scholarly journals Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies

2020 ◽  
Vol 14 ◽  
pp. 117954682095341
Author(s):  
Dinesh K Kalra ◽  
Anvi Raina ◽  
Sumit Sohal
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Clinical Features ◽  
Autonomic Dysfunction ◽  
State Of The Art ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Neurogenic Orthostatic Hypotension ◽  
Standing Blood Pressure ◽  
Secondary Causes

Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension in which patients have impaired regulation of standing blood pressure due to autonomic dysfunction. Several primary and secondary causes of this disease exist. Patients may present with an array of symptoms making diagnosis difficult. This review article addresses the epidemiology, pathophysiology, causes, clinical features, and management of nOH. We highlight various pharmacological and non-pharmacological approaches to treatment, and review the recent guidelines and our approach to nOH.

scholarly journals Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

2021 ◽  
Author(s):  
Horacio Kaufmann ◽  
Ross Vickery ◽  
Whedy Wang ◽  
Jitendra Kanodia ◽  
Cyndya A. Shibao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Orthostatic Hypotension ◽  
Controlled Study ◽  
Neurogenic Orthostatic Hypotension ◽  
Median Dose ◽  
Double Blind ◽  
Supine Blood Pressure ◽  
Part C ◽  
Standing Blood Pressure

Abstract Purpose In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. Methods A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Results Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Conclusion Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. Trial registration NCT02705755 (first posted March 10, 2016).

Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure

2001 ◽  
Vol 101 (6) ◽  
pp. 609-618 ◽  
Author(s):  
Stefano OMBONI ◽  
Adrianus A.J. SMIT ◽  
Johannes J. VAN LIESHOUT ◽  
Jos J. SETTELS ◽  
Gerard J. LANGEWOUTERS ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Orthostatic Hypotension ◽  
Peripheral Resistance ◽  
Pulse Contour Analysis ◽  
Pressure Profile ◽  
Neurogenic Orthostatic Hypotension ◽  
Contour Analysis ◽  
Standing Blood Pressure

In the present study, we have assessed in patients with neurogenic orthostatic hypotension the haemodynamics underlying the reduced tolerance to standing after prolonged recumbency at night. In 10 patients with neurogenic orthostatic hypotension (age 33-68 years), of which seven were being treated with fludrocortisone and/or sleeping in the 12° head-up tilt position, 24h continuous non-invasive finger blood pressure was recorded by a Portapres device. Beat-to-beat blood pressure, heart rate, stroke volume, cardiac output and total peripheral vascular resistance obtained by pulse contour analysis were assessed during 5min of standing in the evening (at 22.30 hours) and in the morning (at 06.30hours). On average, the inverse of the normal 24h blood pressure profile was found, with a large diversity in blood pressure profiles among patients. Supine blood pressure values were similar, but standing blood pressure values were lower in the morning than in the evening (P < 0.01). This resulted from larger falls in stroke volume and cardiac output upon standing in the morning compared with the evening, while total peripheral resistance did not change. There was no relationship between the decrease in body weight during the night (mean 0.9kg; range 0.2-1.6kg) and the evening-morning difference in standing blood pressure. We conclude that, in patients with neurogenic orthostatic hypotension, the impaired tolerance to standing in the morning is due to larger falls in stroke volume and cardiac output. Not only nocturnal polyuria, but also a redistribution of body fluid, are likely mechanisms underlying the pronounced decreases in stroke volume and cardiac output after prolonged recumbency at night.

Progression of Autonomic Dysfunction in Neurogenic Orthostatic Hypotension Patients

2015 ◽  
Vol 192 ◽  
pp. 98
Author(s):  
JL Gilden ◽  
I. Worden ◽  
C. Prades ◽  
R. Bhattaram ◽  
B. Theckedath
Keyword(s):  
Orthostatic Hypotension ◽  
Autonomic Dysfunction ◽  
Neurogenic Orthostatic Hypotension

