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Drug and Therapeutics Bulletin May 2016Midodrine (Bramox-Brancaster Pharma Limited) was authorised in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) in March 2015 for "the treatment... (Review)
Review
Midodrine (Bramox-Brancaster Pharma Limited) was authorised in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) in March 2015 for "the treatment of severe orthostatic hypotension due to autonomic dysfunction in adults when corrective factors have been ruled out and other forms of treatment are inadequate".(1) Previously, midodrine had only been available in the UK as an unlicensed product used on a named-patient basis. It is the first drug to be licensed in the UK for the treatment of orthostatic hypotension. Here we consider the evidence for midodrine in the treatment of severe orthostatic hypotension and how it fits with current management strategies.
Topics: Contraindications; Drug Interactions; Humans; Hypotension, Orthostatic; Midodrine
PubMed: 27173783
DOI: 10.1136/dtb.2016.5.0399 -
Postgraduate Medicine 2015In response to a change in posture from supine or sitting to standing, autonomic reflexes normally maintain blood pressure (BP) by selective increases in arteriovenous... (Review)
Review
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 cardiac output cause BP to drop excessively, resulting in inadequate perfusion, with predictable symptoms such as dizziness, lightheadedness and falls. The condition may represent a central failure of baroreceptor signals to modulate cardiovascular function, a peripheral failure of norepinephrine release from cardiovascular sympathetic nerve endings, or both. Symptomatic patients may benefit from both non-pharmacologic and pharmacologic interventions. Among the latter, two pressor agents have been approved by the US Food and Drug Administration: the sympathomimetic prodrug midodrine, approved in 1996 for symptomatic orthostatic hypotension, and the norepinephrine prodrug droxidopa, approved in 2014, which is indicated for the treatment of symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure). A wide variety of off-label options also have been described (e.g. the synthetic mineralocorticoid fludrocortisone). Because pressor agents may promote supine hypertension, NOH management requires monitoring of supine BP and also lifestyle measures to minimize supine BP increases (e.g. head-of-bed elevation). However, NOH has been associated with cognitive impairment and increases a patient's risk of syncope and falls, with the potential for serious consequences. Hence, concerns about supine hypertension - for which the long-term prognosis in patients with NOH is yet to be established - must sometimes be balanced by the need to address a patient's immediate risks.
Topics: Accidental Falls; Aged; Aged, 80 and over; Autonomic Nervous System Diseases; Disease Management; Droxidopa; Female; Humans; Hypotension, Orthostatic; Male; Midodrine; Vasoconstrictor Agents
PubMed: 26012731
DOI: 10.1080/00325481.2015.1050340 -
Age and Ageing Dec 2022Many older people with orthostatic hypotension (OH) may not report typical symptoms of dizziness, light-headedness or unsteadiness. However, the relationships between OH...
INTRODUCTION
Many older people with orthostatic hypotension (OH) may not report typical symptoms of dizziness, light-headedness or unsteadiness. However, the relationships between OH and falls in the absence of typical symptoms are not yet established.
METHODS
Continuous orthostatic blood pressure (BP) was measured during active stand using a Finometer at Wave 1 of The Irish Longitudinal Study on Ageing in participants aged ≥ 70 years.OH, with and without dizziness, was defined as a sustained drop in systolic BP ≥ 20 and/or diastolic BP ≥ 10 mm Hg at 30, 60 and 90 seconds post-standing.The association between symptoms of dizziness and orthostatic BP was assessed with multi-level mixed-effects linear regression; logistic regression models assessed the longitudinal relationship between OH and falls at 6-year follow-up (Waves 2-5).
RESULTS
Almost 11% (n = 934, mean age 75 years, 51% female) had OH, two-thirds of whom were asymptomatic.Dizziness was not associated with systolic BP drop at 30 (β = 1.54 (-1.27, 4.36); p = 0.256), 60 (β = 2.64 (-0.19, 5.47); p = 0.476) or 90 seconds (β = 2.02 (-0.91, 4.95); p = 0.176) after standing in adjusted models.Asymptomatic OH was independently associated with unexplained falls (odds ratio 2.01 [1.11, 3.65]; p = 0.022) but not explained falls (OR 0.93 [0.53, 1.62]; p = 0.797) during follow-up.
CONCLUSIONS
Two-thirds of older people with OH did not report typical symptoms of light-headedness. Dizziness or unsteadiness after standing did not correlate with the degree of orthostatic BP drop or recovery. Participants with asymptomatic OH had a significantly higher risk of unexplained falls during follow-up, and this has important clinical implications for the assessment of older people with falls.
Topics: Humans; Female; Aged; Male; Hypotension, Orthostatic; Accidental Falls; Dizziness; Longitudinal Studies; Independent Living; Risk Factors; Blood Pressure
PubMed: 36571778
DOI: 10.1093/ageing/afac295 -
The New England Journal of Medicine Apr 2022Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking...
Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).
