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Approach to the patient with orthostatic symptoms. Abbreviations: BP = Blood pressure; OH = Orthostatic hypotension; PDE-5 = Phosphodiesterase-5.
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In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous resistance and by increased cardiac output, ensuring continued perfusion of the central nervous system. In neurogenic orthostatic hypotension (NOH), inadequate vasoconstriction and c...
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Context 1
... may encounter symptomatic NOH directly, by pre- senting symptoms. However, because of the frequency of NOH in some patient groups (PD, for instance, or other dis- eases associated with autonomic dysfunction), patients or their caretakers should be queried for orthostatic symptoms the patient may not have reported, potentially representing NOH. Patients may be reticent to report problems such as falls or postural instability, for fear that such infirmities might necessitate nursing-home placement or lead to other losses of autonomy. Identification of orthostatic symptoms should be followed by confirmation that standing provokes a BP decrease ‡20/10 mmHg, with subsequent stepwise manage- ment ( Figure ...
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Background
Droxidopa is an orally active prodrug that significantly improved dizziness/lightheadedness measured using the Orthostatic Hypotension Symptom Assessment (OHSA) Item 1 in patients with neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dop...
Pure autonomic failure is challenging as it can be the presenting feature of a central nervous system syncleinopathy such as Parkinson’s disease (PD) or multiple system atrophy (MSA). Because the prognosis of MSA and PD is so different, predictive features for a possible conversion can be extremely valuable. In this paper, we report three cases (tw...
Citations
... Another non-motor symptom that was found to be significantly correlated with FoG was orthostatic hypotension, which is a well-documented symptom of PD and can result from several aetiologies. The most common reason is neurogenic, whereby it occurs as a result of the progressive autonomic failure seen in PD [45,46]. Non-neurogenic causes can include the side-effects of certain medications such as levodopa [47] and dopaminergic agonists (e.g. ...
The World Health Organisation (WHO) reports that morbidity and mortality due to Parkinson’s disease (PD) are increasing faster than for other neurodegenerative conditions. People with Parkinson’s (PwP) present with a variety of motor symptoms, such as tremor, bradykinesia, and rigidity. Freezing of gait (FoG) is a significant motor symptom that manifests as temporary episodes of inability to move one’s feet, despite the intention to walk.
This study examined the impact of FoG on quality of life (QoL) within an Irish cohort of PwP, from the perspectives of both PwP and their carers, using validated questionnaires that had been adapted for online use.
PwP and their carers were recruited by outreach to the Irish Parkinson’s Community. Anonymous online questionnaires were distributed, which combined a demographic survey with several clinically validated surveys, including Freezing of Gait Questionnaire (FoG-Q), Parkinson’s Disease Questionnaire 8 (PDQ-8), and Parkinson’s Disease Carer Questionnaire (PDQ-C).
There was a strong correlation (p < 0.001) between severity of FoG and lower QoL among PwP. Significant correlation was also found between FoG severity and several motor symptoms, such as postural instability and difficulty with balance, and non-motor symptoms, such as cognitive changes and pain/discomfort. FoG severity correlated with disease progression. Significant correlation was also found between FoG and symptoms, as assessed from the perspective of the patients’ carers.
This study shows that FoG is a significant detriment to the QoL of PwP, from the perspectives of patients and carers. This method of assessing FoG and QoL using online questionnaires has potential to enhance the reach and flexibility of this type of research. These findings will inform future studies on larger cohorts and highlight unmet clinical needs in PwP.
... While in some patients, the lack of reports of orthostatic symptoms may be due to chronic adaptive changes in cerebral blood flow regulation, in other patients, the inability to recognize symptoms might be attributable to the underlying neurodegenerative process [25]. Importantly, these patients are at a higher risk of falls [26]. Therefore, orthostatic blood pressure measurements are important to identify individuals with OH to prevent falls although the frequency of falls was not assessed in the present study. ...
Patients with Parkinson’s disease (PD) carrying variants in the Glucocerebrosidase (GBA) gene (GBA-PD) suffer from orthostatic symptoms more frequently than idiopathic PD patients (IPD). Systematic measurements of the blood pressure have not yet been performed. In the present study, a prospective analysis of 33 GBA-PD and 313 IPD patients was carried out. Systolic blood pressure upon changing from the supine to the upright position dropped more strongly in GBA-PD compared to IPD patients. Diastolic blood pressure and heart rate did not differ between groups. This study provides further evidence for a pronounced involvement of the autonomic nervous system in GBA-PD.
... It is important to recognize OH because it is a risk factor for falls and it is a predictor of mortality. 3 Our aim is to provide a practical approach to the evaluation and treatment of patients with NOH. Most of our knowledge in this area, and novel therapies highlighted herein, are derived from research in NOH associated with synucleinopathies, a group of neurodegenerative disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF). ...
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.
... It is important to identify the major cause or causes, as this may affect management; common causes are listed in Table 1 [13,[24][25][26]. Among the most common causes of nOH is chronic autonomic failure intrinsic to PD [25,27]. Non-neurogenic causes of OH include the influence of certain medications or clinical conditions that impair cardiac output. ...
... The range of symptoms associated with OH is listed in Table 2 [13,24,26,27,32,33]. The most common experiences are dizziness/lightheadedness, presyncope, and syncope, although patients may present with less specific symptoms, such as weakness or fatigue [13]. ...
... Symptoms of OH and nOH[13,24,26,27]*. ...