CQP 201-403, a new dopamine agonist in the treatment of hyperprolactinemia

1988 ◽  
Vol 117 (4) ◽  
pp. 552-556 ◽  
Author(s):  
L. E. Hanssen ◽  
J. Brownell ◽  
J. Halse ◽  
J. Jervell ◽  
K. T. Stokke ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Side Effects ◽  
Orthostatic Hypotension ◽  
Dopamine Agonist ◽  
Drug Administration ◽  
Pituitary Adenomas ◽  
Adverse Reactions ◽  
Area Under The Curve ◽  
Control Group ◽  
Standing Blood Pressure

Abstract. Current drugs used for hyperprolactinemia may have severe side effects. Effects and side effects of a new propylergoline derivate (CQP 201-403 SANDOZ®) have been evaluated. Twenty-four otherwise healthy women (21–44 years) with hyperprolactinemia (35–318 μg/l) without extrasellar extension of pituitary adenomas took part in a randomized, doubleblind study. Fasting prolactin levels measured on day 7 was significantly decreased when compared with day 1 (P < 0.05) in all CQP groups, to 78% with 0.005 mg daily, to 40% with 0.015 mg daily, and to 27% with 0.025 mg CQP per day for one week. The levels in the control group did not change (96%). The area under the curve of the prolactin day curve (1–8 h after drug administration) decreased significantly (P < 0.05) at all doses when day 7 was compared with day 1, to 77% with 0.005 mg, to 51% with 0.015 mg, and to 37% with 0.025 mg CQP. No change was seen in the control group (96%). Four patients (one on 0.005 mg, one on 0.015 mg, and two on 0.025 mg) experienced orthostatic hypotension while standing blood pressure was to be measured on the first day of treatment, and they had to lie down. CQP 201-403 lowers prolactin levels in hyperprolactinemic women at all doses employed. The effect was seen after the first dose of treatment, and lasted for at least 24 h. The adverse reactions are few and tolerable, and might be less than with current bromocriptine therapy.

Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials

2018 ◽  
Vol 52 (12) ◽  
pp. 1182-1194 ◽  
Author(s):  
Jack J. Chen ◽  
Yi Han ◽  
Jonathan Tang ◽  
Ivan Portillo ◽  
Robert A. Hauser ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Fixed Effects ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Neurogenic Orthostatic Hypotension ◽  
Supine Hypertension ◽  
Treatment Comparison ◽  
Mixed Treatment

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.

scholarly journals Neurogenic Orthostatic Hypotension. Lessons From Synucleinopathies

2020 ◽  
Author(s):  
Juan Francisco Idiaquez ◽  
Juan Idiaquez ◽  
Juan Carlos Casar ◽  
Italo Biaggioni
Keyword(s):  
Blood Pressure ◽  
Orthostatic Hypotension ◽  
Treatment Options ◽  
Lewy Body Dementia ◽  
Cerebral Hypoperfusion ◽  
Neurogenic Orthostatic Hypotension ◽  
Compression Garments ◽  
Novel Treatments ◽  
Mild Disease ◽  
Noradrenergic Fibers

Abstract Maintenance of upright blood pressure critically depends on the autonomic nervous system and its failure leads to neurogenic orthostatic hypotension (NOH). The most severe cases are seen in neurodegenerative disorders caused by abnormal α-synuclein deposits: multiple system atrophy (MSA), Parkinson’s disease, Lewy body dementia, and pure autonomic failure (PAF). The development of novel treatments for NOH derives from research in these disorders. We provide a brief review of their underlying pathophysiology relevant to understand the rationale behind treatment options for NOH. The goal of treatment is not to normalize blood pressure but rather to improve quality of life and prevent syncope and falls by reducing symptoms of cerebral hypoperfusion. Patients not able to recognize NOH symptoms are at a higher risk for falls. The first step in the management of NOH is to educate patients on how to avoid high-risk situations and providers to identify medications that trigger or worsen NOH. Conservative countermeasures, including diet and compression garments, should always precede pharmacologic therapies. Volume expanders (fludrocortisone and desmopressin) should be used with caution. Drugs that enhance residual sympathetic tone (pyridostigmine and atomoxetine) are more effective in patients with mild disease and in MSA patients with spared postganglionic fibers. Norepinephrine replacement therapy (midodrine and droxidopa) is more effective in patients with neurodegeneration of peripheral noradrenergic fibers like PAF. NOH is often associated with other cardiovascular diseases, most notably supine hypertension, and treatment should be adapted to their presence.

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