40: Antiparkinson's Drugs Flashcards
loss of dopaminergic neurons in the basal ganglia leads to altered movement control
parkinson’s and huntington’s disease
what prtns accumulate with parkinson’s disease?
intracytoplasmic aggregates
alpha-synuclein
“lewy bodies”
indicator of parkinson’s disease
pathology of parkinsons
progressive loss of DA containing neurons in the basal ganglia, eventually leads to total loss of motor function and muscle control
what are some “non-motor” effects of PD?
other brain structures are also affected (brainstem, hippocampus, and cerebral cortex)
cognitive decline
affective disorders
sleep disorders
sensory complaints or pain
4 cardinal symptoms of PD
- bradykinesia
- muscular rigidity
- resting tremor
- postural instability
degeneration of ____ neurons in ________ (part of basal ganglia) that project to ______ (putamen and caudate nucleus)
dopaminergic
substantia nigra
striatrum
decreasing DA –> increasing __
Ach
loss of dopaminergic input into striatum is also accompained by increased activity of the cholinergic pathways in the basal ganglia
alpha synuclein accumulation, formation of Lewy bodies, and increased production of free radicals —>
interference with neuronal function that leads to neuronal atrophy and death
5 treatment strategies for PD
- DA replacement
- DA receptor agonists
- L-DOPA degradation inhibitors
- increase in DA release
- Anticholinergic agents
most common drug used to treat PD
L-DOPA (levodopa)
can’t give straight DA because it does not cross BBB
Why use carbidopa and L-DOPA together?
carbidopa is an inhibitor of DA decarboxylase in the periphery –> inhibits premature breakdown of levodopa in the periphery and therfore increases fraction L-DOPA that actually reaches the brain
adverse effects of L-DOPA
- dyskinesia (involuntary movements similar to tics and tremors)
- response fluctuations
- GI disturbance
- Postural hypotension and Tachycardia
- Behavioral disturbances
“drug holiday”
stop taking L-DOPA for a period of time to improve response fluctuation problems
What drugs interact with L-DOPA?
- pyridoxine (vitamin B6)
- will enhance peripheral conversion of LDOPA
also interacts iwth MAOai, antipsychotics, prtn rich meals, and anticholinergics
name three DA receptor agonists
pramipexole
ropinirole
apomorphine
rescue treatment for LDOPA induced dyskinesia
apomorphine
subQ route for temporary relief
clinical uses for DA receptor agonists
-first line or initial therapy for PD; effective as monotherapy for mild parkinsonism
associated with lower incidence of response fluctuations and dyskinesias
DA receptor agonists
LDOPA has worse side effects
DA receptor agonists can be helpful in pts with advanced PD that allows for reduction in LDOPA dose and improvement of response fluctuations
interesting adverse effect of DA receptor agonists
potential problems with impulse control disorders
GI (anorexia, nausea, vomiting, constipation) are more common adverse effects
MOA rasagiline and selegiline
MAO-B inhibitors –> DA degradation blockers
inhibits MAO-B selectively at lower doses and decreases breakdown of DA
clinical use MAO-B inhibitors
adjunctive to levodopa primarily in pts with declining or fluctuating response to levodopa
adverse effects Rasagiline and Selegiline
GI upset
Serotonin syndrome
does not display wine and cheese interaction
MOA entacapone and tolcapone
COMT inhibitors
preferred COMTi for PD
entacapone
because it has not been associated with hepatotoxicity (tolcapone)
what drug causes increased DA release?
amantadine
antiviral agent that has antiparkinsonism properties discovered by chance
short duration of action and effectiveness (12mo)
observe blotchy reddened pattern on legs on PD patient. what drug might be causing this and what is it called?
livedo reticularis caused by amantadine
clears w/i 1 mo after stoppage
MOA benztropine and trihexyphenidly
antagonist at muscarinic receptors in basal ganglia
what are the clinical effects of anticholinergic agents for PD?
reduces tremor and rigidity – little effect on bradykinesia
what are the adverse effects of anticholinergic agents?
drying up - the opposite of SLUDGE
urinary retention dry mouth mydriasis and blurred vision constipation sedation confusion toxic psychosis
advanced PD and drugs aren’t working…
ablative surgical procedures or high-frequency deep brain stimulation may provide beneficial effects or transplantation of dopaminergic fetal tissue
pt is receiving bilateral stimulation of the subthalamic nucleus – should they also be taking meds?
nope
actually do better with this treatment if off meds
