Apomorfina: uma alternativa no controle das flutuações motoras na doença de Parkinson

Ferraz, Henrique B.; Azevedo-silva, Sônia M. C.; Borges, Vanderci; Rocha, Maria Sheila G.; Andrade, Luiz Augusto F.

doi:10.1590/S0004-282X1995000200010

Resumos

As flutuações motoras (FM) decorrentes do uso prolongado de levodopa são uma das principais complicações do tratamento da doença de Parkinson (DP). A utilização da apomorfina, um potente agonista de receptores dopaminérgicos, associada ao domperidone para bloquear seus efeitos eméticos, surge como uma alternativa para contornar as FM dos parkinsonianos. Para adquirirmos experiência inicial com essa droga, decidimos estudar a ação e os efeitos adversos da apomorfina em um grupo de quatro pacientes do nosso ambulatório com o diagnóstico de DP e com flutuaçãoes de rendimento da levodopa. A apomorfina foi administrada por via subcutânea, sendo obtido o estado "on" em todos os pacientes com doses entre 1,5 e 3 mg por aplicação. A latência para o início do efeito variou de 7 a 30 minutos e a duração da ação de 60 a 85 minutos. O estado "on" produzido com a apomorfina foi indistinguível do observado com a levodopa, inclusive com a ocorrência de discinesias. Não foram observados efeitos colaterais significativos. Nossa experiência inicial mostra que a apomorfina, em doses relativamente baixas, é uma alternativa eficaz para as FM da DP, com poucos efeitos colaterais.

doença de Parkinson, tratamento; apomorfina, uso terapêutico; levodopa, efeitos adversos

Levodopa-induced motor fluctuations (MF) is a disabling complication of Parkinson's disease (PD) and is usually refractory to conventional treatment. Apomorphine, a dopamine agonist with affinity for both Dl and D2 receptors, has been emerged as an useful alternative in the management of MF of PD. The frequency of nausea and vomiting prevented its use in the past, but the simultaneous administration of domperidone has proved to be able to control these side effects. Although apomorphine has been successfully used to control levodopa-induced MF in other countries, it has not been considered in the management of PD in Brazil. We report here our initial experience with subcutaneous injections of apomorphine combined to oral domperidone. We administered apomorphine in doses ranging from 1.5 to 3 mg in four PD patients with MF of our outpatient clinic. All the doses administered switched the "off state to a motor response qualitatively similar to what is seen in the "on" phase induced by levodopa, including the occurence of dyskinesia. The latency to turn "on" after apomorphine ranged from 7 to 30 minutes and the duration of the response ranged from 60 to 85 minutes. We observed yawning in all four patients, labial paresthesia in one patient and an inespecific unpleasent sensation in another patient. These side effects were not significant in our four patients. Our data show that the use of apomorphine adds a reliable and effective strategy in the management of MF of PD patients.

Parkinson's disease, treatment; apomorphine, therapeutic use; levodopa, adverse effects

Apomorfina: uma alternativa no controle das flutuações motoras na doença de Parkinson

Apomorphine: an alternative in the management of motor fluctuations of Parkinson's disease

Henrique B. Ferraz^I; Sônia M. C. Azevedo-silva^II; Vanderci Borges^II; Maria Sheila G. Rocha^II; Luiz Augusto F. Andrade^III

^IDoutor em Neurologia, Médico Assistente do Setor

^IIPós-Graduando em Neurologia

^IIIProfessor Adjunto-Livre Docente, Chefe do Setor

RESUMO

As flutuações motoras (FM) decorrentes do uso prolongado de levodopa são uma das principais complicações do tratamento da doença de Parkinson (DP). A utilização da apomorfina, um potente agonista de receptores dopaminérgicos, associada ao domperidone para bloquear seus efeitos eméticos, surge como uma alternativa para contornar as FM dos parkinsonianos. Para adquirirmos experiência inicial com essa droga, decidimos estudar a ação e os efeitos adversos da apomorfina em um grupo de quatro pacientes do nosso ambulatório com o diagnóstico de DP e com flutuaçãoes de rendimento da levodopa. A apomorfina foi administrada por via subcutânea, sendo obtido o estado "on" em todos os pacientes com doses entre 1,5 e 3 mg por aplicação. A latência para o início do efeito variou de 7 a 30 minutos e a duração da ação de 60 a 85 minutos. O estado "on" produzido com a apomorfina foi indistinguível do observado com a levodopa, inclusive com a ocorrência de discinesias. Não foram observados efeitos colaterais significativos. Nossa experiência inicial mostra que a apomorfina, em doses relativamente baixas, é uma alternativa eficaz para as FM da DP, com poucos efeitos colaterais.

