antiparkinson's Flashcards
familial PD
10%
gene that codes for synuclein
sporadic PD
90%
PD risk factors
infections trauma endocrine drugs/toxins: neuroleptics metoclopramadine reserpine pesticides MPTP
gene mutations
mitochondrial dysfunction
impaired protein/organelle degradation
axonal transport
synaptic homeostasis
motor S/S (TRAP)
tremor at rest
rigidity
akinesia
postural reflex impairment
nonmotor S/S (early)
sleep abnormalities
autonomic dysfunction
sensory
nonmotor S/S (late)
psychiatric disorders
cognitive disorders
nigrostriatal pathway
fine motor control
medium spiny striatal neuron
ACh
regulate direct/indirect pathways
overactivated in PD
mesolimbic/mesocortical pathway
memory, motivation, emotions, reward, desire, addiction
tuberoinfundibular pathway
hormonal regulation
Rx goals
1 - restore DAergic transmission
2 - inhibit AChergic transmission
Levodopa (L-dopa)
precursor to DA
doesn’t cross BBB (1-3% enters brain)
extracerebral metabolism: rapidly converted to DA by DDC
indirect (D2)
direct (D1) - stimulate adenyl cyclase
L-dopa loses effectiveness
progressive loss of nigral DA neurons
downregulation of D1/D2 receptors
L-dopa SE
dyskinesias on/off effect (use DA agonists) nausea anorexia hypotension confusion insomnia nightmares schizophrenia
AADH inhibitor (carbidopa)
inhibit decarboxylation of peripheral L-da
doesn’t cross BBB
SE:
increased L-dopa SE
increase COMT degradation of L-dopa
COMT inhibitors
diminish peripheral metabolism of L-dopa
reduce on/off fluctuations
entacapone
COMT inhibitor
orange urine
tolcapone
COMT inhibitor
hepatotoxic
DA receptor agonists
early PD: monotherapy
late PD: adjunctive
reduces on/off motor fluctuations
pramipexole
DA receptor agonist
binds D2/D3/D4
neuroprotective/antioxidant
SE: sleep attacks
ropinirole
DA receptor agonist
D3, then D2/D4
mild disease
neuroprotective/antioxidant
SE: orthostatic hypotension
CYP1A2 metabolism
amorphine
DA receptor agonist
short duration: temp relief of akinesia
SE: dyskinesias, drowsiness, sweating, hypotension
MAO inhibitors
early PD: monotherapy
late PD: adjunctive
reduce on/off motor fluctuations
irreverisble inhibitors of MAO, inhibit degradation of DA
selegiline
MAO inhibitor
SE: forms toxic metabolite in elderly
rasagiline
MAO inhibitor
no toxic metabolite
hypertensive crisis
tyramine rich diet causes peripheral accumulation of NE
fatal hyperthermia
meperidine, cocaine, fluoxetine + selegine
anticholinergics
block central cholinergic receptors
mild cases, younger pts, pts on neuroepileptic drugs
no improvement of bradykinesia
blocks M1 receptors on striatal neurons (presynaptic inhibition of Da release)
SE: atropine-like
amantadine
NMDA receptor antagonist
early PD: monotherapy
late PD: adjunct to reduce L-dopa induced dyskinesias
interferes w/Glu transmission
indirectly modifies DA cycle, binds DA receptors
excreted unchanged in urine
amantadine SE
elderly - restlessness, depression, instability, insomnia, agitation, excitement, hallucinations, confusion
headache, edema postural hypotension, heart failure, GI upset
amantadine OD
acute toxic psychosis
early-onset PD
1) DA agonists
2) adjunctive L-dopa
3) adjunctive MAO-B inhibitors
**lower risk of L-dopa induced dyskinesias
late-onset PD
1) L-dopa
2) adjunctive DA agonists, COMT inhibitors, or MAO-B inhibitors
**best control of motor S/S
