Parkinson's Disease Flashcards
What are the symptoms associated with Parkinson’s Disease?
Bradykinesia + Tremor OR Rigidity OR Postural instability
TRAP (tremor, rigidity, akinesia, pstural instability)
What is the preferred treatment if tremor is the primary symptom?
anticholinergic
What is the recommended treatment to control motor fluctuations?
COMT inhibitors
What can be used for levodopa induced dyskinesia?
amantadine
What is the mechanism of action of monoamine oxidase inhibitors?
prevent the breakdown of dopamine= prolonged dopamine activity
What is the indication of monoamine oxidase-B inhibitors?
- initial monotherapy in early disease
- adjunct therapy in all stages of PD, may allow lower dosing of levodopa and extend the duration
What are the drug interactions of monoamine oxidase-B inhibitors?
- tyramine-containing foods in diet
- opiates
- SSRI/SNRI
- tricyclic antidepressants
- ephedrine (and the other derivatives)
- dextromethorphan
- lithium
What drugs are monoamine oxidase- B inhibitors?
- selegline
- rasagline
- safinamide
Which MAO-B inhibitor has amphetamine-like byproducts?
selegiline
What are the adverse effects of MAO-B inhibitors?
- nausea
- orthostatic hypotension/changes in BP
- weight changes
- balance difficulties
- peripheral edema
- hallucinations
- sleep changes
Avoid use of MOA-B inhibitors in severe ______________ impairment.
hepatic
What is the indication for anticholinergics?
- most useful for tremor
- initial treatment in younger patients (< 60-65) with disabling resting tremor as main symptom with preserved cognitive function
- adjunct to dopaminergic agents in mod-severe disease
avoid or limit use in older patients
What drugs are anticholnergics?
benztropine and trihexyphenidyl
What are the adverse effects of anticholinergics?
anticholinergic SE
- consipation
- dry mouth
- urinary retention
- tachycardia
- confusion, drowsiness
avoid in elderly with history with constipation and memory impairment
What are the indications amantadine?
- limited evidence as monotherapy, but may benefit tremor and ridigity the most
- used for synergistic effects with carbidopa/levodopa and dopamine agonists when used as adjunct in later stages of disease- may supress levodopa-induced dyskinesia
What are the contraindications of amantadine?
- CHF
- seizure disorders
- other stimulants
What are the precautions of amantadine?
- dosage adjustments in renal dysfunction
- do not abruptly withdrawal due to risk of neuroleptic maligant syndrome
What are the adverse effects of amantadine?
anticholinergic SE
- edema
- hallucinations
- GI effects (N/V/D)
- orthostatic hypotension
- depression
- insomnia
- cognitive and withdrawal effects
What drugs are dopamine agonists?
- pramipexole
- ropinole
- rotigitine
- apomorphine
What is the indication of dopamine agonists?
- pramipexole, ropinirole, and rotigitine= monotherapy in early mild disease or adjunct to CD/LD in advance disease
- apomorphine= adjunct/supplemental therapy for the treatment of hypomobility “off” episodes associated with “wearing off” and “on-off” in advanced disease
What are the adverse effects of dopamine agonists?
- postural hypotension, syncope, falls
- confusion
- psychosis
- lower extremity edema
- sleep attacks
- withdrawal emegent hyperpyrexia
- QTc prolongation
- impulse control disorders
apomorphine injection has significant nausea and vomiting
What is given with apomorphine injection to address associated nausea/vomiting?
trimethobenzamide 2 days before and for 2 months after until tolerated
What are the drug interactions of apomorhine?
5HT3 antagonists (ondansetron)
What drug is associated with significant nausea and vomiting?
apomorphine injection
What are the long term complications of carbidopa/levodopa use?
motor fluctuation and dyskinesia
What is the indication of cardidopa/levodopa?
benefits bradykinesia and ridigity the most
in older patients (>60-70) with functional impairment, those with cognitive impairment/dementia or advanced disease
What is the difference between CR and IR carbidopa/levodopa formulation?
CR has slower onset of action and is associated with more erratic absorption and decreased bioavaliability compared to IR
What are the adverse effects of carbidopa/levodopa?
- nausea/vomiting, anorexia
- arrhythmias
- orthostatic hypotension
- sedation, insomnia
- dyskinesia
- cognitive impairment, psychosis
titrate doses slowly
What is the indication of catechol-O-methyltransferase (COMT) inhibitors?
adjunct to CD/LD to reduce “off” time associated with “wearing-off”
What are the adverse effects of COMT inhibitors?
- dyskinesia, dystonia
- nausea
- cramps
- hallucinations, psychosis
- impulse control/compulsive disorders
- withdrawal emergent hyperpyrexia
- rise in blood creatinine kinase
What are the contraindications of COMT inhibitor use?
catecholamine secreting neoplasms and non-selective MAOI use
What drugs are COMT inhibitors?
- tolcapone
- entacapone
- opicapone
What is an adverse effect specifically associated with tolcapone?
diarrhea: excessive, delayed onset, limits use
peripheral and central COMT whereas the others are only peripheral
What is the monitoring needed with tolcapone?
fatal hepatotoxicity possible, basline LFTs then every 2-4 weeks for 6 months, then every 1-2 months
What is the mechanism of action of Istradefylline?
adenosine (A2a) receptor antagonist
What is the indication of Istradefylline?
adjunct to CD/LD for off episodes
What are the dosing adjustments of Istradefylline?
- avoid in hepatic impairment
- dosing adjustment needed for cig use (> 20/day)
What are the complications associated with advancing disease?
- motor complications
- neuropsychiatric manifestations
- sleep disturbances
- autonomic dysfunctions
- falls
How can pharmacotherapy be adjusted if patient is experiencing cognitive impairment?
discontinue anticholinergics and add actylcholinesterase inhibitor (rivastigmine or donepezil)
What can be used for depression and anxiety in PD?
- SSRIs, mirtazapine
- venlafaxine
- DA agonists may have some benefit
avoid lithium
What is the treatment for psychosis in PD?
reduce PD medication: anticholinergics > amantadine > MAO-B inhibitors
What can be used for excessive daytime sleepiness?
modafinil
What can be used to treat constipation?
- diet changes
- increase physical activity
- stop anticholinergics
- stool softeners
- bulk fibers
- PEG3350
What can be used to treat orthostatic hypotension?
- increased salt/food intake
- support stockings
- evaluate hypertensive medications
-elevate head - use caution when rising
- midodrine
