Basal Ganglia Pharmacology Flashcards
What does the indirect pathway of the basal ganglia do?
Suppresses competing nonselected movement
What does the direct pathway of the basal ganglia do?
Releases a selected movement from suppression
What signals does the striatum receive from the cortex?
Glutamate
What does dopamine do to the basal ganglia?
Makes movement happen
What is the end results of Parkinson’s?
Decreased motor cortex stimulation
What triggers cell death in the SNc in Parkinson’s?
Alpha snyuclein
What are the four cardinal signs of Parkinson’s?
Bradykinesia
Cog wheel rigidity
Resting tremor
Mask facees (flat face, no expression)
What drugs are used for treatment of PD (for this lecture)?
L-DOPA Entacapone Carbidopa Selegiline Pramipexole
What is sinemet?
Levodopa + Carbidopa
What does L-DOPA do?
Converted to dopamine by AAAD
What is Carbidopa?
Inhibits AAAD
What does L-DOPA do?
Targets d1 and D2
Why does the effectiveness of L-DOPA decrease with progression of PD?
The dopaminergic neurons that have AAAD are almost all gone
Where is L-DOPA stored in early PD?
Presynaptic dopaminergic terminals of striatum (gradually released)
What are the adverse affects of L-DOPA?
Dyskinesia - abnormal involuntary movements
Chorea of upper body (peak dose)
Diphasic dyskinesia - two phases appearing when the drugs dose is increasing or decreasing
Affect lower limb, repetitive
Off period dystonia - when dose is gone, fixed and painful postures, often feet but can be generalized
What is the on-off phenomenon?
Sudden and rapid loss of clinical effect
30min to 4hrs, 10/day max
How do you fix the wearing off phenomenon?
By adding drugs that prolong the presence of L-DOPA
Why do people taking L-DOPA get schizophrenia?
Because L-DOPA is non specific in its target
Specifically the limbic system and frontal cortex
Why do we get nausea and vomiting?
Because of L-DOPA targeting the brainstem chemoreceptor trigger zone
What you get hypotension with levodopa?
Because it can target the kidneys and pulmonary artery
What is a COMT inhibitor?
Decreased peripheral metabolism of levodopa
A methyl transferase
Same adverse affects as levodopa
What drug for PD is a COMT inhibitor?
Entacapone
What does selegiline do?
MAOI of MAO-B
Stops metabolism of dopamine
A metabolite of this drug may have a neuro protective effect
Smooths off and on switch
What does pramipexole do?
D3 dopamine receptor agonist
Can treat RLS
What does an anticholinergics (muscarinic agonist) do?
Balance of Ach and dopamine is key
BAD side effects
Urinary retention, mental confusion
What can ameliorate tremor?
Thalamotomy
What is wrong in huntington?
Degeneration of striatum neurons to the indirect pathway (D2, inhibitory)
Decrease activity in BG mitochondrial pathway
Extra movement
How do you treat chorea?
Deplete dopamin and other catacolamines
Block dopamine
What is Trihexyphenidyl?
Muscarinic antagonist
Retain the balance of ACh and dopamine
Bad side effects
