Pharm - Parkinson's Flashcards
goals of therapy for Parkinson’s drugs
- manage symptoms
- nothing to slow/prevent disease
basic pathology of Parkinson’s
- depletion of dopinergic neurons in the substantia nigra
- hard to stop/start movements
if there is no response to dopaminergic drugs, then __________
if there is no response to dopaminergic drugs, then RULE OUT Parkinson’s
-Parkinson’s should respond to dopamine
features of Parkinson’s
Classic signs:
- akinesia/bradykinesia
- rigidity
- tremor
- gait disturbances
Differentiating signs
- asymmetry
- resting tremor
- good response to levodopa
co morbid problems of Parkinson’s
- daytime sleepiness
- hallucinations (side fx)
- psychosis (side fx)
- depression
- fatigue
- dementia
restorative/regenerative treatment for Parkinson’s
- surgical procedures
- electrical stimulation
reserved only for pts w ADVANCED DISEASE
symptomatic treatments for Parkinson’s
- levodopa/extenders
- dopamine agonists
why not just use dopamine for Tx of Parkinson’s (instead of levodopa)?
- cannot cross BBB
- low bioavailability (F)
benefits of using L-dopa
- high bioavailability
- crosses BBB
purpose of carbidopa
- peripheral carboxylase inhibitor
- prevents premature conversion of L-dopa to dopamine
- combined with levodopa
dosing schedule of levodopa/carbidopa
- both dosed multiple times per day
- need higher dosage as disease progresses
side fx of levodopa
- nausea/orthostasis (due to incr DA in periphery)
- agitation, confusion, hallucinations, delusions, dyskinesia (due to DA toxicity in CNS)
drug combinations to avoid with Parkinson’s drugs
-avoid combination with NON SELECTIVE MAO inhibitors
non selective MAO inhibitors
- inhibits degradation of all substrates in dopamine pathway
- causes accumulation of NE (hypertension)
concerns with CHRONIC use of levodopa
-wearing off effect (need increased dose)
-toxicity (dyskinesia)
-
-must balance disease progression vs side effects
how is methyldopa formed? what do we want to do with it?
levodopa –> methyldopa
- via COMT
- another pathway depleting L-dopa
- want to inhibit
- Entacapone, Tolcapone inhibit COMT
how do we inhibit formation of methyldopa?
- Entacapone, Tolcapone
- COMT inhibitors
- allow more L-dopa to get to the brain
- stress the liver
- always used in adjunct with levidopa/carbidopa
side effects on COMT inhibitors
- nausea, dizziness, psychotic symptoms, dyskinesia
- avoid use with non selective MAO inhibitors
- diarrhea (explosive), discolored urine, increased LFTs
selective MAO inhibitors
MAO-type B inhibitors
- result in accumulation of dopamine
- degradation of NE remains intact, so no weird side effects from that
side effects of MAO-type B inhibitors
- nausea, dizziness, psychotic symptoms, dyskinesia (too much dopamine)
- insomnia (selegiline)
net effect of dopamine receptor agonists
- act directly on D2 receptors in the striatum
- less fluctuations and dyskinesia
- take longer to work
types of dopamine agonists
- ergot derived (not used for parkinsons)
- non ergot derived
- –less potent, less side fx, effective early on
side fx of ergot-derived dopamine agonists
- nausea
- orthostasis and dizziness
- dyskinesia
- somnolence
- reduced prolactin levels
- FIBROTIC PULMONARY/SKIN REACTIONS (life threatening)
- heart valve damage
side fx of non-ergot derived dopamine agonists
- COMPULSIVE behaviors
- nausea
- orthostasis, dizziness
- dyskinesia
- somnolence
- reduced prolactin levels
NO heart valve, or fibrotic damage
apomorphine (Apokyn)
- used to rescue from “frozen” episodes
- subQ injection
side effects of apomorphine
- nausea/vomiting
- orthostasis
- hypersomnia
- priapism
use of anticholinergic agents for Parkinsons
- corrects imbalance btwn ACh and DA
- better for tremor (not really for rigidity or akinesia)
- many side fx
-or use antihistimine
side fx of blocking post-synaptic muscarinic receptors
- dry mouth
- blurred vision
- urinary retention
- constipation
- tachycardia
- memory/cognition issues
amantadine
- MOA for Parkinson’s unknown
- improvement in rigidity and tremor
- may improve drug-related dyskinesia
side fx of amantadine
- mostly CNS related
- some GI (nausea)
