呼吸道用藥及藥理作用

							     9Narcotics
      Opioids




藥理學科E501
  詹銘煥
     You have to think…
 How do opioids work in your body?


 Why do human beings like to abuse opioids?


 Does your body release opioid-like substances?
              Learning Objectives
 Describe the principal pharmacological effects of
  narcotics and their main therapeutic uses.
 Identify the major side effects of narcotics.
 Describe the association of AIDS with heroin abuse.
 Describe narcotic dependence, tolerance, addiction,
  & withdrawal symptoms.
 Describe how designer drugs have been associated
  with narcotics.
                  Key Terms
 Narcotic: a CNS depressant that produces
  insensibility or stupor
 Analgesics: drugs that relieve pain without
  affecting consciousness
 Opioid: relating to the drugs that are derived from
  opium
 Antitussive: drugs that block coughing
 Speedballing: combining heroin and cocaine
          The history of narcotics

 Opium in antiquity in the eastern Mediterranean
  area
 Opium in China & Asia
 American opium use:
 Morphine was used to treat pain,
& fatigue during the Civil War.
"The Poppy Goddess,
Patroness of Healing" is
about three feet high
with three poppies in the
front of her tiara. Some
"archeologists speculate
that this female deity,
crowned with poppy
pods, presided over an
opium-smoking cult on
Crete over 3,5000 years
ago."
      Opium use in China & Asia
 The opium poppy probably reached China about
  the 7th century A.D. through the efforts of Arab
  traders.
 Opium War from 1839 to 1842.
 The importation of opium from India to China
  continued to increase until 1908.
 Opium use in Taiwan (Formosa).
 Opium Poppy Cultivation in Southeast Asia.
 Golden Triangle region of Southeast Asia
                                In 1839 China
                                attempted to halt the
                                illegal importation of
                                opium by British
                                merchants. Britain
                                responded by
                                bombing Canton
Opium smoking in China (1858)   (Guangzhou), shown
                                here. Britain won the
                                battle easily, and
                                China was forced to
                                cede the island of
                                Hong Kong to Britain.
1882 engraving of the British opium warehouse in Patna, India
In 1900 a new
Government Opium
Factory was completed
in Taihoku and equipped
with the latest facilities.
In 1922 this factory was
producing around 50,000
kg of prepared opium
and 4,000 kg of
morphine.
Unpacking opium cases at the Government Opium Factory in
                    Taihoku (Taipei)
Opium smoker, northern Thailand.




                                   Shan heroin refinery in Thailand
Opium Poppy Cultivation in
     Southeast Asia
  Opium Poppy Cultivation and
Heroin Processing in Southeast Asia
The Golden Triangle Area of Mainland Southeast Asia is ideally
suited for the cultivation of opium poppy. Although the poppy
plant will grow remarkably well in this climate, soil, and humidity
with little to no effort, farmers in this region, nonetheless, expend
a considerable amount of time and effort caring for their crop.
Poppy farmers typically spend 6 months of the year in their poppy
fields, nurturing and safeguarding their family’s primary cash
crop. In contrast, the synthesis of heroin from opium takes only a
day or two. But heroin chemists or, more precisely, heroin “cooks,”
in Mainland Southeast Asia must possess a higher level of
knowledge and skills than the poppy farmers who produce the
opium. In addition, the owners and operators of such heroin
laboratories must provide an elaborate support system of cash,
armed protection, chemicals, equipment, transportation, and
access to reliable wholesale heroin buyers.
             American opium use
 Morphine was used via hypodermic syringe to treat pain,
  dysentery, & fatigue during the Civil War.
 Opiate addition: soldier’s or army disease
 By 1900, 1 million Americans were dependent on opiates.
 In 1914, the Harrison Narcotic Act was passed.
 Heroin, heroic drug, was as a cough suppressant by
  Bayer in 1898. It was banned from U.S. in 1924.
 During the Vietnam War, 40% of the U.S. soldiers used
  heroin.
 Heroin smoking became popular in the mid-1980s in
  response to AIDS epidemic.
  Pharmacological effects
Narcotic analgesics (morphine): they are
 potent analgesics against almost all type of
 pain
Antitussives (codeine): they suppress the
 coughing center of the brain
Respiratory depression
Miosis: pinpoint pupil
Euphoria:
GI tract: constipation; to relieve diarrhea
Emesis: morphine stimulates the
 chemoreceptor trigger zone in postrema
             Side effects
Severe respiratory depression
Constipation
Drowsiness, mental clouding
Nausea, vomiting, itching
Blood pressure drop
Abuse, tolerance, dependence, &
 withdrawal
Schedule classification of narcotics
Heroin              I
Morphine            II
Methadone           II
Fentanyl              II
Meperidine            II
Buprenorphine          II
Pentazocine            IV
Codeine                 II, III, IV
Narcotics combined with NSAIDs
                   Heroin abuse
 Heroin combination: quinine (bitter taste), alcohol, cocaine
 Heroin addicts: death occur by overdoses; combined with
  alcohol or barbiturates; infected with AIDS or hepatitis
 Heroin and crime: antisocial behavior
 Patterns of heroin abuse: adolescents and young adults
 Methods of administration: sniffing, injecting, smoking,
  snorting
 Heroin addicts and AIDS
 Heroin and pregnancy
 Withdrawal symptoms:
Short- & long-term effects of heroin use

