lecture 43 Flashcards
campbell - pharmacotherapy of PD
how does PD develop?
slow over 5-10 years with an increase in motor symptoms with cognitive symptoms may presenting after several years
life expectancy of 15 years after diagnosis
what are motor symptoms associated with PD?
tremor, bradykinesia, rigidity, parkinsonian gait
what are non-motor symptoms associated with PD?
anxiety, depression
constipation
dementia
insomnia
orthostatic hypotension
psychosis/delirium
sexual dysfunction
what are the two assessment of PD?
Unified Parkinson’s Disease Rating Scale (UPDRS)
clinical assessment (observe motor symptoms and impact on QOL)
what is apart of a UPDRS?
standardized rating scale to assess s/sx of PD
scores from 0-4 to assess 42 domains for PD severity
higher = worse symptoms
what are goals of therapy in PD?
minimize/manage motor and non-motor symptoms
maintain highest QOL possible
preserve activities of daily living (ADLs)
minimize/manage ADRs
what are non-pharmacologic therapies?
exercise/physical therapy
nutritional counseling
occupational therapy
psychotherapy/support groups
speech therapy
what is the first line treatment of PD?
rule out drug-induced PD
dopamine precursor
(dopamine agonists)
(MAO-B inhibitor)
what is second line treatment of PD?
COMT inhibitors
amantadine
when should DA agonist as initial treatment be avoided?
over 70y
hx of ICD
cognitive impairment
excessive daytime sleepiness
hallucinations
what are general initiation terms?
initiate with Levodopa
initiate with IR > CR
initiate with lowest effective dose to delay AE or dyskinesia
when is it ok to use a DA agonist as initial treatment?
under 60 years
higher risk for dyskinesia
what drugs are preferred due to efficacy with motor symptoms?
- Levodopa/carbidopa
- DA
- MAO-B inhibitors
what is an important SE of levodopa?
LD motor fluctuations/dyskinesia
what are examples of LD motor fluctations?
wearing off
freezing
delayed onset
peak-dose dyskinesia
what does a wearing off LD motor fluctuation look like?
before next dosing interval, signs of motor symptoms occur
what does a freezing LD motor fluctuation look like?
inability to move due to insufficient or fluctuating DA levels
what does a delayed onset LD motor fluctuation look like?
therapeutics benefits delayed
what does a peak-dose dyskinesia LD motor fluctuation look like?
involuntary body movement caused by high DA levels
what is the starting dose of levodopa?
25/100 mg CD/LD PO TID with meals
what is the maintenance frequency of levodopa?
5-6x per day can increase prn
what DA agonists are non-ergot?
pramipexole, ropinirole, rotigotine, apomorphine
what DA agonists are ergot?
bromocriptine, cabergoline
what DA are first-line for initial PD therapy?
non-ergot (ergot have toxicity)
what are the advantages of DA agonists?
fewer motor fluctuations
long-acting formulations
what drugs are MAO-B inhibitors?
rasagiline
selegiline
safinamide
what are MAO-B inhibitors role in therapy?
first line for mild symptoms
second line as adjunct
adjunctive for PD depression
what are CP associated with MAO-B inhibitors?
risk of serotonin syndrome with drug-drug interactions (serotonergic antidepressants, dextromethorphan, serotonergic opioids)
what drugs are COMT inhibitors?
entacapone, opicapone, tolcapone
what are COMT inhibitors role in therapy?
in combination to manage symptom fluctuation (wearing off)
what are SE of COMT inhibitors?
NV
brown/orange urine discoloration (E)
hepatotoxicity (T)
what is the role of amantadine in therapy?
management of LD motor fluctuations
modest effect in controlling motor symptoms, but rarely used as monotherapy due to tremor
what are SE of amantadine?
insomnia
confusion/hallucinations
livedo reticularis
what are CP of amatadine?
utility limited due to cognitive SE
usually reserved CD/LD peak dose dyskinesias
what drugs are anticholinergics used in PD?
benztropine
trihexyphenidyl
what is the role of anticholinergics in therapy?
management of tremor-dominant symptom in pts under 65 yr
what are SE of anticholinergics?
confusion/dementia
blurry vision
urinary retention
dry mouth
constipation
what are monitoring parameters of PD drugs?
evaluate motor symptoms
assess for SE related to pharmacotherapy
identify medications which can worsen PD
what medications may worsen PD?
dopamine antagonists - antipsychotics, metoclopramide, prochlorperazine, promethazine
what is important patient education for PD?
stress importance of adherence and timing of medication administration to patient/caregiver (make rescue plan, multiple formulations/schedule options to personalize care)
pros/cons of taking med with food
report SE and symptoms to PCP
support group and education referral
what is the pros about using DA agonist as first line?
once daily dosing formulations
better tolerated by younger pts
limited motor fluctuations
what are pros about using carbidopa/levodopa as initial first-line?
gold standard due to symptomatic benefit
cost
variety of dosage forms
what are pros of using MAO-B inhibitors as initial first line?
generally well tolerated
delays onset of motor fluctuations
what are cons of using DA agonists as first line?
expensive (esp long acting)
less symptomatic benefit compared to CD/LD
many AE
what are cons of using carbidopa/levodopa as first line?
motor fluctuations
dosing frequency (can be over 3x)
what are cons of using MAO-B as first line?
least effective first line agent against motor symptoms
calls for dietary restrictions and increases risk of serotonin syndrome
who should use DA agonists as first line?
under age 60 and higher risk of dyskinesia
who should use carbidopa/levodopa as first line?
most
who should use MAO-B inhibitors as first-line?
minor symptoms
higher risk of motor fluctuations
how should wearing off fluctuation be treated?
increase CD/LD dose or frequency
add DA agonist, MAO-B, or COMTi
use XR CD/LD
how should freezing fluctuation be treated?
increase CD/LD dose or frequency
add DA agonist (apomorphine)
add ODT CD/LD
how should delayed onset fluctuation be treated?
take CD/LD on empty stomach
ODT CD/LD
avoid CR/XR CD/LD
how should peak-dose dyskinesia fluctuation be treated?
add amantadine
decrease dose of DA or CD/LD
what drugs should be avoided in correlation to their non-motor symptom?
benzodiazepines - insomnia/anxiety/depression/dementia
anticholinergics - dementia
antihistamines - dementia
sedatives - dementia
psychosis/delirium - haloperidol, olanzapine, paliperidone, risperidone
