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52 Cards in this Set
- Front
- Back
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1. What is Parkinson's disease?
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Chronic and progressive degenerative disease of the CNS that impairs primarily the motor skills and speech of the individual who is affected
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2. What is Parkinson's characterized by?
Four things... |
1. Muscle rigidity
2. Tremor at rest 3. Slowing of physical movement (bradykinesia) 4. Loss of physical movement (akinesia) |
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3. What are the essential NT involved in parkinsonism?
How is the diagnosis of Parkinson's disease made? |
1. Dopamine
-present in substantia nigra 2. Possibly NE -present in locus coerulus Based on medical history and neurological examination |
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4. Presently what is the most effective treatment for this disorder?
What are the three parts of the motor system? |
Enhancing the dopaminergic system w/in the CNS
1. Pyramidal 2. Extra-pyramidal 3. Cerebellar subsystems |
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5. What is the characteristic of the extra-pyramidal component of the motor system?
What are the effects of a lesion here? |
Poli-neuronal slower path
Tremor at rest & rigidity |
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6. What is Parkinson's peak age?
In what ethnicity is it more common? What are several risk factors? |
Peak age is in the 60's
People of European ancestry then East Asian 1. Family history 2. Male gender 3. Head injury 4. Exposure to pesticide 5. Rural living |
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7. What are the motor symptoms of Parkinson's?
Four things... |
1. Tremor
-maximal at rest -decreased w/ voluntary movement -typically unilateral at onset 2. Rigidity -stiffness & ↑ muscle tone 3. Bradykinesia/akinesia -slowness & absence of movement 4. Postural instability |
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8. What are the non-motor symptoms of Parkinson's?
Three things... |
1. Mood disturbances
-depression, anxiety 2. Cognitive disturbances -slow rxn time, difficulties in attention, dementia, memory loss 3. Sleep disturbances |
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9. Where does the deficit for Parkinsonism lie?
What are the four major NT that are involved in the operation of this area? Which ones is current drug therapy involved with? |
In the extra-pyramidal system composed of the basal ganglia and striatum
1. Dopamine (DA) 2. Acetylcholine (ACh) 3. GABA 4. Glutamate DA and ACh |
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10. What do the symptoms of PD result from?
What are the two pathways of the intrinsic basal ganglia connections? |
Loss of DA secreting (dopaminergic) cells in the pars compact of the substantia nigra
1. Direct pathway 2. Indirect pathway |
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11. What is the direct pathway from?
Where does the direct pathway go? What is the net effect of the direct pathway? |
From striatum
To: -globus pallidus internal segment -substantia nigra pars reticulate Excitation of thalamus **Facilitation of movement |
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12. What is the route of the indirect pathway?
What is the net effect of the indirect pathway? |
1. From striatum
2. GP external segment 3. Subthalamus 4. GP internal segment 5. VA/VL thalamus Inhibition of thalamus **Inhibition of movement |
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13. What is the cause of primary or idiopathic Parkinsonism?
What is the pathology? What is typical onset? |
Cause unknown
Degeneration of cells in pigmented nuclei of CNS Over 40 yrs |
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14. How can genetic Parkinsonism or Parkinson-like symptoms by?
What can cause iatrogenic Parkinsonism? What are two examples? |
AD or AD
Drugs that reduce dopamine activity (i.e. anti-psychotic drugs) 1. Haloperidol, phenothiazine -block DA receptors 2. Reserpine, tetrabenzine -deplete brain monoamines from storage sites |
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15. What occurs in the manganese poising form of Parkinsonism?
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Manganese accumulates in substantia nigra
Interferes w/ enzymes systems Oxidizes DA |
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16. What cause arterioscletoric Parkinsonism?
What is the post encephalitic form of Parkinisonism? |
Infarcts produce in the region of the putamen
Slow progressive deterioration and development of Pakrinson symptoms |
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17. How does the MPTP form of Parkinsonism occur?
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Via enzymatic reaction w/ MAOb
MPTP breaks down to MPP+ to form superoxides **MPP+ is similar to pesticide |
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18. How is the clinical course of primary Parkinsonism?
How is the person in the terminal stages? |
Slow progressive disease that has a time course that may extend from 15-20 yrs
Patient is an invalid who is immobile and confined to his or her wheelchair |
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19. What is characteristic of stage 1?
