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Opiates. Lesson 17. Opiates. Alkaloids from opium poppy Opium extract 0.5% codiene 20% morphine alter structure heroin Opioids: synthetic analogs (texts) Major effects: Analgesia & Euphoria ~. Opiate Family. Large family of drugs neuropeptides morphine is prototype
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Opiates Lesson 17
Opiates • Alkaloids • from opium poppy • Opium extract • 0.5% codiene • 20% morphine • alter structure heroin • Opioids: synthetic analogs (texts) • Major effects: Analgesia & Euphoria ~
Opiate Family • Large family of drugs • neuropeptides • morphine is prototype • Difference is potency • compare to morphine = 1 ~
Relative Potency Opiate Potency Morphine 1 Methadone 1 Propoxyphene (Darvon) .05 Codeine .1 Meperidine (Demerol) .1 Oxycodone (Oxycontin, Percodan) .75 Heroin 3-4 Fentanyl 80 ~
Pharmacokinetics • Route: sc, im, iv • p.o. not as effective • ion trapping • 1st pass metabolism • Significant brain levels: 30-60 min • immediate euphoria? • Conditioned effects ~
Pharmacokinetics • Half-life: about 3 hrs • Duration of effects: 4-5 hrs • then withdrawal begins • Heroin: crosses BBB more easily • diacetylmorphine • biotransformed into morphine • Codiene: • 10% transformed to morphine ~
Opiate Effects • Analgesia • Euphoria • Respiratory Depression • Narcosis • drowsiness ~
Opiate Effects • Antitussive • inhibits coughing • Constipation • Impotence & reduced libido • Reduced aggression & social interaction • opioid role in social bonds • Alters food intake, BT, etc. ~
Opioid Receptors • Areas Mapped (1970s) • Pain Pathways: • Periaqueductal Gray (PAG), • Dorsal Horn Spinal Cord • Also: • Hypothalamus • G. I. Tract, • Limbic System (VTA, Nucleus Accumbens) • Medulla ~
Opioid Receptors • 2d messenger systems • Open K+ channels • hyperpolarization • Close Ca++ channels • decreased NT release • Inhibits adenylyl cyclase • cAMP ~
Opioid Receptors: Subtypes • m(mu) • m1 – supraspinal & spinal analgesia • m2 – respiration, HR, euphoria • d (delta) • Modulates m analgesia, positive RFT • k (kappa) • spinal analgesia, pain perception • sedation, dysphoria, hallucinations • gut motility, body temperature ~
Endorphins • Peptide Family: • Hormones, Neuromodulators & NTs • b -Endorphin • Met- & Leu-Enkephalin • Dynorphin ~
Euphoria & Reward • Ventral Tegmental Area (VTA) • opioid neurons • dopamine neurons • GABA neurons? • hypothesized • GABA inhibits DA neurons • Opioids inhibit GABA neurons ~
Opioid - GABA - VTA Nucleus Accumbens DA
Other Opioid-Mediated Behaviors • Social Bond Formation • Various abnormal behaviors • Schizophrenia • Infantile Autism • Self-Mutilation ~
Opiate Problems • High Dependence Liability • Positive & Negative Reinforcer • Withdrawal Symptoms • Tolerance & Cross Tolerance • Different rates for various effects • Euphoria: fast • Respiratory depression: slow ~
Opiate Dependence: Treatment • 2007 National Survey on Drug Use and Health: heroin use / oxycodone • past year: 366, 000 / 1.4 million • past month 153,000 / 369,000 • Methadone Treatment • taken p.o. • half-life about 36 hrs • euphoria & blocks withdrawal • develop methadone dependence ~
Opiate Dependence: Treatment • LAAM: L-alpha-acetylmethadol • (Orlaam) • half-life 2-6 days • slightly more treatment dropouts • not recommended for women of child-bearing age • *Buprenorphine (Subutex) • craving • *Buprenorphine + naloxone (Suboxone) • craving & rewarding effects ~