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1.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434666

RESUMO

A 62-year-old man presented with a 2-year history of syncope, collapse and fluctuating blood pressure (BP). His medications included midodrine (10 mg, three times per day) and fludrocortisone (0.1 mg, two times per day), but neither treatment afforded symptomatic relief. Autonomic testing was performed. Head-up tilt table testing revealed a supine BP of 112/68 mm Hg (heart rate, 74 beats per minute (bpm)) after 6 min, which dropped to 76/60 mm Hg (83 bpm) within 2 min of 80° head-up tilt. Findings from a heart rate with deep breathing test and a Valsalva test were consistent with autonomic dysfunction. The patient was diagnosed with neurogenic orthostatic hypotension and treated with droxidopa (100 mg, two times per day; titrated to 100 mg, one time per day). After initiating treatment with droxidopa, the patient no longer reported losing consciousness on standing and experienced improvement in activities of daily living. These improvements were maintained through 1 year of follow-up.


Assuntos
Antiparkinsonianos/uso terapêutico , Sistema Nervoso Autônomo/fisiopatologia , Droxidopa/uso terapêutico , Hipotensão Ortostática/diagnóstico , Síncope/etiologia , Teste da Mesa Inclinada , Acidentes por Quedas , Atividades Cotidianas , Humanos , Hipotensão Ortostática/tratamento farmacológico , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
2.
Expert Opin Pharmacother ; 20(6): 635-645, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730771

RESUMO

INTRODUCTION: L-threo-3,4-dihydroxyphenylserine (droxidopa), a pro-drug metabolized to norepinephrine in nerve endings and other tissues, has been commercially available in Japan since 1989 for treating orthostatic hypotension symptoms in Parkinson's disease (PD) patients with a Hoehn & Yahr stage III rating, as well as patients with Multiple System Atrophy (MSA), familial amyloid polyneuropathy, and hemodialysis. Recently, the FDA has approved its use in symptomatic neurogenic orthostatic hypotension (NOH). Areas covered: The authors review the effects of droxidopa in NOH with a focus on the neurodegenerative diseases PD, MSA, and pure autonomic failure (PAF). Expert opinion: A few small and short placebo-controlled clinical trials in NOH showed significant reductions in the manometric drop in blood pressure (BP) after posture changes or meals. Larger Phase III studies showed conflicting results, with two out of four trials meeting their primary outcome and thus suggesting a positive yet short-lasting effect of the drug on OH Questionnaire composite score, light-headedness/dizziness score, and standing BP during the first two treatment-weeks. Results appear essentially similar in PD, MSA, and PAF. The FDA granted droxidopa approval in the frame of an 'accelerated approval program' provided further studies are conducted to assess its long-term effects on OH symptoms.


Assuntos
Droxidopa/uso terapêutico , Hipotensão Ortostática/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Neuropatias Amiloides Familiares/tratamento farmacológico , Pressão Sanguínea , Humanos , Japão , Doenças Neurodegenerativas/fisiopatologia , Doença de Parkinson/tratamento farmacológico , Diálise Renal , Inquéritos e Questionários
3.
Expert Opin Pharmacother ; 20(2): 187-199, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30376728

RESUMO

INTRODUCTION: Orthostatic hypotension (OH) is a common yet often overlooked condition. Particularly debilitating is neurogenic orthostatic hypotension (nOH) caused by deficient neurotransmission of norepinephrine, which is the primary neurotransmitter released at sympathetic peripheral vascular nerve terminals in response to orthostatic stress. AREAS COVERED: In this review, the author summarizes and critiques established and emerging pharmacologic approaches for the management of nOH. Two drugs are currently approved. Midodrine, an α1-adrenoreceptor agonist, acts on capacitance vessels to increase peripheral vascular tone, thus increases arterial pressure. Droxidopa, an orally administered prodrug of norepinephrine, increases circulating norepinephrine levels, causes peripheral vasoconstriction, and increases standing blood pressure. Preliminary studies support the selective use of several off-label drugs in difficult cases. All of these drugs can potentially unmask or exacerbate neurogenic supine hypertension (nSH), which occurs in about half of patients with nOH. EXPERT OPINION: Chemical pharmacotherapy of nOH is best individualized to the needs and condition of each patient and guided by the underlying pathophysiology, severity of orthostatic incapacity, and minimization of comorbidities such as nSH. The goal of therapy is to maintain cerebral perfusion and increase the patient's ability to engage in upright daily activities. Advances in pharmacogenetics and ambulatory devices hold promise.


