Welcome to Pharmacology     张岫美 山东大学医学院 药理学研究所 Welcome to Pharmacology
药 理 学   PHARMACOLOGY   张岫美 山东大学医学院 药理学研究所 [email_address]
CHAPTER  16 <ul><li>ANTIPARKINSONISM  DRUGS  </li></ul><ul><li>AND DRUG THERAPY IN  </li></ul><ul><li>ALZHEIMER’S  DISEASE...
Parkinson’s disease <ul><li>Parkinson’s disease (PD) </li></ul><ul><li>Features( paralysis agitants ) </li></ul><ul><li>Tr...
Pathogenesis(dopamine theory) <ul><li>Nigro-striatal(caudate nucleus,  </li></ul><ul><li>putamen and pallidum) </li></ul><...
 
Dopaminomimetic    Drugs Therapeutic    Drugs       Central anti-cholinergic    Drugs
Section 1    Dopaminomimetic Drugs   <ul><li>Levodopa ( L-dopa,  左旋多巴) Levodopa could penetrates into the brain, where it ...
Pharmacokinetics <ul><li>Absorption </li></ul><ul><li>Ready from small intestine, t max  0.5- </li></ul><ul><li>2 hrs, aff...
Pharmacokinetics <ul><li>2. Distribution and metabolism </li></ul><ul><li>about 1% through blood brain barrier by dopa dec...
Pharmacokinetics Decarboxylase   Levodopa  DA Liver 99%   1%  Decarboxylase   Blood-brain  DA  Barrier  Brain
Pharmacological Actions and Uses <ul><li>1.  Parkinson’s disease  </li></ul><ul><li>Levodopa  is  widely  used  for treatm...
Properties   <ul><li>(1)Most effective for mild and  </li></ul><ul><li>younger patients </li></ul><ul><li>(2)More effectiv...
Properties <ul><li>(3)Onset slow, 2-3 wks to effect, </li></ul><ul><li>1-6 months to E max </li></ul><ul><li>(4)No effecti...
Actions and Uses <ul><li>2. Hepatic coma </li></ul><ul><li>Levodopa metabolized to noradrenaline </li></ul><ul><li>to repl...
Adverse Reactions <ul><li>1. Gastrointestinal  Effects  </li></ul><ul><li>2. Cardiovascular  Effects  </li></ul><ul><li>3....
Drug Interactions   <ul><li>Carbidopa  VitB 6 </li></ul><ul><li>(-)  (+) </li></ul><ul><li>L-dopa  DA+R  Effects  </li></u...
Other dopaminomimetics <ul><li>Decarboxylase  inhibitors </li></ul><ul><li>Carbidopa (卡比多巴) </li></ul><ul><li>Benserazide ...
Amantadine ( 金刚烷胺 ) <ul><li>Mechanism of Action </li></ul><ul><li>1.↑release DA from dopaminergic  </li></ul><ul><li>termi...
Amantadine <ul><li>Clinical Uses </li></ul><ul><li>Parkinson’s disease, less effective than levodopa, and more effective t...
Adverse Reactions <ul><li>Livedo reticularis </li></ul><ul><li>Psychotic disorders </li></ul>
Bromocriptine ( 溴隐亭 )   Pergolide ( 培高利特 ) <ul><li>Large dose stimulate D 2  receptor in  </li></ul><ul><li>substantia nig...
Selegiline   <ul><li>MAO-B inhibitor and antioxidants </li></ul>
<ul><li>Section  2 Central Anticholinergic  Drugs </li></ul>
<ul><li>Actions   </li></ul><ul><li>Blocking the M-R ,↓cholinergic neurons  in the basal ganglia. </li></ul><ul><li>Benzat...
Drug Therapy in Alzheimer’s Disease <ul><li>Alzheimer’s disease ( AD )  3/4 </li></ul><ul><li>Vascular dementia ( VD )  1/...
Incidence <ul><li>>65y  3.0%~5.0%  </li></ul><ul><li>65~70y  3.0% </li></ul><ul><li>75~84y  19%  </li></ul><ul><li>>85y  4...
<ul><li>International  Symposium for Alzheimer’s Disease 2000  “If the effective methods for AD treatment is not found, th...
Clinical Features <ul><li>Dementia, cognition dysufficiency, behavioral disorder  </li></ul><ul><li>Pathological Features ...
