Parkinson's

Question 1

Impact of PD

Answer 1

• Financial burden. need for care, changes in cognition/psychology of patient
• Affects speech and tremor
• Mean duration of illness: 15 years

Question 2

PD Presentation

Answer 2

• Resting tremor: most common first symptom, usually asymmetric
• Rigidity: muscle tone increase in flexor and extensor muscles (resistance to passive movements)
• Bradykinesia: difficulty with daily activities like writing, shaving, eating, dressing
• Postural instability: loss of postural reflexes

“TRAP” = primary criteria for diagnosis

Question 3

Essential Tremor

Answer 3

• Not a sign of Parkinson’s
• Symmetric
• Tremulous hand action along with head and voice tremor
• Large tremulous handwriting

Question 4

Other PD Features

Answer 4

• Masked facies
• Hypophonia
• Drooling
• Depression
• Fatigue
• Slow gait
• Difficulty with ADLs
• Pain

Question 5

PD Advanced Symptoms

Answer 5

• Dysphagia
• Falls
• Freezes in gaits
• Dementia
• Psychosis
• Postural hypotension
• Bladder and anal dysfunction

Question 6

PD Non-Pharm

Answer 6

• Patient/caregiver education
• Support/counseling: peers, professional, legal, occupational
• Exercise
• Nutrition
• Surgery

Question 7

Psychological Support + PD

Answer 7

• Depression
• Limited social functioning
• Poor QoL (severe disease)

Question 8

PD + Safety Devices

Answer 8

• Grab bars
• Bath seats
• Emergency alert systems

Question 9

PD Pharmacotherapy Approach

Answer 9

• Plan for short and long term relief/management
• Manage potential SE
• Provide symptom control for daily living
• Timing of inital therapy based on patient functional ability
• Titrate treatment over time to maximize therapeutic response

Question 10

PD Treatment Mechanisms

Answer 10

• Increase endogenous DA: inhibit peripheral metabolism, COMT, or central/peripheral MAO-B metabolism
• DA agonists: D1, D2, D3, partial agonists
• Adenosine A2a
• Anticholinergic: helps with tremor and rigidity (often not preferred in geriatrics)

Question 11

Surgical Therapy + PD

Answer 11

• Deep Brain Stimulation (DBS)
• Most commonly performed PD surgery in America
• Implant electrode connected to a pulse generator that delivers current to thalamus, globus pallidus interna, or subthalamic nucleus
• Adjust amplitude, frequency, and pulse width

Question 12

PD + Psychosis

Answer 12

• 15-40% experience psychosis
• DA or ACh drug induced possibility
• Look for triggers and minimize polypharmacy
• Reduce anti-PD medications, add atypical antipsychotics (Seroquel)
• Add cholinesterase inhibitor (dementia)
• May consider pimavanserin

Question 13

Atypical Antipsychotics

Answer 13

• Tight binding to DA antagonists could worsen condition
• Quetiapine (sedation), clozapine, pimvanserin (titrate as tolerated)
• Black box: dementia
• Acetyl-cholinesterase inhibitors: Donepezil, rivastigmine also options

Question 14

Depression + PD

Answer 14

• Occurs in 25-40% of population
• Difficult to diagnose (symptom overlap)
• Insomnia, fatigue, psychomotor slowing, decreased libido
• Evaluate electrolytes, thyroid, hypogonadism
• SSRI therapy if depression is significant

Question 15

MAO-B Inhibitors

Answer 15

• May delay the need to begin levodopa therapy by 9 mo
• Inconclusive on if selegiline slows PD progression
• Use in patients with intact cognition and experiencing “wearing-off” with L-dopa

Question 16

Selegiline

Answer 16

• Dose: 10 mg/day
• Use with L-dopa to reduce its dose by ~50%
• AE: Minimal, insomnia and jitters
• Rare 5HT syndrome with use with SSRIs

