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Parkinson’s DiseasePRESENTED BY:                    GUIDED BY:Prafulla Chandra Tiwari         Mr. Rupesh GautamM.Pharm (1s...
PARKINSONS DISEASE (PD)Clinical Overview. Parkinsonism is aclinical syndrome consisting of fourcardinal features: bradykin...
EtiologyThe most common cause ofparkinsonism is idiopathic PD, firstdescribed by James Parkinson in 1817as paralysis agita...
Progressive loss of dopamine-containing neurons is a feature ofnormal aging; however, most peopledo not lose the 70% to 80...
Pathophysiology. The primary deficit inPD is a loss of the neurons in thesubstantia nigra pars compacta thatprovide dopami...
The current understanding of thepathophysiology of PD can be tracedto neurochemical investigations thatdemonstrated a redu...
The current understanding of thepathophysiology of PD can be tracedto neurochemical investigations thatdemonstrated a redu...
This paralleled the loss of neurons fromthe substantia nigra, suggesting thatreplacement of dopamine couldrestore function...
Dopamine Synthesis and Metabolism.Dopamine, a catecholamine, issynthesized in the terminals ofdopaminergic neurons from ty...
Dopamine Receptors.The actions of dopamine in the brainare mediated by a family ofdopamine-receptor proteins. Two types of...
The five dopamine receptors can bedivided into two groups on the basis oftheir pharmacological and structuralproperties . ...
The D2, D3, and D4 receptors share alarge third intracellular loop and are ofthe D2 class. They decrease cyclic AMPformati...
The D1 and D2 proteins are abundant inthe striatum and are the mostimportant receptor sites with regard tothe causes and t...
Neural Mechanism of Parkinsonism.Considerable effort has been devotedto understanding how the loss ofdopaminergic input to...
The basal ganglia can be viewed as amodulatory side loop that regulates theflow of information from the cerebralcortex to ...
The basal ganglia can be viewed as amodulatory side loop that regulates theflow of information from the cerebralcortex to ...
The neostriatum is the principal inputstructure of the basal ganglia andreceives excitatory glutamatergic inputfrom many a...
A small but important subgroup ofstriatal neurons consists of interneuronsthat connect neurons within thestriatum but do n...
The outflow of the striatum proceedsalong two distinct routes, termed thedirect and indirect pathways. Thedirect pathway i...
The indirect pathway is composed ofstriatal neurons that project to theglobus pallidus externa (GPe). Thisstructure, in tu...
The dopaminergic neurons of thesubstantia nigra pars compacta (SNpc)innervate all parts of the striatum;however, the targe...
The striatal neurons giving rise to thedirect pathway express primarily theexcitatory D1 dopamine receptorprotein, whereas...
Thus dopamine released in the striatumtends to increase the activity of thedirect pathway and reduce theactivity of the in...
TREATMENT OF PARKINSONS DISEASE
Parkinson's disease ppt
Parkinson's disease ppt
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Transcript of "Parkinson's disease ppt"

  1. 1. Parkinson’s DiseasePRESENTED BY: GUIDED BY:Prafulla Chandra Tiwari Mr. Rupesh GautamM.Pharm (1st sem) Lecturer Pharmacology Jaipur College of pharmacy
  2. 2. PARKINSONS DISEASE (PD)Clinical Overview. Parkinsonism is aclinical syndrome consisting of fourcardinal features: bradykinesia(slowness and poverty of movement),muscular rigidity, resting tremor (whichusually abates during voluntarymovement), and an impairment ofpostural balance leading todisturbances of gait and falling .
  3. 3. EtiologyThe most common cause ofparkinsonism is idiopathic PD, firstdescribed by James Parkinson in 1817as paralysis agitans, or the "shakingpalsy." The pathological hallmark of PDis a loss of the pigmented,dopaminergic neurons of thesubstantia nigra pars compacta, withthe appearance of intracellularinclusions known as Lewy bodies.
  4. 4. Progressive loss of dopamine-containing neurons is a feature ofnormal aging; however, most peopledo not lose the 70% to 80% ofdopaminergic neurons required tocause symptomatic PD.
  5. 5. Pathophysiology. The primary deficit inPD is a loss of the neurons in thesubstantia nigra pars compacta thatprovide dopaminergic innervation tothe striatum (caudate and putamen).
