parkinson's Flashcards
what are some risk factors for parkinson’s disease (PD)
rural living
well water
pesticides
heavy metal exposure
fungus (mushroom alcohol)
what are some protective risk factors for parkinson’s disease
cigarette smoking
caffeine consumption
describe the pathophysiology of PD
decreased dopamine in the brain (SUBSTANTIA NIGRA)
symptoms appear when 70-80% of SN neurons are depleted
what are the roles of dopamine in the brain?
smooth, controlled muscle movement
cognition and frontal cortex function
pleasure and motivation
what acronym describes the cardinal symptoms of PD?
TRAP:
Tremor
Rigidity
Akinesia/bradykinesia
Postural instability
the onset of cardinal signs in PD is usually _____ and ______
unilateral and asymmetric!!
describe the tremor in PD
usually occurs at rest and disappears with voluntary movement or sleep
initially affects upper extremities
can manifest as pill rolling
describe rigidity in PD
manifests as cogwheeling or hypomimia (blank face)
describe akinesia/bradykinesia in PD
slow throughout an intended action, difficulty initiating movement, microglia (letters get smaller as you write), shuffling, freezing
what may be some differential diagnoses to rule out for PD?
insult: TBI, stroke, pugilism, supranuclear palsy
infection: encephalitis, meningitis, HIV/AIDS
intoxication: carbon monoxide, mercury, Wilson’s disease (copper accumulation), drugs
which drugs may induce parkinsonian symptoms
antipsychotics except clozapine
antiemetics like prochlorperazine
methyldopa
anesthesia
opioid overdose
MPTP (contaminant in street drugs)
how can dopamine cross the blood brain barrier?
peripherally administered dopamine CANNOT cross the BBB (it is hydrophilic and there is no DA transporter)
but L-DOPA, the immediate precursor, can cross
why is carbidopa added to L-dopa
to block the decarboxylation of L-dopa to dopamine in the periphery so it can cross into the brain as L-DOPA
what is the gold standard drug for symptomatic PD initial therapy if rigidity or bradykinesia is the chief complain
L-DOPA/carbidopa
which age group is L-DOPA preferred
older adults 65+
safest side effect profile
younger patients report L-DOPA dyskinesias
how long is L-DOPA effective for?
a finite period of time ~10-15 years
how to convert to controlled release/extended release L-DOPA
increase the IR dose by 30%
dosing for L-dopa/carbidopa
initial 25 mg/100 mg daily: start low and go slow- increase by 1 tablet every other day– max dose determined by patient tolerability (~1500 mg/day). after IR stable, can switch to long acting
likely need at least _____ of carbidopa to adequately inhibit peripheral conversion of L-DOPA and prevent nausea/vomiting
75 mg/day
what are the adverse effects of L-DOPA
nausea/vomiting
postural hypotension
dyskinesias, psychiatric disturbances
patient counseling for L-DOPA/carbidopa
IR onset of action may take up to 1 hr; longer for CR
ER: do not crush, can open and sprinkle on applesauce
L-DOPA competes with protein for absorption: counsel on diet
must taper when discontinuing
when are DA agonists the preferred agent
in younger patients (can cause psychiatric disturbance in older patients) as initial therapy option if rigidity or bradykinesia is chief complaint
may be considered early monotherapy in L-DOPA sparing strategy
DA agonist drug names
ergot derivatives: bromocriptine
non ergot derivatives: pramipexole, ropinirole, rotigotine patch
DA agonist dose adjustments
for renal
patient counseling for DA agonists
ropinirole/pramipexole: sleep attacks, a serious problem when driving
rotigotine: application site reactions
MUST taper when discontinuing
adverse effects: hallucinations and impulse control disorders (gambling and shopping)
why do we have to taper DA agonists?
abrupt cessation can lead to physiologic withdrawal including anxiety, panic attacks, n/v/d, depression, etc.
it can also exacerbate underlying PD causing diaphragm rigidity (asphyxiation) and immobility (clots)
how long should tapering last?
