Parkinson's Treatment Flashcards
Goals of therapy for PD include…
Reducing signs and symptoms, both motor + non-motor
Minimize complications of drug therapy
Maintain independence
Improve/maintain quality of life
Non-pharmacological treatment for PD may include…
Physical therapy, occupational therapy, speech therapy
Hearing, vision, dental care
Psychological support
Pharmacotherapy focuses on ____ levels.
Increasing dopamine levels
Cornerstone of PD pharmacotherapy is…
Levodopa
Levodopa is always used in combination with…
Peripheral decarboxylase inhibitor - carbidopa, benserazide
The purpose of peripheral decarboxylase inhibitors is to…
Prevent conversion of levodopa to dopamine outside of the brain - enhance efficacy and reduce AE’s
The BBB relates to levodopa and the decarboxylase inhibitors via…
Ability to cross the BBB. Carbidopa and benserazide cannot cross the BBB,while levodopa can, and gets coverted to dopamine via decarboxylase
Initially, levodopa treatment is universally effective for…
Bradykinesia + rigidity
With initial tx of levodopa, a response is usually seen…
Within days - maximal improvement in ~2 weeks
Levodopa is less likely to help with…
Poor balance, non-motor symptoms
Variable effect on tremor
Bioavailability of levodopa is decreased with…
Co-administration of protein, iron, and antacids
Dosing of levodopa should be ____ to prevent…
Tirated slowly, prevent nausea/dizziness
CR form of levodopa is primarily used at ____. This is due to…
Bedtime/overnight - has delayed and unpredictable onset
AE’s with levodopa may include…
Nausea, GI upset
Dizziness - orthostatic hypotension
Fatigue
Vivid dreams
Confusion/hallucinations (later stages)
Nausea + GI upset with levodopa can be minimized via…
Give with food, but be aware that protein decreases levodopa absorption which may become relevant
Refractory nausea = domperidone
Complications of levodopa therapy start to develop after…
5 years of treatment
Complications of levodopa therapy include…
Wearing off
On-off phenomena (fine one minute, drug worn off the next)
Freezing, inability to move
Dyskinesias; abnormal, uncontrollable, involuntary movements
Dyskinesia = twisting, jerking, twisting, writhing movements; affect different areas
Dyskinesias with levodopa result from…
Increased sensitivity of brain to levodopa as PD progresses; most common shortly after a dose
Other formulations of levodopa that were developed to address some of the oral limitations included…
Intestinal gel infusion
Subcutaneous infusion
Inhaled capsules
The levocarb gel infusion (Duodopa) is administered via…
Enteral - PEG-J tube, delivering low and constant doses of levocarb
Levocarb gel infusion helps with PD by…
Reducing off-time by ~2 hours per day, without increasing dyskinesias
Levocarb subcutaneous infusion administers…
Low and constant doses of levocarb; connected to a pump
Most common AE’s with the levocarb subcutaneous infusion include…
Injection-site reactions
Dyskinesias
Psychosis
Levodopa inhaled capsules are used…
PRN for unexpected off-periods or delayed onset
Dopamine agonists that we use include…
Non-ergot derivatives
Pramipexole
Ropinirole
Rotigotine (transdermal patch)
We do not use the dopamine agonists that are ergot derivatives such as bromocriptine or cabergoline because of…
Pulmonary and cardiac valve toxicities
Dopamine agonists MOA is…
Mimic effect of dopamine by stimulating post-synaptic dopamine receptors
Dopamine agonists may be used as initial therapy for these patients…
Young PD patients under 60, to “save” levodopa for later
Pros and cons with using dopamine agonists as initial therapy include…
Pros: less risk of motor complications seen with levodopa
Cons: Less effective for motor symptoms and more AE’s compared to levodopa
Dopamine agonists are not the preferred agents for older adults, due to…
Poor tolerability
Dopamine agonists may be used for add-on tx, when…
Motor complications develop if refractory/intolerant to other options
Dopamine agonists also have an indication for ____ besides PD.
