ABSTRACT
BACKGROUND: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. METHODS: We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. RESULTS: Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21-0.72; I2 = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28-0.55; I2 = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49-2.64; I2 = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies. CONCLUSION: Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations.
Subject(s)
Antihypertensive Agents , Blood Pressure , Hypertension , Hypotension, Orthostatic , Aged , Aged, 80 and over , Humans , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Hypertension/drug therapy , Hypertension/physiopathology , Hypotension, Orthostatic/drug therapy , PrevalenceABSTRACT
The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.
Subject(s)
Adrenergic Uptake Inhibitors , Atomoxetine Hydrochloride , Hypotension, Orthostatic , Norepinephrine , Humans , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/physiopathology , Adrenergic Uptake Inhibitors/therapeutic use , Adrenergic Uptake Inhibitors/pharmacology , Atomoxetine Hydrochloride/therapeutic use , Atomoxetine Hydrochloride/pharmacology , Norepinephrine Plasma Membrane Transport Proteins/antagonists & inhibitors , Norepinephrine Plasma Membrane Transport Proteins/metabolism , Blood Pressure/drug effects , Blood Pressure/physiologyABSTRACT
Serotonin syndrome (SS) is a drug-induced clinical syndrome characterised by a combination of cognitive, neuromuscular and autonomic dysfunctions. The symptoms may include mild non-specific symptoms such as tremors and diarrhoea to coma and sudden death. Herein, we describe a case of SS in which acute dizziness was associated with supine hypertension and orthostatic hypotension. A man in his mid-30s had a 10-month history of anxiety, depression and chronic tension-type headache. He had been on amitriptyline (25 mg daily) and sertraline (50 mg daily). Increment of sertraline (75 mg daily) and amitriptyline (75 mg daily) and the addition of tramadol led to the development of acute severe dizziness. Physical examinations demonstrate supine hypertension and orthostatic hypotension. He also met the diagnostic criteria of SS. The administration of cyproheptadine provided a complete response to dizziness, supine hypertension, orthostatic hypotension and other clinical features of SS.
Subject(s)
Hypertension , Hypotension, Orthostatic , Serotonin Syndrome , Male , Humans , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Dizziness/chemically induced , Dizziness/diagnosis , Serotonin Syndrome/chemically induced , Serotonin Syndrome/complications , Serotonin Syndrome/diagnosis , Amitriptyline , Sertraline , VertigoABSTRACT
INTRODUCTION: Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood. AREAS COVERED: We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established. EXPERT OPINION: POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.
Subject(s)
Hypotension, Orthostatic , Postural Orthostatic Tachycardia Syndrome , Humans , Postural Orthostatic Tachycardia Syndrome/diagnosis , Postural Orthostatic Tachycardia Syndrome/drug therapy , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Heart Rate , Fatigue/complications , DizzinessABSTRACT
SOURCE CITATION: Juraschek SP, Hu JR, Cluett JL, et al. Orthostatic hypotension, hypertension treatment, and cardiovascular disease: an individual participant meta-analysis. JAMA. 2023;330:1459-1471. 37847274.
Subject(s)
Cardiovascular Diseases , Hypertension , Hypotension, Orthostatic , Humans , Blood Pressure , Hypertension/drug therapy , Hypotension, Orthostatic/drug therapyABSTRACT
PURPOSE: Antipsychotic use in Alzheimer disease (AD) is associated with adverse events and mortality. Whilst postulated to cause/exacerbate orthostatic hypotension (OH), the exact relationship between antipsychotic use and OH has never been explored in AD-a group who are particularly vulnerable to neuro-cardiovascular instability and adverse effects of medication on orthostatic blood pressure (BP) behaviour. METHODS: We analysed longitudinal data from an 18-month trial of Nilvadipine in mild-moderate AD. We assessed the effect of long-term antipsychotic use (for the entire 18-month study duration) on orthostatic BP phenotypes measured on eight occasions, in addition to the relationship between antipsychotic use, BP phenotypes and incident falls. RESULTS: Of 509 older adults with AD (aged 72.9 ± 8.3 years, 61.9% female), 10.6% (n = 54) were prescribed a long-term antipsychotic. Over 18 months, long-term antipsychotic use was associated with a greater likelihood of experiencing sit-to-stand OH (ssOH) (OR: 1.21; 1.05-1.38, p = 0.009) which persisted on covariate adjustment. Following adjustment for important clinical confounders, both antipsychotic use (IRR: 1.80, 1.11-2.92, p = 0.018) and ssOH (IRR: 1.44, 1.00-2.06, p = 0.048) were associated with a greater risk of falls/syncope over 18 months in older adults with mild-moderate AD. CONCLUSION: Even in mild-to-moderate AD, long-term antipsychotic use was associated with ssOH. Both antipsychotic use and ssOH were associated with a greater risk of incident falls/syncope over 18 months. Further attention to optimal prescribing interventions in this cohort is warranted and may involve screening older adults with AD prescribed antipsychotics for both orthostatic symptoms and falls.
