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1.
Expert Rev Clin Pharmacol ; 13(2): 85-101, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32011195

RESUMO

Introduction: Many patients with advanced Parkinson's disease (PD) have inadequate control of motor symptoms despite optimized treatment. Predictable and unpredictable OFF periods severely interfere with the quality of life. A drug that easily and rapidly reverts the OFF state is still needed. Subcutaneous apomorphine, the only approved drug for this indication, although efficacious, is not widely used probably due to its potential side effects and complicated administration.Levodopa is the most efficacious drug for the treatment of PD motor symptoms. However, issues related to the oral route and intestinal absorption in later disease stages render this route lengthy and inefficacious.Areas covered: Literature on the development of an inhaled formulation of levodopa has been reviewed. Significant advances in the field of pulmonary delivery systems and in dry powders have enabled the development of a new formulation of levodopa that can be inhaled and adequate blood levels rapidly achieved, bypassing intestinal absorption. Several clinical trials have reported efficacy, safety, and tolerability data. Some pulmonary-related adverse events have been reported but are mostly mild.Expert opinion: This new way of administering levodopa is likely to be very welcome and may fill a gap for OFF rescue treatments, at least for some patients.


Assuntos
Antiparkinsonianos/administração & dosagem , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Administração por Inalação , Animais , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/farmacologia , Sistemas de Liberação de Medicamentos , Humanos , Levodopa/efeitos adversos , Levodopa/farmacologia , Doença de Parkinson/fisiopatologia , Qualidade de Vida
3.
J Ethnopharmacol ; 247: 112226, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31574343

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice preparations are used as neuroprotective remedies in Persian ethnomedicine, in order to prevent from disabilities in neurodegenerative conditions like Parkinson's disease (PD). AIM OF THE STUDY: This study was designed to determine the licorice (root of Glycyrrhiza glabra L.) effectiveness as an adjunct treatment in the PD management. MATERIAL AND METHODS: In this double-blinded trial, 128 patients were assessed for eligibility criteria. Seventy-eight patients were ineligible and 11 of them refused from participating. Thirty-nine PD patients (YAHR staging ≤ 3) were divided into two groups by random. The patients received oral licorice or placebo syrups with a dose of 5 cc, twice a day for 6 months. High-performance liquid chromatography and spectrophotometric instruments determined licorice syrup constituents. The patients' situation for Unified Parkinson's rating scale (UPDRS) was assessed every 6 weeks for the duration of six months. In addition, patients' blood pressure, blood glucose, sodium and potassium levels, quality of life and dizziness were determined. RESULTS: Six weeks after intervention, total UPDRS, daily activities and tremor were significantly improved with a considerable effect size. A significant better motor test and rigidity scores were observed 4 months after licorice intake (p > 0.05). No electrolyte abnormality, significant changes in blood pressure or blood glucose levels were observed during the study. Each 5cc of syrup contained 136 mg of licorice extract with 12.14 mg glycyrrhizic acid, and also 136 µg of polyphenols. CONCLUSION: The licorice intake could improve the symptoms in PD patients without serious adverse events.


Assuntos
Antiparkinsonianos/administração & dosagem , Glycyrrhiza/química , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/efeitos adversos , Glicemia/análise , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Etnofarmacologia , Feminino , Humanos , Irã (Geográfico) , Masculino , Medicina Arábica/métodos , Pessoa de Meia-Idade , Destreza Motora/efeitos dos fármacos , Rigidez Muscular/sangue , Rigidez Muscular/tratamento farmacológico , Rigidez Muscular/etiologia , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Placebos , Extratos Vegetais/efeitos adversos , Raízes de Plantas/química , Qualidade de Vida , Resultado do Tratamento
4.
Expert Opin Ther Pat ; 29(12): 979-985, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31694421

