Opium CultivationHistory of OpiumMorphineHeroinOpioid Abuse Before Harrison ActOpioid Use After Harrison ActHeroin Use in VietnamHeroin Production and PurityAbuse of Prescription OpioidsOpioid Chemical CharacteristicsPrescription Narcotic AnalgesicsMechanism of ActionOpioid AntagonistsBeneficial UsesDependence PotentialTolerancePhysical dependencePsychological dependenceOpioid Withdrawal SymptomsToxicity PotentialAcute toxicityChronic toxicityLife of a Heroin UserMisconceptionsChapter 13: Opioids - Opium is a naturally occurring substance derived from the poppy plant Papaver somniferum Opium has a 6,000-year history of medical use- Opioids are either: Drugs derived directly from opium or Synthetic drugs with opium-like effects- Major effects of opioids: relieves pain and suffering delivers pleasure and relief from anxietyOpium Cultivation- Opium is collected for only a few days of the plant’s life- Opium harvesters make shallow cuts into the unripe seedpods The resinous substance that oozes from the cuts is scraped and collected- Opium products Morphine extracted from raw opium Heroin is derived from morphineHistory of Opium- Egypt 1500 BC: Ebers papyrus described medical uses- Greece Had an important role in medicine- Arabic world Opium used as a social drug Physicians wrote widely about use of opium and described opioid dependence- Europe Opium used widely beginning in the sixteenth century Physicians developed a preparation called laudanum, a combination of strained opium and other ingredients- Writers and Opium 1821: Thomas De Quincey “Confessions of an English Opium-Eater” Elizabeth Barrett Browning and Samuel Taylor Coleridge famously used opium- The Opium Wars 1729: Opium smoking outlawed in China But smuggling was widespread- British East India Company was involved in opium trade Legally in India and illicitly (but indirectly) in China- Pressure grew and eventually war broke out between the British and ChineseMorphine- Morphine is the primary active ingredient in opium First isolated in 1806 Named morphium after Morpheus, the god of dreams 10 times as potent as opium- Codeine is a secondary active alkaloid First isolated in 1832 Named codeine from the Greek word for “poppy head” - Morphine use spread due to two developments Technological development:o 1853: Hypodermic syringe allowed delivery of morphine directly into the blood- Political development:o Widespread use during war provided relief from pain and dysentery Veterans returned dependent on morphine Dependence was later called “soldier’s disease” or “army disease” Heroin- Heroin = diacetylmorphine 1874: two acetyl groups were attached to morphine 1898: marketed as Heroin (brand name) by Bayer- Three times as potent as morphine due to increased lipid solubility of the heroin molecule- Originally Marketed as a non-addictive cough suppressant Replacement for codeine and morphine Later linked to dependenceOpioid Abuse Before Harrison Act- Three types of opioid dependence in the U.S.:1. Oral intake via patent medicines2. Opium smoking mostly by Chinese laborers3. Injection of morphineo the most dangerous form of use- % of population dependent on opioids Peaked at the start of 20th century Possibly as high as 1% of the population- Initially, opioid dependence was not viewed as a major social problem Opium smoking was limited to certain ethnic groups Patent medicines were socially acceptable Opioid dependence was viewed as a “vice of middle life”- Typical user: 30-to-50-year-old middle class white woman Drugs purchased legally in patent medicinesOpioid Use After Harrison Act- Enforcement of the 1914 Harrison Act made opioids difficult to obtain Only sources of drugs were illegal dealers- Resulted in changes in opioid use patterns Oral use declined Primary remaining group of users were those who injected morphine or heroin Cost and risk of use increasedo Thus, the most potent method (intravenous injection of heroin) was favored  Addicts were looked upon as criminals rather than as victims- After WWII Use of heroin increased in low-income areas of large cities- The 1960s and 70s Heroin use further increased in large cities Heroin use was associated with minority populations In New York, users were prosecuted under the Rockefeller Drug Lawso Strictest drug laws in U.S.Heroin Use in Vietnam- Heroin in Vietnam was relatively Inexpensive Pure Easy to obtain- About 5% of personnel tested positive for opioids Due to the purity, most users smoked or sniffed the drug Most users stopped when they returned to the U.S.- Vietnam experience showed  Under certain conditions, a relatively high percent of individuals will use opioids recreationally Opioid dependence is not inevitable among occasional users Heroin Production and Purity- Most of the heroin used in the U.S. is derived from poppies grown in Mexico and Colombia- Purity of heroin has increased dramatically in recent years 1970s: purity was 5% 1980s: 25% Currently: 40–60%- Important note: few Americans use heroin 0.2% report past-year use Abuse of Prescription Opioids- Popular prescription opioids Hydrocodone (Vicodin, Lortab) Oxycodone (Oxycontin, Percocet)- Prevalence of use: 2010: 12 million Americans reported past year use Routes of administration include oral, insufflation, injection- Safety concerns: DAWN data: prescription opioids rank 3rd for ER visits and 1st for deaths Most opioid overdoses occur in combination with other sedatives such as alcoholOpioid Chemical Characteristics- Narcotic agents isolated or derived from opiumPrescription Narcotic Analgesics- Natural products Morphine Codeine- Semisynthetics Heroin- Synthetics Methadone Meperidine Oxycodone Oxymorphone Hydrocodone Hydromorphone Dihydrocodeine Propoxyphene Pentazocine Fentanyl Mechanism of Action- Naturally occurring opioid-like neurotransmitters Enkephalins: morphinelike neurotransmitters found in the brain and adrenals Endorphins: morphinelike neurotransmitters found in the brain and pituitary gland- Endogenous opioids and opioid drugs are agonists of several types of opioid receptors mu and kappa (play a role in pain perception) delta (function not well understood)Opioid Antagonists- Drugs that block the action of opioids