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1.
Artigo em Russo | MEDLINE | ID: mdl-34037362

RESUMO

The article presents data from recent studies on the mechanisms of action and clinical efficacy of amantadines, and also describes a possible protective effect against COVID-19.


Assuntos
Doença de Parkinson , Amantadina/uso terapêutico , Antiparkinsonianos/uso terapêutico , Humanos , Levodopa , Doença de Parkinson/tratamento farmacológico
2.
Artigo em Russo | MEDLINE | ID: mdl-33834716

RESUMO

OBJECTIVE: To develop and implement the tactics of the differentiated complex (medication in combination with surgery) treatment of the form of Parkinson's disease (PD) associated with dyskinesias, according to the severity of atrophic changes in the brain. MATERIAL AND METHODS: The study included 40 patients with PD associated with dyskinesias and motor fluctuations. Patients of the main group received medication and surgical treatment, patients of the comparison group received only medication. The patient's health was assessed every 3 months during 1.5 years. Three atrophy indices were proposed to describe atrophic changes in the brain. RESULTS: We have determined the values of the indices when the complex treatment was optimal for patients. CONCLUSION: The results of the study are supposed to be used in the practice of neurologists and neurosurgeons.


Assuntos
Discinesias , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Atrofia/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia
3.
Molecules ; 26(8)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920326

RESUMO

Neurodegenerative diseases (ND), including Alzheimer's (AD) and Parkinson's Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Inibidores da Colinesterase/uso terapêutico , Dopaminérgicos/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Antiparkinsonianos/síntese química , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Inibidores da Colinesterase/síntese química , Ensaios Clínicos como Assunto , Simulação por Computador , Dopaminérgicos/síntese química , Desenho de Fármacos , Antagonistas de Aminoácidos Excitatórios/síntese química , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação da Expressão Gênica , Humanos , Fármacos Neuroprotetores/síntese química , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Sirtuínas/antagonistas & inibidores , Sirtuínas/genética , Sirtuínas/metabolismo
4.
Clin Drug Investig ; 41(4): 321-339, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33674954

RESUMO

BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes. METHODS: PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed. RESULTS: Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence. CONCLUSION: Overall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.


Assuntos
Alanina/análogos & derivados , Antiparkinsonianos/uso terapêutico , Benzilaminas/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Alanina/administração & dosagem , Alanina/efeitos adversos , Benzilaminas/efeitos adversos , Agonistas de Dopamina/administração & dosagem , Humanos , Levodopa/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Brain Nerve ; 73(3): 273-281, 2021 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-33678619

RESUMO

The current therapeutic approach for Parkinson's disease (PD) is mainly dopamine replacement with levodopa and other anti-parkinsonian drugs. As PD progresses, the number of these drugs used steadily increases. Using prescription-based database for 10 or more years up to October 2019, we investigated actual prescribing patterns for anti-parkinsonian drugs in Japan. The main analyses included data from patients continuously prescribed levodopa for 1 or more years (n=16,270), and of these, those continuously prescribed adjuvants to levodopa for 1 or more years (n=3,675). The results showed that the number of anti-parkinsonian drugs, their daily dose frequencies, and the number of tablets increased over time. These trends were observed not only for levodopa but also for adjuvants to levodopa; the number of adjuvants, their daily dose frequencies and number of tablets also increased. As the daily number of tablets increased, the proportion of dopamine agonists increased. Moreover, as the daily dosage of levodopa increased, the daily number of tablets increased for both overall anti-parkinsonian drugs and adjuvants to levodopa. This study revealed the process of polypharmacy in PD treatment objectively. Our results are valuable for maintaining and improving therapeutic adherence in PD. (Received 25 August, 2020; Accepted 23 October, 2020; Published 1 March, 2021).


