Term
| What are the 4 main clinical features of Parkinson's? |
|
Definition
Bradykinesia
Muscular rigidity
Resting Tremor
Postural Instability and impaired gait |
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Term
| What is the Hallmark pathophysiologic feature of parkinson's disease? |
|
Definition
| selective loss of the pigmented neurons in the substantia nigra pars compacta |
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Term
| Describe the Direct pathway of the Basal Ganglia. |
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Definition
| SNpc -> Dopamine -> D1 -> activates striatal neurons ---> SNpr/MGP -> Thalamus -> Cortex |
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Term
| Describe the Indirect pathway |
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Definition
| SNpc -> Dopamine -> D2 -> Inhibits striatal neurons -> LGP -> STN -> SNpr -> Thalamus -> Cortex |
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Term
| Under Normal conditions what pathway is favored? |
|
Definition
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Term
| In Parkinson's Disease what pathway predominates? |
|
Definition
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Term
| What is the single most effective treatment for PD? |
|
Definition
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Term
| What are the DA replacement therapy agents? |
|
Definition
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|
Term
| What is the mechanism of DA replacement therapy? |
|
Definition
DA cannot cross BBB, precursor L-DOPA is used to replenish DA stores in Striatum
L-DOPA -> DA by L-AAD in periphery and Brain |
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Term
| Why is L-DOPA co-administered with carbidopa? |
|
Definition
can not cross BBB, prevents coversion of L-DOPA -> DA in periphery.
reduces amount of L-DOPA needed to be administered, and reduces side effects caused by peripheral DA |
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Term
|
Definition
a L-AAD inhibitor
Can Not cross BBB |
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Term
| What adverse effects come primarily from L-DOPA monotherapy? |
|
Definition
GI - anorexia, nausea, vomiting
Cardiovacular - arrhythmias, ventricular extrasystoles, A. Fib, orthostatic hypertension |
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|
Term
| What adverse effects occure in response to combination therapy of L-DOPA and carbidopa? |
|
Definition
Behavioral effects
Dyskinesias |
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Term
| What vitamin increases L-DOPA metabolism? What is needed because of this? |
|
Definition
Vitamin B6
(pyridoxine)
Decarboxylase inhibitor also needed |
|
|
Term
| What agents should be avoided when taking L-DOPA, due to risk of hypertensive crisis? |
|
Definition
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Term
| Why should L-DOPA be given before meals? |
|
Definition
| due to competition with L-amino acids in food for transporters in GI tract |
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|
Term
| How long is L-DOPA therapy effective? |
|
Definition
3-5 years
often delayed until symptoms of PD yield functional impairment |
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|
Term
| What are the Dopamine Receptor Agonists? |
|
Definition
Bromocriptine
Pergolide
Pramipexole |
|
|
Term
| What is the rationale for Dopamine Agonist therapy? |
|
Definition
| to principally activate D2 receptors to reduce activation of the indirect pathway |
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|
Term
| What are the advantages to DA receptor agonist therapy? |
|
Definition
Does not need to be converted to active compound
No Toxic metabolites
No competition for GI absorption or crossing BBB
More selective = less side effects |
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|
Term
| What is the preferred therapeutic stratey for early PD? |
|
Definition
|
|
Term
| Which DA agonist is a D2 agonist/D1 partial agonist? |
|
Definition
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|
Term
| Which DA agonist appears more effective than Bromocriptine and is a D1/D2 agonist? |
|
Definition
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|
Term
| Which DA agonist is D2 selective and also acts as a free radical scavenger? |
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Definition
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Term
| Why is use of L-DOPA controversial in PD treatment? |
|
Definition
thought that L-DOPA may exacerbate progression of PD due to generation of free radicals
(use with Pramipexole?) |
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|
Term
| What drug is a selective inhibitor of COMT? |
|
Definition
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|
Term
What does inhibition of COMT do?
(Entacapone) |
|
Definition
inhibits conversion of L-DOPA -> 3OMD, which does not cross BBB
Prolongs actions of L-DOPA, Increases bioavailability of L-DOPA |
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|
Term
| What is Entacapone indicated for? |
|
Definition
- Prolong bioavailability and action of L-DOPA by inhibiting DA metabolism by COMT
- Reduce fluctuation responses to L-DOPA |
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|
Term
| What COMT inhibitor is strictly peripheral? |
|
Definition
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|
Term
| What muscarinic antagonists are used in the treatment of PD? |
|
Definition
| Benztropine Diphenhydramine |
|
|
Term
| What are the Muscarinic Antagonists used for? |
|
Definition
| To block cholinergic activation in the striatum. |
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|
Term
| When are Muscarinic Agents used in the treatment of PD? |
|
Definition
Early PD
Prior to L-DOPA therapy
or as adjunct to L-DOPA |
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|
Term
| What adverse effects do the muscarinic antagonists have? (Benztropine, Diphenhydramine) |
|
Definition
| Drowsiness mental slowness delusions hallucinations Anticholinergic Effects |
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