RESUMO

Introduction: Parkinson's disease (PD), is a disorder debilitant characterized by the reduction of nigrostriatal dopaminergic neurons within the midbrain, specifically in the substantia nigra pars compacta, which results for the dopamine (DA) depletion in the striatum. Dopamine replacement therapies with the 3,4-dihydroxy-L-phenylalanine (Levodopa or L-DOPA) represent the most common strategy to treat PD. However, chronic administration of L-DOPA results in abnormal involuntary movement (AIMs). Thus, the present study aimed to prospect patents of alternative treatment strategies for L-DOPA-induced dyskinesias.Areas covered: This review covers the therapeutic patents published over the 2001-2019 period in the WIPO, INPI, and ESPACENET, which report treatment strategies for L-DOPA induced dyskinesias (LIDs).Expert opinion: In recent years, several pharmaceutical companies, as well as universities and researchers have tested effective compounds for LIDs treatment, showing substances that act on central pathways as antagonists and agonists of the serotonergic system, which may result in the key to onset of LIDs in animal models of PD. Future works aiming to elucidate the L-DOPA, Flibanserin, Eltoprazine, and Pridopidina mechanisms of action on the receptors of the serotonergic system and D2 receptors of the indirect pathway, will allow the development of effective therapies for LIDs.


Assuntos
Antiparkinsonianos/efeitos adversos , Discinesia Induzida por Medicamentos/tratamento farmacológico , Levodopa/efeitos adversos , Animais , Antiparkinsonianos/administração & dosagem , Modelos Animais de Doenças , Dopamina/metabolismo , Humanos , Levodopa/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Patentes como Assunto
5.
Expert Opin Drug Saf ; 18(12): 1203-1218, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31619083

RESUMO

Introduction: Dyskinesia is a motor complication of Parkinson's disease (PD) characterized by clinical heterogeneity and complex pathogenesis and associated with long-term levodopa therapy. Recent and controversial views on the management of PD patients have suggested that overall dyskinesia rates, and particularly troublesome dyskinesia, may be declining due to more conservative levodopa dosing regimens, widespread availability and early introduction of deep brain stimulation, and use of continuous drug delivery strategies. Nevertheless, anti-dyskinetic agents continue to be evaluated in clinical trials and recent efforts have focused on non-dopaminergic drugs.Areas covered: In this review, the authors discuss the clinical phenomenology and current understanding of dyskinesia in PD with a focus on up-to-date therapeutic strategies to prevent and manage these drug-related involuntary movements.Expert opinion: The way dyskinesia in PD is currently managed should be changed and attention should be focused toward a more personalized medicine rather than a one-fits-all-approach. The correct identification of dyskinesia types and tailored treatments are crucial for a better management of these involuntary movements together with a holistic approach which considers additional influencing factors. The future for dyskinesia treatment is likely to be found in non-dopaminergic approaches, first set into motion by the introduction of amantadine.


Assuntos
Antiparkinsonianos/administração & dosagem , Discinesias/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/efeitos adversos , Estimulação Encefálica Profunda , Sistemas de Liberação de Medicamentos , Discinesia Induzida por Medicamentos/prevenção & controle , Discinesias/etiologia , Discinesias/fisiopatologia , Humanos , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Doença de Parkinson/fisiopatologia
7.
AAPS PharmSciTech ; 20(8): 312, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529266

RESUMO

To enhance efficiency, convenience, and safety of Parkinson's disease (PD) treatment for geriatric patients, an advanced suspension of Levodopa/Benserazide hydrochloride (LD/BH) has been prepared by cation-exchange resin and used to synchronize sustained release of LD and BH by optimizing coating parameters and prescription. For the purpose, LD and BH were immobilized on the surface of cation-exchange resin, respectively. Based on HPLC results, the cation-exchange resin showed high loading capacity. The studies on drug loading mechanism indicated that both drugs were immobilized by electrostatic interaction rather than physical adsorption. After PEG modification, pretreated drug-resin complexes were coated by emulsion-solvent evaporation method. In order to control drug release in a sustained manner, coating parameters of drug-resin microcapsules were optimized respectively by single-factor analysis. Further, coating prescription of the microcapsules was optimized to synchronize sustained release of LD and BH in vitro by orthogonal design. Utilizing optimal LD-resin microcapsules and BH-resin microcapsules, LD/BH suspension, containing both of them, was prepared by an optimal formulation and characterized by accelerated test and pharmacokinetic study in vivo. The accelerated test confirmed high stability of LD/BH suspension. According to pharmacokinetic results in vivo, in contrast with LD/BH commercial tablets, LD/BH suspensions did not only synchronize sustained release of both drugs but also show good bioequivalence. As LD/BH sustained release suspension can synchronize sustained release of multiple active ingredients by oral administration, the suspension presents promising oral dosage forms for geriatric patients with PD. An advanced Levodopa/Benserazide hydrochloride (LD/BH) suspension, prepared by cation-exchange resin and optimized microencapsulation, synchronizes sustained releases of LD and BH in vivo to benefit Parkinson's disease treatment for geriatric patients.