Subject(s)
Alzheimer Disease , Antipsychotic Agents , Hypotension, Orthostatic , Aged , Female , Humans , Male , Accidental Falls/prevention & control , Alzheimer Disease/complications , Alzheimer Disease/drug therapy , Alzheimer Disease/epidemiology , Antipsychotic Agents/adverse effects , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/epidemiology , Hypotension, Orthostatic/complications , Syncope/complications , Aged, 80 and overABSTRACT
BACKGROUND AND PURPOSE: Levodopa (LD) is the main treatment for parkinsonism, but its use may be limited by a potential hypotensive effect. METHODS: We evaluated the cardiovascular effect of LD performing head-up tilt test (HUTT) before and 60 min after 100/25 mg LD/dopa-decarboxylase inhibitor (pre-LD vs. post-LD HUTT) in 164 patients with parkinsonism on chronic LD treatment. Features predictive of LD-induced orthostatic hypotension (OH) were assessed by logistic regression analysis. RESULTS: Basal supine blood pressure (BP) and heart rate (HR) decreased after LD. During post-LD HUTT, BP drop and HR increase were significantly greater than at pre-LD HUTT. Thirty-eight percent of patients had OH at post-LD HUTT compared to 22% of patients presenting OH at pre-LD HUTT (p < 0.001). Risk factors for LD-induced/worsened OH were pre-LD OH (odds ratio [OR] = 36, 95% confidence interval [CI] = 10-131), absence of overshoot at Valsalva maneuver (OR = 9, 95% CI = 4-20), and pathological Valsalva ratio (OR = 6, 95% CI = 2-15). CONCLUSIONS: LD administration caused/worsened hypotension in both supine and orthostatic conditions. Patients with cardiovascular autonomic failure had a higher risk of developing LD-induced OH. In clinical practice, LD-induced OH could represent a red flag for cardiovascular autonomic failure.
Subject(s)
Hypotension, Orthostatic , Parkinsonian Disorders , Humans , Hypotension, Orthostatic/drug therapy , Levodopa/adverse effects , Blood Pressure/physiology , Heart , Tilt-Table Test/adverse effects , Heart RateABSTRACT
Background Midodrine was the first medication approved by the Food and Drug Administration (FDA) for the treatment of orthostatic hypotension. Pharmacologically, midodrine is a peripheral selective alpha-1-adrenergic agonist that can improve standing, sitting, and supine systolic blood pressure. Common side effects include bradycardia, supine hypertension, and paresthesia. A novel side effect of midodrine-induced nightmares has been reported in our patient. To our knowledge, this is the first reported case of midodrine-induced nightmares. Objective To investigate and report a clinically significant and unique drug adverse event of midodrine in the treatment of orthostatic hypotension. Case Presentation This report describes a case of persistent nightmares associated with midodrine use in an 83-year-old male who experienced frequent syncope episodes treated with midodrine for orthostatic hypotension (OH). After the initiation of midodrine, the patient complained of increased nightmares, which quickly led to his refusal of the medication, despite the initial improvements in his blood pressure. The timing of administration included an evening dose at 21:00. This novel adverse event of midodrine-induced nightmares will be highlighted and explored in this case report. Conclusion This case demonstrated a unique adverse event of nightmares caused by midodrine. It is hypothesized that autonomic dysfunction plays a role and further investigations should be conducted to confirm this theory. We hope that our case report highlights the importance of careful consideration when prescribing midodrine in older people with orthostatic hypotension.
Subject(s)
Hypotension, Orthostatic , Midodrine , Aged, 80 and over , Humans , Male , Adrenergic alpha-Agonists/adverse effects , Blood Pressure , Dreams , Hypotension, Orthostatic/chemically induced , Hypotension, Orthostatic/drug therapy , Midodrine/adverse effects , United StatesABSTRACT
Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29â¯235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.
