zhang xiu-mei department of pharmacology, school of medicine, sdu e-mail: zhangxm@sdu

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Zhang Xiu-mei Department of Pharmacology, School of Medicine, SDU E-mail: zhangxm@sdu.edu.cn Tel: 88383146. Drug Dependence and Abuse. Conflict of Interest. I have no financial relationships or support from commercial interests to disclose. Case - ecstasy. - PowerPoint PPT Presentation

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  • Zhang Xiu-meiDepartment of Pharmacology, School of Medicine, SDUE-mail: zhangxm@sdu.edu.cnTel: 88383146

    * Drug Dependence and Abuse

  • I have no financial relationships or support from commercial interests to disclose. *Conflict of Interest

  • Sarah J, a vivacious 17-year-old, went out with her friend James on a Friday night, to meet other friends, drink and dance, and have a good time before the end-of-year examinations. Everything went well until around midnight, when Sarah took two ecstasy pills. As short time after that, she started feeling ill and dizzy. The temperature in the club had been high, and Sarah kept drinking alcoholic drink and a lot of water, to compensate for the dehydration caused by hours of dancing. About 3 am, she felt sick and vomited several times, complaining of a terrible headache. James took her to a friends house nearby, for a rest, but Sarahs state deteriorated rapidly. She kept vomiting, and drifted in and out of consciousness. James and his friends took her to hospital around 6 am. and phoned her parents. The doctors immediately suspected intoxication with ecstasy, and her blood Na+ level (123mmol/L) confirmed their suspicion. After a day in hospital, her situation remained critical and the consultant expressed reserved optimism as to her survival. Sarahs state gradually started improving the next day. James is puzzled, and explained that she only took some ecstasy pills, as usual, and cannot see the harm in it. He argues that it was only a little bit of fun, and that neither he nor Sarah have done any stuff like cocaine, as some of his old friends do. *Case - ecstasy

  • 1. What has led to Sarahs critical state after her use of ecstasy?2. Is ecstasy a safe drug and what differentiates it from cocaine?3. What is the incentive that leads to the use of life-threatening drugs?4. Is it correct to assume that there are hard and unsafe drugs of abuse, in contrast to light and generally safe drugs?5. What treatment saved Sarahs life after admission to hospital?

    *Questions

  • Objectives1. Terms related to the drug dependence and abuse. 2. Classifications of the dependence-potential drugs.3. The harm and major symptoms of dependence and withdrawal of drug.4. The main mechanisms of drug dependence. 5. The principles of treatment for drug addiction.*Drug Dependence and Abuse

  • Refers to drug induced adaption in cells and tissues after prolonged use, which lead to the need to continue drug intake. A characteristic of drugs on central nervous system (including inhibitors and stimulants of CNS).

    (1)Drug dependence*1. Terms Related to Drug Dependence and Abuse.

  • The compulsion of humans to use certain substances in order to get a general feeling of wellbeing and pleasure, to relieve sadness or induce euphoria, or to avoid uncomfortable feeling of withdrawal.*WHO Expert Committee(1964)

  • (WHO)*Drug dependence

  • An adaptive physiological state produced by repeated use of a drug, which is characterized by occurring abstinence syndromes (withdrawal syndromes) if drug administration is stopped. *(2)Physical/physiological dependence

  • (abstinence syndrome) DiarrheaVomitingChills FeverLacrimation RhinorrheaTremorAbdominal cramps Pain*

  • The feeling of satisfaction and psychic drive that require periodic or continuous administration of the drug to produce a desired effect or to avoid discomfort.(craving)Euphoria: rush and high.Some times people have habituation to nicotine and alcohol.

    *(3)Psychic (psychological) dependence

  • Refers to a compulsion to take a drug, with loss of control over drug-taking.Dependence to some drugs.Including physical and psychical dependence.*(4)Addiction

  • No medical use of dependence-potential drugs., Stop use abstinence syndrome compulsive drug-seeking behavior abuse.*(5)Drug abuse ()

  • Refers to the necessity to escalate the dose of drug in order to obtain the same effects as those obtained initially.*(6)Tolerance

  • (1)Death by acute poising.