Palavras-chave:doença de Parkinson, tratamento; apomorfina, uso terapêutico; levodopa, efeitos adversos.

SUMMARY

Levodopa-induced motor fluctuations (MF) is a disabling complication of Parkinson's disease (PD) and is usually refractory to conventional treatment. Apomorphine, a dopamine agonist with affinity for both Dl and D2 receptors, has been emerged as an useful alternative in the management of MF of PD. The frequency of nausea and vomiting prevented its use in the past, but the simultaneous administration of domperidone has proved to be able to control these side effects. Although apomorphine has been successfully used to control levodopa-induced MF in other countries, it has not been considered in the management of PD in Brazil. We report here our initial experience with subcutaneous injections of apomorphine combined to oral domperidone. We administered apomorphine in doses ranging from 1.5 to 3 mg in four PD patients with MF of our outpatient clinic. All the doses administered switched the "off state to a motor response qualitatively similar to what is seen in the "on" phase induced by levodopa, including the occurence of dyskinesia. The latency to turn "on" after apomorphine ranged from 7 to 30 minutes and the duration of the response ranged from 60 to 85 minutes. We observed yawning in all four patients, labial paresthesia in one patient and an inespecific unpleasent sensation in another patient. These side effects were not significant in our four patients. Our data show that the use of apomorphine adds a reliable and effective strategy in the management of MF of PD patients.

Key words:Parkinson's disease, treatment; apomorphine, therapeutic use; levodopa, adverse effects.

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Aceite: 22-novembro-1994.

Setor de Investigação em Moléstias Extrapiramidais, Disciplina de Neurologia, Escola Paulista de Medicina:

Dr. Henrique B. Ferraz - Al. Casa Branca 799 apto 72 - 01408-001 São Paulo SP - Brasil.