Subject(s)
Hypertension , Hypotension, Orthostatic , Aged , Female , Humans , Male , Blood Pressure , Blood Pressure Determination , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Hypertension/complications , Hypertension/diagnosis , Hypertension/drug therapy , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Middle AgedSubject(s)
Antihypertensive Agents , Blood Pressure , Hypertension , Hypotension, Orthostatic , Humans , Blood Pressure/drug effects , Hypertension/complications , Hypertension/drug therapy , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/drug therapy , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: To determine if outpatient screening for orthostatic hypotension (OH) in the geriatric population results in fewer prescribed antihypertensive medications and if a relationship exists between OH and specific pharmacologic classes of antihypertensive medications. MATERIALS AND METHODS: Patients ≥ 65 years were screened for OH, defined as a decrease in systolic blood pressure (SBP)â ≥â 20â mm Hg or a decrease in diastolic blood pressure (DBP)â ≥â 10â mm Hg after standing for 3 minutes. Sitting blood pressure (BP) was measured after patients had been seated quietly in an exam room. Patients then stood for approximately 3 minutes at which time standing BP was recorded. RESULTS: OH prevalence was 18%. Standing DBP was significantly different between the two groups (70â mmHg ± 18, 80â mmHg ± 13, P â =â 0.007). Compared to patients without OH, patients with OH were more likely to have been previously prescribed beta-blockers (56% vs. 32%, P â =â 0.056) and potassium-sparing diuretics (11% vs. 1%, P â =â 0.026). Physicians discontinued an antihypertensive medication more often in patients who screened positive for OH than in to those who did not (17% vs. 4%, P â =â 0.037). Calcium channel blockers were the most frequently discontinued class of medication. CONCLUSION: Asymptomatic OH is prevalent in geriatric patients. Screening for OH may lead to de-escalation of antihypertensive regimen and a reduction in polypharmacy. Positive screening for OH was associated with de-prescribing of antihypertensive medications. Prior use of beta-blockers and potassium-sparing diuretics was most largely associated with OH.
Subject(s)
Hypertension , Hypotension, Orthostatic , Humans , Aged , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Blood Pressure/physiology , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/epidemiology , Diuretics/therapeutic use , Primary Health Care , PotassiumABSTRACT
Orthostatic hypotension (OH) is a common vegetative symptom of Parkinson's disease (PD), which is predominantly neurogenic in nature. Detection and treatment of OH is of great importance, since it affects daily activity and increases the risk of falls. In the long term it damages target organs - the heart, kidneys and brain. In this regard, the review discusses the issues of classification, pathogenesis of OH, stages of diagnosis and correction of blood pressure, as well as measures for lifestyle changing, non-drug and drug treatment of orthostasis. Strategies for the management of patients with postprandial hypotension, hypertension in the supine position and nocturnal hypertension are considered separately. Despite modern combined methods of treatment, the burden of OH in patients with PD remains heavy, and fluctuations in blood pressure due to concomitant hypertension in the supine position are a significant problem. This highlights the need to initiate scientific research and new therapeutic approaches.
Subject(s)
Hypertension , Hypotension, Orthostatic , Orthostatic Intolerance , Parkinson Disease , Humans , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/etiology , Parkinson Disease/complications , Patients , Hypertension/complications , Hypertension/drug therapyABSTRACT
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.
Subject(s)
Hypotension, Orthostatic , Nervous System Diseases , Humans , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/diagnosis , Blood PressureABSTRACT
BACKGROUND AND PURPOSE: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. RESULTS: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). CONCLUSIONS: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.
Subject(s)
Hypertension , Hypotension, Orthostatic , Hypotension , Humans , Antihypertensive Agents/adverse effects , Hypotension, Orthostatic/diagnosis , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/epidemiology , Blood Pressure , Syncope/diagnosis , Syncope/drug therapy , Syncope/chemically induced , Hypertension/diagnosis , Hypertension/drug therapy , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs. METHODS: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30th, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05). CONCLUSIONS: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.