What is characteristic of stage 2? What is characteristic of stage 3? |
Unilateral tremor at rest
Slow movements (bradykinesia) Gait disturbances **retropulsion; steps become shorter & shorter; center of gravity shifts forward & individual falls |
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20. What is characteristic of stage 4?
What is characteristics of stage 5? |
Increase in muscle and motor rigidity
Chronic invalid, little voluntary movement (akinesia), dementia is possible |
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21. How does normal functioning of the basal ganglia/striatal region operate?
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Balanced system comprising the excitatory/inhibitory (D1/D2 receptors) influence of the dopaminergic (DA) system and excitatory influence of the cholingergic system (muscarinic ACh)
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22. In Parkinson how do these two system operate?
What does treatment try to do then? |
DA system is severely compromised and cholingergic system operates unopposed
Restore balance bwt these 2 systems by enhancing DA's influence or inhibiting ACh's influence |
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23. What are the dopaminergic drugs that increase dopamine activity?
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1. DA precursors
2. DA agonists (ergot) 3. DA agonist (non-ergot) 4. MAO inhibitors 5. COMT inhibitors 6. Other (Amantadine) |
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24. What are three DA precursors?
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1. Levodopa (L-dopa)
2. L-Dopa + carbidopa 3. L-Dopa + Benserazide |
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25. What are two DA agonists that are ergot?
What are two DA agonists that are non-ergot? |
1. Bromocriptine
2. Pergolide 1. Pramipexole 2. Ropinirole |
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26. What are two MAO (monoamine oxidase) inhibitors?
What are two COMT (catechol-o-methyl-transferase) inhibitors? |
1. Selegiline
2. Rasagiline 1. Entacapone 2. Tolcapone |
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27. What is L-dopa effective for treating?
What is the MOA of L-dopa? |
Treatment of all Parkinsonism and all symptoms of Parkinsonism
Cross BBB and is converted to DA that supplements the reduced amounts of DA **95% of L-dopa is converted to DA in the periphery and does not reach the CNS |
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28. What are the toxic sides of effects of L-dopa due to?
What are some side effects? |
↑ in peripheral DA
1. Nausea & vomiting 2. Orthostatic hypotension 3. Dyskinesia (chorea) 4. Mental effects (agitation, delusions, insomnia) |
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29. What can L-dopa cause nausea & vomiting?
How can orthostatic hypotension be treated? What is dyskinesia (chorea)? What should be done for both dyskinesia and mental effects? |
DA in periphery stimulates the Area Postrema and Chemo-Trigger Zone
Wear tight stockings Excess involuntary movements due to excess does of L-dopa Reduce the amount of L-dopa until symptoms go away or decrease in intensity |
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30. What do both Carbidopa and Benserazide do?
Which one has a longer action of duration? Does Carbidopa cross the BBB? |
Inhibit decarboxylase activity which converts L-dopa to DA in periphery
Benserazide No so it does not interfere w/ conversion in CNS |
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31. What are the advantages of L-dopa + Carbidopa?
(Sinemet, Atamet) Three things... |
1. Reduces nausea present w/ L-dopa taken alone
2. Reduces time required to achieve therapeutic effect from mos to wks 3. Eliminates interaction w/ vit. B6 (pyridoxine) which occurs in periphery |
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32. What is the MAO of Bromocriptine?
How does its action compare to L-dopa? How is Bromocriptine used? What is a particular useful aspect of it? |
Agonist of D2 and partial antagonist to D1 receptors
Longer duration than L-dopa Used as adjunct in late treatment Combats on-off effect |
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33. What is the MOA of Pergolide?
How does it compare to Bromocriptine? How does its duration compare to L-dopa? |
DA agonist (D1 & D2)
More potent than Bromocriptine Longer duration and less of on-off effect |
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34. What is the MOA of Pramipexole?
How is it used clinically? How is Pramipexole possibly neuroprotective? |
DA agonist (affinity for D3)
1. Monotherapy for mild cases 2. Adjunct w/ L-dopa, combats on-off effect Scavenges H2O2 |
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35. What is the MOA of Ropinirole?