1. Bonuccelli U, Piccini P, Del Dotto P, Rossi G, Corsini GU, Muratorio A. Apomorphine test for dopaminergic responsiveness: a dose assesment study. Mov Disord 1993,8:158-164.
2. Bravi D, Mouradian MM, Roberts JW, Davis TL, Sohn YH, Chase TN. Wearing-off fluctuations in Parkinson's disease: contribution of postsynaptic mechanisms. Ann Neurol 1994, 36:27-31.
3. Clough CG. Parkinson's disease: management. Lancet 1991,337:1324-1327.
4. Corsini GU, Del Zompo M, Gessa GL, Mangoni A. Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease. Lancet 1979, 1:954-956.
5. Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I. Similarities between neurologic effects of L-dopa and of apomorphine. N Engl J Med 1970,282:31-33.
6. Cotzias GC, Papavasiliou PS, Tolosa ES, Mendez JS, Bel-Midura M. Treatment of Parkinson's disease with aporphine: possible role of growth hormone. N Engl J Med 1976,294:567-572.
7. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967,276:374-378.
8. Deffond D, Durif F, Tournilhac M. Apomorphine in treatment of Parkinson's disease: comparison between subcutaneous and sublingual routes. J Neurol Neurosurg Psychiatry 1993,56:101-103.
9. Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN. Motor fluctuation in Parkinson's disease: central pathophysiological mechanisms, Part I. Ann Neurol 1988,24:366-371.
10. Fahn S. "On-off" phenomenon with levodopa therapy in parkinsonism. Neurology 1974, 24:431-441.
11. Fahn S, Elton RL, and members of the UPDRS Development Committee. Unified Parkinson's disease rating scale. In:Fahn S, Marsden CD, Calne DB, Goldstein M (eds). Recent developments in Parkinson's disease, vol 2. Florahm Park-NJ: MacMillan Health Care Information 1987:153-164.
12. Frankel JP, Lees AJ, Kempster PA, Stern GM. Subcutaneous apmorphine in the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry 1990,53:96-101.
13. Gancher ST, Nutt JG. Diurnal responsiveness to apomorphine. Neurology 1987,37:1250-1253.
14. Gancher ST, Nutt JG, Woodward WR. Absorption of apomorphine by various routes in parkinsonism. Mov Disord 1991,6:212-216.
15. Gervason CL, Pollak PR, Limousin P, Perret JE. Reproducibility of motor effects induced by successive subcutaneous apomorphine injections in Parkinson's disease. Clin Neuropharmacol 1993,16:113-119.
16. Grandas F, Gancher S, Lera G, Rodriguez M, Woodward WR, Nutt J, Obeso JA. Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. Neurology 1992,42:1287-1290.
17. Hughes AJ, Bishop S, Kleedorfer B, Turjanski N, Fernandez W, Lees AJ, Stern GM. Subcutaneous apomorphine in Parkinson's disease: response to chronic administration for up to five years. Mov Disord 1993,8:165-170.
18. Hughes AJ, Lees AJ, Stern GM. The motor response to sequential apomorphine in parkinsonian fluctuations. J Neurol Neurosurg Psychiatry 1991,54:358-360.
19. Hughes AJ, Webster R, Bovingdon M, Lees AJ, Stern GM. Sublingual apomorphine in the treatment of Parkinson's disease complicated by motor fluctuations. Clin Neuropharmacol 1991,6:556-561.
20. Kempster PA, Frankel JP, Stern GM, Lees AJ. Comparison of motor response to apomorphine and levodopa in Parkinson's disease. J Neurol Neurosurg Psychiatry 1990,53:1004-1007.
21. Kempster PA, Iansek R, Larmour I. Intermitent subcutaneous apomorphine injection treatment for parkinsonian motor oscillations. Aust NZ J Med 1991,21:314-318.
22. Kleedorfer B, Turjanski N, Ryan R, Lees AJ, Milroy C, Stern GM. Intranasal apomorphine in Parkinson's disease. Neurology 1991,41:761-762.
23. Marsden CD, Parkes JD. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1977,1:345-349.
24. Mouradian MM, Juncos JL, Fabbrini G, Schlegel J, Bartko JJ, Chase TN. Motor fluctuation in Parkinson's disease: central pathophysiological mechanisms, Part II. Ann Neurol 1988,24:372-378.
25. Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The "on-off' phenomenon in Parkinson's disease: relation to levodopa absortion and transport. N Engl J Med 1984,310:483-488.
26. Poewe W, Kleedorfer B, Wagner M, Bosch S, Schelosky L. Continuous subcutaneous apomorphine infusions for fluctuating Parkinson's disease. Adv Neurol 1993,60:656-659.
27. Steiger MJ, Quinn NP, Marsden CD. The clinical use of apomorphine in Parkinson's disease. J Neurol 1992,239:389-393.
28. Stibe CMH, Lees AJ, Kempster PA, Stern GM. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988, 1:403-406.
29. Tolosa ES, Martin WE, Cohen HP, Jacobson RL. Patterns of clinical response and plasma dopa in Parkinson's disease. Neurology 1975, 25:177-183.

Datas de Publicação

Publicação nesta coleção
20 Jan 2011
Data do Fascículo
Jun 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Bonuccelli U, Piccini P, Del Dotto P, Rossi G, Corsini GU, Muratorio A. Apomorphine test for dopaminergic responsiveness: a dose assesment study. Mov Disord 1993,8:158-164.

[2] 2. Bravi D, Mouradian MM, Roberts JW, Davis TL, Sohn YH, Chase TN. Wearing-off fluctuations in Parkinson's disease: contribution of postsynaptic mechanisms. Ann Neurol 1994, 36:27-31.

[3] 3. Clough CG. Parkinson's disease: management. Lancet 1991,337:1324-1327.

[4] 4. Corsini GU, Del Zompo M, Gessa GL, Mangoni A. Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson's disease. Lancet 1979, 1:954-956.

[5] 5. Cotzias GC, Papavasiliou PS, Fehling C, Kaufman B, Mena I. Similarities between neurologic effects of L-dopa and of apomorphine. N Engl J Med 1970,282:31-33.

[6] 6. Cotzias GC, Papavasiliou PS, Tolosa ES, Mendez JS, Bel-Midura M. Treatment of Parkinson's disease with aporphine: possible role of growth hormone. N Engl J Med 1976,294:567-572.

[7] 7. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967,276:374-378.

[8] 8. Deffond D, Durif F, Tournilhac M. Apomorphine in treatment of Parkinson's disease: comparison between subcutaneous and sublingual routes. J Neurol Neurosurg Psychiatry 1993,56:101-103.

