Pharmacotherapy of movement disorders Flashcards
4 Cardinal symptoms of Parkinson’s Disease
1) Bradykinesia- slow movements
2) Rigidity- inc muscle tone and resistance
3) Resting tremor that goes away with voluntary movement
4) Postural instability
Hallmark feature of Parkinsons pathophysiology
Loss of dopaminergic neurons in the substantia nigra pars compacta
When Basal Ganglia decides we need to move, how does it react?
Shuts down the indirect pathway and cranks up the direct.
Why do D2 blockers have the potential to cause parkinsonism?
Because they prevent dopamine from binding the D2 receptors inhibiting the indirect pathway. Indirect pathway is always on.
4 methods of parkinson dz treatment?
1) Replacement of Dopamine
2) Stmulate D2 receptor
3) Increase Dopamine release
4) Inhibit dopamine metabolism
Can dopamine cross the BBB
no
What do you give instead of just giving dopamine?
L- DOPA
L-Dopa tx is inhibited by?
Food
99% of L-Dopa is converted in the periphery to DA. This is problematic because as we just discussed, Dopamine cannot cross the BBB. How do you get around this?
Give L-DOPA with Carbidopa….Blocks peripheral L-AAD so that more of the L-DOPA enters the CNS before it is converted to Dopamine.
Adverse effects of L-DOPA
GI, CV (arrhythmias and orthostatic htn)
LDOPA + Carbidopa AE
Behavioral change and Dyskinesia
Treatment with L-DOPA usually quits working after how long
3-5 years
See Contraindications for L-DOPA
psychotics, CV dz, PUD, Melanoma
What is the preferred initial course of therapy for parkinsons
Stimulate the D2 receptor with a D2 receptor agonist
Amorphine
Non-specific dopamine receptor agonist
