69. Parkinson Disease Flashcards
Parkinson is a neurological disorder that occurs when neurons in the ____ (part of the brain) die or become impaired. These cells produce the NT ____ which allows smooth, coordination function and movement of body muscles.
substantia nigra
Dopamine (less dopamine»_space; less instructions to the brain»_space; movement problems (TRAP major symptoms)
What are the TRAP major symptoms of parkinson disease?
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
Other symptoms to know:
Small, cramped hand writing (micrographia)
Shuffling walk, stooped posture
muffled speech, drooling, dysphagia
Depression, anxiety (psychosis in advanced disease)
Constipation, incontinence
What tool can be used to measure involuntary movements (e..g tardive dyskinesias) from medications?
Abnormal involuntary movement scale (AIMS)
Dopamine blocking drugs that can worsen Parkinson Disease
Phenothiazines (e.g. prochlorperazine) used for psychosis, nausea, agitation
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 pts
Even with high doses of Parkinson Disease drugs and various combinations, the disease will progress, including extended periods of “off time”. What does this mean?
When symptoms of the disease worsen before the next dose of med is due. An “off” episode, with muscle stiffness, slow movements and difficulty starting movement, is one of the most frustrating aspects of living with parkinson disease.
Patients with parkinson disease have a high incidence of depression. ___ are commonly used for treatment (concerns with may contribute tremor or increased risk of serotonin syndrome with other serotonergic drugs).
Other options include ___ (preferably secondary amines such as ____) and dopamine agonist pramipexole (reported to provide antidepressant effects).
SSRIs, SNRIs
TCAs - despiramine and nortriptyline
Psychosis can occur with advanced parkinson disease or can be d/t side effects of drug treatment. ____ is preferred d/t low risk of movement disorders but can cause _____ complications. ___ has low risk of movement disorders but high risk of seizures, agranulocytosis (requires frequent monitoring and reporting of WBC) and other serious complciations.
Quetiapine
metabolic complications (increased lipids and BG)
Clozapine
Rapid withdrawal of levodopa or dopamine agonists can lead to a condition similar to ___ which is a life-threatening condition sometimes seen with antipsychotics. Taper slowly when d/c.
neuroleptic malignant syndrome (NMS)
___ is the most effective drug treatment for Parkinson Disease
Levodopa (prodrug of Dopamine)
PD drug treatment: ___ is given with levodopa (in the combination product____ ) to prevent peripheral metabolism of levodopa which would destroy most of the drug before it crosses BBB
carbidopa
Sinemet
Note: important to provide right amt of carbidopa without causing excess side effects
Initial treatment with ____ is sometimes better tolerated in elderly pts with PD than the dopamine agonists
carbidopa/levodopa
___ are eventually used in most pts. As PD progresses, treatment will be directed at both reducing ___ and limiting ____. This will require multiple therapies such as _____ and ____.
Dopamine agonists
Reducing “off periods” and limiting dyskinesias
COMT inhibitors and MAO-B inhibitors
Tremor-predominant PD in younger pts can be treated with _____. Considerable side effects of these drugs make them difficult to use in elderly pts (Beers criteria says “avoid” use)
centrally-acting anticholintergic (e.g. benztropine)
PD treatment principles - primary treatment is to replace ____ by administering ____
dopamine
Precursor to dopamine that becomes dopamine in the brain (levodopa in Sinemet)
Dopamine agonist that acts like dopamine
Give other drugs for specific symptoms (e.g. benztropine for resting tremor)
How do carbidopa/levodopa in Sinemet work together for PD?
Levodopa is precursor of dopamine = replaces dopamine
Carbidopa inhibits dopa decarboxylase enzymes = prevents peripheral metabolism of levodopa
Starting dose of carbidopa/levodopa (Sinemet) IR
25/100mg PO TID
T/F: Sinemet ER tab cannot be cut in half
False - can be cut in half but do not crush or chew
T/F: carbidopa/levodopa (Rytary ER Capsule) can be opened and sprinkled on small amount of applesauce
True - take whole or sprinkle on applesauce
Contraindications of carbidopa/levodopa
Non-selective MAOi (e.g. phenelzine, isocarboxazid) within 14 days,
narrow angle glaucoma
Side effects of carbidopa/levodopa
Nausea, dizziness, orthostasis, dyskinesias, hallucinations, psychosis, xerostoia (dry mouth), dystonias (occasional, painful), confusion
Can cause brown, black, or dark discoloring of urine, saliva or sweat (may discolor clothing
Positive Coombs test = d/c drug (hemolysis risk)
Usual sexual urges, priapism
Increased uric acid
Rytary: suicidal ideations and attempts
___ mg/day of carbidopa required to inhibit dopa decarboxylase
70-100mg
Long-term use of carbidopa/levodopa can lead to ___
fluctuations in response and dyskinesias
T/F: Carbidopa/levodopa must be titrated up cautiously but can be d/c immediately
False - titrate up cautiously and taper off
COMT inhibitor MOA
increase duration of action of levodopa; inhibit enzyme COMT to prevent peripheral conversion of levodopa - should ONLY be used with levodopa
Examples of COMT inhibitors
Entacapone (Comtan)
Entacapone/carbidopa/levodopa (Stalevo)
Opicapone (Ongentys)
Olcapone (Tasmar)
Entacapone (Comtan) dose
200mg PO with each dose of carbidopa/levodopa
Max = 1600 mg/day
Decrease in ____ dose of 10-30% is usually necessary when adding COMT inhibitor
levodopa
Why is COMT inhibitor tolcapone (Tasmar) rarely used?