Assuntos
Droxidopa/uso terapêutico , Hipotensão Ortostática/tratamento farmacológico , Midodrina/uso terapêutico , Pressão Sanguínea , Comorbidade , Humanos , Hipertensão/epidemiologia
4.
Neurology ; 91(16): e1539-e1544, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30232253

RESUMO

OBJECTIVE: To test whether the plasma levels of norepinephrine (NE) in patients with neurogenic orthostatic hypotension (nOH) predict their pressor response to droxidopa. METHODS: This was an observational study, which included patients with nOH. All patients had standardized autonomic function testing including determination of venous plasma catecholamine levels drawn through an indwelling catheter while resting supine. This was followed by a droxidopa titration with 100 mg increments in successive days until relief of symptoms, side effects, or the maximum dose of 600 mg was reached. No response was defined as an increase of <10 mm Hg in systolic blood pressure (BP) after 3-minute standing 1 hour after droxidopa administration. Nonlinear regression models were used to determine the relationship between BP response and plasma NE levels. RESULTS: We studied 20 patients with nOH due to Parkinson disease, pure autonomic failure, multiple system atrophy, or autoimmune autonomic neuropathies. Their supine plasma NE levels ranged from 44 to 850 pg/mL. Lower supine plasma NE levels were associated with greater pressor effect 1 hour after dose (R2 = 0.49) and higher standing BP (R2 = 0.45). Patients with no pressor response to droxidopa had higher NE levels (382 ± 100 vs 115 ± 20 pg/mL, p = 0.0014). A supine NE level of <219.5 pg/mL had 83% sensitivity and 93% specificity to predict a pressor response (area under the curve = 0.95, p = 0.0023). CONCLUSIONS: In patients with nOH, lower supine resting plasma NE levels are associated with a greater pressor effect of droxidopa treatment. This finding should help identify patients with nOH most likely to respond to standard doses of droxidopa. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that lower supine plasma NE levels accurately identify patients with nOH more likely to have a greater pressor effect from droxidopa.


Assuntos
Antiparkinsonianos/uso terapêutico , Droxidopa/uso terapêutico , Hipotensão Ortostática/sangue , Hipotensão Ortostática/tratamento farmacológico , Norepinefrina/sangue , Decúbito Dorsal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Pressão Sanguínea , Criança , Droxidopa/administração & dosagem , Feminino , Humanos , Hipotensão Ortostática/etiologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Resultado do Tratamento , Adulto Jovem
5.
Rev Med Suisse ; 14(618): 1581-1587, 2018 Sep 12.
Artigo em Francês | MEDLINE | ID: mdl-30226654

RESUMO

Arterial hypotension is a frequently encountered phenomenon in clinical practice. It is responsible for multiple consultations and/or hospitalizations, mostly in elderly people. It is associated with an increased morbidity and mortality. Arterial hypotension can be constitutional, part of a syndrome, orthostatic, or secondary (drug induced, hypovolemia). The diagnosis can be done by measuring the blood pressure in the supine position, sitting and standing position, and by 24h ambulatory blood pressure monitoring. The first line of treatment is non-drug therapies . The most frequently used medical treatments are midodrine, and fludrocortisone. However specific molecules as droxidopa, pyridostigmine, erythropoietin can also sometimes be indicated.


Assuntos
Hipotensão Ortostática , Hipotensão , Idoso , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Droxidopa/uso terapêutico , Humanos , Hipotensão/diagnóstico , Hipotensão/terapia , Hipotensão Ortostática/tratamento farmacológico , Midodrina/uso terapêutico
6.
Ann Pharmacother ; 52(12): 1182-1194, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29972032

RESUMO

BACKGROUND: The comparative effects of droxidopa and midodrine on standing systolic blood pressure (sSBP) and risk of supine hypertension in patients with neurogenic orthostatic hypotension (NOH) are unknown. OBJECTIVE: To perform a Bayesian mixed-treatment comparison meta-analysis of droxidopa and midodrine in the treatment of NOH. METHODS: The PubMed, CENTRAL, and EMBASE databases were searched up to November 16, 2016. Study selection consisted of randomized trials comparing droxidopa or midodrine with placebo and reporting on changes in sSBP and supine hypertension events. Data were pooled to perform a comparison among interventions in a Bayesian fixed-effects model using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled mean changes in sSBP and risk ratios (RRs) for supine hypertension with associated 95% credible intervals (CrIs). RESULTS: Six studies (4 administering droxidopa and 2 administering midodrine) enrolling a total of 783 patients were included for analysis. The mean change from baseline in sSBP was significantly greater for both drugs when compared with placebo (droxidopa 6.2 mm Hg [95% CrI = 2.4-10] and midodrine 17 mm Hg [95% CrI = 11.4-23]). Comparative analysis revealed a significant credible difference between droxidopa and midodrine. The RR for supine hypertension was significantly greater for midodrine, but not droxidopa, when compared with placebo (droxidopa RR = 1.4 [95% CrI = 0.7-2.7] and midodrine RR = 5.1 [95% CrI = 1.6-24]). Conclusion and Relevance: In patients with NOH, both droxidopa and midodrine significantly increase sSBP, the latter to a greater extent. However, midodrine, but not droxidopa, significantly increases risk of supine hypertension.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Droxidopa/uso terapêutico , Hipotensão Ortostática/tratamento farmacológico , Midodrina/uso terapêutico , Posição Ortostática , Decúbito Dorsal , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Teorema de Bayes , Pressão Sanguínea/fisiologia , Droxidopa/efeitos adversos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipotensão Ortostática/epidemiologia , Hipotensão Ortostática/fisiopatologia , Midodrina/efeitos adversos , Meta-Análise em Rede , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Decúbito Dorsal/fisiologia , Resultado do Tratamento , Vasoconstritores/efeitos adversos , Vasoconstritores/uso terapêutico
7.
Curr Opin Cardiol ; 33(1): 66-72, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28984649

