PARKINSONISM:PARKINSON DISEASE- Clinical Features:
- Cardinal: Tremor, Bradykinesia, Rigidity, Postural Instability
- Motor: See Below in Movement D/O in PD
- Non-motor: Anxiety (Even Panic), Inner Restlessness (Akathasia), Extreme Apathy, Depression, Insomnia,
- Pathophysiologically
- Dopaminergic Clinical Features
- Non-Dopaminergic Clinical Features
- Diagnosis: Clinical
- Rest Tremor, Asymmetry, Good Response to Levodopa (99% Correct Pathologically)
- 2 of the 3 (Tremor, Rigidity, Bradykinesia; 22% error on autopsy)
- Rx:
- Dopaminergic Agents (for Tremor, Bradykinesia, Rigidity):
- Carbidopa-Levodopa (is still the best)
- Anti-PD effect occurs in 2 patterns
- Long-Duration Response (First several years on treatment)
- Short-Duration Response (SDR) (Response mirror the LD concentration in circulation; occurs after several years of treatment)
- SDR Dose adjustment based on TWO concepts (Similar to Furosemide and Morphine)
- Is does enough to capture the optimum peak effect? (Larger dose does not last much longer)
- Assess duration of response (Do not worry about number of doses per day; there is no cumulative toxicity)
- Always check orthostatics BP before and after starting
- BP fluctuates with different times of the day (as much as 90/60)
- Space from meal (1 hr before or 2 hr after)
- Non-dopaminergic agents (solely or primarily for tremor reduction)
- COMT Inhibitor (Entacapone): Blocks COMT outside the BB
- Can Increase Levodopa Dyskinesia
- Helps to amplify the potency of CP-LD
- Insomnia: Common due to akathisia, stiffness, cannot turnover in bed
- Bedtime LD-CD will help
- If they wake up in middle of the night, LD-CD may need to be given
- Insomnia also responds in ALL-or-NONE fashion, if under treated even potent sleep aid medications will be ineffective
- Nausea:
- LD effect at Brain-Stem N/V Center will cause N
- Avoid anti-dopaminergic anti-emetics (Metoclopramide, Prochlorperazine - Compazine); Ondansetron can be used.
- Hallucinations and Delusions
- Drugs for the treatment of PD can cause these symptoms especially Dopamine agonists than LD-CD (50% dose reduction is reasonable)
- Avoid anti-psychotic agents (all most all will block Dopamine); Exception: Quetiapine (can be started at 25 mg)
- Often they act out their dreams (REM Behavior). Do not confuse this with Hallucinations
- Pain
- Directly due to PD (painful leg cramps, toe curling, dystonic limbs): Highly responsive to treatment with LD
- Pain from other source are worse in LD worn off state, and pain threshold reduced and severity enhanced if undertreated
- Dyskinesia (Chorea like; LD Excess) and Dystonia (Low LD)
- Anxiety: Is also ALL-OR-NONE phenomenon
- References
Freezing of GaitMovement Disorders in patient with PD (details in movement disorder: see below): Pre-diagnosis :
Restless Leg Syndrome, Dystonia (Task-specific, Exertion-induced), Inner sense of Tremor Akathisia
At Diagnosis:
Resting / Action Tremor, Akinesia / Bradykinesia, Postural Instability
Post-Diagnosis: Two Concepts
Levodopa Dyskinesia (Chorea, Choreo-Dystonia)
- Excessive Levodopa Effect
- Usually "short duration" effect
- Related to individual dose and not cumulative dose
- Decreasing the dose to the level that prevents dyskinesia is the simple strategy
- AMANTADINE reduces dyskinesia. Usually added if dose reduction of LD-CD leads to Parkinsonism symptoms.
- Amantadine can induce hallucinations esp in higher dose
Levodopa MOTOR FLUCTUATIONS Pure Dystonia (especially if painful), Akathisia(restlessness)
- Due to Levodopa Insufficiency
- Distinguish it from Levodopa excess effect as above
- Somewhat similar to pre-diagnosis stage (which has dopa insufficiency)
ATYPICAL PARKINSONISM - MSA:
- MSA-c (previously described at olivopontocerebellar atrophy),
- MSA-p (previously described at stritonigral degeneration),
- (previously described as Shy-Dragar Syndrome that has autonomic features),
- PSP,
- CBGD,
- FTLD
Other Myoclonos Additional Resources on PD and PharmacologyLevodopa for the Treatment of Parkinson’s Disease Advances in the Pharmacologic Management of Early Parkinson Disease Practice Parameter: Treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review) (2006, American Academy of Neurology) Parkinson's Disease (Medical Letter)
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