised detoxification treatment has
  traditionally been seen as the golden standard
  and as the logical starting point of treatment.
• Traditional detox has involved treatment with
  prescription medications, which produces similar
  physiological responses, less psycho-activation,
  and which can be more precisely regulated and
  tapered as the patients metabolism readjusts to
  functioning without the addictive drugs.
• Traditional detox takes an average of 3 to 15
  days, depending on the abused drug.
• Medical detox controls but does not eliminate
  subjectively uncomfortable withdrawal symptoms.
  

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• Universally accepted addiction treatment
  approaches are beginning to be challenged by the
  emergence of innovative treatment approaches
  based on the new understanding of the
  neurochemistry of addiction.
• Rapid detox has emerged as an alternative that is
  gaining in both acceptance and popularity,
  evidence by recent showcasing in television
  episodes of E.R.
• Rapid detox is an umbrella term that has come to
  represent new treatment approaches specifically
  designed to detox patients addicted to natural
  and synthetic opiate drugs within hours rather
  than the traditional days and to almost
  completely eliminate the subject of discomfort of
  withdrawal symptoms.
• Started in Europe in the late 1980s and brought
  to the United States in late 1996.

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Common trade names for rapid detox treatment
programs

• Rapid detox (RO)
• Neuroregulated detox
• Neuro-adaptation treatment
• OADUSA (opioid antagonist agent detox under
  sedation or anesthesia)
• IND (intensive narcotic detox)
• UROD (Ultra-rapid opiate detox)
• RAND (rapidly accelerated narcotic detox)
• KIYSR (kick in your sleep rapid relief)

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Rapid Detox

• Rapid detox procedures has been done by employing
  two novel approaches.
• First, general anesthesia is to ensure no
  subjective distress is felt.
• Second, use of large dosages of opiate antagonist
  in order to rapidly and completely remove the
  exogenous opiate drugs from the opiate receptors
  in the brain.
• Because patient can not feel no subjective
  distress from withdrawal, detox can be completed
  within few hours (4-6) rather than 3 to 15 days
  with traditional detox.

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• It is important to differentiate between
• Rapid detox, similar to traditional detox
  strategies, but patient receives more sedation
  than usual during the withdrawal .sedation is
  accomplished through the use of benzodiazepines
  and can decrease the time of withdrawal by a day
  or two. The sedation is done to minimize the
  subjective distress of withdrawal symptoms
  allowing detox to progress more rapidly.
• Ultra-rapid detox. An approach using general
  anesthesia to induce complete unconsciousness,
  thus ensure complete comfort during detox.

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Procedures

• Rapid detox programs require either overnight
  monitoring or one day program where individuals
  checks-in early in the morning and leaves at the
  same day.
• All programs require pre-evaluation entails drug
  history, psychological evaluation, medical
  history and current health status evaluation.
• Start I.V. and induce general anesthesia.

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• Ultra-rapid detox (UROD) has become potent
  protected treatment name however literature still
  refer to it as rapid detox.

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• Most programs offering rapid detox require an
  anesthesiologist to be present to monitor the
  anesthesia and perform the procedure in the
  location (hospital) where emergency services are
  quickly available should complication arise.
• Once general anesthesia has been induced and no
  subjective withdrawal discomfort felt by the
  patient. opiate receptor blockade is accomplished
  with the use of opiate antagonist agents.
• Three common opiate antagonists exist
  Naltrexone, naloxone and nalmefene. By far
  naltrexone is the most widely used opiate
  antagonist during rapid detox.

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Comparison of Opiate Antagonist Agents
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• The opiate antagonists have competitive binding
  at opiate receptor level, washing out any
  exogenous opiates and assisting the receptors to
  begin to reestablish normal sensitivity.
• The amount of opiate antagonist required and
  therefore the length of time anesthesia must be
  maintained depends on patient weights and the
  duration and intensity of their addictions.
• Procedure average time 4-6 hours.
• A short recovery period should follow, including
  mild nausea and diarrhea.
• The patient is continued on the opiate antagonist
  agent, usually Naltrexone, as once a day oral
  dosage for 6 to 12 months.

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Treatment Indications

• Addiction to opiate agents
• Motivated for treatment
• No co-morbid health condition
• Failure of past traditional detox programs
• Normal liver function lab values
• Normal thyroid function lab values
• Limited cardiovascular risk factors.

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Treatment contraindications

• Poly-substance abuse to primarily non-opiates
• Little internal motivation
• Medically compromised or unstable
• No attempts at detox
• Liver disease
• Thyroid disease
• Cardiovascular disease.

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Advantages of ultra-rapid detox

• Minimizing the very clinical significant,
  subjectively distressing withdrawal symptoms of
  opiate addiction.
• Rapid detox occurs at the neuroreceptor level and
  affords the patient an opportunity to start
  intensive follow up immediately while feeling
  physically capable to engage in ongoing
  treatment.

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• Confidentiality can be facilitated when patients
  do not require protracted hospitalization, making
  treatment more acceptable to some.
• Continuous use of opiate antagonists post detox
  affords the patient a measure of protection
  against relapse and decreases cravings and
  increases the likelihood of successful treatment.

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Intensive follow up counseling is required after
the rapid detox to address needed lifestyle
changes, psychological factors and continued
abstinence.
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Disadvantages of ultra-rapid detox

• Risks related to general anesthesia use the risk
  of death associated with general anesthesia is 1
  in 250,000 and risk of adverse events rises to 1
  in 10,000.
• Rapid detox accomplishes medical detox or removal
  of the physiological effects of the opiate. It
  does little to affect the physiological
  withdrawal syndrome, and substantial
  psychological support and counseling are required
  for the patient to maintain a drug-free
  lifestyle.

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• Because rapid detox is considered experimental,
  insurance companies do not cover the cost.
• Lack of reliable and valid empirical studies
  regarding the efficacy of the treatment.