Parkinson's Disease Flashcards
What are the risk factors associated with PD?
- Rural living
- well water
- pesticides
- heavy metal exposure
- fungus (mushroom alcohol)
What are the protective factors associated with PD?
- Cigarette smoking
- caffeine consumption
Where is the dopamine depleted in the brain?
Substantia nigra
* Striatum
* Globus pallidus
* Thalamus
What is the role of dopamine in the brain?
- Smooth, controlled muscle movement
- Cognition and frontal cortex function
- Pleasure and motivation
What is the role of dopamine in the cardiovascular?
Vasodilator
What is the role of dopamine in the renal?
INCREASE sodium excretion and urine output
What is the role of dopamine in the digestive?
DECREASE GI motility and protects intestinal mucosa
What is the role of dopamine in the immune?
DECREASE activity of lymphocytes
Symptoms appear when
____ of SN neurons are depleted?
70-80%
What are the cardinal signs of Parkinson’s?
- Onset is usually unilateral, asymmetric
- Tremor
- Usually occurs at rest
- May disappear with voluntary movement or sleep
- Initially affects upper extremities
- May manifest as “pill-rolling”
- Rigidity
- May manifest as “cogwheeling” or hypomania
- Akinesia/Bradykinesia
- Slow throughout an intended action
- Difficulty initiating movement
- May manifest as micrographia, shuffling, freezing
- Postural instability
- Common in advanced stages of PD
- Increased risk of falls
What are the differential diagnosis of PD?
- Insult (stroke, TBI, pugilism)
- Infection
- Intoxication (Carbon monoxide, mercury, Wilson’s)
- Drug-induced
Which drugs can induce PD?
- Antipsychotics (except clozapine)
- Antiemetics (DA antagonists)
- Others
- Methyldopa
- Anesthesia
- Opioid overdose
- MPTP–> contaminant in some street drugs
L-DOPA
- Drug of choice for symptomatic PD
- Initial therapy if rigidity or bradykinesia is chief complaint
- Preferred in older adults (65+)
- Safest side effect profile
- Younger patients report LDOPA dyskinesias
- Only effective for a finite period of time
How do you get CR/ER dose of Cabidopa/L-DOPA?
Increase IR dose by 30%
What dose do you need if patient is experiencing nausea/vomiting with Carbidopa/L-DOPA?
75 mg/day of cabidopa
What are the adverse effects of L-DOPA?
- DECREASE GI motility and protects intestinal mucosa
- Vasodilator
- Smooth, controlled muscle movement
- Cognition and frontal cortex function
- Nausea/vomiting
- Postural hypotension
- Dyskinesias, psychiatric disturbances
What are some patient counseling of C/L?
- IR onset of action may take up to 1 hour
- Longer for CR formulation–> may give IR in AM
- ODT administration technique
- ER formulation:
- Do not chew/divide/crush capsules
- May open capsule and sprinkle on 1-2 tbsp applesauce
- L-DOPA competes with protein for absorption
- Must taper when discontinuing
DA Agonist
- May be considered as early monotherapy in initial L-DOPA sparing strategy (LDOPA only works for finite time)
- Reserved for younger patients
- Can cause psychiatric disturbance in older patients
- Initial therapy option if rigidity or bradykinesia is chief complaint
- Renally cleared–> dose adjustments required
Rotigotine (Neupro)
- Daily transdermal patch
- Useful in advanced PD when swallowing is difficult
- Must counsel on application/removal/disposal
What are some patient counseling of Ropinirole and Pramipexole?
- Sleep attacks - serious problems when driving
- Must taper when discontinuing
What are the adverse effects of dopamine agonist?
- Hallucinations
- Impulse control disorders
- Gambling, compulsive shopping
Why must we taper?
Abrupt cessation can lead to physiological withdrawal (DA agonist) or exacerbating of underlying PD (DA agonist & L-DOPA)
What are some physiological withdrawal of DA agonist?
- Anxiety
- Panic attacks
- Depression
- N/V/D
- Pain
- Diaphoresis
- Suicidal ideation
- Drug cravings
What are some exacerbation of underlying PD?
- Diaphragm rigidity–> asphyxiation
- Immobility–> clots
Most problematic in advanced PD
Motor complications of L-DOPA
- More than half of patients develop complications after 5-10 years
- More common in younger patients (<60 years)
- Dyskinesias
- Chorea: Irregular rapid purposeless movement
- Dystonia: Sustained contractions
What should you do if patient is experiencing a “wearing off” effect?