Subject(s)
Hypotension, Orthostatic , Urogenital Diseases , Humans , Doxazosin/therapeutic use , Tamsulosin/therapeutic use , Hypotension, Orthostatic/chemically induced , Hypotension, Orthostatic/epidemiology , Hypotension, Orthostatic/drug therapy , Adrenergic alpha-Antagonists/adverse effects , Prazosin/adverse effectsABSTRACT
BACKGROUND: Individuals with spinal cord injury (SCI) above thoracic level-6 (T6) experience impaired descending cortical control of the autonomic nervous system which predisposes them to blood pressure (BP) instability, including includes hypotension, orthostatic hypotension (OH), and autonomic dysreflexia (AD). However, many individuals do not report symptoms of these BP disorders, and because there are few treatment options that have been proven safe and effective for use in the SCI population, most individuals remain untreated. OBJECTIVE: The primary aim of this investigation was to determine the effects of midodrine (10â mg) prescribed TID or BID in the home environment, compared to placebo, on 30-day BP, study withdrawals, and symptom reporting associated with OH and AD in hypotensive individuals with SCI. DESIGN/METHODS: Participants were randomly assigned to received midodrine/placebo or placebo/midodrine, with a 2-weeks washout period in between, and both the participants and investigators were blinded to randomization order. Study medication was taken 2 or 3 times/day, depending on their sleep/wake schedule, BP, and any related symptoms were recorded before and 1â h after each dosage and periodically throughout the day. RESULTS: Nineteen individuals with SCI were recruited; however, 9 withdrew prior to completion of the full protocol. A total of 1892 BP recordings (75 ± 48 recordings/participant/30-day period) were collected in the 19 participants over the two 30-day monitoring periods. Average 30-day systolic BP was significantly increased with midodrine compared to placebo (114 ± 14 vs. 96 ± 11â mmHg, respectively; P = 0.004), and midodrine significantly reduced the number of hypotensive BP recordings compared to placebo (38.7 ± 41.9 vs. 73.3 ± 40.6, respectively; P = 0.01). However, compared to placebo, midodrine increased fluctuations in BP, did not improve symptoms of OH, but did significantly worsen the intensity of symptoms associated with AD (P = 0.03). CONCLUSION: Midodrine (10â mg) administered in the home environment effectively increases BP and reduces the incidence of hypotension; however these beneficial effects come at the expense of worsened BP instability and AD symptom intensity.
Subject(s)
Autonomic Dysreflexia , Hypotension, Orthostatic , Hypotension , Midodrine , Spinal Cord Injuries , Humans , Midodrine/therapeutic use , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Blood Pressure Monitoring, Ambulatory/adverse effects , Hypotension/etiology , Hypotension/complications , Hypotension, Orthostatic/drug therapy , Hypotension, Orthostatic/etiology , Autonomic Dysreflexia/drug therapy , Autonomic Dysreflexia/etiologyABSTRACT
Patients who require antipsychotic drug treatment are at increased risk of fractures, including osteoporosis-related fragility fractures, for reasons related to demographics, illness-related factors, and treatment-related factors. As examples, patients with dementia may be vulnerable to falls due to cognitive and psychomotor impairment, patients with schizophrenia may be vulnerable to injury related to physical restlessness or physical aggression, and patients receiving antipsychotics may suffer falls related to sedation, psychomotor impairment, bradykinesia, or postural hypotension. Antipsychotics may also increase the risk of fracture through long-term hyperprolactinemia and resultant osteoporosis. A meta-analysis of 36 observational studies conducted in mostly elderly samples found that antipsychotic exposure was associated with an increased risk of hip fracture as well as increased risk of any fracture; the findings were consistent in almost all subgroup analyses. An observational study that controlled for confounding by indication and illness severity found that fragility fractures in patients with schizophrenia were associated with higher daily doses, higher cumulative doses, longer duration of treatment, and prolactin-raising rather than prolactin-sparing antipsychotics; in patients receiving prolactin-raising antipsychotics, the concurrent use of aripiprazole appeared protective. The absolute risks of fracture are unknown and could vary depending on patient age, patient sex, indication for antipsychotic use, nature of the antipsychotic (and associated risk of sedation, psychomotor impairment, bradykinesia, and postural hypotension), daily dose prescribed, duration of antipsychotic exposure, baseline risk of fracture, and other risk factors. Patients should therefore be individually evaluated for risk factors for falls and fractures related to sociodemographic, clinical, and treatment-related risk factors. Patients identified to be at risk should be advised about risk-mitigating strategies. If prolactin-raising antipsychotics are required in the long term, prolactin levels should be monitored and prolactin-lowering strategies should be considered. Osteoporosis should be investigated and managed, if identified, to prevent fragility fractures.