Topics: Accelerometry; Atrophy; Blood Pressure; Electric Stimulation Therapy; Electrodes, Implanted; Epidural Space; Humans; Hypotension, Orthostatic; Multiple System Atrophy; Posture; Thoracic Vertebrae
PubMed: 35388667
DOI: 10.1056/NEJMoa2112809 -
Hypertension (Dallas, Tex. : 1979) Mar 2020
Topics: Blood Pressure; Blood Pressure Determination; Cardiovascular System; Humans; Hypotension, Orthostatic
PubMed: 31983303
DOI: 10.1161/HYPERTENSIONAHA.119.14474 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
Monaldi Archives For Chest Disease =... Jun 2016The prevalence of hypertension increases with the age. Diagnostic criteria are the same as for the young, but in older adults isolated systolic hypertension is more... (Review)
Review
The prevalence of hypertension increases with the age. Diagnostic criteria are the same as for the young, but in older adults isolated systolic hypertension is more frequent, due to loss of vascular compliance. Blood pressure should be measured on both sides in the seated position, moreover in the supine and upright position to detect orthostatic hypotension. Ambulatory blood pressure monitoring is useful to detect white coat hypertension and masked hypertension, to tailor the treatment and search for diurnal and nocturnal blood pressure pattern abnormalities. Given that frailty can affect the relationship between blood pressure and mortality, the clinician should properly evaluate and monitor physical performance and cognitive status, throughout specific tools, as the Fried Frailty Phenotype, aiming at a systolic blood pressure target between 130 and 150 mmHg. Before starting hypotensive drugs, a careful risk and benefits' evaluation should be performed given the high risk of hypertension and hypotension consequences and the frequent coexistence of orthostatic hypotension, which predisposes to syncope and falls.
Topics: Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Frailty; Humans; Hypertension; Hypotension, Orthostatic; Syncope
PubMed: 27374043
DOI: 10.4081/monaldi.2015.729 -
Clinical Autonomic Research : Official... Jul 2017
Topics: Blood Pressure Monitoring, Ambulatory; Disease Management; Humans; Hypertension; Hypotension, Orthostatic
PubMed: 28620715
DOI: 10.1007/s10286-017-0437-3 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Orthostatic hypotension is a phenomenon characterized by reduction in blood pressure secondary to the inability to adapt to changes in blood volume distribution (pooling... (Review)
Review
Orthostatic hypotension is a phenomenon characterized by reduction in blood pressure secondary to the inability to adapt to changes in blood volume distribution (pooling of blood in the lower extremities) observed when standing from a seated or supine position. Orthostatic hypotension is classified into neurogenic and non-neurogenic types. Neurogenic orthostatic hypotension due to autonomic failure may occur in most neurological diseases and is a major concern encountered in daily practice. In this review, I present an overview of the pathophysiology and diagnosis of neurogenic orthostatic hypotension and describe the therapeutic strategies and characteristics of drugs used for this condition.
Topics: Humans; Hypotension, Orthostatic; Nervous System Diseases; Blood Pressure
PubMed: 37194542
DOI: 10.11477/mf.1416202389 -
American Journal of Hypertension Nov 2018Orthostatic hypotension (OH) is an important and common medical problem, particularly in the frail elderly with multiple comorbidities and polypharmacy. OH is an... (Review)
Review
Orthostatic hypotension (OH) is an important and common medical problem, particularly in the frail elderly with multiple comorbidities and polypharmacy. OH is an independent risk factor for falls and overall mortality. Hypertension is among the most common comorbidities associated with OH, and its presence complicates the management of these patients because treatment of one can worsen the other. However, there is evidence that uncontrolled hypertension worsens OH so that both should be managed. The limited data available suggest that angiotensin receptor blockers and calcium channel blockers are preferable antihypertensives for these patients. Patients with isolated supine hypertension can be treated with bedtime doses of short-acting antihypertensives. Treatment of OH in the hypertensive patients should focus foremost on the removal of drugs that can worsen OH, including ones that are easily overlooked, such as tamsulosin, tizanidine, sildenafil, trazodone, and carvedilol. OH and postprandial hypotension can be prevented with abdominal binders and acarbose, respectively, without the need to increase baseline blood pressure. Upright blood pressure can be improved by harnessing residual sympathetic tone with atomoxetine, which blocks norepinephrine reuptake in nerve terminals, and pyridostigmine, which facilitates cholinergic neurotransmission in autonomic ganglia. Oral water bolus acutely but transiently increases blood pressure in autonomic failure patients. If traditional pressor agents are needed, midodrine and droxidopa can be used, administered at the lowest dose and frequency that improves symptoms. Management of OH in the hypertensive patient is challenging, but a management strategy based on understanding the underlying pathophysiology can be effective in most patients.
Topics: Antihypertensive Agents; Blood Pressure; Clinical Decision-Making; Comorbidity; Humans; Hypertension; Hypotension, Orthostatic; Posture; Risk Factors; Treatment Outcome
PubMed: 29982276
DOI: 10.1093/ajh/hpy089