PD pharmacotherapy Flashcards
Motor symptoms
Tremor
Bradykinesia (cardinal sign)
Rigidity
Parkinsonian gait
Non-motor symptoms
anxiety, depression
constipation
dementia
insomnia
orthostatic hypotension
psychosis/delirium
sexual dysfunction
Assessment of disease
Unified Parkinson’s disease rating scale (UPDRS)
Standardized rating scale to assess signs/symptoms of PD
Scale scores from 0-4 to assess 42 domains for PD severity
Higher UPDRS score=worse PD symptoms
Goal of therapy
Minimize/manage motor and non-motor symptoms
Maintain high QOL possible
Preserve activities of daily living
Minimize/manage adverse drug reactions
Non-pharmacological therapy
Exercise/physical therapy
Nutritional counseling
Occupational therapy
Psychotherapy/ support groups
Speech therapy
Initial treatment
1st line:
Rule out drug-induced PD
Dopamine precursor
Dopamine agonists
MAO-B inhibitor
2nd line:
COMT inhibitors
Amantadine
Treatment initiation
For most, initiate with Levodopa (dopamine precursor)
Dopamine agonist may be used as initial treatment if age < 60 years and higher risk for dyskinesia
Avoid dopamine agonists as initial treatment if: >70, those with hx of ICD, cognitive impairment, sleepiness, hallucinations
IR>CR
Initiate with lowest effective lowest dose to delay adverse effects
Efficacy with motor symptoms: Levodopa/carbidopa>DA>MAOB-I
Levodopa/carbidopa
dopamine precursor
1st line for initial treatment and throughout
gold standard
adjunctive therapy with dopamine agonists and other agents
SE: N/V, LD motor fluctuations/dyskinesias, hallucinations
Starting dose: 25/100 mg CD/LD TID with meals
maintenance frequency can increase as needed (5-6x/day) or switch to CR/XR as needed
Dose-response curves
SLIDE 18
Wearing off
before next dosing interval, signs of motor symptoms
Increase CD/LD dose or frequency
Add DA agonist, MAO-I, or COMT, XR CD/LD
Freezing
inability to move due to insufficient or fluctuating DA levels
Increase CD/LD dose or frequency
Add DA agonist (apomorphine)
Add ODT CD/LD
Delayed onset
Therapeutic benefits delayed
Take CD/LD on empty stomach
ODT CD/LD
Avoid CR/XR CD/LD
Peaked-dose dyskinesias
involuntary body movement caused by high DA levels
Add Amantadine?
Decrease dose of DA or CD/LD
Pramipexole, Ropinirole, Rotigotine, Apomorphine
Non-ergot DA agonists for initial PD tx
Minimize LD motor fluctuations
Ergots used rarely due to toxicity
SE: N/V, ICD, Hallucinations, orthostatic hypotension
Advantages: few motor fluctuations, long-acting formulations
Bromocriptine, Cabergoline
Ergot DA agonists
Same stuff as non-ergots
Rasagiline, Selegiline, Safinamide
MAO-B inhibitors
1ST line for mild symptoms
2ND line for adjunctive therapy
SE: N/V, HA, Insomnia, hypo/hypertension
Rasagiline: 0.5 mg po qd
Selegiline: 5 mg po BID
Safinamide: 50 mg po qd
Risk of serotonin syndrome with use of serotonergic antidepressants, dextromethorphan, serotonergic opioids
Entacapone (CD/LD as Stalevo)
Opicapone
Tolcapone
COMT inhibitors
Used in combo to manage symptom fluctuation
SE: N/V, BROWN/ORANGE URINE DISCOLORATION, Hepatotoxicity
In early PD, no benefit of COMT inhibitors with CD/LD compared to CD/LD alone
Entacapone: 200 mg po with each CD/LD dose
Tolcapone 200 mg po TID
Opicapone 50 mg po QHS
Benztropine, Trihexyphenidyl
Anticholinergics
Management of tremor-dominant symptoms in patients < 65 yo
SE: confusion/dementia, blurry vision, urinary retention, dry mouth, constipation
Benztropine: 0.5 mg po QHS
Trihexyphenidyl 1 mg PO daily
Monitoring
Evaluate motor symptoms
Assess for SE related to pharmacotherapy
Identify medications which can worsen PD
Patient education
Stress importance of adherence and timing of medication
Pros/cons of taking medication with food
Report side effects and symptoms to provider
support group
Treatment initiation and flow
Treatment warranted: non pharm
DA: Contingent: Dop precursor, MAO-B, COMT
Dop precursor: most: DA, MAO-B, COMT
MAO-B: Contingent: DA, dop precursor
DA PROS
Once daily dosing
Better tolerated by younger patients
Limited motor fluctuations
DA CONS
Expensive
Less symptomatic benefit compared to CD/LD
Many AE
CD/LD PROS
GOLD STANDARD
COST
VARIETY OF DOSAGE FORMS
