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