Restless legs syndrome
AE’s of dopamine agonists include…
Nausea, GI upset
Orthostatic hypotension
Hallucinatrions + confusion
Drowsiness, sudden sleep attacks
Leg swelling
Impulse control disorders
Worse than levodopa
The only dopamine agonist that needs to be dose-adjusted in renal impairment is…
Pramipexole
Apomorphine is…
A very potent dopamine agonist, used for rescue therapy (freezing)
The two forms of apomorphine are…
Injectable (Movapo) and sublingual (Kynmobi)
Movapo is injected via…
Subcutaneous
Notable AE’s and issues with Movapo is…
High incidence of nausea and vomiting; concurrent antiemetic recommended
May not be possible to administer without help of others
Kynmobi onset of action…
Is slower compared to Movapo - may take up to 30 minutes to work; considered as adjunctive therapy for “off-periods”
Function of MAO-A and MAO-B is to…
MAO-A breaks down NE and 5-HT preferentially
MAO-B breaks down dopamine and other amines preferentially
MAO-B inhibitors MOA for PD is…
Increasing dopamine by preventing breakdown of dopamine
Non-selective MAO inhibitors that inhibit both MAO-A and MAO-B are not used often anymore because of…
Strict dietary tyramine restriction - body cannot break down tyramine = hypertensive crisis, cardiac arrythmias
MAO-B inhibitors lose selectivity at ____ the recommended dose
2-5 times the recommended therapeutic dose
Therefore no need to restrict dietary tyramine at doses used for PD
Can MAO-B inhibitors be used as monotherapy?
Yes, for mild symptoms; but will be less effective than levodopa
MAO-B inhibitors may be used later in disease course, to help…
Manage motor complications with levodopa therapy - wearing off, freezing
AE’s with MAO-B inhibitors include…
Fairly well tolerated
Nausea, headaches, insomnia
The two drugs that are MAO-B inhibitors are…
Rasagline
Selegiline
A notable DI with MAO-B inhibitors is…
SSRI’s - possibility of causing serotonin syndrome
Unlikely to cause at recommended doses, so if warranted lowest effective dose should be used
A COMT inhibitor is…
Entacapone
COMT inhibitors need to be given with ____ because…
Levodopa - COMT inhibitor prevents levodopa from being metabolized to 3-OMD in periphery, so more levodopa can get into the brain.
COMT inhibitors are used for…
Prolonging action of levodopa, once motor complications develop (wearing-off, freezing)
Once entacapone is started, we need to reduce…
Levodopa by 30%, to minimize dyskinesia risk
AE’s with entacapone include…
Fairly well-tolerated
Nausea, diarrhea
Discoloration of urine and sweat to orangey-brown color
Amantadine’s role in PD treatment is…
Limited to treating bothersome dyskinesias later in the disease course
AE’s of amantadine include…
Nausea, dose related
CNS - confusion, hallucinations
Peripheral edema
Benign rash on legs
Not as well tolerated in older adults due to CNS
When dosing amantadine, we need to be aware of…
Dose adjusting in renal impairment
The anticholinergics that may be used in PD include…
Benztropine
Tryhexylphenidyl
Procyclidine
MOA of anticholinergics in PD is…
Decrease amount of ACh in the brain, which restores dopamine/ACh balance in the striatum
Anticholinergics are effective mainly for…
Tremor - not really for other motor symptoms
Anticholinergics are not used often due to…
Poor toleration in older adults - anticholinergic AE’s of worsening fall risk, cognitive decline, etc.