RESUMO

PURPOSE OF REVIEW: Orthostatic hypotension is a phenomenon commonly encountered in a cardiologist's clinical practice that has significant diagnostic and prognostic value for a cardiologist. Given the mounting evidence associating cardiovascular morbidity and mortality with orthostatic hypotension, cardiologists will play an increasing role in treating and managing patients with orthostatic hypotension. RECENT FINDINGS: The American College of Cardiology, American Heart Association, and Heart Rhythm Society recently published consensus guidelines on the diagnosis, treatment, and management of syncope and their instigators, including orthostatic hypotension. Additionally, consensus guidelines have also been recently updated, reinforcing the universal definition orthostatic hypotension and its closely associated pathologies. Finally, the United States Food and Drug Administration (FDA) recently approved droxidopa, a synthetic oral norepinephrine prodrug, in 2014 for the treatment of neurogenic orthostatic hypotension (nOH), and it represents a well tolerated, effective, and easy to use intervention for nOH. This represents only the second drug approved by the FDA for orthostatic hypotension, the first being midodrine in 1986. A handful of smaller head-to-head studies have pitted not only pharmacologic agents to one another but also nonpharmacologic interventions to pharmacologic agents. Additionally, recent studies have also reported on more convenient screening tools for orthostatic hypotension. SUMMARY: Though there have been many advances in the management of orthostatic hypotension, nOH remains a chronic, debilitating, and often progressively fatal condition. Cardiologists can play a very important role in optimizing hemodynamics in this patient population to improve quality of life and minimize cardiovascular risk.


Assuntos
Antiparkinsonianos/uso terapêutico , Droxidopa/uso terapêutico , Hipotensão Ortostática/terapia , Midodrina/uso terapêutico , Simpatomiméticos/uso terapêutico , Cardiologistas , Humanos , Hipotensão Ortostática/diagnóstico , Postura , Teste da Mesa Inclinada
8.
J Spinal Cord Med ; 41(1): 115-118, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28114866

RESUMO

CONTEXT: Orthostatic hypotension (OH) is a common complication in patients with a spinal cord injury, mainly affecting complete injuries above neurological level T6. It is generally more severe during the acute phase but can remain symptomatic for several years. FINDINGS: A 65-year-old male with a grade ASIA A post-traumatic cervical spinal cord injury, at neurological level C4, presenting with symptomatic refractory OH. Increased blood pressure (BP) levels and an overall clinical improvement was observed after administering an increasing dose of droxidopa. Treatment was started at a dose of 100 mg twice daily (bid), one to be taken upon rising in the morning and another one in the afternoon, at least three hours before bedtime. According to the patient's symptomatic response, each individual dose was increased by 100 mg at 48-hour intervals. Both increased mean BP levels and a subjective symptomatic improvement were evidenced at a dose of 300 mg bid. CLINICAL RELEVANCE: Treatment with droxidopa increases BP levels and improves symptoms related to refractory OH using all physical and pharmacological measures available. It could therefore constitute an effective alternative treatment for OH in patients with a spinal cord injury.


Assuntos
Antiparkinsonianos/uso terapêutico , Droxidopa/uso terapêutico , Hipotensão Ortostática/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Idoso , Antiparkinsonianos/administração & dosagem , Droxidopa/administração & dosagem , Humanos , Hipotensão Ortostática/etiologia , Masculino
9.
JBI Database System Rev Implement Rep ; 15(9): 2287-2294, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28902695

RESUMO

REVIEW QUESTION: The question of this review is: what is the effectiveness of droxidopa compared to midodrine on standing blood pressure and orthostatic intolerance symptoms in adults with neurogenic orthostatic hypotension?


Assuntos
Antiparkinsonianos/uso terapêutico , Pressão Sanguínea/fisiologia , Droxidopa/uso terapêutico , Hipotensão Ortostática/tratamento farmacológico , Midodrina/uso terapêutico , Vasoconstritores/uso terapêutico , Humanos , Revisão Sistemática como Assunto
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