Assuntos
Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/química , Benserazida/administração & dosagem , Benserazida/química , Levodopa/administração & dosagem , Levodopa/química , Administração Oral , Animais , Antiparkinsonianos/farmacocinética , Benserazida/farmacocinética , Cápsulas , Resinas de Troca de Cátion , Preparações de Ação Retardada , Combinação de Medicamentos , Composição de Medicamentos , Levodopa/farmacocinética , Lipídeos/química , Masculino , Ratos , Suspensões , Comprimidos com Revestimento Entérico
8.
BMJ Case Rep ; 12(7)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31337633

RESUMO

Freezing of gait (FOG) and postural instability are challenging motor symptoms that present a serious therapeutic dilemma in Parkinson's disease. Appropriate distinction between FOG subtypes may be difficult during routine clinical visits, as shown in the case we present. The patient was examined in three different states in relation to levodopa (L-DOPA) and apomorphine subcutaneous (sc) tests with video documentation: (1) 'overnight-off', after 12 hours without medication; (2)'on', 60 min after intake of regular levodopa dose (200 mg) and 20 min after 2 mg of apomorphine sc; and (3) 'supra-on', after 350 mg of L-DOPA and 3 mg of apomorphine sc. The patient clearly showed a dose-dependent paradoxical response to L-DOPA treatment with the emergence of severe FOG and postural instability. The tendency to develop these axial symptoms was less pronounced with apomorphine at doses that achieved similar improvements of other Parkinsonian features.


Assuntos
Antiparkinsonianos/efeitos adversos , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Transtornos Neurológicos da Marcha/induzido quimicamente , Levodopa/efeitos adversos , Oxidiazóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Equilíbrio Postural , Transtornos das Sensações/induzido quimicamente , Idoso , Antiparkinsonianos/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Levodopa/administração & dosagem , Masculino , Doença de Parkinson/fisiopatologia
9.
Int J Pharm ; 567: 118493, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31279054

RESUMO

Effective inhaler therapy requires correct handling of the inhaler, including being able to prepare the inhaler for use. Motor function impairment and cognitive disabilities, may impose problems on patients with Parkinson's disease when they have to prepare medication, such as inhalers, for use. The aim of the present study was to examine whether Parkinson's patients are able to correctly prepare the Cyclops inhaler for use. At first, 12 patients, 6 in an off state and 6 in an on state, were asked to open 5 inhalers with ascending peel resistance of the cover foil. It was investigated up to which peel resistance they were able to successfully pull the foil from the inhaler. For the second part of the study, 48 participants, 24 on and 24 off, were asked to open 2 pouches and the 2 inhalers selected in part 1. For pouch 1, 70.8% of the patients in an on state and 58.3% in an off state were able to open the pouch correctly. For pouch 2, this was 79.2% and 75.0%, respectively. Both Cyclops inhalers were opened correctly by 95.8% of the participants in the on state and 91.7% of the participants in the off state.


Assuntos
Embalagem de Medicamentos , Inaladores de Pó Seco , Doença de Parkinson/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Feminino , Humanos , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade
10.
Drug Deliv ; 26(1): 700-707, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31290705

