Parkinson's Disease Flashcards
What is PD?
degenerative neurological disorder
What causes PD?
Neurons die in the substantia nigra and other places in the brain that produce DA which normally enables coordinated muscle function/movement
What are s/sx of PD?
Major: TRAP
1. Tremor (resting; usually starts unilateral then becomes bilateral)
2. Rigidity (legs, arms, trunk, face)
3. Akinesia/bradykinesia (lack of/slowed start in movement)
4. Postural instability
Additional:
5. small, cramped handwriting
6. shuffling walk/stooped posture
7. muffled speech, drooling, dysphagia
8. depression/anxiety
9. constipation/incontinence
What is used to measure involuntary movements due to medications?
Abnormal Involuntary Movement Scale (AIMS)
What drugs can worsen PD (block DA)?
- Phenothiazines (prochlorperazine) used for psychosis, nausea, agitation
- Butyrophenones (haloperidol, droperidol)used for psychosis, nausea
- 1st and 2nd generation antipsychotics (risperidone high dose, paliperidone); Quetiapine has lowest risk
- Metoclopramide (renally cleared drug can accumulate in elders)
What are non-motor symptoms that might appear much earlier in PD?
- loss of smell (anosmia)
- constipation
- sleep difficulties
- low mood/depression
- orthostasis
What is an “off” period/episode?
symptoms of the disease worsen before the next dose of medication is due
What are options for treating depression in PD patients?
- SSRIs/SNRIs (may contribute to tremor/serotonin syndrome)
- Secondary amine TCAs (desipramine, nortriptyline)
- Pramipexole (dopamine agonist)
What are options for treating psychosis related to advanced disease or medications with low risk of worsening movement disorders?
- Quetiapine preferred (metabolic complications)
- Clozapine (high seizure risk, agranulocytosis)
- Pimavanserin (Nuplazid) FDA approved for hallucinations/delusions in PD
Why must levodopa/ DA agonists be slowly tapered off?
Neuroleptic malignant syndrome
What are first line agents for PD?
- Levodopa (prodrug of DA)
- Carbidopa (prevents breakdown of levodopa in the periphery)
- Dopamine agonists (COMT inhibitors and MAOI)
- Centrally acting anticholinergics (tremor/dyskinesia)
What medications are used for young patients with tremor predominant sx?
Centrally acting anticholinergics (benztropine)
What medications are added on as the disease progresses to reduce off periods?
Dopamine agonists (COMT inhibitors and MAOi)
What may be better tolerated for initial treatment in older individuals?
Carbidopa/levodopa (Sinemet)
What medications are helpful for dyskiesias?
- amantidine
- apomorphine sc inj
- droxidopa (Northera)-indicated for orthostatic hypotension
What is the MOA of carbidopa?
inhibits the dopa decarboxylase enzyme preventing peripheral breakdown (metabolism) of levodopa
What are CIs with carbidopa/levodopa?
- Non-selective MAO inhibitors (phenelzine, isocarboxazid) within 14 days
- narrow angle glaucoma
What are SEs with carbidopa/levodopa?
- Nausea
- Orthostasis/dizziness
- Dyskinesia
- Hallucination/psychosis
- Can cause brown/black dark urine, saliva, sweat, and can discolor clothing
- Positive Coombs test (D/C drug hemolysis risk)
- Unusual sexual urges
- Priapism
- xerostomia (dry mouth)
- dystonia (occasional, painful)
- confusion
elevated uric acid - suicidal ideation/attempts (Rytary)
- GI complications (Duopa)
What is important to note about administration of carbidopa/levodopa?