as long (if not longer) than the titration period
what are complications from L-DOPA?
wearing off effect when an adequate dose of L-DOPA does not last and symptoms return before the next dose
dyskinesias such as chorea, dystonia
prevalence of L-DOPA complications
more than half of patients develop complications after 5-10 years. more common in younger patients <60 years
what are options when L-DOPA is wearing off
change L-DOPA administration by either decreasing the dose and increasing the frequency, or give a combination of IR and CR formulations
or can augment L-DOPA with other therapies such as COMT inhibitors, MAO-B inhibitors, apomorphine
COMT inhibitor mechanism
selective & reversible inhibition of COMT (catecyl-o-methyl-transferase) inhibits degradation of DA
why are COMT inhibitors used?
to extend the life of L-DOPA in patients with motor fluctuations: it is ineffective when given as monotherapy so must administer simultaneously with L-DOPA
what drugs are the COMT inhibitors?
entacapone, tolcapone, opicapone
dosing considerations for COMT inhibitors
decrease L-DOPA dose by 25% when starting COMT
ADEs of COMT inhibitors
dopaminergic ADRs, urine discoloration
mechanism of MAO-B inhibitors
selective & irreversible inhibition of MAO-B in brain interferes with degradation of DA
which drugs are the MAO-B inhibitors
rasagiline, selegiline (PO only– patch not used in parkinson’s), safinamide
dosing considerations for MAO-B inhibitors
decrease L-DOPA dose by 10% when starting MAO-B
patient counseling for MAO-B inhibitors
drug interactions: contraindicated with opioids and serotonin drugs, even after stopped (x2 weeks)
interaction with foods containing tyramine (wine, beer, aged cheese, overripe food)
describe the use of apomorphine in PD?
DA agonist used in L-DOPA off episodes
apomorphine requires _____ due to risk of _____
test dose under medical supervision due to risk of severe hypotension
start _____ 3 days prior to apomorphine
trimethobenzamide
what new special formulations can be used for L-DOPA off episodes
CD/LD intestinal gel that is administered via external pump & jejunal tube (morning bolus, continuous dose, on-demand doses)
levodopa inhalation powder that can be used up to 5x/day as an on demand rescue for “off episodes”– 10 minute onset and lasts an hour but not recommended for asthma/COPD
when is istradefylline used
once daily for “off periods” as an add-on to CD/LD
considerations for istradefylline
special dosing (smokers, strong CYP3A4 inhibitors and inducers)
side effects are dyskinesias, hallucinations, insomnia
but does not cause orthostatic hypotension as other dopaminergic agents do
when might anticholinergics be used for PD?
as monotherapy in patients <65 if only tremor
or as adjunct therapy if persistent tremor despite DA therapy
which anticholinergics may be used for tremor in PD
benztropine or trihexyphenidyl
what factor limits the use of anticholinergics for PD
adverse effects– dry mouth, blurred vision, urinary retention, constipation, confusion, sedation
what is the role of amantadine in PD
adjunct therapy to decrease the intensity of L-DOPA dyskinesias
what is the mechanism of amantadine
it is an antiviral with mild and transient antiparkinsonian activity by increasing DA release, preventing reuptake, and directly stimulating the DA receptors
adverse effects of amantadine
hallucinations, confusion, dizziness, edema
older adults especially susceptible to CNS effects
what are the most common nonmotor symptoms of PD
depression
psychosis
constipation
genitourinary symptoms (sexual dysfunction, urinary incontinence)
treating depression in PD?
most common
SSRI/SNRI first line
psychosis in PD is characterized by ___ and treated by ___
characterized by hallucinations & delusions
treatment:
1. discontinue offending agents (anticholinergics, amantadine, MAO-B inhibitors, COMT inhibitors, DA agonists) but unlikely to d/c L-DOPA
2. consider low dose atypical antipsychotics (quetiapine>clozapine)
treatment of constipation in PD
try non pharm with increasing water and fiber
may consider PEG
AVOID PSYLLIUM