RESUMO

Efficient delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate borneol and lactoferrin co-modified nanoparticles (Lf-BNPs) encapsulated dopamine as a novel drug delivery system to achieve maximum therapeutic efficacy and reduce side effects for PD. Dopamine Lf-BNPs were prepared using the double emulsion solvent evaporation method and evaluated for physicochemical and pharmaceutical properties. In vitro cytotoxicity studies indicated that treatment with dopamine Lf-BNPs has relatively low cytotoxicity in SH-SY5Y and 16HBE cells. Qualitative and quantitative cellular uptake experiments indicated that Lf modification of NPs increased cellular uptake of SH-SY5Y cells and 16HBE cells, and borneol modification can promote the cellular uptake of 16HBE. In vivo pharmacokinetic studies indicated that AUC0-12 h in the rat brain for dopamine Lf-BNPs was significantly higher (p < .05) than that of dopamine nanoparticles. Intranasal administration of dopamine Lf-BNPs effectively alleviated the 6-hydroxydopamine-induced striatum lesion in rats as indicated by the contralateral rotation behavior test and results for striatal monoamine neurotransmitter content detection. Taken together, intranasal administration of dopamine Lf-BNPs may be an effective drug delivery system for Parkinson's disease.


Assuntos
Antiparkinsonianos/administração & dosagem , Encéfalo/metabolismo , Dopamina/administração & dosagem , Lactoferrina , Nanopartículas/química , Administração Intranasal , Animais , Antiparkinsonianos/farmacocinética , Antiparkinsonianos/farmacologia , Células Cultivadas , Dopamina/farmacocinética , Dopamina/farmacologia , Sistemas de Liberação de Medicamentos , Nanopartículas/toxicidade , Doença de Parkinson/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
11.
Continuum (Minneap Minn) ; 25(4): 896-918, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31356286

RESUMO

PURPOSE OF REVIEW: Parkinson disease is a common neurodegenerative disorder that affects millions of people worldwide. Important advances in the treatment, etiology, and the pathogenesis of Parkinson disease have been made in the past 50 years. This article provides a review of the current understanding of Parkinson disease, including the epidemiology, phenomenology, and treatment options of the disease. RECENT FINDINGS: Parkinson disease is now recognized to be a heterogeneous condition marked by both motor and nonmotor symptoms. It is composed of preclinical, prodromal, and clinical phases. New medications with improved ease of administration have been approved for its treatment. Innovative surgical therapies for Parkinson disease may be used when motor symptoms persist despite optimal medical management. SUMMARY: Parkinson disease is a complex, heterogeneous neurodegenerative disorder. Considerable progress has been made in its treatment modalities, both pharmacologic and surgical. While its cure remains elusive, exciting new research advances are on the horizon.


Assuntos
Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Exercício Físico/fisiologia , Levodopa/administração & dosagem , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Idoso , Combinação de Medicamentos , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/psicologia , Terapias em Estudo/métodos , Terapias em Estudo/tendências
12.
Clin Neuropharmacol ; 42(4): 111-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192808

RESUMO

OBJECTIVES: Although commercially available levodopa (LD) formulations include carbidopa (CD) or benserazide for gastrointestinal L-aromatic amino acid decarboxylase inhibition, little is known how manipulating CD delivery affects the pharmacokinetics of LD. Our research systematically evaluated the peripheral and central pharmacokinetics of LD during continuous subcutaneous CD delivery. METHODS: We conducted pharmacokinetic experiments in pigs, mice, and humans to characterize effects of continuous subcutaneous CD delivery co-administered with LD as compared with oral LD/CD administration on LD pharmacokinetics. The porcine and human studies compared peripheral LD pharmacokinetic parameters (area under the curves [AUCs], peak plasma concentrations [Cmax], and plasma elimination half-life [t1/2]) and the mouse studies compared brain LD and dopamine concentrations. RESULTS: In the pig, supplementary subcutaneous CD delivery significantly increased the LD t1/2 and AUC versus LD/CD alone and versus additional oral CD administration. In mice, administration of supplementary subcutaneous CD substantially increased mean plasma concentrations of both LD and CD versus oral LD/CD alone at all time points. These increases were mirrored by increased brain dopamine levels for at least the 7 hours of study. In healthy human subjects, continuous subcutaneous CD administration, 3.33 mg/h x24h, increased the plasma LD t1/2, Cmax, and AUC by 17.4%, 40.5%, and 22.3%, respectively (P < 0.003). CONCLUSIONS: This series of studies demonstrates that small continuous dosing of subcutaneous CD has an unexpected effect on LD pharmacokinetics greater than the extent of decarboxylase inhibition achieved by additional oral CD administration.


