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2001 pharmacology 10th lecture
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2001 pharmacology 10th lecture

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2001 pharmacology 10th lecture Presentation Transcript

  • 1. Neuropharmacology of CNS & Substance Abuse
    • Story of MPTP (1-methyl-4-phenyl 1,2,3,5-tetrahydropyridine)
    • Monoamine oxidase (MAO) in astrocytes
    • Oxidative phosphorylation
  • 2. Anatomy of the nervous system
    • Neurons
    • Interstitial cells
      • Astrocytes
      • Oligodendrocytes, Neurolemma, Schwan cells
    • Myelin Sheaths
    • Nodes of Ranvier
    • Anterograde, Retrograde, Microtubules
    • Motor proteins
    • Kinesin, Dynein
    • Microglials, phagocytic cells macrophage/monocyte
  • 3. Morphological considerations
    • Nutritional and biochemical aspects
    • Brain-blood-barrier
    • Tight junctions, Endothelial
    • Anoxic or hypoglycemic
  • 4. The Synapse
    • Three elements: Presynaptic, Postsynpatic, Synaptic cleft
    • 4 steps: 1. synthesis storage; 2. transmitter release; 3. receptor activation; 4. neurotransmitter inactivation
  • 5. Specific neurotransmitter system
    • Acetylcholine
      • Muscarinic,
      • Nicotinic
    • Glutamate- excitatory
      • AMPA, Kainate, NMDA
    • GABA - inhibitory
      • Subtype A and B
    • Glycine- inhibitory, Spinal cord, strychnine
  • 6. Substance abuse
    • Background
      • main types of abused drugs Table
      • no insulin or penicillin "junkies"
  • 7. Tolerance
    • diminishing drug effect following repeated administration. Higher doses are needed to produce the same effect.
    • May be pharmacokinetic or pharmacodynamic tolerance
    • pharmacokinetic : induction of hepatic metabolic enzymes e.g. barbiturates;
    • pharmacodynamic: alteration at receptor levels e.g. decrease of GABA receptors followed by increase of barbiturate administration; morphine and its receptor.
    • Tolerance may be developed only one effect of the drug but not the others; e.g. in opiates, euphoric and analgesic effects are tolerated but the respiratory depression is not.
  • 8. Cross-tolerance means that individuals tolerant to one drug will be tolerant to other drugs in the same class, but not to drugs in other class. Cross-tolerance
  • 9. Drug dependence
    • signs and symptoms upon withdrawal when drug levels fall
  • 10.
      • 1. opiates inhibits the firing of locus ceruleus (LC) neurons by interacting with  receptors.
      • 2. long term opiate administration causes molecular adaptations in the signaling properties of neurons.
      • 3. decrease signaling; without decreasing the numbers or affinity of the receptors.
      • 4. cAMP cascade is up-regulated,  phosphorylation of a slow depolarizing Na + channel,  neuronal excitability.
      • 5. hyper-excitable state becomes manifested when withdrawn
    drug dependence with opiates
  • 11.
    • withdrawal symptoms vary with drugs. barbiturates, alcohol, possible death
    • cross-dependence : drug A that show cross-tolerance with drug B of the same class also support the dependence of B .
  • 12. Caffeine
    • competitive antagoinst of adenosine receptors
    • sedative
    • caffeine is an addicting drug because it shows reinforcement and its withdrawal induces symptoms: headache, drowsiness, fatigue, decreased performance, depression
  • 13. Methadone maintenance
    • opiate agonist, analgesic, to replace the addict's heroine
    • maintenance basis (same dose, chronic use), withdrawal basis (gradually reducing dose, 1-6 months)
  • 14.
    • cocaine,
      • HCl, freebase, crack, 1-2 min peak CNS effects
      • dopamine receptor agonists
  • 15. Addiction Liability
    • animal behavior paradigm self-administer
    • Table of Addiction risk of major psychoactive drugs
    • reward pathway center, dopaminergic neurons ventral tegmental area; forebrain,
    • euphoria reinforcement cycle
  • 16. War on drugs
    • a perceived threat, moral principle
    • Table. Number of yearly drug-related deaths
    • Tobacco, Alcohol >> Cocaine, Heroine, Aspirin
  • 17. Descriminalization
    • Netherlands, soft and hard drugs coffee shop 4.6% use cannabis vs 4.8% in U.S.
