Parkinson's Disease Therapeutics Flashcards
Stages of Disease
Stage 1 (unilateral; symptoms not disabling; tremor in one limb but no posture or facial expression changes)
Stage 2 (bilateral; slowed speech, decreased posture and abnormal gait; no balance impairment)
Stage 3 (Worsening; significant posture and balance problems; bradykinesia; mild to moderate disability)
Stage 4 (rigidity and bradykinesia; needs walking assistance; unable to live alone; severe disability)
Stage 5 (Unable to stand or walk; constant care)
Somatic Non-motor symptoms of PD
Sweating, hypotension, constipation, overactive bladder, seborrheic dermatitis, soft voice, decreased facial expression, decreased on arm swing (first side involved), decreased sense of smell and rapid eye movement disorder
Behavioral PD symptoms
Depression, anxiety, psychosis (visual hallucinations usually pleasant; delusions/paranoia), dementia (increased risk because of hallucinations)
Parkinson’s Medications provide control for _________ years
4-6
In PD, health related quality of life is largely determined by ______________________
non-motor features
Factors contributing to rapid progression of PD
Older age at onset, male with initial gate difficulty/postural instability, decreased response to L-DOPA, psychosis
Factors contributing to milder PD progression
Tremor only major sign at initial diagnoses, good response to L-DOPA
Essential tremor vs PD
In essential tremor, tremor is only symptom (PD presents with rigidity, tremor, balance, falling, slowness of movement, etc.)
In essential tremor, tremor occurs when hands are in use (resting tremor in PD)
In essential tremor, hands, head and voice impacted (no head or voice in PD)
In essential tremor, alcohol reduces tremor (no effect in PD)
Pharmacologic options for PD
Dopamine precursor (L-DOPA - carbidopa; Sinemet CR)
1st Generation Dopamine Agonists (Bromocriptine, Apomorphine)
2nd Gen (Pramipexole, Ropinerole, Rotigotine Patch)
MAO-B Inhibitors (Selegiline, Rasagiline)
COMT Inhibitors (Tolcapone, Entacapone)
Antiviral NMDA (Amantadine)
Anticholinergics (Benztropine, Trihexyphenidyl)
Levodopa/Carbidopa
First line (wait until symptoms are disabling)
Greatest benefit with fewest ADE in short term (most effective for bradykinesia then tremor and rigidity; not effective for instability or freezing)
TID to QID; titrated q 3 day then switch to CR BID-QID
Best use in stage 2-5 or as initial treatment in older person
Levodopa-Carbidopa Side Effects
Nausea, insomnia, akathisia, dyskinesias, confusion, elevated liver enzymes, postural hypotension, visual hallucinations
On-off phenomenon (freezing off period to dyskinetic movement on period) –> unrelated to dose time, sign of becoming refractory
L-DOPA Induced Dyskinesia
Occurs afte 5-6 years or early in therapy (6 months) if high doses are used initially
Off-period dystonia (painful feet spasms when LDOPA levels are low)
Diphasic dyskinesia (occurs when levels are rising or falling; rigidity or involuntary movement with muscles of lower limbs)
Peak-Dose dyskinesia (most common form; correlates with peak plateau plasma levels and impacts upper limbs, head, trunk and respiratory muscles)
Treatment for L-DOPA Side Effects
End of dose wearing off (increase frequency or change to CR; add COMT or MAO inhibitor; dopamine agonist)
Delayed onset (take on empty stomach, use ODT or IR form; avoid taking with high protein food/drink; crush tablet and take with water only)
Start hesitation/Freezing (increase dose; add DA or MAO-B inhibitor; Physical therapy)
Peak Dose Dyskinesia (use smaller doses more frequently; add amantadine)
Lillipuition hallucinations
PD see tiny people (could be medication OR disease related)
Major contributors for psychosis/hallucinations in PD
Amantadine, COMT inhibitors, dopamine agonists, levodopa
Anticholinergic medications (oxybutynin, tolterodine, benzotropine, diphenhydramine)
Psychosis/Hallucination Treatment in PD
Reduce or withdraw anticholinergics, then anti-PD meds
Clozapine, olanzapine, quetiapine and risperidone (antipsychotics)
Pimvanserin
New drug for PD psychosis
Works at Serotonin receptors (5HT2a, 5HT2c) with minimal action at D2, muscarinic, histaminergic or adrenergic receptors
Those with more severe psychosis showed better results with drug
Serious risks (risk of death 2.38x greater with 34 mg compared with placebo; QT prolongation, bradycardia, hypokalemia, falls, severe nausea, constipation, UTIs, fatigue, worsening of hallucinations)
Pramipexole and Ropinerole have both been known to cause _________________
impulse control and compulsive behavior issues (hypersexuality, gambling, shopping, binge eating)
Reduction in dose will usually help
Second Generation DA
Pramipexole, Ropinirole, Rotigotine patch
Used in younger patients with good cognition to delay LDOPA
Useful in all stages; may delay dyskinesias or reduce frequency of off periods
Impulse control issue, hypersexuality, gambling and shopping
Sleep attacks during day, abrupt onset (pramipexole reported the most)
Bromocroptine
DA NOT USED
Ergot derivative with increased risk of pulmonary fibrosis
Less effective in PD
Higher risk of motor complications
MAOB Inhibitors
Rasagiline, Selegiline (comes in ODT)
Adjunct with LDOPA or DA in stages 2-4 (not useful in stage 5)
Selegiline SE (insomnia, confusion, psychosis in elderly)
Rasagiline (more hypertensive crisis and tyramine interactions than selegiline, impulse control disorders)
Drug interactions with antidpressants are concern
COMT Inhibitors
Tolcapone, Entacapone, Stalevo
Most useful adjunct to LDOPA for motor fluctuations
Allows LDOPA to work longer (1-2 hours)
Useful when LDOPA end of dose wearing off occurs
Not for initial PD, or add-on to LDOPA when no motor complications (Tolcapone has serious liver issues; Entacapone has hypotension, syncope, fibrotic complications, hallucinations, orange colored urine and increased risk in melanoma)
Amantadine
Mildly helps bradykinesia, rigidity and tremor in stages 1-4 monotherapy or adjunct to LDOPA, dopamine agonists)
Tolerance develops and may need drug holiday
May be useful in treating LDOPA dyskinesias
SE (peripheral edema, psychosis, hallucinations, nightmares and confusion)
Anticholinergic Agents
Benztropine, Trihexyphenidyl
Used as 2nd line for tremor alone or with other agents
SE (decreased cognition and memory, confusion, hallucinations, constipation, urinary retention, dry mouth, blurred vision, sedation, tachycardia)
Don’t use in elderly or dementia patients
Risk factors for PD to progress to PD Dementia
Older age, greater severity of motor symptoms, cognitive impairment, hallucinations prior to dementia diagnosis, and greater postural instability and gait disturbance
Dementia in PD
Ranges from 20-40% with PD increasing dementia risk 2-6 fold
Cognitive impairment typically occurs 8 years or more after onset
Dementia onset within 1 year of onset of motor features suggests Lewy body dementia
Alzheimer’s also common but later; Lewy body dementia can be diagnosed in those without PD
Anticholinergic Toxicity Mnemonic
Blind as a bat Dry as a bone Hot as a hare Red as a beet Mad as a hatter