Assuntos
Antiparkinsonianos/administração & dosagem , Inibidores das Descarboxilases de Aminoácidos Aromáticos/administração & dosagem , Carbidopa/administração & dosagem , Levodopa/farmacocinética , Adulto , Animais , Quimioterapia Combinada , Feminino , Voluntários Saudáveis , Humanos , Levodopa/administração & dosagem , Levodopa/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Suínos
13.
Medicine (Baltimore) ; 98(24): e16082, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192971

RESUMO

BACKGROUND: In recent years, L-3-n-butylphthalide (L-NBP) has been used for Parkinson disease dementia (PDD) to attenuate cognitive impairments in China. Therefore, we selected published and qualified clinical trials to conduct a systematic review and meta-analysis with the aim of assessing the effectiveness and safety of L-NBP in the treatment of PDD. OBJECTIVE: This systematic review and meta-analysis aimed to assess the effectiveness and safety of L-NBP in the treatment of PDD. METHODS: We searched PubMed, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP database), and Wan-Fang Database to collect eligible articles. We calculated pooled estimates of odds ratios or the standard mean deviation with 95% confidence intervals. RESULTS: Eight randomized controlled trials were included in our meta-analysis. Our meta-analysis showed that L-NBP combined with Western medicine (WM) had a better effect on improving cognitive dysfunction, the total effective rate, symptoms of Parkinson disease (PD), and activities of daily living function than WM alone. Regarding safety, no serious adverse events were observed in the experimental group. CONCLUSION: We found that L-NBP as a complementary therapy may have a positive therapeutic effect for improving cognitive dysfunction, the total effective rate, symptoms of PD, quality of life, and the related serum factors in the treatment of PDD. Furthermore, L-NBP was a safe treatment for PDD. However, the findings of our meta-analysis may be influenced by the low quality of the included studies. We highlight the need to conduct trials with higher methodological quality.


Assuntos
Antiparkinsonianos/administração & dosagem , Benzofuranos/administração & dosagem , Demência/tratamento farmacológico , Nootrópicos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Benzofuranos/efeitos adversos , Cápsulas , Demência/etiologia , Humanos , Nootrópicos/efeitos adversos , Doença de Parkinson/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Science ; 364(6445)2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31196984

RESUMO

The human gut microbiota metabolizes the Parkinson's disease medication Levodopa (l-dopa), potentially reducing drug availability and causing side effects. However, the organisms, genes, and enzymes responsible for this activity in patients and their susceptibility to inhibition by host-targeted drugs are unknown. Here, we describe an interspecies pathway for gut bacterial l-dopa metabolism. Conversion of l-dopa to dopamine by a pyridoxal phosphate-dependent tyrosine decarboxylase from Enterococcus faecalis is followed by transformation of dopamine to m-tyramine by a molybdenum-dependent dehydroxylase from Eggerthella lenta These enzymes predict drug metabolism in complex human gut microbiotas. Although a drug that targets host aromatic amino acid decarboxylase does not prevent gut microbial l-dopa decarboxylation, we identified a compound that inhibits this activity in Parkinson's patient microbiotas and increases l-dopa bioavailability in mice.


Assuntos
Actinobacteria/enzimologia , Antiparkinsonianos/metabolismo , Proteínas de Bactérias/metabolismo , Enterococcus faecalis/enzimologia , Microbioma Gastrointestinal , Levodopa/metabolismo , Tirosina Descarboxilase/metabolismo , Tirosina/análogos & derivados , Actinobacteria/efeitos dos fármacos , Actinobacteria/genética , Animais , Antiparkinsonianos/administração & dosagem , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/genética , Descarboxilação/efeitos dos fármacos , Dopamina/metabolismo , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Microbioma Gastrointestinal/genética , Genoma Bacteriano , Células HeLa , Humanos , Levodopa/administração & dosagem , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Tirosina/administração & dosagem , Tirosina/química , Tirosina/farmacologia , Tirosina Descarboxilase/antagonistas & inibidores , Tirosina Descarboxilase/genética
16.
BMJ Case Rep ; 12(5)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092485