  • 18. Drugs in Sports
    • Background
      • not drug abuse but illicit use of banned substances
    • History
      • Scandinavian warriors, muscarine, psychoactive alkaloids
      • 1800s amphetamine, strychnine and ephedrine commercially available
      • IOC ban (1) substances of selected groups; (2) doping methods.
      • rationales : clearly enhanced performance, medical safety, social acceptability
  • 19. Stimulants
    • amphetamine, cocaine and strychnine
    • delay onset of fatigue
    • caffeine, phenylpropanolamine, ephedrine
    • problem for legitimate health medication
      • Rick DeMont episode
    • alternatives salbutamol terbutalin by inhaler only
  • 20. Narcotics
    • morphine, pain killers, alternative
    • OTC cold cough remedies contain dextromethorphan
  • 21. Anabolic agents
    • anabolic androgenic steroids (AAS) testosterone and its derivatives
    • treatment bone marrow failure anemias
    • moderately high dose  gain 13 lbs pure muscle
    • side effects females masculinization low vocie
    • use of AAS in international sports competitions
    • urine test testosterone:epitestosterone T:E ratio
    •  -2 agonist asthma relief clenbuterol
    • livestock industry growth promote
      • drug treated meat
        • Alekey Petrov story
  • 22. Diuretics
    • urine excretion conceal evidence of the misuse of drugs
    • rapid weight loss
    • weight classes boxing wrestling
    • masking agents probenecid prevent secretion of AAS
    • epitestosterone T:E ratio
    • absolute level : no more than 200 ng/ml
  • 23. Miscellaneous drugs
    •  - blockers ,  blood pressure
    • cardiac output, hypertension, cardiac arrythmia, angina
    • shooting archery
    • chorionic gonadotropin  androgenic steorids
    • testosterone 
    • corticotropin (adrenal stimulatory trophic hormone) corticosteroids
    • erythropoetin (EPO) red blood cell production blood samples
  • 24. Blood doping
    • oxygen-carrying capacity
    • technique
    • withdrawing 1 liter blood, store frozen 9-12 weeks
    • hemoglobin return, reintroduce
  • 25. 俗稱或快樂丸的毒品事實上屬於安非他命的衍生物, 英文叫作 MDMA(3,4-methylenedioxy-methamphetamine) 或 Ecstasy. 搖頭丸是在 1914 年,由德國默克 (E. Merk) 公司合成為減肥藥用途, 後來發現此藥最主要作用與興奮劑及迷幻效藥物類似。 因此,未能上市。直到了 1980 年,雖然 FDA 未能通過, 卻有不少此類藥物,被用來作精神治療的輔助劑。 自從 1983 年起,搖頭丸逐漸的被美國大學生廣泛的使用。 美國政府乃在 1985 年,加以立法管制。 國內自 1990 年起安非他命廣泛流行後, 最近幾年來在舞廳及,才開始流行搖頭丸。 事實上市面上販售的搖頭丸有些不只含有 MDMA 的成份, 更有添潻加甲基安非他命及安非他命、或咖啡因等成份‧會增加其毒性作用。 搖頭丸
  • 26. commonly abused benzodiazepines drugs such as Flunitrazepam (FM2 ), Diazepam (Valium), Triazolam (Halcion), Lorazepam, and Oxazepam Flunitrazepam (FM2 )
  • 27. RU468 abortion drug, anti-progesterone effect
  • 28.
    • 望找到的資料是老師所要的 ...
    • 白 板 :
    • 來源:屬禁用之安眠鎮靜類製劑。
    • 性狀:主成分為 Methaqualone(Mandrax) 甲口奎酮,白色結晶性粉末製成錠劑。
    • 醫藥用途 : 沒有
    • 濫用方式:口服。常被混在酒精、鎮定劑、可待因及大麻中服用。
    • 毒害:抑制中樞神經,成癮者服用後感到高潮式快感,隨之有平靜祥和感,發生感覺異常及異常出血現象、流鼻血、白血球稀少及再生不良性貧血等致命併發症。為達更大快感,增加劑量後產生之中毒現象如:全身痙攣式抽搐、肌張力增加、瞳孔放大、發抖、支氣管分泌及唾液增多,肺水腫。造成低血壓、呼吸抑制、休克現象,如未及時急救會導致死亡。停藥三至五天後產生頭痛、噁心、厭食、腹絞痛、發抖、失眠等禁斷症候。