Parkinson's Disease Flashcards
Drug induced causes of PD
antipsychotics (phenothiazines, butyrophenones, atypical agents)
antiemetics (metoclopramide, prochlorperazine)
Toxic substances (manganese dust, carbon monoxide poisonning, MPTP)
Clinical Presentation of PD
Cardinal features (resting tremor, rigidity (cogwheeling), bradykinesia)
Motor sxs (gait abnormalities, impaired fine movements, micrographia, masked face, decreased blinking, dysphagia, drooling)
Autonomic sxs (orthostatic hypotension, constipation, bladder & sexual dysfunction)
Cognitive & psychiatric sxs (cognitive decline, hallucinations (can also be tx related), anxiety, depression, sleep disorders, behavioral sxs, agitation)
Diagnosis of PD
Neurologic exam. Cardinal features: resting tremor, bradykinesia, rigidity.
Possible (1 feature)
Probable (2 features)
Definite (at lease 2 features and a positive response to levodopa)
Anticholinergics for PD
benztropine, trihexyphenidyl, diphenhydramine
Help correct imbalance b/t dopamine & acetylcholine.
Mainly beneficial for tremors (can be used for initial therapy if tremors are predominant)
ADEs limit utility (confusion, urinary retention, constipation)
Levodopa/carbidopa
Levodopa - dopamine precursor, most clinically effective PD therapy
Carbidopa - dopa decarboxylase inhibitor, prevents peripheral conversion of levodopa to dopamine; reduces levodopa requirement; improves tolerability; need 75-100mg/day to saturate enzymes.
Most pts eventually devlop motor complications (dyskinesias (tics, involuntary movements), on-off phenomenon, freezing) after several years. In younger pts, this tx is sometimes delayed to avoid these adverse effects in the future.
Given in several daily doses.
ADE: n/v, hallucinations, delusions, syncope, arrhythmias, edema, hypotension
Dopamine agonists for PD
pramiprexole, ropinorole, apomorphine (injection)
(non-ergot derviatives)
Initial therapy or adjunct with levodopa. Not as clinically effective as levodopa, but fewer long-term (motor) complications.
Decrease levodopa when adding on a dopamine agonist to avoid dopaminergic ADEs (nausea, hallucinations, dyskinesias).
ADEs: daytime sleepiness, aggression, n/v, hallucinations, postural hypotension, somnolence, confusion, edema
When switching from IR to ER, choose ER dose that most closely matches daily IR dose
apomorphine
Dopamine agonist
2-6mg injected subq for intermittent freezing episodes
MAO-B inhibitors
Selegiline (amphetamine metabolite may cause insomnia, give 2nd dose at noon), rasagaline (no amphetamine metabolite)
Block degredation of dopamine. Can be used as initial therpay or add-on to levodopda. Possible neuroprotective effects, but control of motor sxs inferior to levodopa. May improve motor complications related to long-term levodopa (may have to lower levodopa dose when adding on)
MAO-B inhibition should not be an issue with tyramine containing foods @ recommended doses.
Potential fro drug interactions is low at recommended doses.
Selegiline ODT contraindiated for use with dextromethorphan, methadone, propxyphene, tramadol, other MAO inhibitors.
selegiline ADEs
MAO-B inhibitor
h/a, insomnia, hallucinations, dizziness
rasagiline ADEs
MAO-B inhibitor with no amphetamine metabolite
postural hypotension, dyskinesias, h/a, nausea, weight loss
COMT inhibitors for PD
Entacapone
inhibits metabolism of levodopa.
Not useful as monotherapy (only used in combo with levodopa) Decrease levodopa dose when adding.
tolcapone not used d/t fatal hepatotoxicity; severe diarrhea being more common.
ADEs: brown/orange urine, nausea, dyskinesias, postural hypotension, diarrhea, hyperkinesia
amantadine
increase synthesis and release of dopamine, decrease dopamine reuptake, anticholinergic effects, NMDA modulation
initial monotherapy of mild-mod dx (not typically done) or adjunctive to levopda in advanced dx.
may improve tremor, rigidity and bradykinesia
Most useful for treating dyskinesias (motor complications) associated with long-term dopaminergic tx.
Renal dose adjustment required.
ADEs:
Coenzyme Q10 for PD
1200mg/day showed improved UPDRS scores relative to placebo, greatest effects in daily function
Initial PD therapy
when sxs become sufficiently bothersome.
levodopa has superior control of motor sxs.
MAO-B inhibitors considered in pts with mild sxs.
risk of hallucinations: dopamine agonists > levodopa
end of dose wearing off
increase frequency of levodopa
then
consider adding MAO-B inhib, COMT inhib, or dopamine agonist if needed