Change L-DOPA administration
* DECREASE dose but INCREASE frequency of C/L
* Give combination of IR and CR formulations
COMT Inhibitors
- Selective and reversible inhibition of COMT (catecyl-o-methyl-transferase) inhibits degradation of DA
- Used to “extend life” of L-DOPA in patients with motor fluctuations
- Ineffective when given as monotherapy
- Administer simultaneously with L-DOPA
What medications are the COMT inhibitors?
- Entacapone–> peripheral inhibition
- Tolcapone–> central inhibition (no longer used b/c severe hepatoxicity)
- Opicapone–> once daily, expensive
Entacapone (Comtan)
- DECREASE L-DOPA dose by ~25% when starting COMT
- Available as combination tablet with carbidopa/L-DOPA (Stalevo®)
- May DECREASE pill burden and INCREASE adherence, BUT…
- Not able to titrate component agents
What are the adverse effects of Entacapone (Comtan)
- Dopaminergic ADRs
- Urine discoloration
MAO-B inhibitors
- Selective and irreversible inhibition of MAO-B in brain interferes with degradation of DA
- May take 1-2 months to see a (modest) effect
- DECREASE L-DOPA dose by ~10% when starting MAOI
Which medications are MAO-B inhibitors?
- Selegiline–> tablet (Eldepryl), ODT (Zelapar)
- Safinamide (Xadago)
- Rasagiline (Azilect)
What are some drug interactions of MAO-B inhibitors?
- Prolonged potential for DDIs even after stopped
- Contraindicated with opioids/serotonin drugs
- ?Interaction with foods containing tyramine
- E.g., wine & beer, aged cheese, overripe foods
Generally well-tolerated
Apomorphine (SQ Apokyn and SL film Kynmobi)
- DA agonist used in L-DOPA “off” episodes
- Intermittent subcutaneous injection
- Requires test dose under medical supervision due to risk of severe hypotension
- Start trimethobenzamide 3 days prior
- If treatment interrupted for > 1 week, must restart at 2 mg and gradually titrate dose
What are some new special formulations for “off”?
- CD/LD intestinal gel (Duopa)
- Levodopa inhalation powder (Inbrija) - NOT recommended for pts with asthma or COPD due to bronchospasm
Istradefylline (Nourianz)
- Once daily dosing for “off” periods as add on to CD/LD
- Special dosing
- Smokers (> 20 cig/day) – 40 mg/day - Strong CYP3A4 inhibitors – 20 mg/day
- Strong CYP3A4 inducers – AVOID USE
- Beneficial effects – increased “on-time” and decreased “off-time”
- Not causing orthostatic hypotension as other dopaminergic agents
What are the ADE of Istradefylline?
- dyskinesia
- hallucinations
- insomnia
Benztropine (Cogentin®) or trihexyphenidyl (Artane®)
- Anticholinergics
- Monotherapy in patients < 65 yo if ONLY tremor
- Adjunct therapy if persistent tremor despite DA therapy
Amantadine
- Antiviral with mild, transient antiparkinsonian activity
- INCREASE DA release, prevent DA reuptake, & directly stimulates DA receptors
- Exerts central anticholinergic activity
- Antagonizes NMDA receptor
- Adjunct therapy to DECREASE intensity of L-DOPA dyskinesias
- Renally cleared–> requires dose adjustments
What are the ADE of amantadine?
- Hallucinations, confusion, dizziness, edema
- Older adults especially susceptible to CNS effects
How to treat psychosis in PD?
Discontinue offending agents
* AC–> Amantadine–> MAOBI–> COMT/DA agonists
Consider low-dose atypical antipsychotics
* Efficacy: Clozapine (Level B) ≥ Quetiapine (Level C)
* New FDA approved agent: Pimavanserin $$$$
* Safety: Quetiapine > Clozapine (granulocytopenia)
How to treat constipation in PD?
- May consider PEG
- Avoid psyllium
How do you treat sexual dysfunction in PD?
- PDE-5 inhibitors
- Sildenafil 50 mg
- PGE-1 analogue
What is the treatment of urinary incontinence of PD?
- ? urinary antispasmodic
- Botulinumtoxin A
