Opiates Lesson 18 Opiates Alkaloids l from opium

Opiates Lesson 18

Opiates Alkaloids l from opium poppy n Opium extract l 0. 5% codiene l 20% morphine n ualter structure heroin Opioids: synthetic analogs (texts) n Major effects: Analgesia & Euphoria ~ n

Opiate Family Large family of drugs l neuropeptides l morphine is prototype n Difference is potency l compare to morphine = 1 ~ n

Relative Potency Opiate Potency Morphine Methadone Propoxyphene (Darvon) Codeine Meperidine (Demerol) Oxycodone (Oxycontin, Percodan) Heroin Fentanyl 1 1. 05. 1. 1. 75 3 -4 80 ~

Pharmacokinetics n Route: sc, im, iv l p. o. not as effective uion trapping u 1 st pass metabolism n Significant brain levels: 30 -60 min l immediate euphoria? l Conditioned effects ~

Pharmacokinetics Half-life: about 3 hrs n Duration of effects: 4 -5 hrs l then withdrawal begins n Heroin: crosses BBB more easily n udiacetylmorphine biotransformed into morphine n Codiene: l 10% transformed to morphine ~ l

Opiate Effects Analgesia n Euphoria n Respiratory Depression n Narcosis n udrowsiness ~

Opiate Effects n Antitussive uinhibits coughing Constipation n Impotence & reduced libido n Reduced aggression & social interaction l opioid role in social bonds n Alters food intake, BT, etc. ~ n

Opioid Receptors n n Areas Mapped (1970 s) Pain Pathways: l Periaqueductal Gray (PAG), l Dorsal Horn Spinal Cord l Also: u. Hypothalamus u. G. I. Tract, u. Limbic System (VTA, Nucleus Accumbens) u. Medulla ~

Opioid Receptors 2 d messenger systems n Open K+ channels l hyperpolarization n Close Ca++ channels l decreased NT release n Inhibits adenylyl cyclase l c. AMP ~ n

Opioid Receptors: Subtypes n m (mu) m 1 – supraspinal & spinal analgesia l m 2 – respiration, HR, euphoria n d (delta) l Modulates m analgesia, positive RFT n k (kappa) l spinal analgesia, pain perception l sedation, dysphoria, hallucinations l gut motility, body temperature ~ l

Endorphins Peptide Family: l Hormones, Neuromodulators & NTs n b -Endorphin n Met- & Leu-Enkephalin n Dynorphin ~ n

Euphoria & Reward n Ventral Tegmental Area (VTA) l opioid neurons l dopamine neurons l GABA neurons? uhypothesized GABA inhibits DA neurons n Opioids inhibit GABA neurons ~ n

Nucleus Accumbens VTA Opioid GABA - - DA

Other Opioid-Mediated Behaviors Social Bond Formation n Various abnormal behaviors l Schizophrenia l Infantile Autism l Self-Mutilation ~ n

Opiate Problems High Dependence Liability l Positive & Negative Reinforcer l Withdrawal Symptoms n Tolerance & Cross Tolerance l Different rates for various effects l Euphoria: fast l Respiratory depression: slow ~ n

Opiate Dependence: Treatment 2007 National Survey on Drug Use and Health: heroin use / oxycodone l past year: 366, 000 / 1. 4 million l past month 153, 000 / 369, 000 n Methadone Treatment l taken p. o. l half-life about 36 hrs l euphoria & blocks withdrawal l develop methadone dependence ~ n

Opiate Dependence: Treatment n LAAM: L-alpha-acetylmethadol u(Orlaam) half-life 2 -6 days l slightly more treatment dropouts l not recommended for women of childbearing age *Buprenorphine (Subutex) l craving *Buprenorphine + naloxone (Suboxone) l craving & rewarding effects ~ l n n