What is it used for clinically? |
DA agonist (D2)
1. Patients w/ mild symptoms 2. Smooth fluctuation in response to L-dopa treatment |
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36. What is the MOA of Selegiline?
What is it used for clinically? |
Prolongs DA activity by inhibiting it breakdown
**inhibits MAOb activity selectively & irreversibly 1. Supplement to L-dopa treatment b/c acts centrally 2. Before L-dopa treatment is initiated sometimes |
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37. What is the MOA of Rasagiline?
How does it compare to Selegiline? Why may Rasagiline have neuroprotective effects? |
Increase DA activity by inhibiting MAOb
More potent than Selegiline Protects against MPTP induced Parkinsonism |
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38. What is the MOA for both Entacapone and Tolcapone?
How are both used clinically? Where does Entacapone act? Where does Tolcapone acti? |
COMT inhibitor
Adjunct w/ L-dopa to prolong L-dopa action **↓ L-dopa metabolism in periphery so more is available centrally Peripherally Peripherally & centrally |
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39. How dose Tolcapone compare to Entacapone?
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Tolcapone is more potent and more hepatotoxic
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40. What is the MOA of Amantadine?
How does it compare to anti-cholinergic drugs? How dose it compare to L-dopa? What is it used for? |
↑ availability of endogenous DA by acting on release, synthesis, & re-uptake
More effective Less effective Used for short term therapy (2-3 wks) b/c losses effectiveness in 6-8 wks (max effects achieved in 1-2 days) **also an anti-viral agent against A2 influenza |
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41. What are the side effects of Amantadine?
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When used w/ anti-cholinergic drugs can get hallucinations and confusion
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42. What are two long-term complications of L-dopa?
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1. Dyskinesia or abnormal movement
2. Fluctuations in motor performance -"wearing off" phenomenon, end-of-dose deterioration -"on-off" phenomenon |
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43. What is the "wearing off" phenomenon or end-of-dose deterioration?
What is the "on-off" phenomenon? |
Ongoing neuronal loss and lack of synaptic storage
Further neuronal loss, change to phasic dopaminergic transmission **rapid shift from akinesia "off" to chorea or hyperkinesia "on" |
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44. What other drugs and foods can interact w/ L-dopa?
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1. Multi-vitamins
2. Drugs that ↓ DA activity -anti-psychotics block DA receptors -Reserpine depletes stores of central DA 3. Drugs that ↑ DA activity -MAO inhibitors 4. High protein meal |
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45. How can multi-vitamins affect L-dopa?
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Reduce effectiveness of L-dopa
Vitamin B6 (pyridoxime) ↑ dopa decaboxalyse activity lessening the effect of L-dopa **less of a problem when Sinemet is used |
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46. How can high protein meals affect L-dopa?
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Interfere w/ the absorption of L-dopa from the gut
Sinemet should be prior to eating |
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47. What are drugs that decrease cholinergic activity used for?
What do they alleviate? What are two possible SE? |
1. Drug induced Parkinson-like symptoms
2. Adjuncts in patients w/ mild Parkinsonsism symptoms **less effect than dopaminergic drugs Alleviate tremors and rigidity Drowsiness and mental confusion |
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48. For which patients are anti-cholinergic drugs contra-indicated for?
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1. Closed angle glaucoma
2. Obstructive GI disease 3. Prostatic hyperplasia |
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49. What are five anti-cholinergic drugs?
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1. Benztropine
(also H1 blocker) 2. Biperiden 3. Orphenadrine 4. Procycldine 4. Trihexyphenidyl (synthetic) **all are ACh (muscarinic) blockers |
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50. What drug can cause permanent Parkinsonism?
What is this? |
MPTP
Neurotoxin selectively toxic to the substantia nigra cells producing almost all symptoms of PD |
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51. Who is surgical therapy for PD reserved for?
Theoretically what does surgery do? |
Individuals ailing medical therapy
**Usually have to have had maximal tolerated doses of L-dopa, agonist, amantidine Lessens L-dopa metabolism so surgery protective |
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52. What does a thalamotomy do?
What does a pallidotomy do? What does a palldial stimulator do? |
Reduces tremor, less effect on motor fluctuations
Lessens motor fluctuations (permanent) Lessens fluctuations, can be regulated higher technical difficulty |