Assuntos
Antiparkinsonianos , Preparações Farmacêuticas , Antiparkinsonianos/uso terapêutico , Humanos , Japão , Levodopa/uso terapêutico , Prescrições
7.
J Parkinsons Dis ; 11(2): 445-454, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33749619

RESUMO

BACKGROUND: Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected patients enrolled in most studies did not allow to draw robust conclusions on the COVID-19 impact in PD. OBJECTIVE: We aimed to assess whether the prevalence and outcome of COVID-19 in PD patients are different from those observed in the general population. METHODS: We conducted a systematic review of studies reporting data on PD patients with a diagnosis of COVID-19 (PD-COVID+). We extracted prevalence, clinical-demographic data, outcome, and mortality. We also analyzed risk or protective factors based on comparisons between PD-COVID+ and control populations with PD without COVID-19 or without PD with COVID-19. RESULTS: We included 16 studies reporting on a total of 11,325 PD patients, 1,061 with a confirmed diagnosis of COVID-19. The median infection prevalence ranged from 0.6% to 8.5%. PD-COVID+ patients had a median age of 74 and a disease duration of 9.4 years. Pooling all PD-COVID+ patients from included studies, 28.6% required hospitalization, 37.1% required levodopa dose increasing, and 18.9% died. The case fatality was higher in PD-COVID+ patients than the general population, with longer PD duration as a possible risk factor for worse outcome. Amantadine and vitamin D were proposed as potential protective factors. CONCLUSION: Available studies indicate a higher case fatality in PD patients affected by COVID-19 than the general population. Conversely, current literature does not definitively clarify whether PD patients are more susceptible to get infected. The potential protective role of vitamin D and amantadine is intriguing but deserves further investigation.


Assuntos
Antiparkinsonianos/uso terapêutico , Doença de Parkinson/epidemiologia , /sangue , Estudos de Casos e Controles , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Vitamina D/uso terapêutico
8.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542006

RESUMO

Atraumatic trismus can be one of the presentations of medication-induced acute dystonia, particularly by antipsychotics and less commonly antidepressants. A case of an unusual emergency presentation of atraumatic trismus on initiation of duloxetine is reported. The patient was a 40-year-old woman experiencing sudden difficulty in mouth opening and speaking due to a stiffened jaw after taking 5 days of duloxetine prescribed for her fibromyalgia-related chest pain. Assessment of vital signs is prudent to ensure there is no laryngeal involvement. Other physical examinations and her recent investigations were unremarkable. She was treated for acute dystonia and intravenous procyclidine was given together with oral diazepam. Her symptoms improved immediately and her duloxetine was suggested to be stopped. To our knowledge, this is the first case of isolated trismus induced by duloxetine. Clinicians should be aware of this risk, especially considering the limitation of important physiological functions (such as swallowing, eating, etc) associated with this condition.


Assuntos
Antidepressivos , Cloridrato de Duloxetina , Distonia/induzido quimicamente , Fibromialgia/tratamento farmacológico , Trismo/induzido quimicamente , Adulto , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antiparkinsonianos/uso terapêutico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Cloridrato de Duloxetina/efeitos adversos , Cloridrato de Duloxetina/uso terapêutico , Feminino , Humanos , Prociclidina/uso terapêutico
9.
BMC Neurol ; 21(1): 51, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535984

RESUMO

BACKGROUND: There is no established pathogenesis of hemiparkinsonism-hemiatrophy syndrome (HPHA), and the varied clinical presentations have been reported in several case studies. To the best of our knowledge, the present report describes the first case of HPHA with unusual brain imaging findings. CASE PRESENTATION: A 20-year-old man presented with a 6-month history of weakness and clumsiness in his right limbs. He showed right-sided parkinsonism with dystonic hand posture; however, body asymmetry was not noted. Brain imaging revealed hemiatrophy of the left hemisphere subcortical structures and brainstem, and iron deposition in the left globus pallidus and substantia nigra. In addition, dopamine transporter imaging demonstrated normal presynaptic dopaminergic function. The patient was treated with levodopa, which had little to no effect. CONCLUSIONS: This case demonstrates the unique imaging characteristics of HPHA associated with widespread brain hemiatrophy and iron deposition. Further studies are needed to elucidate the diagnostic criteria for this heterogeneous syndrome.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/patologia , Antiparkinsonianos/uso terapêutico , Atrofia/patologia , Lateralidade Funcional , Humanos , Ferro , Levodopa/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Transtornos Parkinsonianos/tratamento farmacológico , Adulto Jovem
10.
J Parkinsons Dis ; 11(2): 431-444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33492244