[9] 9. Fabbrini G, Mouradian MM, Juncos JL, Schlegel J, Mohr E, Chase TN. Motor fluctuation in Parkinson's disease: central pathophysiological mechanisms, Part I. Ann Neurol 1988,24:366-371.

[10] 10. Fahn S. "On-off" phenomenon with levodopa therapy in parkinsonism. Neurology 1974, 24:431-441.

[11] 11. Fahn S, Elton RL, and members of the UPDRS Development Committee. Unified Parkinson's disease rating scale. In:Fahn S, Marsden CD, Calne DB, Goldstein M (eds). Recent developments in Parkinson's disease, vol 2. Florahm Park-NJ: MacMillan Health Care Information 1987:153-164.

[12] 12. Frankel JP, Lees AJ, Kempster PA, Stern GM. Subcutaneous apmorphine in the treatment of Parkinson's disease. J Neurol Neurosurg Psychiatry 1990,53:96-101.

[13] 13. Gancher ST, Nutt JG. Diurnal responsiveness to apomorphine. Neurology 1987,37:1250-1253.

[14] 14. Gancher ST, Nutt JG, Woodward WR. Absorption of apomorphine by various routes in parkinsonism. Mov Disord 1991,6:212-216.

[15] 15. Gervason CL, Pollak PR, Limousin P, Perret JE. Reproducibility of motor effects induced by successive subcutaneous apomorphine injections in Parkinson's disease. Clin Neuropharmacol 1993,16:113-119.

[16] 16. Grandas F, Gancher S, Lera G, Rodriguez M, Woodward WR, Nutt J, Obeso JA. Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease. Neurology 1992,42:1287-1290.

[17] 17. Hughes AJ, Bishop S, Kleedorfer B, Turjanski N, Fernandez W, Lees AJ, Stern GM. Subcutaneous apomorphine in Parkinson's disease: response to chronic administration for up to five years. Mov Disord 1993,8:165-170.

[18] 18. Hughes AJ, Lees AJ, Stern GM. The motor response to sequential apomorphine in parkinsonian fluctuations. J Neurol Neurosurg Psychiatry 1991,54:358-360.

[19] 19. Hughes AJ, Webster R, Bovingdon M, Lees AJ, Stern GM. Sublingual apomorphine in the treatment of Parkinson's disease complicated by motor fluctuations. Clin Neuropharmacol 1991,6:556-561.

[20] 20. Kempster PA, Frankel JP, Stern GM, Lees AJ. Comparison of motor response to apomorphine and levodopa in Parkinson's disease. J Neurol Neurosurg Psychiatry 1990,53:1004-1007.

[21] 21. Kempster PA, Iansek R, Larmour I. Intermitent subcutaneous apomorphine injection treatment for parkinsonian motor oscillations. Aust NZ J Med 1991,21:314-318.

[22] 22. Kleedorfer B, Turjanski N, Ryan R, Lees AJ, Milroy C, Stern GM. Intranasal apomorphine in Parkinson's disease. Neurology 1991,41:761-762.

[23] 23. Marsden CD, Parkes JD. Success and problems of long-term levodopa therapy in Parkinson's disease. Lancet 1977,1:345-349.

[24] 24. Mouradian MM, Juncos JL, Fabbrini G, Schlegel J, Bartko JJ, Chase TN. Motor fluctuation in Parkinson's disease: central pathophysiological mechanisms, Part II. Ann Neurol 1988,24:372-378.

[25] 25. Nutt JG, Woodward WR, Hammerstad JP, Carter JH, Anderson JL. The "on-off' phenomenon in Parkinson's disease: relation to levodopa absortion and transport. N Engl J Med 1984,310:483-488.

[26] 26. Poewe W, Kleedorfer B, Wagner M, Bosch S, Schelosky L. Continuous subcutaneous apomorphine infusions for fluctuating Parkinson's disease. Adv Neurol 1993,60:656-659.

[27] 27. Steiger MJ, Quinn NP, Marsden CD. The clinical use of apomorphine in Parkinson's disease. J Neurol 1992,239:389-393.

[28] 28. Stibe CMH, Lees AJ, Kempster PA, Stern GM. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988, 1:403-406.

[29] 29. Tolosa ES, Martin WE, Cohen HP, Jacobson RL. Patterns of clinical response and plasma dopa in Parkinson's disease. Neurology 1975, 25:177-183.