Treatment of Parkinson s Disease Joo-Hyuk Im, M.D., Ji Hoon Kang, M.D., Myoung Chong Lee, M.D. Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center Joo-Hyuk Im, M.D. Copyright 2001 by the Korean Neurological Association 315
Table 1. Medications available for Parkinson s disease A.Dopaminergic agents Dopamine precursor : Decarboxylase inhibitor : Dopamine agonists : Catechol-O-methyltransferase inhibitors : Dopamine receptor blocker : Monoamine oxidase B inhibitors : Monoamine oxidase A & B inhibitors : B.Non-dopaminergic agents Antimuscarinics : Antihistaminics : Antiglutamatergics : Antidepressants : Antipsychotics : Anti-stress : Anti-orthostasis : Muscle relaxants : Antioxidant vitamins : Mitochondrial enhancer : Adenosine A 2A receptor antagonists Neutrophins : levodopa carbidopa, benserazide bromocriptine, pergolide, ropinirole, pramipexole, cabergoline, lisuride, piribedil, apomorphine entacapone, tolcapone domperidone selegiline, lazabemide, rasagiline tranylcypromine, phenelzine trihexyphenidyl, benztropine, ethopropazine, biperiden, etc. diphenhydramine, orphenadrine amantadine, riluzole, dextromethorphan selective serotonin reuptake inhibitors, tricyclics clozapine, olanzapine, quetiapine benzodiazepines; diazepam, lorazepam, alprazolam fluodrocortisone, midodrine cyclobenzaprine, diazepam, baclofen ascorbate, tocopherol coenzyme Q10 neuroimmunophilins, GDNF Table 2. Dopamine agonists and dopamine receptors Agonist D1 D2 D3 D4 D5 Bromocriptine - ++ + + + Lisuride - +++??? Pergolide + +++ +++? + Cabergoline + +++??? Ropinirole 0 +++ ++++ +? Pramipexole 0 +++ ++++ +? +=Agonist (low affinity); ++=agonist (medium affinity); +++= agonist (high affinity); ++++=very high affinity; -=antagonist; 0=no affinity;?=unknown 316 J Korean Neurol Assoc / Volume 19 / July, 2001
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Table 3. Major fluctuations and dyskinesias as complications of levodopa Fluctuations (offs) Sensory and behavioural offs Dyskinesias wearing off pain peak-dose chorea, ballism and dystonia sudden off akathisia diphasic chorea and dystonia random off depression off dystonia yo-yo-ing anxiety myoclonus episodic failure to respond dysphoria simultaneous dyskinesia and parkinsonism delayed on panic weak response at end of day response varies in relationship to meals sudden transient freezing 320 J Korean Neurol Assoc / Volume 19 / July, 2001
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Table 4. Summary of results of surgical treatment for Parkinson s disease Indication Thalamotomy Vim DBS Pallidotomy Gpi DBS STN DBS Brain grafts* Bradykinesia 0 ++~+++ +++ + Tremor +++ ++ +++ + Rigidity + ++~+++ +++ + PIGD - 0~+ 0~++ - Freezing 0 + + 0 Dyskinesia 0~+ +++ +++ - - =deterioration; 0= no improvement; + =mild improvement; ++ =moderate improvement; +++ =marked improvement *Based on a double blind study (Freed CR, et al, 2001), Some patients experienced dyskinesia even without levodopa. Vim; ventrointermediate thalamic nucleus, GPi; internal segment of glubus pallidus, STN; subthalamic nucleus DBS; deep brain stimulation, PIGD; postural impairment and gait disturbance 324 J Korean Neurol Assoc / Volume 19 / July, 2001
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Table 8. Advantages and disadvantages of DBS Advantages -lmmediate symptomatic and functional improvement -Stimulation is suitable and can be customized -Lower risk of lesion-related complications -Lower risk with bilateral procedures Disadvantages -Long-term outcome unclear -Replacement of batteries -lmplantation of a foreign body (hardware) -Cost to the patient and the neurologist 328 J Korean Neurol Assoc / Volume 19 / July, 2001
