Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many astronauts exhibit post-spaceflight orthostatic hypotension due to inadequate norepinephrine release when in an upright posture. We hypothesized that an alpha1-adrenergic agonist, midodrine, would be an effective countermeasure. A female astronaut, who had problems with postflight orthostatic hypotension after a previous flight, consumed 10 mg midodrine after a subsequent flight, prior to her tilt test. Hemodynamic variables were compared between the two flights. Midodrine prevented severe falls in stroke volume, cardiac output and systolic pressure, and severe increases in heart rate without increasing vascular resistance, thus preventing orthostatic hypotension. This is the first report showing that midodrine has the potential to improve post-spaceflight orthostatic hypotension and suggesting that reduced venous return contributes to the etiology.
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PMID:Midodrine prescribed to improve recurrent post-spaceflight orthostatic hypotension. 1519 85

Orthostatic hypotension (OH) may be dependent upon various neurogenic and non-neurogenic disorders and conditions. Neurogenic causes include the main autonomic failure syndromes, primary (multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinson's disease) and secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). Non-neurogenic causes of OH include cardiac impairment, fluid and electrolyte loss, vasodilatation, and old age. A number of drugs may also cause OH, through their vasoactive action or by interfering with the autonomic nervous system. Symptoms of OH are debilitating, often confining patients to bed, and longitudinal studies have shown that OH increases the risk of stroke, myocardial ischemia and mortality. The therapeutic goal is to decrease the incidence and severity of postural symptoms, rather than restore normotension. In non-neurogenic OH, treatment of the underlying cause may be curative. In neurogenic OH a combination of non-pharmacological and pharmacological measures is often needed. Patient education and non-pharmacological measures represent the first step; among these interventions, fluid repletion and physical countermanoeuvres have been proven very effective. Pharmacological treatment comprises a number of agents acting on blood vessels, on blood volume or with other pressor mechanisms. The drugs most currently used are fludrocortisone and midodrine. Fludrocortisone expands the extravascular body fluid volume and improves alpha-adrenergic sensitivity. Midodrine is a peripheral, selective alpha1-adrenergic agonist that causes arterial and venous vasoconstriction. Despite the wide use of these drugs, multicentre, randomised and controlled studies for the treatment of OH are still scarce and limited to few agents and groups of patients. Pharmacological management of OH substantially improves the quality of life of patients, although it may be problematic. The development of supine hypertension and subsequent congestive heart failure should be avoided, especially in those patients with a pre-existing cardiovascular risk, such as in diabetes or ischemic heart disease.
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PMID:Orthostatic hypotension: evaluation and treatment. 1734 29

Chronic low blood pressure is typically accompanied by symptoms such as fatigue, reduced drive, dizziness, headaches and cold limbs. Reduced cognitive performance, diminished cerebral blood flow and autonomic dysregulation have been furthermore documented in this condition. The present contribution reports two studies exploring systemic hemodynamics in chronic hypotension and their modification through vasopressor application. In study I, effects of the alpha-sympathomimetic midodrine were examined in 54 hypotensive individuals using a placebo-controlled double-blind design. Hemodynamic parameters were assessed at rest and during mental stress. They were derived from continuous blood pressure recordings using Modelflow analysis. The drug led to marked increases in blood pressure, total peripheral resistance and stroke volume. However, due to strong heart rate deceleration, cardiac output remained virtually unchanged. In study II, 40 hypotensive and 40 normotensive control persons were compared with respect to hemodynamics. While groups did not differ in total peripheral resistance, hypotensives exhibited markedly diminished stroke volume and heart rate, resulting in a reduction in cardiac output of 25% at rest and of 33% during mental stress. The data provide relevant knowledge about the hemodynamic mediation of chronic hypotension. In contrast to elevated blood pressure, which is mainly determined by increased peripheral resistance, reduced cardiac output may be the cardinal hemodynamic aberration in chronic hypotension. Midodrine proved to be effective in elevating blood pressure. However, given the cardiac origin of chronic hypotension and the lack of drug effect on cardiac output, alpha-sympathomimetic treatment may be suboptimal.
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PMID:Hemodynamic determinants of chronic hypotension and their modification through vasopressor application. 1934 May 50