Drugs Used in Movement Disorders Flashcards
Function of acetylcholine in the movement pathway
Activates the MSNs in the indirect pathway, prevents movement.
L-Dopa
Gold standard for treating PD, pro-drug that gets converted to dopamine by dopa decarboxylase
Why not administer dopamine itself?
Because it doesn’t pass through BBB well. L-dopa passes much faster
What happens when DOPA interacts with COMT?
It gets degraded into an inactive product instead of dopamine
Carbidopa
A peripheral inhibitor of DOPA decarboxylase. Prevents the nausea that occurs when dopa broken down peripherally. Also causes more of the DOPA to reach the brain
L-Dopa pharmacokinetics
Absorbed in small intestine, t1/2 of 3 hours
Does l-dopa ever lose efficacy?
Yes, after months to years of treatment. Mobility declines a few hours after each dose.
Dopa-dyskinesias
L-Dopa can cause dyskinesias, like Michael J. Fox.
Why use direct dopamine agonists?
As monotherapy when PD is mild, delay use of L-dopa and prevent loss of efficacy. Also can use as adjunct with l-dopa.
Which DA agonists are used? Mechanism of action
Pramipexole and Ropinirole. Direct D2 agonists.
Apomorphine, also direct DA agonist
Pramipexole and Ropinirole PK
P: Excreted unchanged.
R: Metabolized by a cyp that also metabolizes caffeine and warfarin, so there can be an interaction there.
How is apomorphine administered?
SC. Use is relatively limited to off periods when nothing else works. Causes nausea and cardiovascular effects. Rapid halflife and is excreted unchanged.
MAO-B inhibitors
Work by preventing the breakdown of dopamine, does not work on 5HT or NE (like MAOa). Irreversible inhibitors, used as adjuncts.
Adverse effect of MAOI and meperidine (opioid analgesic)
Serotonin syndrome– causes agitation, delirium, coma, death. Treat with 5HT antagonists
What MAO-B inhibitors are used?
Selegiline, Rasagiline
