Medication for motor symptoms of Parkinson's disease
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An overview of medication for motor symptoms of Parkinson's disease, including levodopa, dopamine agonists, anticholinergics, amantadine.
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Medication for motor symptoms of Parkinson's disease
- 1. Pharmacological Treatment of Motor Symptoms in Parkinson’s Disease By Yung-Tsai Chu 2019 August
- 2. Reference • 台灣巴金森之友協會 http://www.pdcare.org.tw/ • 台大藥劑部網站 https://www.ntuh.gov.tw/phr/query2.aspx
- 3. Motor Symptoms of Parkinson’s Disease(PD) • Bradykinesia- Core symptoms of PD • Rigidity • Tremor • Postural Instability • Not necessarily well responsive to medication • If present early → consider atypical parkinsonism such as MSA, PSP • Long-term motor complications: Motor fluctuation(MF), Levodopa- induced dyskinesia(LID)
- 5. Levodopa +AADC inhibitor Dopamine Agonist Dopaminergic Non-Dopaminergic MAO-B Inhibitor COMT Inhibitor Add-on Therapy Of Levodopa
- 6. Levodopa +AADC inhibitor Dopamine Agonist Anticholinergic Amantadine Dopaminergic Non-Dopaminergic MAO-B Inhibitor COMT Inhibitor Mainly for tremor Special mechanism(NMDA antagonist) Helpful for dyskinesia and freezing of gait
- 7. Levodopa +AADC inhibitor • Gold standard of treatment, best efficacy for motor performance • Fragile, easily degraded by different enzymes • (AADC, MAO-B, COMT etc.) • Absorption is easily influenced by food intake (esp. high protein) • 30 minutes before meals, or one hour after meals • Short-half life (~1.5 hours) in vivo (HBS cap: prolonged release capsule) Commonly seen Picture from 台灣巴金森之友協會 巴金森病常用藥物一覽表（2015版） http://www.pdcare.org.tw/
- 8. Levodopa +AADC inhibitor • Initial dose: 50-100 mg levodopa BID-TID • Max dose: 800mg levodopa/day ? • may be more (up to 1500mg/day if needed) • May be combined with MAO-B inhibitor or COMT inhibitor • Side effect: • Nausea, vomiting: tolerate after a while • Orthostatic hypotension • Psychosis, hallucination (consider atypical parkinsonism if early prominent psychosis) • Long-term motor complication: motor fluctuation (MF), levodopa-induced dyskinesia(LID)(~50% after 5 years)
- 9. MAO-B Inhibitor & COMT Inhibitor • Both could prolong the half life of levodopa → improve MF • MAO-B Inhibitor: could be used as initial monotherapy • hypertension, serotonin syndrome • Selegiline: insomnia (but may improve daytime sleepiness) • COMT inhibitor: take with levodopa, no effect by itself • Orange-colored urine, elevated liver function Picture from 台灣巴金森之友協會 巴金森病常用藥物一覽表（2015版） http://www.pdcare.org.tw/
- 10. Dopamine Agonist Picture from 台灣巴金森之友協會 巴金森病常用藥物一覽表（2015版） http://www.pdcare.org.tw/
- 11. Dopamine Agonist- Overview • Different Form: Prolonged release(PR), Transdermal patch, Subcutaneous(Apomorphine pen) • Ergot: rarely used • Long term: fibrosis of heart valves • Non-ergot: mainstream now • Daytime sleepiness, even sleep attacks • Impulsive control disorder (ICD) • Psychosis • Nausea, vomiting, orthostatic hypotension(like levodopa)
- 12. Different Dopamine Agonist Feature Dose Bromocriptine For neuroleptic malignant syndrome(NMS) or parkinsonism-hyperpyrexia syndrome DO NOT stop the dopaminergic agents abruptly 2.5-5mg Q6-8H in NMS Pramipexole Available PR form Helpful for PD-related depression (higher D3 affinity) Higher risk for ICD Also indicated for restless leg syndrome Start from 0.375mg/day Max 4.5mg/day Ropinirole Available PR form Also indicated for restless leg syndrome Start from 0.25 mg TID/ 2mg PR QD Max: 24mg/day Rotigotine Transdermal patch (24 hours for one patch) Stable concentration → relieve MF & midnight discomfort Skin reaction→ change location every day Start from 2mg/day Usual target: 8mg/day Max 16mg/day
- 13. Comparison Between LD and DA Efficacy Form Common Side Effect Feature and Specific Side Effect LD Better Gold Standard PO only Short dosing interval (except HBS) Nausea, vomiting, orthostatic hypotension, Psychosis Easily degraded by enzymes (consider MAO-B or COMT inhibitor) Absorption is influenced by food Long-term: Motor fluctuation LD-induced dyskinesia DA Less than LD PR form, patch, injection Daytime sleepiness, even sleep attacks Impulsive control disorder (ICD)
- 14. Anticholinergic • Mainly for tremor • Common dose: B.H.L. 5mg/Biperin 2mg TID • Side effect: constipation, urinary retention, blurred vision etc. • Negative effect for cognition, worsen psychosis→ less used in elderly Picture from 台灣巴金森之友協會 巴金森病常用藥物一覽表（2015版） http://www.pdcare.org.tw/
- 15. Amantadine • Like Unicorns, special mechanism and effects • Glutamatergic pathway, NMDA antagonist • Reduce LID and freezing of gait(FOG) • 1#: 100mg, max dose 300-400mg/day • Usually 100mg TID • Side effects • Leg edema, livedo reticularis • Confusion, psychosis • Beware of renal dose, avoid in ESRD patients Photo from 台大藥劑部網站 https://www.ntuh.gov.tw/phr/query2.aspx
- 16. Levodopa Equivalent Dose Estimation 1mg of Levodopa Equivalent Dose Levodopa 1 Entacapone +33% of levodopa Pramipexole *100 Ropinorole *20 Rotigotine *30 Amantadine 1 Rasagiline(monotherapy) *100 Selegiline(monotherapy) *10 Tomlinson CL et al. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010 Nov 15;25(15):2649-53.
- 17. Recap of Side Effects • Nausea, vomiting • Transient, less if slower titration • Domperidone • Orthostatic hypotension (partly due to disease itself) • More water and salt intake • Midodrine, Domperidone • ICD!!! Dopamine agonist, especially younger, past history of addiction • Confusion, psychosis (partly due to disease itself) • May stop anticholinergic, amantadine, taper dopamine agonist • Consider quetiapine, clozapine
- 18. Initial Treatments Levodopa +AADC inhibitor Dopamine Agonist MAO-B Inhibitor For mild symptoms Might have neuroprotection effect (insufficient evidence) Delay motor complication(MF, LID) Start for younger patients (<60-65 years of age) Beware of ICD Best efficacy for motor performance Long-term use→ MF, LID
- 19. Levodopa +AADC inhibitor Dopamine Agonist Anticholinergic Amantadine Dopaminergic Non-Dopaminergic Mainly for tremor Special mechanism(NMDA antagonist) Helpful for dyskinesia and freezing of gait MAO-B Inhibitor COMT Inhibitor Many forms: oral, extended release, transdermal patch, injection Some are helpful for depression Gold Standard Precursor of Dopamine Fragile, easily degraded by many enzymes
- 21. Image bibliography • pocket knife by Umut Büyükekmekci from the Noun Project • Unicorn by Mooms from the Noun Project • parkinson's tremors by Becris from the Noun Project • Jewelry by Azmi Anshori from the Noun Project