Figure 1. The management of Parkinson s disease J Korean Neurol Assoc / Volume 19 / July, 2001 329
CH, Fahn S, et al. A multicenter trial of ropinirole as adjunct to treatment for Parkinson s disease. N e u r o l o g y 1998;51:1057-1062. 18. Pinter MM, Pogarell O, Oertel WH. Efficacy, safety, and 11. Hornykiewicz O. Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966;18:925-964. 12. Perachon S, Schwartz JC, Sokoloff P. Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D-1, D-2 and D-3 receptors. Eur J Pharmacol 1999;366:293-300. 13. Poewe W. Adjuncts to levodopa therapy; dopamine agonists. Neurology 1998;(Suppl 6):S23-S26. 14. Watts RL. The role of dopamine agonists in early Parkinson s disease. N e u r o l o g y 1997;49(Suppl 1):S34- S48. 15. Schrag AE, Brooks DJ, Brunt E, Fuell D, Korczyn A, Poewe W et al. The safety of ropinirole, a selective nonergoline dopamine agonist, in patients with Parkinson s disease. Clin Neuropharmacol 1998;21:169-175. 16. Im JH, Ha JH, Cho IS, Lee MC. Ropinirole as an adjunct to levodopa in the treatment of Parkinson s disease. J Kor Neurol Assoc 2001;19(2):102-109. 17. Lieberman A, Olanow CW, Sethi K, Swanson P, Waters tolerance of non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson s disease: a double blind, placebo controlled, randomised, multicenter study. J Neurol Neurosurg Psychiat 1999;66:436-441. 19. Kieburtz K, Shoulson I, McDermott M, Fahn S, Lang AE, et al. Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson s disease: a randomized dose-ranging study. JAMA 1997;278:125-130. 10. Brooks DJ, Abbott RJ, Lees AJ, Martignoni E, Philcox DV, Rascol O. A placebo-controlled evaluation of ropinirole, a novel D-2 agonist, as sole dopaminergic therapy in Parkinson s disease. Clin Neuropharmacol 1 9 9 8 ; 2 1 : 1 0 1-107. 11. Sethi KD, O Brien CF, Hammerstad JP, Adler CH, Davis TL, Taylor RL, et al. Ropinirole for the treatment of early Parkinson s disease: A 12-month experience. Arch Neurol 1998;55:1211-1216. 12. Rinne UK, Bracco F, Chouza C, Dupont E, Gershanik O, Masso JFM, et al. Cabergoline in the treatment of early Parkinson s disease: results of the first year treatment in a double-blind comparison of cabergoline and levodopa. Neurology 1997;48:363-368. 13. Kulisevsky J, Lopez-Villegas D, Garcia-Sanchez C, Barbanoj M, Giornell A, Pascual-Sedano B. A six-month study of pergolide and levodopa in de novo Parkinson s disease patients. Clin Neuropharmacol 1998;21:358-362. 14. Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. N e u r o l o g y 1 9 9 9 ; 5 2 : 1 9 0 8-1 9 9 0. 15. Hoehn MM. Falling asleep at the wheel: motor vehicle mishaps in people taking pramipexole and ropinirole. Neurology 2000;54:275. 16. Schapira AHV. Sleep attacks (sleep episodes) with pergolide. Lancet 2000;355:1332-1333. 17. Ferreira JJ, Galitzky M, Montastruc JL, Rascol O. Sleep attacks and Parkinson s disease treatment. Lancet 2 0 0 0 ; 3 5 5 : 1 3 3 3-1 3 3 4. 18. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson s disease in DATATOP subjects not requiring levodopa. Ann Neurol 1 9 9 6 ; 3 9 : 2 9-3 6. 19. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson s disease in DATATOP patients requiring levodopa. Ann Neurol 1996;39:37-45. 20. Golbe LI, Lieberman AN, Muenter MD, Ahlskog JE, Gopinathan G, Neophytides AN, et al. Deprenyl in the treatment of symptom fluctuations in advanced Parkinson s disease. Clin Neuropharmacol 1988;11:45-55. 21. Parkinson Study Group. A controlled trial of lazabemide (RO 19-6327) in untreated Parkinson s disease. A n n 330 J Korean Neurol Assoc / Volume 19 / July, 2001
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