RESUMO

Parkinsonism-hyperpyrexia syndrome (PHS) is a neurologic potentially fatal emergency that mimics neuroleptic malignant syndrome. It commonly presents as systemic inflammatory response syndrome, acute onset worsening of muscular rigidity, autonomic instability, hyperpyrexia, confusion, diaphoresis and high creatine phosphokinase. The most common trigger for PHS is reduction or withdrawal of anti-Parkinson's medications, especially levodopa. It was also reported in a few cases following deep brain stimulation of the subthalamic nucleus surgery shortly after anti-Parkinson's medications were discontinued. Rare causes of PHS include deep brain stimulator (DBS) malfunction due to battery depletion. To the best of our knowledge, PHS following DBS battery depletion was reported only in three occasions. Here, we report a case of PHS due to DBS battery depletion presented as sepsis and was successfully treated with the administration of dopamine agonists, intravenous fluids and changing the DBS battery.


Assuntos
Antiparkinsonianos/efeitos adversos , Estimulação Encefálica Profunda/efeitos adversos , Doença de Parkinson/terapia , Síndrome de Abstinência a Substâncias/diagnóstico , Doença Aguda , Idoso , Antiparkinsonianos/administração & dosagem , Feminino , Humanos
17.
J Neurol ; 266(9): 2164-2176, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31134377

RESUMO

INTRODUCTION: The GREENFIELD observational study assessed the effect of levodopa/carbidopa intestinal gel (LCIG) on motor and non-motor symptoms, and the related impact on patient quality of life and caregiver burden up to 8 years. METHODS: Final results of a large Italian cohort of patients who started LCIG in routine care between 2007 and 2014 are presented. Comparison between baseline (before LCIG) and follow-up visits on yearly basis (visit 2/3) is reported. Primary endpoint was Unified Parkinson's Disease Rating Scale (UPDRS-IV) Item 39; secondary endpoints were UPDRS I and II, dyskinesia items, PD Quality of Life Questionnaire-39, Parkinson's Disease Sleep Scale-2, Gait and Falls Questionnaire, Questionnaire on Impulsive Disorders, and Relative Stress Scale. RESULTS: Overall, 145 patients from 14 centers were assessed with a mean time since LCIG start of 2.8 ± 1.7 years at visit 2. The mean UPDRS-IV item 39 score showed significant reductions compared to baseline (mean score 2.0 ± 0.81) at visit 2 (mean score 0.9 ± 0.69; - 55%; p < 0.001) and at visit 3 (mean score 1.0 ± 0.75; - 50%; p < 0.001). At visit 3, significant reductions were observed for dyskinesia duration score (- 28%; p < 0.001), dyskinesia disability (- 40%; p < 0.001), and painful dyskinesia (- 50%; p < 0.001). Overall, 40 (27.6%) patients experienced 49 serious adverse events which were considered related to PEG/J procedure or to device in 16.3% of the cases. CONCLUSIONS: The results of this study support the long-term efficacy of LCIG on PD symptoms as well as on activities of daily living. The adverse events were consistent with the established LCIG safety profile.


Assuntos
Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Bombas de Infusão , Jejuno/efeitos dos fármacos , Levodopa/administração & dosagem , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Combinação de Medicamentos , Feminino , Seguimentos , Gastrostomia , Géis , Humanos , Itália/epidemiologia , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
18.
Clin Neuropharmacol ; 42(4): 123-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31045589

RESUMO

OBJECTIVES: The aim of this open-label study was to investigate the long-term safety and efficacy of selegiline as monotherapy in Japanese patients with early Parkinson disease (PD). METHODS: We conducted a 56-week prospective study in patients with early PD (N = 134) who had previously completed the randomized, double-blind, placebo-controlled phase III trial of selegiline monotherapy for 12 weeks. In the present study, dosing was titrated from 2.5 to 10 mg/d in increments of 2.5 mg/d for 2 weeks. From the seventh week, the dosage was maintained at 10 mg/d until week 56. The primary outcome was any change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score (part I + II + III) from baseline. Secondary outcomes, including changes in the UPDRS subscores and safety profile, were also evaluated. RESULTS: Ninety-one (67.9%) patients completed the 56-week study. Treatment with selegiline significantly reduced total UPDRS score from week 4 (mean ± SD, -2.62 ± 3.83; P < 0.0001) to week 56 (-3.39 ± 9.27; P < 0.01). The peak effect was seen at week 20 (-5.79 ± 5.57; P < 0.0001). In addition, we found similar improvements in the UPDRS parts II and III scores. The incidence rate of adverse drug reactions was 44.3% (58 patients) and did not increase during the period of 10 mg selegiline administration. CONCLUSIONS: Long-term monotherapy with selegiline (10 mg/d) was effective and well tolerated in patients with early PD in this 56-week study.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Selegilina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Escala de Avaliação Comportamental , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Estudos Prospectivos , Selegilina/administração & dosagem
19.
Expert Opin Drug Metab Toxicol ; 15(5): 429-435, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31017021