    15*2.The Harm of Drug Abuse

  • *Drug taking

  • Bacteria

    tetanus. *(2)Infections by pathogens

  • 30HIVHIV1526978978877HIV *(3) Acquired immune deficiency syndrome, AIDS

  • *4On production of woman and newborn

  • (cold turkey): 5-HT*Newborn

  • * (5)On family and children

  • * On family and children

  • *(6)On the society

  • *

  • (1) Narcotic drugsa. Opioids (a)Natural opium and its phenanthrenes components:morphine codeine*3.Classifications of Dependence-potential Drugs

  • Powdered dried exudate of the fruit capsule (opium)*

  • Is it a beautiful flower or a poison ?Papaver somniferum( )*

  • *

  • *

  • *

  • 2010% Greek mythologySleepiness*

  • Dried juice of the unripe seed capsule of the poppy: opium*

  • Opium

  • 1803F.W. SerturnerMorphus *Morphus

  • PoppyOpiumBrown poulticesNatural Compounds Morphine, CodeineSynthetic Compounds Pethidine, fentanyl*Opioid analgesics

  • Morphine CH3CH3COCH3COCH2CH=CH2Opioids structure Codeine (1832, methyl-morphine) Heroin (1874, acetomorphine)Nalorphine Antitussive, euphoria More hydrophobic Drug abuse, addiction More hydroxyl groups, more hydrophilic*Opioid receptor antagonist

  • *

  • *

  • Opioids(b)Artificial synthetic and semi-syntheticsHeroine ()Pethidine ()Methadone()Fentanyl () Dihydroetophine(, DHE)

    *

  • *Heroin

  • *

  • b. CocainesCocaine base(), cocaine hydrochloride(), coca leaf()coca paste().leaf*Narcotic drugs

  • c. Cannabis()Preparation of cannabis from India are called marihuanathe effective component is 9-tetrahydrocannabinol(9-9-THC).*Narcotic drugs

  • a. Sedative-hypnotics and antianxiety drugsBarbituratesBenzodiazepinesRefers to acting on CNS, exciting or inhibiting, dependence may induced by repeated use.*2Psychotropic substances

  • Amphetamine Methamphetamine, 3,4-methylenedioxymethamphetamine, , ecstasyc. HallucinogensLysergic acid diethylamide , LSD

    b. Psychostimulants*

  • TobaccoAlcoholVolatile organic solventsPhencyclidine, PCPNMDA agonist.Ketamine(K)

    d. Others*

  • Since 80th last century, designer drugs were occurred from narcotic derivatives by changing structure, more effective and toxic. PethidineFentanyl Amphetamine analogues*(3)New trends for drugs

  • Drugs Molecular targetsOpiates and receptorsBZs and barbiturates GABAA receptorCocaine and amphetamine monoamine transporterMarijuana(cannabis) CB1 receptorNicotine N receptorEthanol GABAA and NMDA receptorPhencyclidine NMDA receptorInhalants not knownMDMA(ecstasy) 5-HT transporter

    *Examples of drugs abuse

  • (1)Craving and compulsive drug-seeking behaviorrush and high*4. Manifestations of Drug Dependence

  • AdaptabilityAbstinence syndrome*(2) Abstinence syndrome

  • *Abstinence syndrome!

  • (1) Reinforcement and rewardReinforcementReinforcer: *5. Brain Reward System and Drug Dependence

  • (reward)(reward effect)(brain reward system)a. Positive reinforcer *

  • b. Negative reinforcer *

  • DA*VTAGABADADADADA D1D2Brain reward system, VTA, NAC, PF

  • (locus ceruleus)NANANA*

  • nucleus accumbensreward area pleasure center (2)The neurobiological basis of reinforcement *

  • *The neurobiological basis of reinforcement

  • *(ventral tegmental area, VTA)( nuclues accumbens, NAC) (prefrontal cortex, PF)(amygdala) globus pallidus and the ventral mouth, VP dorsal hippocampus, DH) central gray, CG(lateral hypothalamus, LH)cingulate gyrusThe neurobiological basis of reinforcement

  • a. (CG)(VTA)(DH)(NAC)(LH)(PF)(AMG)VTANAC*The neurobiological basis of reinforcement

  • GABAGABA(VTA)DADA*

  • b. (PF) (VTA)(N AC) c. (NAC) d. (VTA)e. (VTA)*VTANAC

  • DA(NE, 5-HT)DADADAMAO

    *Coca cola brain tonic and cure for all nervous afflictions till 1904. The major cause of stroke and heart attacks in people under the 35 in USA.

  • (1) D2(2) D1D2D1(3)The receptor mechanism of reinforcement *

  • D2D1*

  • 1. Opiods 2. Cocaine DA3. Aphetamine DADAMAO DA*6.The Mechanism of Drug Dependence

  • 4. Ethanol Activates DA mesolimbic system in VTA, increase nucleus accumbens DA release, stimulate D2 receptor.5-HT3, GABA and NMDA may involved. Ethanol increases the inhibitory effects of GABA, and decrease the stimulatory effect of glutamate.5. Sedative-hypnotics GABA*The Mechanism of Drug Dependence

  • 6. Cannabis acts on its receptorsCB1 and CB2 receptors, endogenous ligand is anandamide. CB1 receptor found in neocortex, hippocampus, basal ganglia, cerebellum, thalamus, hypothalamus, midbrain, medulla and spinal cord. Activation of CB1 receptor leads inhibition of N- and P