Parkinson disease (PD) is often associated with postural instability and gait dysfunction that can increase the risk for falls and associated consequences, including injuries, increased burden on healthcare resources, and reduced quality of life. Patients with PD have nearly twice the risk for falls and associated bone fractures compared with their general population counterparts of similar age. Although the cause of falls in patients with PD may be multifactorial, an often under-recognized factor is neurogenic orthostatic hypotension (nOH). nOH is a sustained decrease in blood pressure upon standing whose symptomology can include dizziness/lightheadedness, weakness, fatigue, and syncope. nOH is due to dysfunction of the autonomic nervous system compensatory response to standing and is a consequence of the neurodegenerative processes of PD. The symptoms associated with orthostatic hypotension (OH)/nOH can increase the risk of falls, and healthcare professionals may not be aware of the real-world clinical effect of nOH, the need for routine screening, or the value of early diagnosis of nOH when treating elderly patients with PD. nOH is easily missed and, importantly, healthcare providers may not realize that there are effective treatments for nOH symptoms that could help lessen the fall risk resulting from the condition. This review discusses the burden of, and key risk factors for, falls among patients with PD, with a focus on practical approaches for the recognition, assessment, and successful management of OH/nOH. In addition, insights are provided as to how fall patterns can suggest fall etiology, thereby influencing the choice of intervention.
... Presión arterial y frecuencia cardiaca: se recomienda medir la PA a 1 y 5 minutos de adoptar la posición de bipedestación en los ancianos diabéticos y en otras situaciones en las que la HO pueda sospecharse. La medida de la frecuencia cardiaca (FC) permite diferenciar las causas no neurógenas (aumento de la FC > 15 latidos/min al ponerse en pie), de las neurógenas (no hay taquicardia compensadora) 8 . ...
... Another 2.0% had symptomatic OH presenting as dizziness, light headedness or faintness. 11,12 In aged care facilities and acute hospital settings, OH prevalence as high as 50% has been reported. 3 It has also been reported that OH affects 25% of patients with type 2 diabetes mellitus (T2DM) and 70% of patients with Parkinson's disease. ...
Orthostatic hypotension (OH) is common in older people and is associated with a range of adverse outcomes. Although age‐related changes like decreased baroreflex sensitivity make older people prone to OH, medications are often a contributor. Diagnosis of OH can be challenging in older people, because the condition may present with atypical or non‐specific symptoms, such as visual disturbances, shortness of breath, mental fluctuation. Non‐pharmacological management is often a starting point for OH treatment. Fludrocortisone and midodrine remain the most studied drugs for pharmacological management, but newer agents are being tested. In this review we present the current evidence for existing and emerging treatments for OH and address the management of supine hypertension associated with the treatment of OH in patients with autonomic failure. In the management of OH, it is imperative that treatment is tailored to the individual, rather than focusing on attaining an arbitrary blood pressure target.
... We found impaired veno-arteriolar reflex in fourteen of the fifteen elderly fall patients (93%) diagnosed with peripheral neuropathy at the Fall clinic indicating peripheral autonomic neuropathy 26,42 . ...
... The heat-washout method examines the small, unmyelated C fibre in the peripheral autonomic nervous system, which may be associated with postural hypotension 26,42 . A previous study found that the venoarteriolar reflex seems to be reduced in patients with distal peripheral neuropathy causing postural hypotension, when examined with the laser Doppler Flowmetry 43 . ...
Libro de texto para estudiantes de pregrado y profesionales nobeles sobre geriatría. Esta tercera edición, corregida, mejorada y ampliada da continuidad a las dos primeras iniciadas en la Universidad de Salamanca, España. Un texto que se constituye como un primer escalón para la enseñanza y aprendizaje de la geriatria y gerontologia.
In the past decade (2011–2020), there was a growing interest in the discovery and development of orphan drugs for the treatment of rare diseases. However, rare diseases only account for a population of 0.65‰–1‰ which usually occur with previously unknown biological mechanisms and lack of specific therapeutics, thus to increase the demands for the first-in-class (FIC) drugs with new biological targets or mechanisms. Considering the achievements in the past 10 years, a total of 410 drugs were approved by U.S. Food and Drug Administration (FDA), which contained 151 FIC drugs and 184 orphan drugs, contributing to make up significant numbers of the approvals. Notably, more than 50% of FIC drugs are developed as orphan drugs and some of them have already been milestones in drug development. In this review, we aim to discuss the FIC small molecules for the development of orphan drugs case by case and highlight the R&D strategy with novel targets and scientific breakthroughs.
Etilefrine hydrochloride (ET) is an important drug in the treatment of hypotension, and parenteral injections and oral tablets are the conventional dosage forms. However, parenteral injections may cause abnormally high plasma levels as well as pain and necrosis, and oral tablets undergo first-pass metabolism. Although fast-dissolving buccal tablets were previously reported, the initial absorption rate was a little slow and the plasma levels were varied extensively. Recently, many films have been developed as novel dosage forms. Therefore, in the present study, film dosage forms containing ET were produced using water-soluble polymers and glycerin (GLY) as excipients to obtain a practical buccal dosage form. Films composed of ET, GLY, and sodium alginate (AL) exhibited good physical characteristics and rapid release in vitro (more than 70% at 2 min). The compacted AL film containing 2 mg ET (1 × 1 cm) exhibited rapid absorption (> 19 ng/mL at 0.5 h), maintained an effective plasma level (> 7 ng/mL) for a long time period (0.5 – 4 h), and had an adequate plasma concentration-time profile with a smaller standard error (< 15.3 ng/mL). These results suggest that the present compacted buccal film is a superior dosage form of ET for practical use.