RESUMO

INTRODUCTION: Brain function depends considerably on the neurotransmission of biogenic monoamines. Their metabolism employs monoamine oxidase-B in neuronal and glial cells. Inhibition of monoamine oxidase-B elevates biogenic amine levels. Accordingly, monoamine oxidase-B inhibitors provide a symptomatic effect via dopamine on motor symptoms in patients with Parkinson's disease. Areas covered: This narrative review aims to describe the pharmacokinetic characteristics of the available reversible and irreversible monoamine oxidase B inhibitors for the treatment of Parkinson's disease in daily practice. All these compounds are administered on a daily basis. Expert opinion: Reversibility or irreversibility of available monoamine oxidase-B inhibition is not relevant, due to their daily intake and half-life in clinical practice. Irreversible monoamine oxidase-B inhibitors slowed the progression of neuronal dying in experimental models of Parkinson's disease. In patients, concomitant inhibition of monoamine oxidase-B caused less increase of levodopa dosages over five years. The curve of levodopa increment diverged from the placebo curve. This reduced need for L-dopa monotherapy may be discussed as an indirect biomarker for disease severity and reflects a disease-modifying effect. In case of a symptomatic effect only, parallel curves would have occurred. Long-term L-dopa treatment should be combined with monoamine oxidase-B inhibitors when tolerated by patients.


Assuntos
Antiparkinsonianos/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/farmacocinética , Progressão da Doença , Dopamina/metabolismo , Humanos , Levodopa/administração & dosagem , Monoaminoxidase/efeitos dos fármacos , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacocinética , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença
20.
Rev Neurol (Paris) ; 175(4): 233-237, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30935674

RESUMO

Impulse control disorders (ICDs) in Parkinson's disease (PD) comprise a class of psycho-behavioral disorders often associated with dopamine agonist treatment. The aim of our study was to determine the prevalence of ICDs in a group of Moroccan PD patients and to bring forward some specific aspects in our population. One hundred twenty-five PD patients, without memory impairment and treated for at least six months, were studied. They were questioned about ICDs using the QUIP-RS, and simultaneously evaluated on the motor symptoms and their treatment. Our sample was then divided into two groups: ICDs (+) and ICDs (-) groups. ICDs were identified in 28% of patients: pathological gambling in 3.2%, compulsive sexual behavior in 7.2%, pathological buying in 9.6%, eating behavior disorder in 7.2%, punding-hobbyism in 11.1%. At least two ICDs were found in 14% of patients and dopamine dysregulation syndrome in 10.4%. We also noticed another kind of "ICDs-mimics" specific to our own social context such as "excessive charity" in 18.4%, or excessive reading of the Qur'an in 9.6%. These aspects were not included in the calculation of ICDs prevalence. The ICDs (+) group was younger than the ICDs (-) group (P=0.042) and ICDs were more frequent in men (P=0.031). Dopamine agonist equivalent daily dose (DAED) was significantly higher (P=0.01) in the ICDs (+) group. There are no differences between classes of dopamine agonist used. Young age, male gender and DAED are risk factors for the occurrence of ICDs in Moroccan PD patients, as already described in the DOMINION cohort, but the prevalence found in our study was higher. We highlighted some specific ICDs-mimics in our Arab-Muslim population.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Doença de Parkinson/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/uso terapêutico , Estudos Transversais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Agonistas de Dopamina/uso terapêutico , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Marrocos , Doença de Parkinson/psicologia , Fatores de Risco , Fatores Sexuais , Comportamento Sexual , Adulto Jovem
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