Parkinson's Tx (plus HD and ALS) Flashcards
1
Q
Levodopa (L-DOPA)
A
- DA precursor –> rapidly converted to DA in plasma by peripheral AAD
- administer with Carbidopa
- adverse side effects: wearing off effect, dyskinesias, on-off phenomenon, hallucinations, NMS
2
Q
Dopamine
A
- doesnt cross BBB
- low doses causes othostatic hypotension, high doses can cause HTN + tachycardia (stimulation of alpha1 adrenergic receptor), N + V
3
Q
carbidopa
A
- AAD inhibitor (Aromatic AA Decarboxylase)
- given in combo with L-DOPA (prevents conversion in periphery so that L-DOPA can get to brain)
- wearing off effect, dyskinesias, on-off phenomenon, NMS upon withdrawal
- ** too much DA and PT looks hyperkinetic like Huntington’s (too much inhibition of BG –> BG can’t brake enough –> hyperkinetic)
4
Q
Bromocryptine
A
- ergot derivative
- D2 agonist, D1 antagonist
- must be titrated slowly due to acute hypotension
- peripheral DA-like side effects, can cause pleural effusions, cough, SOB, pulmonary fibrosis
think: old men are cryptic
5
Q
Pramipexole
A
- Non-ergot D2 receptor agonist (no D1 activity like ergot derivs)
- can cause compulsive/addictive behaviors (ie: gambling, sex)
- *DAR agonist of choice today along with Ropinorole
*think pramSEXipole
6
Q
Ropinorole
A
- non-ergot D2 receptor agonist (no D1 activity)
- can cause sudden daytime sleep attacks
7
Q
Rotigotine
A
non-ergot D2 agonist (no D1 activity)
transdermal patch (not in US)
**think goti= old man with a goatee that has Parkinson’s
8
Q
limitations of DAR therapy
A
- less effective at controlling motor symptoms
- more acute side effects (psychosis, nausea, fatigue, GI disturbances, edema, somnolence)
9
Q
apomorphine
A
- non-ergot DAR agonist
- rescue tx for sudden “off”times (frozen condition)
- more severe side effects: emesis, hypotension with 5-HT receptor antagonists
**morphine addict is rescued by morphine
10
Q
Entacapone and Tolcapone
A
- COMT inhibitors (primarly peripheral)
- adjunctive tx- used to tx motor fluctuations
- Entacapone well tolerated, short acting, given in combo with levidopa/carbidopa to prolong levodopa t1/2
- Tolcapone is more potent COMT inhibtors, fatal hepatotoxicity (use when unresponsive to entacapone)
- usual DA side effects also diarrhea and urine discoloration
**think entaCapOne and tolCapOne = COmt inhibs
11
Q
Selegiline and Rasagiline
A
- MAO-B inhibitors
- MAO-B converts DA to DOPAC in presynaptic terminal
- adjunctive tx to treat motor fluctuations
12
Q
anticholinergics
A
- benzotropine, trihexyphenadyl, ethopropazine, biperidine, procyclidine
- treat tremor and drool
- little effect on motor symptoms
- typical anticholinergics side effects + mental confusion, impaired memory, hallucinations —> contraindicated in PD with dementia
13
Q
amantadine
A
- Influenza A antiviral drug
- dopaminergic, anticholinergic and anti-NMDA activities
- most effective as adjunct to levodopa/carbidopa in long term tx bc it reduces dyskinesias associated with long-term levodopa tx
- also treats chorea in Huntington’s
14
Q
deep brain stimulation
A
- DBS of subthalamic nucleus
- used to tx dyskinesias and motor fluctuations
- PTs must still be responsive to levodopa/carbidopa tx!
15
Q
Huntington’s Disease
A
- autosomal dominant
- net effect is opposite of Parkison’s: decreased GABAergic inhibitory drive from BG onto VA/VL –> excitatory input to motor cortex –> excessive movement
- no tx to prevent disease progression
- tx psychosis with low dose antipsychotics
- tx movement disorder/chorea with tetrabenazine, amantadine, reserpine
- tx stress/anxiety with clonazepam (chorea increaseswith stress/anxiety)
- tx rigidity with antiseizure meds
19
Q
mechanism of Parkinson’s
A
- loss of DA neurons in the SNpc (80%) —> no DA to the neostriatum –> no inhibitory output to the BG –> no inhibition of BG –> excessive inhibition of VA/VL (thalamus)
