A walk through the management of Parkinson s disease.
BACKGROUND
Patients with Parkinson s disease are known to develop motor complications after a few years of therapy. Motor fluctuations and dyskinesias develop with increasing severity of disease, and were formerly thought to be an inevitable consequence of the disease.


METHODS
Literature review of articles on the aetiopathogenesis of Parkinson s disease, the mechanisms underlying the development of motor fluctuations and dyskinesias, and strategies for delaying the onset of dyskinesias.


RESULTS
Motor fluctuations develop with increasing severity of the disease, owing to loss of dopaminergic neurons and loss of the buffering capacity of the neurons to fluctuating dopamine levels. Dyskinesias develop as a result of pulsatile stimulation of the receptors, causing changes in plasticity, dysregulation in gene and protein expression and alterations in neuronal firing patterns. Continuous dopaminergic stimulation, through long-acting dopa agonists and frequent administration of levodopa, is known to delay the development of dyskinesias. The use of catechol-O-methyl transferase (COMT) inhibitors likewise increases the bioavailability and brings about a smooth drug profile. The use of dopa agonists is associated with sedation and confusion, particularly in the elderly.


CONCLUSIONS
Initiation of therapy in Parkinson s disease should begin with a dopa agonist agent, unless the patient is elderly or has cognitive impairment, in which case levodopa therapy should be given.
Lim
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Division of Neurology, National University Hospital, Singapore. mdcelch@nus.edu.sg
D000978:Antiparkinson Agents / Q000008:administration & dosage*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D046690:Deep Brain Stimulation; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000009:adverse effects / Q000494:pharmacology; D020820:Dyskinesias; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D011954:Receptors, Dopamine; D007980:Levodopa; D002394:Catechol O-Methyltransferase; D004298:Dopamine