Chapter 69 - Parkinson's disease Flashcards
parkinson background
- Neurological disorder.
- > = 65
- Neurons in substantia nigra die or become impaired.
- These cells produce the neurotransmitter dopamine (DA), which allows smooth, coordinated function of body muscles and movement.
- When -80% of the dopamine-producing cells are damaged, the motor symptoms of the disease appear
low dopamine causes parkinson - high dopamine causes schizophrenia (psychosis)
PD Sx
In ParkinsonDisease:
Less dopamine ➔ less instructions to the brain ➔ movement problems (called the TRAP major symptoms)
TRAP Major Symptoms:
- Tremor: when resting
- Rigidity: in legs, arms, trunk and face (mask-like face)
- Akinesia/ Bradykinesia: lack of/ slow start in movement
- Postural Instability: imbalance, falls
AdditionalSymptoms:
- Small, cramped handwriting (micrographia)
- Shuffling walk, stooped posture
- Muffled speech, drooling, dysphagia
- Depression, anxiety (psychosis in advanced disease)
- Constipation, incontinence
- Tremor: first noticeable symptom; usually starts in one hand or foot (on just one side, unilateral) and eventually spreads to both sides (bilateral).
- Resting tremor means it appears when the hand is not moving, such as when a person’s hand is resting in their lap.
Abnormal involuntary movement scale (AIMS) is used to
Measure involuntary movements from medications (Tardive dyskinesia)
Dopamine blocking drugs that can worsen PD:
■ Phenothiazines (e.g., prochlorperazine) used for nausea, agitation, psychosis,
■ Butyrophenones (e.g., haloperidol, droperidol) used for psychosis and behavior disorders or nausea
■ First and second-generation antipsychotics (e.g.,risperidone at higher doses, paliperidone); lowest risk with quetiapine
■ Metoclopramide, a renally-cleared drug that can accumulate in elderly patients
Non-motor Sx
- loss of smell (anosmia), constipation, sleep difficulties, low mood/depression and orthostasis.
What are off times or off episodes in PD?
Even with high doses of PD drugs and various combinations, the disease will progress, including extended periods of “off time.”
This is when symptoms of the disease worsen before the next dose of medication is due.
An “off” episode, with muscle stiffness, slow movements and difficulty starting movement, is one of the most frustrating aspects of living with the disease.
How to treat depression caused by PD?
- SSRI or SNRI
–> Concern: may contribute to tremor or inc risk of serotonin syndrome in patients taking other serotonergic agents - Tricyclic antidepressants, preferably the secondary amines (such as desipramine and nortriptyline), and the dopamine agonist pramipexole (reported to provide antidepressant effects), are other options.
Antipsychotic that has the lowest risk of movement disorders?
And what SE does it cause more than others?
Quetiapine is the preferred antipsychotic due to a low risk of movement disorders
but it can cause metabolic complications, including increased cholesterol and blood glucose.
Which antipsychotic has a low risk of worsening movement disorders
but has a high risk of agranulocytosis, seizures and other serious complications.
What should you monitor with it?
Clozapine
Requires frequent monitoring and reporting of white blood cells.
Pimavanserin (Nuplazid)
a 5HT2A/2C receptor inverse agonist, is FDA-approved to treat hallucinations and delusions in PD
when does NMS occur and how can you prevent it?
Rapid withdrawal of levodopa or dopamine agonists can lead to a condition similar to neuroleptic malignant syndrome (NMS),which is a life-threatening condition sometimes seen with antipsychotics.
These medications must be tapered off slowly if discontinued to prevent this condition.
Levodopa
Levodopa, a prodrug of dopamine, is the most effective agent.
why do you give carbidopa with levodopa?
What is the brand name of this combination?
Carbidopa is given with levodopa (in the combination product Sinemet) to prevent the peripheral (i.e., outside of the CNS) metabolism of levodopa, which would destroy most of the drug before it crosses the blood-brain barrier.
It is important to provide the right amount of carbidopa without causing excess side effects (see the drug table on the following page).
Initial treatment with … is sometimes better tolerated in the elderly than …
… are commonly used for initial treatment in younger patients and eventually in most patients.
Initial treatment with carbidopa/levodopa is sometimes better tolerated in the elderly than the dopamine agonists.
Dopamine agonists are commonly used for initial treatment in younger patients and eventually in most patients.
As the disease progresses, treatment will be directed at
This will require multiple therapies, such as
both reducing “off” periods and limiting dyskinesias (abnormal movement).
catechol-o-methyltransferase (COMT) inhibitors and MAO-B inhibitors.
Tremor-predominant disease in younger patients can be treated with:
Can you use these drugs for elderly? Why?
… or … are other options for initial treatment of tremor.
A centrally-acting anticholinergic.
Amantadine or a selective monoamine oxidase (MAO) inhibitor are other options for initial treatment of tremor.
The considerable side effects of these drugs make them difficult to use in elderly patients; the Beers criteria for potentially inappropriate medication use in older adults recommends to “avoid” use.
Do u use selective or non selective MAO I in PD?
And which one do you use in depression and why are they CI for PD?
For PD, selective MAO inhibitors are used; the non-selective inhibitors that are used for depression are contraindicated with dopaminergic drugs because they would block drug metabolism.
… can be useful to help with dyskinesias, in addition to tremor.
Amantadine
… treats severe freezing episodes that usually occur in more advanced disease, but it requires subcutaneous (SC) administration, has worrisome side effects and provides increased movement for just about an hour.
Apomorphine
… is a newer drug indicated for orthostatic hypotension, which can affect PD patients.
Droxidopa (Northern)
DOPAMINE REPLACEMENT DRUGS & AGONISTS + MOA
1) Carbidopa/levodopa:
MOA: levodopa is a precursor of dopamine. Carbidopa inhibits dopa decarboxylase nz metabolism of levodopa.
2) COMT inhibitors:
MOA: increase the duration of action of levodopa; inhibit the enzyme catechol-O-methyltransferase (COMT) to prevent peripheral conversion of levodopa. COMT inhibitors should only be used with levodopa.
3) Dopamine agonists:
MOA: act similar to dopamine at the dopamine receptor.
4) Dopamine agonist injection for advanced disease:
Indication: A “rescue”movement drug for “off”periods
Carbidopa/ Levodopa Brand names + doses
- Sinemet IR,
DOSE: 25/100 mg PO TID (Carbi must be 70-100 mg/day)
-Sinemet CR Tablets:
DOSE: 50/200 PO BID (double the IR)
Can be cut in half - do not crush or chew
- Rytary: ER capsule
DOSE: start at 23.75/95 mg PO TID if levodopa-naive; take whole or sprinkle on a small amount of applesauce - Duopa: Enteral suspension given via J-tube
- lnbrija: Levodopa capsule for oral inhaler, used as needed for symptoms during off periods
DOSE: lnbrija: 84 mg (2 capsules) inhaled up to 5 times daily as needed,
max dose: 420 mg/day
Titrate cautiously
CARBIDOPA/ LEVODOPA CI
- Non-selective MAO inhibitors within 14 days, (cz they block drug metabolism)
- Narrow angle glaucoma
CARBIDOPA/ LEVODOPA SE
- Can cause brown, black or dark discoloring of urine, saliva or sweat and can discolor clothing
- Positive Coombs test: discontinue drug (hemolysis risk)
- Unusual sexual urges, priapism
- inc uric acid
- Nausea
- Dizziness, orthostasis,
- Dyskinesias, dystonias (occasional, painful),
- Hallucinations, psychosis, confusion
- Xerostomia (dry mouth)
Rytary: suicidal ideation and attempts
Duopa: GI complications
