Basal Ganglia Pharmacology Flashcards
What is the pathological basis of Parkinsons?
Loss of DA neurons in the substantia niagra >
Less DA in striatum >
decreased activity in the direct pathway and increased activity in the indirect pathway >
increased inhibition oif the thalamus >
decreased excitation of the motor cortex
What is a replacement tx for Parkinsons?
L- DOPA!
When the medium spiny neurons are dying and DA is decreasing in the striatum you need a substitute. LDOPA is a metabollic precursor of DA. L DOPA is transported across the BBB then converted to DA
What are the side effects of L-DOPA?
The side effects of L-DOPA are d/t increased DA peripherally. L- DOPA hanging out in the periphery gets converted to DA. This activates the vomiting/nausea centers of the brain and can also lead to orthostatic hypertension.
What are the potential drug interactions of L-DOPA?
L-DOPA is often paired with Carbidopa. This is the GOLD STANDARD for Parkinsons tx. Why?
Carbidopa inhibits ACCCD which is an enzyme that converts L-dopa to DA in the periphery.
This decreases side effects, and also decreases the necessary dosage.
What does L-DOPA do specifically?
LDOPA increases DA in the striatum and acts on both D1 and D2. This activates the direct pathway and inhibits the indirect pathway leading to an overall increase in voluntary movement.
Sometimes you can have too much of a good thing….Too much DA can lead to abnormal involuntary movement, On/Off (sudden rapid loss of clinical effect), and wearing off (fluctuations of sx between dosages)
What is a COMT inhibitor?
Entacapone
When there is a decrease in LAAD (d/t Carbidopa), there often is an increase in COMT, the enzyme that convert LDOPA to 3-OMD (A DA derivative). Entacapone (COMT inhibitor) inhibits the COMT enzyme decreasing the amount of DA in the periphery.
Entacapone/COMT inhibitors are often used as conjunctive tx. They often help to decrease on/off fluctuations and wearing off effects.
What is an MAOI?
Selegiline
Selegeline acts on MAO-B which is stored in glial cells and metabolizes DA.
Selegeiline (MAO inhibitor) prevents the glial cell from uptaking DA.
This smooths on/off fluctuations, and also means that a lower dose of L-dopa is needed.
What is a dopamine receptor agonist?
Prarinezole
Prarinezole (DR agonist) acts directly on D2 receptors, inhibiting the indirect pathway and leading to an increase in voluntary movement.
Prarinezole bypases the conversion of L-DOPA > DA and can help smooth on/off fluctuations.
What is the role of muscarinic antagonists?
Trihexyphenidyl
Normally DA and ACh are in balance. Loss of DA throws off this balance leading to excess ACh. The excess ACH causes sedation, mental confusion, confusion and urinary retention.
What is Amantidine?
An anti-viral that randomly worked to decrease the sx of parkinsons. Sadly it only works initially and is transient. It also has may side effects.