Question 17

Rasagiline

Answer 17

• Azilect
• Selective MAO-B inhibitor
• 5x more potent than selegiline
• 0.5-1mg/day when used with levodopa
• CYP1A2 metabolization
• Approved for early PD patients monotherapy

Question 18

Levodopa

Answer 18

• Starting Dose: 200-300 mg/day, Max: 800-1600 mg/day
• Titrate 100mg/week
• Carbidopa: 75 mg/day to prevent peripheral AE
• Several combination products available in various formulations

Question 19

Carbidopa/Levodopa

Answer 19

• Most common prescription for PD symptoms
• Virtually all PD patients experience a clinical benefit with the medication
• After sustained usage, effects usually wear off between doses

Question 20

Carbidopa/L-dopa Complications

Answer 20

• Motor flunctuations: “on-off”
• Non-motor fluctuations: sensory, cognitive, psychiatric
• Diminishing efficacy
• Refractory loss of balance
• Cognitive deficiency
• Episodic vs continual dosing

Question 21

“Wearing-Off”

Answer 21

• Benefits from each L-dopa dose gets shorter over time and symptoms return between doses
• Disease could be worsening or more frequent dosing could be needed
• Seen with prolonged usage (4-5+ years)

Question 22

Wearing-Off Strategies

Answer 22

• Increase L-dopa dose or number of doses
• Add DA-agonist or increase its dose
• Use COMT-I

Question 23

DDA

Answer 23

• Direct DA Agonists
• Use alone or in conjunction with carbidopa/levodopa
• Pramipexole or ropinirole are most commonly used

Question 24

DA Agonists Benefits

Answer 24

• Less risk of motor complications and dyskinesias compared to carbidopa/levodopa
• Improve effects and durations when used in combination with levodopa/carbidopa
• May be beneficial as a monotherapy in a early disease patient
• Potentially neuroprotective compared with levodopa/carbidopa

Question 25

DA Side Effects

Answer 25

• N/V
• Orthostasis
• Psychosis
• Narcolepsy
• *Occurs in higher doses or rapid titrations**
• Often a limiting factor for the use of these medications

Question 26

Pramipexole (D2)

Answer 26

• Dose: 0.125 mg TID, titrate every 5-7 days as toelrated
• 1.5mg/day is as effective as higher doses and has less SE
• Adjust for renal insufficiency

Question 27

Ropinirole

Answer 27

• D3 > D2 > D4
• Dose: 0.25 TID and titrate by 0.25 every week
• Max: 25 mg/day
• Metabolized by CYP1A2

Question 28

Transdermal DA

Answer 28

• Rotigotine (Neupro)
• More continuous DA stimulation
• Less possibility of motor fluctuation and dyskinesias
• AE: application site rxn, nausea, somnolence, narcolepsy
• Allows for lower L-dopa doses

Question 29

COMT-I

Answer 29

• ONLY use as adjunct to carbidopa/levodopa
• NO ROLE MONOTHERAPY
• Indicated for those experiencing wearing off
• Comtan (entacapone) or Tasmar (tolcapone)
• *Latter has LFT issues, don’t really use**
• Increase L-dopa levels in brain and reduce its burden for more consistent and continuous levels

Question 30

Entacapone

Answer 30

• Dopaminergic effects most common
• Allows for reduced doses of L-dopa
• Brown/orange fluid discoloration is common
• No hepatotoxicity evidence
• SE: diarrhea, orthostasis
• Dose: 200mg up to 8x a day used with Carbidopa/levodopa

Question 31

Amantadine

Answer 31

• Monotherapy for newly diagnosed patients for mild tremor
• Exact MoA unknown
• Limit use with elderly due to neuropsychiatric effects (confusion, nightmares, hallucinations)
• Withdrawal slowly to avoid worsening PD symptoms

Question 32

Anticholinergics

Answer 32

• Option for younger patients with mainly resting tremor
• Options: Trihexyphenidyl (Artane), Benztropine (Cogentin)
• AE: memory impairment, agitation, confusion, hallucination, antimuscarinic effects, dysphoria
• AE limit its use