Defining successful treatment of neurogenic orthostatic hypotension with droxidopa in a patient with multiple system atrophy

Goodman, Brent P.; Gupta, Fiona

doi:10.1007/s10286-017-0432-8

Cited by 6 publications

(4 citation statements)

References 6 publications

(6 reference statements)

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“…Droxidopa is not approved in Europe. Extensive clinical experience shows that droxidopa is safe and well tolerated . Peak plasma concentrations of droxidopa are reached ∼3 hours after oral administration.…”

Section: Cardiovascular Autonomic Dysfunctionmentioning

confidence: 99%

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

2018

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Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology-based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society.

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Section: Cardiovascular Autonomic Dysfunctionmentioning

confidence: 99%

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

2018

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“…Extensive clinical experience shows that droxidopa is safe and well tolerated. [69][70][71][72][73][74][75][76][77] Peak plasma concentrations of droxidopa are reached ~3-h after oral administration. The dosage used in clinical trials was 100-600 mg three times/day although clinical experience indicates that the dosage should be tailored to each patient's needs considering the periods of time when he/she is going to be active or inactive.…”

Section: Droxidopamentioning

confidence: 99%

Orthostatic Hypotension in Parkinson Disease

Palma

2020

Clinics in Geriatric Medicine

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neurons are also affected. 7,8 Autonomic dysfunction in synucleinopathies occurs at all stages of the disease and occasionally is its only manifestation. 9Among the most debilitating manifestations of autonomic dysfunction in PD is orthostatic hypotension (OH), which is a sustained fall in blood pressure (BP) on standing. The current definition of OH, based on expert consensus, 10 is a fall of at least 20 mmHg in systolic BP or 10 mmHg in diastolic BP within 3 minutes of standing or upright tilt. OH can impair perfusion to organs above the heart, most notably the brain, resulting in symptoms of tissue hypoperfusion. Symptoms can be very disabling, have a profound impact on a patient's quality of life, and increase morbidity and mortality. 11,12 In PD and other synucleinopathies, OH is neurogenic (nOH), i.e., due to reduced norepinephrine release from postganglionic efferent sympathetic nerves, resulting in defective vasoconstriction when assuming the upright posture (Figure 1). 10 Complicating nOH management is arterial hypertension when supine (SH), which occurs in up to 50% of patients with efferent baroreflex failure. 13,14 When recognized, nOH can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, non-pharmacological approaches, and pathophysiology-based drug therapy are key to an effective management.Here we review the epidemiology, evaluation, and management of nOH, with emphasis on patients with PD, summarize the non-pharmacologic and pharmacologic treatment strategies, and provide practical advice on the management of patients with this debilitating condition.

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“…Extensive clinical experience shows that droxidopa is safe and well tolerated. [81][82][83][84][85][86][87][88][89] Peak plasma concentrations of droxidopa are reached approximately 3 hours after oral administration. The dosage used in clinical trials was 100 to 600 mg three times a day, although clinical experience indicates that the dosage should be tailored to each patient's needs considering the patient's daily activities, with higher dosages before he/she is going to be physically active.…”

Section: Droxidopamentioning

confidence: 99%

Clinical Trials for Neurogenic Orthostatic Hypotension: A Comprehensive Review of Endpoints, Pitfalls, and Challenges

Palma

2020

Semin Neurol

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Neurogenic orthostatic hypotension (nOH) is among the most debilitating nonmotor features of patients with Parkinson's disease (PD) and other synucleinopathies. Patients with PD and nOH generate more hospitalizations, make more emergency room visits, create more telephone calls/mails to doctors, and have earlier mortality than those with PD but without nOH. Overall, the health-related cost in patients with PD and OH is 2.5-fold higher compared with patients with PD without OH. Hence, developing effective therapies for nOH should be a research priority. In the last few decades, improved understanding of the pathophysiology of nOH has led to the identification of therapeutic targets and the development and approval of two drugs, midodrine and droxidopa. More effective and safer therapies, however, are still needed, particularly agents that could selectively increase blood pressure only in the standing position because supine hypertension is the main limitation of available drugs. Here we review the design and conduct of nOH clinical trials in patients with PD and other synucleinopathies, summarize the results of the most recently completed and ongoing trials, and discuss challenges, bottlenecks, and potential remedies.

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Defining successful treatment of neurogenic orthostatic hypotension with droxidopa in a patient with multiple system atrophy

Cited by 6 publications

References 6 publications

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

Orthostatic Hypotension in Parkinson Disease

Clinical Trials for Neurogenic Orthostatic Hypotension: A Comprehensive Review of Endpoints, Pitfalls, and Challenges

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