 Short-term effects:
   "Rush“, depressed respiration, clouded mental
  functioning, nausea and vomiting, suppression of
  pain, spontaneous abortion

 Long-term effects:
 Addiction, infectious diseases, for example,
  HIV/AIDS & hepatitis B and C, collapsed veins,
  bacterial infections, infection of heart lining and
  valves, arthritis and other rheumatologic problems
     Symptoms of withdrawal from
     heroin, morphine, & methadone

 Craving for drugs; anxiety
 Yawning打呼, perspiration出汗, running nose, tears
 Pupil dilation, muscle twitches, aching bones &
  muscles, loss of appetite
 Insomnia, raised BP, fever, nausea
 Curled-up position, vomiting, diarrhea, foot kicking
  Treatment of heroin dependence
 Stops using heroin
 No longer associates with dealers or users of
  heroin
 Avoids dangerous activities associated with heroin
  use
 Improves employment status
 Refrains from criminal activity
 Is able to enjoy normal family and social
  relationship
              Other Narcotics
 Morphine:
 Methadone:
 Fentanyls: >200X potency of morphine
 Hydromorphone: an analgesic and cough suppressant
 Oxycodone: a moderate narcotic analgesic
 Meperidine: 1/10 potency of morphine
 Buprenorphine: to treat narcotic abuse & dependence
 Codeine: treatment of moderate pain & cough
 Pentazocine: slighter potent than codeine
 Propoxyphene: ½ potency of codeine
 MPTP: a designer tragedy, Parkinson-like disease
                      Morphine
 It relieves moderate to intense pain since it was first
  isolated in 1803.
 Analgesic potency:
 Heroin : morphine : codeine=24 : 12 : 1
 Side effects: constricted pupils, respiratory arrest,
  drowsiness, constipation, nausea, blurred vision, etc
 The first exposure of morphine is unpleasant, with
  nausea & vomiting, followed euphoric response in
  continual use.
 Tolerance
 The effects of heroin and morphine are almost identical.
                    Methadone
 It was first synthesized in Germany in 1943, World War
  II.
 Its physiological effects are the same as those of
  heroin and morphine
 Treatment of narcotic withdrawal and dependence
 Psychological dependence, tolerance, and then
  physical dependence and addition if repeated use
 Methadone reduces the cravings associated with
  heroin use and blocks the high from heroin, but it does
  not provide the euphoric rush.
 Its longer action and a less intense withdrawal
  response.
      Narcotic-related drugs
 Dextromethorphan: treatment of cough
 It is mixed with drugs such as alcohol, cocaine, &
 amphetamine, to give unusual psychoactive
 interactions.
 Clonidine: anti-hypertension
 It relieves some of the physical effects of opiate
 withdrawal (vomiting & diarrhea).
 Naloxone/naltrexone: narcotic antagonists
 Naloxone is a useful antidote in the treatment of
 narcotic overdoses.
Dextromethorphan produces a feeling of
disassociation or intoxication, but its abuse can lead
to psychotic behavior. In the long term, overdose of
DM can cause depression, memory problems, &
suicidal tendencies.
Naloxone has an extremely high affinity for μ-opioid
receptors in the central nervous system. Naloxone is a μ-
opioid receptor competitive antagonist, and its rapid
blockade of those receptors often produces rapid onset of
withdrawal symptoms. Naloxone also has an antagonist
action, though with a lower affinity, at κ- and δ-opioid
receptors.
Opium smuggling didn’t just make money. At times, opium
was money. Opium built empires and had a hand in financing
much of the world’s infrastructure.