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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.
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