- Long-term use can lead to fluctuations in response/dyskinesias
- Separate from oral iron and high protein foods
- Do not D/C abruptly; must be tapered
- 70-100mg/day carbidopa required to inhibit enzyme
- Duopa cassettes: store in freezer thaw in refrigerator prior to dispensing (good up to 12 weeks upon refrigeration)
Carbidopa/Levodopa
Sinemet
Dhivy (scored IR tablet to facilitate trituration)
Rytary (ER capsule)
Duopa (enteral suspension given via J-tube)
Inbrija (capsule for oral inhaler, used prn during off periods)
How is carbidopa/levodopa dosed?
IR tablet: 25/100mg PO TID (starting dose) and titrate cautiously
ER tablet (can be cut in half; do not crush/chew): 50/200mg PO BID (starting dose)
Rytary: start at 23.75/95mg PO TID if levodopa naive (take whole or sprinkle on a small amount iof apple sauce
Inbrija: 84mg (2 capsules) inhaled up to 5x daily prn; max dose: 420mg/day
What is the MOA of COMT inhibitors?
increase action and duration of levodopa; inhibit catechol-O-methyltransferase enzyme to prevent peripheral conversion of levodopa
What are SEs with COMT inhibitors?
similar to levodopa because it extends its action
What is important to note about administration of COMT inhibitors?
- decrease levodopa by 10-30% usually necessary when adding a COMT inhibitor
- dyskinesia can occur earlier with COMT inhibitors
- Tolcapone is rarely used due to hepatotoxicity risk
- ONLY used with levodopa
How is Entacapone dosed?
200mg (max=1,600mg/day) PO with each dose of carbidopa/levodopa (Stalevo 4:1 ratio carbidopa:levodopa) (max=1,600mg/day)
What COMT inhibitors need dose adjustment for renal inpairment?
Opicapone
Tolcapone (avoid)
Entacapone
Comtan
Entacapone/carbidopa/levodopa
Stalevo
Opicapone
Ongentys
Tolcapone
Tasmar
What is the MOA of dopamine agonists (pramiprexole, ropinerole, rotigotine)?
act similar to DA at the DA receptor
What are warnings with DA agonists?
- Somnolence (including sudden daytime sleepiness)
- Orthostasis
- Hallucinations
- Dyskinesia
- impulse control disorder
- Application site skin reactions (rotigotine patch)
- postural deformity (bent spine, dropped head) and rhabdomyolysis (pramipexole)
What are SEs with dopamine agonists?
- N/V
- dizziness
- dry mouth
- peripheral edema
- constipation
- hyperhidrosis (rotigotine)
What is important to note about administration of dopamine agonists?
- slow titration is required to avoid withdrawals (anxiety, depression, insomnia, sweating)
- Do not D/C abruptly
- CYp1A2 substrate; caution with CYP1A2 inhibitors
- bromocriptine no longer recommended
What is important about the administration of rotigotine patch?
- apply once daily at the same time each day to the stomach, hip, thigh, side of body, shoulder, upper arm
- Do not use the same site for at least 14 days
- Remove patch before MRIs
- avoid if sensitive/allergy to sulfites
What drug is an DA agonist used as a rescue movement drug for off periods?
Apomorphine
Pramipexole
Mirapex- also used for restless leg syndrome
Mirapex ER
Ropinerole
Requip XL
Rotigotine
Neupro
What are CIs with apomorphine?
Do not use with 5HT3 antagonists (ondansetron) due to severe hypotension and loss of conciousness
What are SEs with apomorphine?
- Severe N/V
- Hypotension
- yawning
- dyskinesia
- somnolence/dizziness
- QT prolongation
What should be used to prevent emesis with apomorphine injection?
Trimethobenzamide (Tegan) 300mg PO TID started 3 days prior to SC dose
What should be monitored with apomorphine?
- must be started with a test dose under medical supervision
- supine and standing BP
How is apomorphine dosed?
0.2mL SC up to 5 times daily (max dose 0.6mL); lasts 45-60 min
What are DIs with carbidopa/levodopa?
- CI with non selective MOAis
- do not use with DA blockers
- iron and protein rich foods can decrease absoprtion
Apomorphine
Apokyn
