Term
| Why are anticholinergics used as an adjunct in Parkinson's therapy? |
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Definition
the loss of dopamine from PD results in an excess of activity in cholinergic pathways, thus a cholinergic antagonist can partially compensate for this overactivity
in the control of motor movement, ACH has excitatory influence, whereas dopamine has an inhibitory influence |
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Term
| Describe the on/off effect of levodopa therapy |
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Definition
After several years of levodopa therapy, it can produce exaggerated dyskinesias immediately after dosage, and later as plasma levels decline, the drug fails to provide any effect
dyskinesias and on/off effects are major problems with long term levodopa therapy |
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Term
| what enzyme is responsible for converting L-DOPA to dopamine? |
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Definition
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Term
| What is required in ergoline-derived anti-parkinson agents? |
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Definition
| -a hydrogen bond donating group, usually NH |
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Term
| Why did apomorphine work better than other D2/D3 agonists? |
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Definition
-because it was also a D1 agonist
-D1 receptors have recently been found to be an important target for PD therapy |
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Term
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Definition
-first discovered as a demerol (heroin) analogue
-destroys cell bodies of SN and leads to rapid parkinsonian
-allowed for breakthrough in PD research |
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Term
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Definition
-activated by oxidation with MAO-B to produce MPP+, which is the ultimate toxicant
-MPP+ causes massive dopamine release from dopaminergic terminals and then binds to complex I in the electron transport chain and shuts down mitochondrial respiration |
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Term
| What is the basis of MAO-B inhibitors? |
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Definition
| -initially developed because it was though that an endogenous neurotoxic was being activated by MAO-B; really their efficacy comes from increasing dopamine |
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Term
| How do COMT inhibitors work? |
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Definition
-COMT is an enzyme that methylates the 3-OH function of dopamine and L-DOPA
-inhibitors do 2 things
1. decreases metabolism of L-DOPA, allowing more to reach the brain
2. allows CNS levels of dopamine to remain higher, and increases elimination time of dopamine by 30-50%
2nd is more important
increases duration of effect of Sinemet, not potency of Sinemet |
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