RESUMO

Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson's disease (PD) have provided conflicting results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: 'Parkinson's disease' and 'parkinsonism' combined with: 'COVID-19'; 'SARS-CoV-2' and 'coronavirus'. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.


Assuntos
/diagnóstico , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Antiparkinsonianos/uso terapêutico , Humanos , Mortalidade/tendências , Pandemias/prevenção & controle , Doença de Parkinson/tratamento farmacológico , Fatores de Risco
11.
Eur J Pharmacol ; 895: 173862, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33450279

RESUMO

Parkinson's disease is a neurodegenerative disease which is associated with different motor, cognitive and mood-related problems. Though it has been established that Parkinson's disease is less prevalent in women in comparison to men, the differences tend to diminish with the advancing age. Different genetic, hormonal, neuroendocrinal and molecular players contribute towards the differences in the Parkinson's disease pathogenesis. Furthermore, data available with respect to the therapeutic management of Parkinson's disease in females is limited; women often tend to suffer more from the side effects of the currently available drugs. The present review highlights the sex-specific differences which play a role in the manifestation of these symptoms and side effects of the currently available therapeutic strategies. We have also discussed the current and upcoming therapeutic strategies which are in the clinical trials such as adenosine 2A (A2A) receptor antagonists, estrogen replacement therapy, α-synuclein targeting vaccines and antibodies, Botulinum toxin A, Fas-associated factor-1 (FAF-1) inhibitors, thiazolidinediones, 5-HT1A receptor agonists, dopamine D1/D5 receptor agonists, Glucagon-like peptide 1 (GLP-1) analogues and certain plant based principles for the treatment of Parkinson's disease in women.


Assuntos
Antiparkinsonianos/uso terapêutico , Disparidades nos Níveis de Saúde , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Animais , Antiparkinsonianos/efeitos adversos , Terapia de Reposição de Estrogênios , Feminino , Predisposição Genética para Doença , Hormônios Esteroides Gonadais/metabolismo , Humanos , Masculino , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais
12.
Neurosci Lett ; 740: 135426, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33075420

RESUMO

The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3ß have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6-OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6-OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3ß along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6-OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6-OHDA model of PD.


Assuntos
Antiparkinsonianos/uso terapêutico , Quinase 3 da Glicogênio Sintase/biossíntese , Hesperidina/uso terapêutico , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/biossíntese , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson Secundária/tratamento farmacológico , Proteínas de Peixe-Zebra/biossíntese , Animais , Caspases/metabolismo , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroxidopaminas , Locomoção/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/enzimologia , Peixe-Zebra
13.
Eur J Med Genet ; 64(1): 104123, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33338668

RESUMO

PPP2R5D-related neurodevelopmental disorder (NDD) is a rare autosomal-dominant disease with developmental delay and mild to severe intellectual disability. So far, fewer than 30 affected individuals with mostly recurrent, de novo missense variants in PPP2R5D were reported. Recently, parkinsonism with an onset between 20 and 40 years was reported in four adult individuals with the same p.(Glu200Lys) variant in PPP2R5D. By trio exome sequencing we now identified the variant p.(Glu198Lys) in a 29 year old woman presenting with typical clinical manifestations of PPP2R5D-related neurodevelopmental disorder and additionally with motor decline and levodopa responsive, early-onset parkinsonism from her mid-twenties on. Accordingly, a clear reduction of dopamine transporter in the striatum on both sides was revealed by brain scintigraphy. Our findings further expand the molecular and clinical spectrum of PPP2R5D-related NDD and confirm the association with parkinsonism in early adulthood. This has marked implications for prognosis of PPP2R5D-related NDDs and for the therapeutic management of motor decline and parkinson-like symptoms in affected individuals.