Pathogenesis <ul><li>Neuron toxication of   amyloidβ-protein(Aβ,β- 淀粉样蛋白 )  。 </li></ul><ul><li>Aβ 可能是胆碱能神经系统高强度、高选择性的负性调节...
Therapy for AD <ul><li>1.Potentiate cholinergic function  AChEI 、 M-R agonists </li></ul><ul><li>2.Potentiator of neuronal...
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chapter 16

  1. 1. Welcome to Pharmacology   张岫美 山东大学医学院 药理学研究所 Welcome to Pharmacology
  2. 2. 药 理 学 PHARMACOLOGY   张岫美 山东大学医学院 药理学研究所 [email_address]
  3. 3. CHAPTER 16 <ul><li>ANTIPARKINSONISM DRUGS </li></ul><ul><li>AND DRUG THERAPY IN </li></ul><ul><li>ALZHEIMER’S DISEASE </li></ul>
  4. 4. Parkinson’s disease <ul><li>Parkinson’s disease (PD) </li></ul><ul><li>Features( paralysis agitants ) </li></ul><ul><li>Tremor, rigidity, akinesia and </li></ul><ul><li>bradykinesia(ataxia) </li></ul><ul><li>Parkinson’s syndrome </li></ul>
  5. 5. Pathogenesis(dopamine theory) <ul><li>Nigro-striatal(caudate nucleus, </li></ul><ul><li>putamen and pallidum) </li></ul><ul><li>DA neuronal degeneration </li></ul><ul><li>Dopaminergic neuron activity↓ </li></ul><ul><li>Cholinergic neuron activity↑ </li></ul><ul><li>Oxidative stress theory </li></ul>
  6. 7. Dopaminomimetic Drugs Therapeutic Drugs Central anti-cholinergic Drugs
  7. 8. Section 1 Dopaminomimetic Drugs <ul><li>Levodopa ( L-dopa, 左旋多巴) Levodopa could penetrates into the brain, where it is decarboxylated to dopamine. </li></ul>
  8. 9. Pharmacokinetics <ul><li>Absorption </li></ul><ul><li>Ready from small intestine, t max 0.5- </li></ul><ul><li>2 hrs, affected by gastric emptying, </li></ul><ul><li>gastric acid and amino acids </li></ul>
  9. 10. Pharmacokinetics <ul><li>2. Distribution and metabolism </li></ul><ul><li>about 1% through blood brain barrier by dopa decarboxylase to dopamine. </li></ul><ul><li>99% peripheral transfore to dopamine. </li></ul><ul><li>a little to melonnin, most metabolized </li></ul><ul><li>by COMT and MAO </li></ul><ul><li>3. Elimination kidney, t 1/2 1-3 hrs. </li></ul>
  10. 11. Pharmacokinetics Decarboxylase Levodopa DA Liver 99% 1% Decarboxylase Blood-brain DA Barrier Brain
  11. 12. Pharmacological Actions and Uses <ul><li>1. Parkinson’s disease </li></ul><ul><li>Levodopa is widely used for treatment of all type of Parkinsonism except that associated with antipsychotic drug therapy. </li></ul>
  12. 13. Properties <ul><li>(1)Most effective for mild and </li></ul><ul><li>younger patients </li></ul><ul><li>(2)More effective for rigidity and akinesia, less effective for tremor </li></ul>
  13. 14. Properties <ul><li>(3)Onset slow, 2-3 wks to effect, </li></ul><ul><li>1-6 months to E max </li></ul><ul><li>(4)No effective for Parkinson’s syndrome caused by phenothiazines. </li></ul>
  14. 15. Actions and Uses <ul><li>2. Hepatic coma </li></ul><ul><li>Levodopa metabolized to noradrenaline </li></ul><ul><li>to replace octopamine( false neurotransmitter theory) </li></ul>
  15. 16. Adverse Reactions <ul><li>1. Gastrointestinal Effects </li></ul><ul><li>2. Cardiovascular Effects </li></ul><ul><li>3. Abnormal involuntary movement “on-off” phenomena </li></ul><ul><li>4. Psychic disorders and epilepsy </li></ul>
  16. 17. Drug Interactions <ul><li>Carbidopa VitB 6 </li></ul><ul><li>(-) (+) </li></ul><ul><li>L-dopa DA+R Effects </li></ul><ul><li>Decarboxylase </li></ul><ul><li>(-) </li></ul><ul><li>Antipsychotic drugs </li></ul>
