Parkinsons Flashcards
What are the 3 cardinal symptoms of PD?
1) Tremors
- Resting tremors that decreases with movement
- Increases with stress
2) Cogwheel and lead-pipe rigidity
3) Akinesia/Bradykinesia
- Subjective sense of weakness
- Loss of dexterity, facial expressions, reduced blinking
- Difficulty getting out of bed/chair/turning while walking
What are the non-motor symptoms of PD? (5) Do they present before or after motor symptoms?
1) Cognitive impairment (dementia)
2) Psychiatric disorders (depression, psychosis)
3) Sleep disorders
4) Autonomic dysfunction (constipation, GI motility, orthostatic hypotension, sialorrhea)
5) Fatigue
Non-motor sx usually present before clinical onset of physical (motor sx) [prodrome].
Briefly describe the pathophysiology of PD.
- Loss of dopaminergic neurons in the substantia nigra
- 80% loss by the time clinical sx are apparent
Other influencing factors include age, environmental toxins, pesticides, genetic predisposition and abnormalities.
List the main classes of medications that can cause drug-induced Parkinsonism. (7)
High risk:
1) Typical antipsychotics: Haloperidol, prochlorperazine
2) Atypical antipsychotics (at higher doses): Olanzapine, risperidone, aripiprazole
3) Tetrabenazine, reserpine (Dopamine depleters)
Intermediate risk:
4) Anti-seizure medications: Valproate, phenytoin, levetiracetam
5) Antiemetics & GI motility agents: Metoclopramide, Prochlorperazine
6) Mood stabilizers: Lithium
7) Calcium channel blocker (non-DHP; some high risk also e.g flunarizine)
Describe Levodopa’s place in therapy for PD.
- Most commonly used drug for PD
- Most effective drug for symptomatic treatment (esp bradykinesia and rigidity); less so for speech, reflex and gait disturbances
- NOT first-line for younger/early-onset PD (due to motor complications from prolonged use)
List the adverse effects of taking Levodopa (7).
- Nausea/vomiting
- Orthostatic hypotension
- Drowsiness, Sudden sleep onset
- Hallucinations, psychosis
- Motor complications (dyskinesias) - usually within 3-5y of initiation
What are some of Levodopa’s DDIs? (4)
1) Pyridoxine
2) Iron (space out administration)
3) Protein (space out administration)
4) Dopamine antagonists (metoclopramide, prochlorperazine, FGA, risperidone)
What are some administration instructions for Levodopa?
- Space out from iron supplements and protein-containing foods/supplements
- Space apart from high fat/protein meal (eat with or after light snack)
- Do not crush (Sinemet SR) or open capsule (Madopar HBS)
Generally, space apart from heavy meal and iron containing products.
Describe the place in therapy of dopamine agonists in PD.
- Monotherapy in young-onset PD
- Adjunct to levodopa in moderate-to-severe PD (management of motor complications)
- For freezing episodes (Apomorphine)
State the 2 broad types of dopamine agonists.
1) Ergot derivatives (bromocriptine, cabergoline, pergolide)
2) Non-ergot derivatives (rotigotine, pramipexole, ropinirole, apomorphine)
State the adverse effects of dopamine agonists (8; 3 types).
1) Peripheral dopaminergic effects
- N/V, orthostatic hypotension, leg edema
2) Central dopaminergic effects
- Hallucinations (visual > auditory)
- Somnolence, daytime sleepiness
- Compulsive behaviors (gambling, shopping, hypersexuality)
3) Non-dopaminergic effects
- Fibrosis (pulmonary, pericardiac, peritoneal)
- Valvular heart disease
- Higher risk w ergot derivatives
What is the place in therapy of MAO-B inhibitors in PD?
- Monotherapy in early PD stages, especially young-onset PD
- Adjunct in later PD stages; not as effective as levodopa or dopamine agonists
Can Selegiline (MAO-B inhibitor) be administered in the evening?
No.
Selegiline is hepatically metabolised to amphetamines, which are stimulating.
Administer 2nd dose ideally by 2pm, latest 4pm, to minimise sleep disturbances.
Rasagiline can be administered in evening as it does not get metabolised into amphetamines
What are some DDIs with MAO-B inhibitors?
- SSRIs, SNRIs, TCAs (washout period recommended)
- Pethidine, tramadol
- Linezolid
- Dextromethorphan
- Dopamine
- Sympathomimetics (nasal decongestants)
- Another MAOi
What is a key FDI with MAO-B inhibitors?
- Tyramine (aged cheese, meats, fermented products, banana peels, draft beer)
- Advise pts to avoid such foods to minimise hypertensive crisis episodes
What is the place of therapy of COMT inhibitors in PD?
- Adjunct to levodopa (NEVER used alone)
- Decreases the “off” time in response to levodopa
Can I take levodopa and COMT inhibitor separately?
No.
Both should be taken at the same time
What are some of the adverse effects of COMT inhibitors? (4)
- Diarrhea
- Urine discoloration (orange)
- Dyskinesia (upon initiation)
- Potentiation of other dopaminergic effects (N/V, orthostatic hypotension)
What is the place in therapy of NMDA antagonists in PD?
- Adjunct to levodopa
- Manage levodopa-induced dyskinesias
What are some of the adverse effects of NMDA antagonists?
- Nausea
- Light-headedness (hypotension)
- Insomnia
- Confusion
- Hallucinations
- Livedo reticularis
What are some of the non-pharmacological management options for PD?
1) Physiotherapy
- Stretching, transfers, posture
- Walking
2) Occupational therapy
- Mobility aids
- Home and workplace safety
3) Speech and swallowing
4) Surgery
What are the management options for drug-induced Parkinsonism?
- Withdrawal of offending drug (sx not alw reversible)
- Anticholinergics or amantadine may be used
What catalyses the peripheral conversion of levodopa to dopamine (3)
DOPA decarboxylase, MAO, COMT
Peripheral conversion of dopamine causes what adverse effects? (3)
nausea/vomiting, hypotension
List the motor complications associated with Levodopa use and their managements where applicable
1) On-off phenomenon
* ON= response to levodopa, OFF= no response to levodopa
* Unpredictable, not related to dose/dosing interval (= “throwing a light switch”)
* Mechanism unclear
* Difficult to control with meds
2) Wearing off
* Effect of levodopa wanes before the end of the dosing interval = Shortened “ON” time
* Associated with disease progression
* Management:
o Modify times of administration, and/or
o Replace with modified-release preparations at the appropriate time
3) Dyskinesias
* Usual onset: within 3-5 years of initiating treatment with levodopa
* Gets more unpredictable as disease progresses and often irreversible -> flattening peak dose may not help
* Involuntary, uncontrollable twitching/jerking
* Forms:
o Peak dose dyskinesia -> give smaller but more frequent doses
o Dystonia
* Management:
o Add amantadine
o Replace specific doses with modified release levodopa
State what Levodopa sustained release forms are useful for, their F compared to normal immediate release Levodopa as well as any dose adjustment required when switching between preparations
Good for decreasing stiffness on waking
Lower F compared to IR
- Switch from IR to CR: inc dose by 25-50%
- Switch from CR to IR: dec dose
What are protective factors for PD?
Smoking, caffeine
State the COMT inhibitor used for PD
Entacapone (Tolcapone not used anymore due to ADRs)
List the names of Anticholinergics
Benztropine, Benzhexol (Trihexyphenidyl)