Subject(s)
Antipsychotic Agents , Dementia , Hyperprolactinemia , Hypotension, Orthostatic , Osteoporosis , Schizophrenia , Humans , Aged , Antipsychotic Agents/adverse effects , Prolactin , Schizophrenia/complications , Hypokinesia/chemically induced , Hypokinesia/complications , Hypokinesia/drug therapy , Hypotension, Orthostatic/chemically induced , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/drug therapy , Hyperprolactinemia/chemically induced , Hyperprolactinemia/complications , Hyperprolactinemia/drug therapy , Osteoporosis/chemically induced , Osteoporosis/complications , Osteoporosis/drug therapy , Risk Factors , Dementia/complications , Observational Studies as TopicABSTRACT
Aim: This study explores the burden of caring for an individual with neurogenic orthostatic hypotension (nOH) and an underlying neurodegenerative disease (Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies). Materials & methods: A survey including several validated instruments was conducted with informal caregivers of individuals with Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. Results: Caregivers of patients with nOH (n = 60) reported greater burden across all outcomes compared with those without nOH (n = 60). Receiving pharmacological treatment for nOH was the variable most consistently associated with significantly better caregiver health-related quality-of-life (p < 0.05). Conclusion: This study demonstrates the burden of nOH on informal caregivers and highlights the potential benefit of pharmacological treatment not only for patients but also indirectly, their caregivers.
Neurogenic orthostatic hypotension (nOH) causes blood pressure to fall when you stand up, meaning you can feel dizzy or lightheaded. This study looked at how providing day to day caregiving support to someone who has nOH as well as another neurological condition impacts the caregiver's health and wellbeing. These neurological conditions included Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. A survey was conducted with informal caregivers (e.g., family members) of people with a neurological condition, with or without nOH. Caregivers completed questions about their own health-related quality-of-life, anxiety, depression and experience of caregiving. Caregivers of patients with nOH reported higher amounts of burden compared with those without nOH. Patients taking a treatment for nOH was most often associated with better caregiver health-related quality-of-life. This study shows the burden nOH can have on informal caregivers and highlights that treatment potentially benefits both patients and, indirectly, caregivers.
Subject(s)
Hypotension, Orthostatic , Lewy Body Disease , Multiple System Atrophy , Parkinson Disease , Pure Autonomic Failure , Humans , Hypotension, Orthostatic/complications , Hypotension, Orthostatic/drug therapy , Caregivers , Parkinson Disease/complications , Pure Autonomic Failure/complications , Lewy Body Disease/drug therapy , Quality of LifeABSTRACT
PURPOSE: To determine if the menstrual cycle and oral contraceptives (OC) influence responses to acute orthostatic stress and if these factors are clinically relevant to the diagnosis of initial orthostatic hypotension (iOH). METHODS: Young, healthy women were recruited, including OC users (n = 12) and non-users (NOC; n = 9). Women were tested during the low hormone (LH; placebo pills; days 2-5 natural cycle) and high hormone (HH; active dose; days 18-24 natural cycle) menstrual phases. Changes in mean arterial pressure, cardiac output, heart rate, the 30:15 heart rate ratio and cerebrovascular resistance indices within 30 s of standing were examined. RESULTS: There were no effects of OC or menstrual cycle on hemodynamic responses during standing (all p>0.05). In the LH phase, OC users had a greater fall in mean middle cerebral artery blood velocity (MCAV) compared to NOC (p<0.05). However, this was reversed in the HH phase, where OC users had a reduced fall in mean MCAV (p<0.05). Interestingly, 8 women (OC and NOC) had drops in systolic/diastolic blood pressure meeting the criteria for iOH, and 7 of those 8 women displayed this drop in a single phase of the menstrual cycle. CONCLUSION: Our results indicate that chronic versus acute OC use (i.e., long-term use observed via LH phase versus short-term use observed via HH phase) have opposing effects on cerebral blood velocity during standing. Further, our results highlight that multiple assessments across the cycle may be necessary to accurately diagnose iOH, as most women met the diagnostic criteria during a single menstrual phase.
Subject(s)
Hypotension, Orthostatic , Menstrual Cycle , Humans , Female , Menstrual Cycle/physiology , Contraceptives, Oral/pharmacology , Contraceptives, Oral/therapeutic use , Blood Pressure/physiology , Heart Rate/physiology , Hypotension, Orthostatic/drug therapy , Hormones/pharmacologyABSTRACT
We propose a consensus definition of "an exaggerated orthostatic pressor response" in subjects in whom systolic blood pressure increases ≥ 20 mmHg when going from supine to standing posture. This definition can be extended for seated to standing measurements. We reserve the term "orthostatic hypertension" for when this pressor response leads to an upright systolic blood pressure ≥ 140 mmHg. We believe this consensus definition will help in the study of the pathophysiology, clinical impact, and potential treatment of these entities, and identification of patients who are at greater cardiovascular risk.