  17. 18. Other dopaminomimetics <ul><li>Decarboxylase inhibitors </li></ul><ul><li>Carbidopa (卡比多巴) </li></ul><ul><li>Benserazide (苄丝肼) </li></ul><ul><li>Compound Preparations </li></ul><ul><li>Sinemet (息宁 ) </li></ul><ul><li>Levodopa : Carbidopa (10 : 1) </li></ul><ul><li>Madopar (美多巴) </li></ul><ul><li>Levodopa : Benserazide (4 : 1) </li></ul>
  18. 19. Amantadine ( 金刚烷胺 ) <ul><li>Mechanism of Action </li></ul><ul><li>1.↑release DA from dopaminergic </li></ul><ul><li>terminals. </li></ul><ul><li>2.↓reuptake of DA. </li></ul><ul><li>3. dopamine receptor agonism </li></ul>
  19. 20. Amantadine <ul><li>Clinical Uses </li></ul><ul><li>Parkinson’s disease, less effective than levodopa, and more effective than anticholinergic agents. Effective for Parkinson’s syndrome caused by phenothiazines, synergized by l-dopa. Onset rapidly, 2 wks; Last short about </li></ul><ul><li>4-8 wks. </li></ul>
  20. 21. Adverse Reactions <ul><li>Livedo reticularis </li></ul><ul><li>Psychotic disorders </li></ul>
  21. 22. Bromocriptine ( 溴隐亭 ) Pergolide ( 培高利特 ) <ul><li>Large dose stimulate D 2 receptor in </li></ul><ul><li>substantia nigro-striatal </li></ul><ul><li>Small dose stimulate D 2 receptor in </li></ul><ul><li>tubero-infundibular, reduce PRL and GH </li></ul><ul><li>release </li></ul><ul><li>Used to treat PD and hyperprolactinemia </li></ul>
  22. 23. Selegiline <ul><li>MAO-B inhibitor and antioxidants </li></ul>
  23. 24. <ul><li>Section 2 Central Anticholinergic Drugs </li></ul>
  24. 25. <ul><li>Actions </li></ul><ul><li>Blocking the M-R ,↓cholinergic neurons in the basal ganglia. </li></ul><ul><li>Benzatropine ( 苯扎托品 ) </li></ul><ul><li>Trihexyphenidyl ( 苯海索 ) </li></ul><ul><li>Improve the tremor and rigidity of PD, little effect on bradykinesia . </li></ul>
  25. 26. Drug Therapy in Alzheimer’s Disease <ul><li>Alzheimer’s disease ( AD ) 3/4 </li></ul><ul><li>Vascular dementia ( VD ) 1/4 </li></ul>
  26. 27. Incidence <ul><li>>65y 3.0%~5.0% </li></ul><ul><li>65~70y 3.0% </li></ul><ul><li>75~84y 19% </li></ul><ul><li>>85y 47% </li></ul><ul><li>Course of disease: 3~20y </li></ul>
  27. 28. <ul><li>International Symposium for Alzheimer’s Disease 2000 “If the effective methods for AD treatment is not found, the AD patients will be 22 000 000 in 2025; 45 000 000 in 2050 in whole world.” </li></ul>
  28. 29. Clinical Features <ul><li>Dementia, cognition dysufficiency, behavioral disorder </li></ul><ul><li>Pathological Features </li></ul><ul><li>Senile plaque (SP, 老年斑 ) was found in brain , Neurofibrillary tangles (NFT, 神经元纤维缠结 ) and selective death of neuron. </li></ul>
  29. 30. Pathogenesis <ul><li>Neuron toxication of amyloidβ-protein(Aβ,β- 淀粉样蛋白 ) 。 </li></ul><ul><li>Aβ 可能是胆碱能神经系统高强度、高选择性的负性调节物 , AChE 对 Aβ 的神经毒性起重要的加强和易化作用。 </li></ul>
  30. 31. Therapy for AD <ul><li>1.Potentiate cholinergic function AChEI 、 M-R agonists </li></ul><ul><li>2.Potentiator of neuronal nutrition factor and neuron cell growth factor </li></ul><ul><li>3.Activator brain metabolism 吡拉西坦 </li></ul><ul><li>4.Drugs improving microcirculation 麦角类衍生物、都可喜等 </li></ul><ul><li>5.Calcium antagonists </li></ul>
  31. 32. SEE You !
  32. 33. Thank You !

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