  6. 6. The current understanding of thepathophysiology of PD can be tracedto neurochemical investigations thatdemonstrated a reduction in thestriatal dopamine content in excess of80%.
  7. 7. The current understanding of thepathophysiology of PD can be tracedto neurochemical investigations thatdemonstrated a reduction in thestriatal dopamine content in excess of80%.
  8. 8. This paralleled the loss of neurons fromthe substantia nigra, suggesting thatreplacement of dopamine couldrestore function. These fundamentalobservations led to an extensiveinvestigative effort to understand themetabolism and actions of dopamineand to learn how a deficit in dopaminegives rise to the clinical features of PD.
  9. 9. Dopamine Synthesis and Metabolism.Dopamine, a catecholamine, issynthesized in the terminals ofdopaminergic neurons from tyrosineand stored, released, and metabolized
  10. 10. Dopamine Receptors.The actions of dopamine in the brainare mediated by a family ofdopamine-receptor proteins. Two types of dopamine receptorswere identified in the mammalian brainusing pharmacological techniques: D1receptors, which stimulate the synthesisof the intracellular second messengercyclic AMP, and D2 receptors, whichinhibit cyclic AMP synthesis as well assuppress Ca2+ currents and activatereceptor-operated K+ currents.
  11. 11. The five dopamine receptors can bedivided into two groups on the basis oftheir pharmacological and structuralproperties . The D1 and D5 proteinshave a long intracellular carboxy-terminal tail and are members of theclass defined pharmacologically as D1;they stimulate the formation of cyclicAMP and phosphatidyl inositolhydrolysis.
  12. 12. The D2, D3, and D4 receptors share alarge third intracellular loop and are ofthe D2 class. They decrease cyclic AMPformation and modulate K+ and Ca2+currents. Each of the five dopaminereceptor proteins has a distinctanatomical pattern of expression in thebrain.
  13. 13. The D1 and D2 proteins are abundant inthe striatum and are the mostimportant receptor sites with regard tothe causes and treatment of PD. The D4and D5 proteins are largely extrastriatal,whereas D3 expression is low in thecaudate and putamen but moreabundant in the nucleus accumbensand olfactory tubercle.
  14. 14. Neural Mechanism of Parkinsonism.Considerable effort has been devotedto understanding how the loss ofdopaminergic input to the neurons ofthe neostriatum gives rise to the clinicalfeatures of PD .
  15. 15. The basal ganglia can be viewed as amodulatory side loop that regulates theflow of information from the cerebralcortex to the motor neurons of thespinal cord.
  16. 16. The basal ganglia can be viewed as amodulatory side loop that regulates theflow of information from the cerebralcortex to the motor neurons of thespinal cord
  17. 17. The neostriatum is the principal inputstructure of the basal ganglia andreceives excitatory glutamatergic inputfrom many areas of the cortex. Mostneurons within the striatum areprojection neurons that innervate otherbasal ganglia structures..
  18. 18. A small but important subgroup ofstriatal neurons consists of interneuronsthat connect neurons within thestriatum but do not project beyond itsborders. Acetylcholine andneuropeptides are used as transmittersby these striatal interneurons
  19. 19. The outflow of the striatum proceedsalong two distinct routes, termed thedirect and indirect pathways. Thedirect pathway is formed by neurons inthe striatum that project directly to theoutput stages of the basal ganglia, thesubstantia nigra pars reticulata (SNpr)and the globus pallidus interna (GPi);these, in turn, relay to theventroanterior and ventrolateralthalamus, which provides excitatoryinput to the cortex.
  20. 20. The indirect pathway is composed ofstriatal neurons that project to theglobus pallidus externa (GPe). Thisstructure, in turn, innervates thesubthalamic nucleus (STN), whichprovides outflow to the SNpr and GPioutput stage.
  21. 21. The dopaminergic neurons of thesubstantia nigra pars compacta (SNpc)innervate all parts of the striatum;however, the target striatal neuronsexpress distinct types of dopaminereceptors
  22. 22. The striatal neurons giving rise to thedirect pathway express primarily theexcitatory D1 dopamine receptorprotein, whereas the striatal neuronsforming the indirect pathway expressprimarily the inhibitory D2 type.
  23. 23. Thus dopamine released in the striatumtends to increase the activity of thedirect pathway and reduce theactivity of the indirect pathway,whereas the depletion that occurs inPD has the opposite effect.
  24. 24. TREATMENT OF PARKINSONS DISEASE
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