Assuntos
Transtornos Parkinsonianos/genética , Proteína Fosfatase 2/genética , Idade de Início , Antiparkinsonianos/uso terapêutico , Corpo Estriado/diagnóstico por imagem , Feminino , Humanos , Levodopa/uso terapêutico , Mutação de Sentido Incorreto , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , Fenótipo , Adulto Jovem
14.
PLoS One ; 15(8): e0237472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817705

RESUMO

A higher levodopa dose is a strong risk factor for levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD). However, levodopa dose can change during long-term medication. We explored the relationship between levodopa dose and time to onset of LID using longitudinal multicenter data. Medical records of 150 patients who were diagnosed with de novo PD and treated with levodopa until onset of LID were collected. Levodopa dose were assessed as the dose at 6 months from levodopa initiation and rate of dose increase between 6 months and onset of LID. The groups with earlier LID onset had higher levodopa and levodopa-equivalent dose at the first 6 months of treatment and rapid increase in both levodopa and levodopa-equivalent dose. Multivariable linear regression models revealed that female sex, severe motor symptom at levodopa initiation, and higher rate of increase in both levodopa and levodopa-equivalent dose were significantly associated with early onset of LID. The present results demonstrated that rapid increase in levodopa dose or levodopa-equivalent dose is associated with early onset of LID.


Assuntos
Antiparkinsonianos/uso terapêutico , Discinesia Induzida por Medicamentos/diagnóstico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/efeitos adversos , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos/etiologia , Feminino , Humanos , Levodopa/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
15.
Expert Opin Pharmacother ; 21(14): 1659-1665, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32640853

RESUMO

INTRODUCTION: Heterogeneity of symptoms and individual variability of progression characterizes Parkinson's disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients' needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications. AREAS COVERED: This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research. EXPERT OPINION: Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.


Assuntos
Antiparkinsonianos/administração & dosagem , Apomorfina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Apomorfina/efeitos adversos , Apomorfina/uso terapêutico , Progressão da Doença , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Humanos , Reação no Local da Injeção , Injeções Subcutâneas , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/imunologia
16.
Medicine (Baltimore) ; 99(27): e20758, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629653

RESUMO

BACKGROUND: Medicines optimisation is important for the management of Parkinson's disease (PD). As many patients with PD have other long-term conditions, treatment is complex and risk of adverse events for these patients is high. OBJECTIVE: To explore the role of pharmacists and impact of pharmacy interventions for PD patients. METHODS: We comprehensively searched PubMed, Embase, the Cochrane Library and Chinese databases Sinomed, China National Knowledge Infrastructure to identify studies reporting pharmacist interventions and pharmacy services for PD patients using a predefined search strategy. The search period was from inception to March 2019. We also manually searched the reference list of included studies and ClinicalTrials.gov. We conducted meta-analyses to synthesize the evidence quantitatively. RESULTS: A total of 1607 studies were identified by applying the search criteria. After screening, 19 cross-sectional and case-controlled studies with 1458 PD patients from 9 countries were included. Pharmacist interventions for PD patients most commonly related to adverse drug reactions (ADRs) (13 studies), adherence assessment (12 studies), medication review (12 studies), identification of drug interactions (11 studies), monitoring response to medication therapy (11 studies), identification of inappropriate medication (11 studies), and patient education (10 studies). Most pharmacy services were provided in outpatient settings (13 studies). Reported impact measures included adherence (8 studies), quality of life (7 studies), and identification of drug-related problems (6 studies) such as ADRs (393 times out of 1760 times, 22.33%, 6 studies), inappropriate drug choice (349 times, 19.83%, 6 studies), inappropriate dosage (335 times, 19.03%, 6 studies), inappropriate drug use (257 times, 14.60%, 3 studies) and drug-drug interactions (146 times, 8.3%, 4 studies). Pooled results from 3 studies indicated no statistically significant impact of pharmacy services on all subscales of PD Questionnaire-39. CONCLUSION: ADRs were the most widely reported drug-related problems for PD patients; pharmacy services may have a role to play in medication adherence but were not found to impact on quality of life.


