Usefulness of Midodrine in Patients with Severely Symptomatic Neurocardiogenic Syncope: A Randomized Control Study

Perez-Lugones, Alejandro; Schweikert, Robert A.; Pavia, S.; Sra, Jasbír; Akhtar, Masood; Jaeger, Déborah; Tomassoni, Gery; Saliba, Walid; Leonelli, Fabio M.; Bash, R N Dianna; Beheiry, R N Salwa; Shewchik, R N Jeanne; Tchou, Patrick; Natale, Andrea

doi:10.1046/j.1540-8167.2001.00935.x

Cited by 151 publications

(61 citation statements)

References 9 publications

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“…In the former, L-DOPS treatment might provide pharmacologic supplementation of NE delivery to cardiovascular adrenoceptors and counter a tendency to decreased cardiac noradrenergic outflow (23). Thus, treatment with the á-adrenoceptor agonist, midodrine, has been reported to improve at least some patients with neurocardiogenic syncope (31,82). Any of several abnormalities can manifest as POTS.…”

Section: L-dops 197mentioning

confidence: 99%

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

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L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

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Section: L-dops 197mentioning

confidence: 99%

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

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“…28,29 The improvement in orthostatic tolerance with water drinking may be related to a similar mechanism.…”

Section: Schroeder Et Al Water Drinking and Orthostatic Tolerancementioning

confidence: 99%

Water Drinking Acutely Improves Orthostatic Tolerance in Healthy Subjects

et al. 2002

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Background-Orthostatic symptoms and syncope are common, even in apparently healthy subjects. In patients with severe autonomic dysfunction, water drinking elicits an acute pressor response and improves orthostatic hypotension. We tested the hypothesis that water drinking also improves orthostatic tolerance in healthy subjects. Methods and Results-In a randomized, controlled, crossover fashion, 13 healthy subjects (9 men, 4 women, 31Ϯ2 years) ingested 500 mL and 50 mL of mineral water 15 minutes before head-up tilt on two separate days. Finger blood pressure, brachial blood pressure, heart rate, thoracic impedance, and blood flow velocity in the brachial artery and the middle cerebral artery were measured. Orthostatic tolerance was determined as the time to presyncope during a combined protocol of 20 minutes of 60°head-up tilt alone, followed by additional increasing steps of lower body negative pressure (Ϫ20, Ϫ40, and Ϫ60 mm Hg for 10 minutes each or until presyncope). Drinking 500 mL of water improved orthostatic tolerance by 5Ϯ1 minute (range, Ϫ1 to ϩ11 minutes, PϽ0.001). After drinking 500 mL of water, supine mean blood pressure increased slightly (PϽ0.01) as the result of increased peripheral resistance (PϽ0.01). It also blunted both the increase in heart rate and the decrease in stroke volume with head-up tilt. Cerebral blood flow regulation improved after water drinking. Conclusions-Water drinking elicits an acute hemodynamic response and changes in cerebrovascular regulation in healthy subjects. These effects are associated with a marked improvement in orthostatic tolerance.

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“…There are trials demonstrating some efficacy but in practice only some patients gain benefit and the frequency of medication, three to four times per day because of its short half-life, its limited availability being unlicensed in most western countries and its lack of information on its teratogenicity all militate against its widespread use. Midodrine will be the subject of a large RCT based in Canada, which is greatly needed (Sheldon R personal communication POST Prevention of Syncope 4) [6][7][8][9].…”

Section: Pharmaceutical Agentsmentioning

confidence: 99%

Treatment of Reflex Syncope

Sutton

2013

J Med Diagn Meth

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This review assesses the role of all types of therapy for reflex syncope including physical counter-measures, diet, behavior, drugs and implantable devices. There are no drugs currently demonstrated to have convincingly beneficial effect by randomized controlled trial. However, provided that the patient experiences warning of an impending attack physical counter-measures are demonstrably effective. Implantable cardiac pacemakers have a role in a carefully selected minority of patients with vasovagal syncope. Pacing, dual chamber of cardio-inhibitory Carotid Sinus Syndrome is the treatment of choice. Modification of lifestyle in terms of fluid, caffeine and salt consumption is necessary in many cases but has little scientific background. Educating and reassuring the patient is an important part of management. The patient must understand that attacks are not as dangerous as they might seem in most cases and learning to anticipate those permits evasive measures.

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Usefulness of Midodrine in Patients with Severely Symptomatic Neurocardiogenic Syncope: A Randomized Control Study

Abstract: Midodrine appeared to provide a significant benefit in patients with neurocardiogenic syncope. To prevent recurrence of symptoms, dose adjustments were required in about one third of patients.

Cited by 151 publications

References 9 publications

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Water Drinking Acutely Improves Orthostatic Tolerance in Healthy Subjects

Treatment of Reflex Syncope

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