Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease

Abstract

Objectives-To determine whether continous waking day dopaminergic stimulation with the dopamine agonist apomorphine can reduce levodopa induced dyskinesias in Parkinson's disease Methods-19 patients with severe unpredictable refractory motor fluctuations and functionally disabling levodopa induced dyskinesias were treated with continuous subcutaneoius apomorphine monotherapy for a minimum duration of 2.7 years Results-A mean 65% reduction in dyskinetic severity and a mean 85% reduction in frequency and duration occurred. On discontinuing levodopa a concomitant reduction in oV period time was also seen (35% of waking day "oV" reduced to 10%) Conclusion-Continuous waking day dopaminergic stimulation with apomorphine reset the threshold for dyskinesias and led to a pronounced reduction in their frequency. Apomorphine should be considered as a less invasive alternative to pallidotomy or deep cerebral stimulation in controlling levodopa induced interdose dose dyskinesias. (J Neurol Neurosurg Psychiatry 1998;64:573-576)

Levodopa in the treatment of Parkinson’s disease: an old drug still going strong

“…[58][59][60] The same differences have also been observed in studies comparing pulsatile versus continuous delivery of the same dopaminergic agent. 61,62 Such results are consistent with clinical studies of continuous infusions of DAs, such as apomorphine 63,64 or lisuride, 65 which were found to downregulate pre-existing LD-induced dyskinesia. Indeed, when given as continuous intraduodenal infusions, marked reductions in dyskinesia have been reported for LD itself 49,53,66,67 and the gel preparation of LD (Duodopa ® , Solvay Pharmaceuticals GmbH).…”

Consideraciones sobre las complicaciones motoras y neurotoxicidad de la levodopa en la enfermedad de Parkinson

“…Así se ha demostrado que Levo-Dopa asociada a Entacapone, un inhibidor de Catecol Orto Metil Transferasa, enzima que degrada Levo-Dopa, retarda la aparición de disquinesias en el modelo experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (14) . Una vez aparecida, la disquinesia se debe manejar con agonistas dopaminérgicos, que poseen una vida media más larga, fraccionando las dosis de Levo-Dopa o agregando fármacos que prolonguen su vida media, como se mencionó antes (15)(16)(17) . Cabe destacar que en nuestro medio ha sido de gran utilidad la utilización de soluciones de Levo-Dopa, esto se logra disolviendo el fármaco en agua o bebidas, y administrando esta solución de manera continua, habitualmente cada una hora vía oral.…”

Long-term Efficacy and Safety with Continuous Dopaminergic Stimulation Pump Treatments in Parkinson’s Disease

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The general finding is that APO provides more time in motor states near normal performance and less time in 'off' and dyskinetic states as compared to conventional optimised therapy. Improvement in quality of life (QoL) may accompany the increased 'on' time, but so far publications on this aspect of APO infusion are sparse.…”