Flashcards in Pharmacotherapy of movement disorders Deck (28):
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
What do you give instead of just giving dopamine?
L-Dopa tx is inhibited by?
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
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
Non-specific dopamine receptor agonist
D2 and D1
D2 specific, free radical scavengar
D2 specific. CYP 1A2
Antiviral that increases dopamine release
Adverese effects of Amantadine therapy
Psychosis with overdose
Dopamine is metabolized into what by what?
DOPAC by Monoamine oxidase- B
Then DOPAC is converted in HVA by COMT
Monoamine oxidase B inhibitors
Selegilline and Rasagilline
Depression in Huntington's disease is treated with
Fluoxetine (SSRI) and Carbamezapine (voltage gated Na blocker)
Reserpine in HD?
Reserpine depletes DA
Tetrabenzine in HD
Tetrabenzine depletes DA
D2 Antagonist in parkinsons
Haloperidol in HD