For levodopa-associated motor complications, if someone is having issues with end-of-dose “wearing off” and has mild/no dyskinesia, our options could include…
Increase frequency of levodopa
Add entacapone
Add dopamine agonist
Add rasagiline
Consider tolerability and risk of dyskinesia
For levodopa-associated motor complications, if someone is having issues with end-of-dose “wearing off” and is experiencing moderate/severe dyskinesia, our options could include…
Add amantadine
Increase frequency, but use smaller doses of levodopa
Decrease levodopa and add dopamine agonist
For levodopa-associated motor complications, if someone is having issues with dyskinesia, with no problem with “wearing off,” our options could include…
Add amantadine
Decrease levodopa dosing, or increase frequency
Discontinue anticholinergics or MAO-B if patient was using
If levodopa is failing, general principles we can consider
Take on empty stomach as much as possible (spacing from protein)
If issues at bedtime, add dose of levocarb CR at night
Tailor levocarb dosing to off-times
If all routes of pharmacotherapy are ineffective for treating PD symptoms, we could consider
Surgical treatment - deep brain stimulation
Continuous levocarb infusion
For constipation, we may recommend…
Non-pharm: increasing fiber, fluids, exercise
Consider PEG 1st line
Stimulant/laxative, domperidone
For depression/anxiety in PD, they can be managed…
Similar to depression + anxiety in patients without PD
We should avoid this antidepressant, because…
Bupropion - additive dopaminergic effect may contribute to restlessness, insomnia, dyskinesias
It is important to frequently re-evaluate necessity of antidepressant use in PD patients and describe if possible, due to…
Increased fall risk
Contribution to orthostatic hypotension
Orthostatic hypotension may be caused by…
Autonomic dysfunction related to PD
PD medications
Orthostatic hypotension is important to treat due to…
An increased risk of falls, whether symptomatic or asymptomatic
Non-pharm treatments for orthostatic hypotension include…
Ensuring adequate hydration
Eat smaller meals more frequently
Increase salt intake
Stand slowly
Taper/stop antihypertensives
Re-evaluate other medications that may contribute
If orthostatic is refractory and severe, we could consider drug treatment with…
Domperidone
Midodrine (alpha-1 agonist)
Fludrocortisone (mineralocorticoid)
Domperidone efficacy wise is…
Has the least efficacy but is the most safe as it does not cause supine hypertension
Midodrine and fludricortisone usage is limited due to…
Safety risk of supine hypertension - dose must be decreased or stopped if lying SBP is above 160 mmHg
Urinary incontinence may be caused by…
Autonomic dysfunction
Decreased mobility
Age-related changes
For urinary incontinence, this treatment is preferred…
Non-pharm; pharmacotherapy only if refractory
Non-pharm urinary incontinence management includes…
Regular toileting
Decreasing caffeine + fluid intake in the evening
Usage of assistive devices
Pelvic floor muscle training
Erectile dysfunction may be caused by…
Autonomic dysfunction in PD
1st line drugs for erectile dysfunction in PD are…
Phosphodiesterase-5 inhibitors
Sialorrhea in PD may be caused by…
Decrease in mouth movements and swallowing frequency
Non-pharm measures to help with sialorrhea may include…
Chewing gum
Sucking on soft candy to trigger swallowing reflex
Pharmacological treatments to help with sialorrhea may include…
Ipratropium spray to mouth
Atropine eye drops administered sublingually
Botox if refractory or issues with atropine
Anticholinergic to dry up mouth
Non-pharm measures for insomnia may include…
Usual sleep hygiene measures
Ensure adequate control of PD motor symptoms at night
Pharmacotherapy for insomnia may include…
Melatonin
Low-dose doxepin
Trazedone (risk of orthostatic hypotension)
Ideally these would be short term strategies
If treatment of REM sleep behaviour disorder is needed, we could try…
Melatonin
Clonazepam
Remember all the issues with BZD’s in older adults…
Excessive daytime somnolence is usually multifactorial, considering causes such as…
Medications
Sleep disorders
Degeneration of sleep regulation centers in brainstem as PD progresses
Exercising caution
Adjust contributing medications!
If an individual wants to try a medication for excessive daytime drowsiness, they could try…
Modafinil - stimulant indicated for narcolepsy
Psychosis in PD usually entails…
Hallucinations, usually visual
Paranoid delusions
Hallucinations may not require treatment when…
Patient is not distressed
Relatively infrequent, not bothersome
Insight preserved
If hallucinations are distressing, course of action should be…
Slowly discontinue medications that may be contributing (dopamine agonist, anticholinergic)
Avoid typical antipsychotics
These medications could be used for psychosis + PD…
Quetiapine - less consistent efficacy, but has not been shown to worsen PD symptoms
Clozapine is efficacious but has significant AE’s
Pimavanserin
Cholinesterase inhibitors in PD dementia, but may worsen movement sx’s
