Drugs for Movement Disorders - Kruse Flashcards
Dopamine vs. ACh in the basal ganglia
Dopamine - inhibit GABA output from striatum
ACh - excite GABA output from striatum
How does loss of dopaminergic neurons lead to difficult movements?
Less inhibition of the inhibitor (striatum), thus leading to decreased movements
So, how would you treat Parkinson’s?
Increase Dopamine activity onto the GABAergic striatum neurons via Dopamine agonists or metabolism antagonists
Why treat with L-dopa, not dopamine?
L-dopa can cross BBB, but dopamine cannot
What is L-dopa?
Immediate metabolic precursor to dopamine
Levodopa action
Downside to levodopa alone
Dopamine receptor agonist
97-99% is metabolically altered before reaching the brain, via decarboxylation into dopamine
How to increase the effects of levodopa?
Give w/ a DOPA decarboxylase inhibitor
= CARBIDOPA
Causes reduced peripheral metabolism, so more enters the brain unaltered
A patient is taking Levodopa therapy for a long time. Eventually, each dose ends and rapidly leads to a return of symptoms. This is an example of?
Can you just give more levodopa?
Wearing-off phenomenon
Eventually you impair voluntary movements (dyskinesia)
A patient is on levodopa (with or without carbidopa). What symptoms are she most likely to exhibit? (4)
Anorexia, nausea, vomiting, choreoathetosis
Does carbidopa help with the side effects of levodopa?
Yes, but only in 20% of patients
A patient is on levodopa but has trouble with vomiting. What causes the vomiting?
Activation of chemoreceptor trigger zone within the brainstem (outside the BBB)
What is the choreoathetosis side effect of levodopa?
Intermediate-speed movements of the face and distal extremities
A patient is taking Levodopa therapy for a long time. Eventually, the patient starts having occasional episodes of inability to move at all. This is an example of?
How is this problem fixed?
On-off phenomenon
Apomorphine - DOPAMINE agonist that can provide temporary relief
A patient is taking Levodopa, but needs another drug to supplement. Which drug type should NOT be taken with Levodopa?
Why?
Non-selective MAO or selective MAO-A inhibitors
Lack of MAO-A leads to build-up of norepinephrine, which can cause a HYPERTENSIVE CRISIS in the patient
Contraindications for Levodopa therapy
Psychosis, closed-angle glaucoma, melanoma, active peptic ulcer
Why would a patient take a dopamine receptor agonist rather than Levodopa?
Less response fluctuation phenomena and dyskinesias
Can dopamine receptor agonists be given WITH Levodopa?
What about for wearing-off or on-off phenomena?
YES
YES (Apomorphine is a dopamine receptor agonist)
Bromocriptine
D2 agonist, ergot alkaloid
Extensive first pass metabolism (3A4)
Pramipexole
D3 agonist
Treats RLS also
A patient is taking Pramipexole and develops renal insufficiency. What might the doctor have to do?
Change the dose of Pramipexole, sine 90% is excreted renally
Ropinirole
D2 agonist
Treats RLS also
Metabolized by 1A2