Assuntos
Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Assistência Farmacêutica , Antiparkinsonianos/administração & dosagem , Humanos , Farmacêuticos
17.
Neurology ; 95(11): e1461-e1470, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32651292

RESUMO

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tremor/tratamento farmacológico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/fisiopatologia
19.
Arch Phys Med Rehabil ; 101(9): 1580-1589, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32540135

RESUMO

OBJECTIVE: To compare participants with Parkinson disease (PD) motor subtypes, postural instability and gait difficulty (PIGD) (n=46) and tremor dominant (TD) (n=28), in cognitive and motor-cognitive assessments with the purpose of identifying associations between subtype and visuospatial, whole-body spatial, inhibition and/or switching, and planning and/or organizational aspects of cognitive and motor-cognitive function. DESIGN: Retrospective cohort study. Fisher exact test was used for categorical variables, while 2-sample independent t tests were used to analyze continuous variables. SETTING: Assessments took place at Emory University. PARTICIPANTS: Participants (N=72) were 40 years and older, had a clinical diagnosis of PD, exhibited 3 of the 4 cardinal signs of PD, had shown benefit from antiparkinsonian medications, and were in Hoehn and Yahr stages I-IV. Participants could walk 3 m or more with or without assistance. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Balance and mobility tests included Fullerton Advanced Balance Scale and the time needed to turn 360 degrees. Cognitive assessments included Montreal Cognitive Assessment, Brooks Spatial Memory Task, Color-Word Interference Test, Tower of London, Trail Making Test, Corsi Blocks, Serial 3s Subtraction, and Body Position Spatial Task. Motor-cognitive function measures included Four Square Step Test and Timed Up and Go. RESULTS: Participants with PIGD performed lower than those with TD symptoms on mental status (P=.005), spatial memory (P=.027), executive function (P=.0001-.034), and visuospatial ability (P=.048). CONCLUSIONS: Findings suggest that PIGD subtype is linked to greater deficits in spatial cognition, attentional flexibility and organizational planning, and whole-body spatial memory domains. These findings support the need for more personalized approaches to clinically managing PD.


Assuntos
Doença de Parkinson/classificação , Doença de Parkinson/fisiopatologia , Idoso , Agnosia/fisiopatologia , Antiparkinsonianos/uso terapêutico , Transtornos Cognitivos/fisiopatologia , Função Executiva/fisiologia , Feminino , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/tratamento farmacológico , Equilíbrio Postural/fisiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Navegação Espacial/fisiologia
20.
Fortschr Neurol Psychiatr ; 88(9): 620-633, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32588409

RESUMO

Inhibitors of COMT and MAO-B are well established in the pharmacotherapy of Parkinson's disease (PD). MAO-B inhibitors are used as monotherapy as well as in combination with levodopa, whereas COMT inhibitors exert their effects only in conjungtion with levodopa. Both classes of compounds prolong the response duration of levodopa and optimise its clinical benefit. As a result, the ON-times are prolonged significantly. In the past, MAO-B inhibitors were also adminstered for neuroprotection; however, despite convincing scientific reasoning in support of neuroprotective effects, these could not be substantiated in clinical studies performed so far.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Catecol O-Metiltransferase/metabolismo , Humanos , Levodopa/uso terapêutico , Monoaminoxidase/metabolismo
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