hepatotoxicity risk
Examples of dopamine agonists used in parkinson disease
Pramipexole (Mirapex, Mirapex ER)
Ropinirole (Requip XL)
Others:
Rotigotine (Neupro) - patch, also approved for RLS
Apomorphine (Apokyn injection, Kynmobi SL film) - used as “rescue” movement drug for “off” periods
Warnings with dopamine agonists
Somnolence (including sudden daytime sleep attacks), orthostasis, hallucinations, dyskinesias, impulse control disorders
Rotigotine (Neurpo) patch: application side reactions
Rotigotine (Neupro) patch administration notes
apply once daily at the same time each day to stomach, thigh, hip, side of body, shoulder, or upper arm
Do not use same site for at least 14 days
Remove patch before MRI
Avoid if sensitivity/allergy to sulfites
Rotigotine (Neupro) patch should avoid if sensitivity/allergy to ___
sulfites
Pt is prescribed Apomorphine (Apokyn) injection. What must be done before starting?
Must be started with test dose in medical office
Contraindications with apomorphine
do not use with 5-HT-3 antagonists (e.g. ondansetron) d/t severe hypotension and loss of consciousness
Side effects with apomorphine
Severe N/V, hypotension, yawning, dyskinesias, somnolence, dizziness, QTprolongation
SL film: dry mouth, tongue pain
Apomorphine can cause severe N/V. For emesis prevention what can be given?
Trimethobenzamide (Tigan) 300mg PO TID or a similar antiemetic, started 3 days prior to initial dose
Do NOT give ondansetron (5HT-3 antagonist) d/t severe hypotension and loss of consciousness
_____ can decrease absorption of carbidopa/levodopa (Sinemet)
iron and protein-rich foods
Amantadine MOA
blocks dopamine reuptake into presynaptic neurons and increases dopamine release from presynaptic fibers
Primarily used to treat dyskinesias a/w peak-dose of carbidopa/levodopa
Warnings with amantadine
Somnolence (including falling asleep without warning during ADLs)
compulsive behaviors
Psychosis (hallucinations, delusions, paranoia)
Side effects with amantadine
Dizziness, orthostatic hypotension, cutaneous reaction called livedo reticularis (reddish skin mottling = can require drug d/c)
Others: syncope, insomnia, abnormal dreams, dry mouth, constipation
Examples of Selective MAO-B inhibitors used in PD
Selegiline
Rasagiline (Azilect)
Safinamide (Xadago)
MAO of Selective MAO-B inhibitors used in PD
block breakdown of dopamine which increases dopaminergic activity
Primarily used as adj treatment to carbidopa/levodopa
Rasagiline has indication for monotherapy
Contraindications of Selective MAO-B inhibitors used in PD (selegiline, rasagiline, safinamide)
Use in combo with other MAO inhibitors (including linezolid), opioids, SNRIs, TCAs, and others
Safinamide (Xadago) - severe hepatic impairment
Warnings with Selective MAO-B inhibitors used in PD (selegiline, rasagiline, safinamide)
Serotonin syndrome, HTN
Others: nausea, CNS depression, dyskinesias, impulse control disorders, caution in pts with psychotic disorders (may exacerbate), or ophthalmic disorders (Xadago)
Rasagiline (monotherapy): HA, joint pain, indigestion
Centrally-acting anticholinergics used in PD
Benztropine (Cogentin)
Others: trihexyphenidyl
Side effects of benztropine (Cogentin)
Dry mouth, constipation, urinary retention, blurred vision, mydriasis, somnolence, confusion, tachycardia
