Disease relevance of midodrine

• Efficacy of midodrine for neurogenic orthostatic hypotension [1].
• The response of patients to the alpha1-agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of alpha1-agonists to pharmacologically replace lower-extremity postganglionic sympathetics is an appropriate overall goal of therapy [2].
• These results indicate that midodrine significantly improves orthostatic tolerance during head-up tilt in patients with recurrent neurally mediated syncope [3].
• Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites [4].
• Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide [5].

Psychiatry related information on midodrine

• Acute dystonia induced by adding midodrine, a selective alpha 1 agonist, to risperidone in a patient with catatonic schizophrenia [6].
• Midodrine enhanced amphetamine-stimulated locomotor activity and reduced the amphetamine and apomorphine sterotypy [7].
• First-line treatments include midodrine for orthostatic hypotension, prokinetic drugs for gastroparesis, broad-spectrum antibiotics for diabetic diarrhea, and sildenafil for erectile dysfunction [8].

High impact information on midodrine

• The aim of this study was to determine the efficacy of transjugular intrahepatic portosystemic stent shunt (TIPS) as a treatment for type 1 HRS in ascitic cirrhotic patients, following improvement in systemic hemodynamics with a combination of midodrine, octreotide, and albumin (medical treatment) [9].
• In the supine position, midodrine produced no significant change in blood pressure or heart rate [3].
• Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study [3].
• We conducted a double-blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective alpha-1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head-up tilt [3].
• After 20 days of treatment with midodrine and octreotide, an impressive improvement in renal plasma flow (RPF), glomerular filtration rate, and urinary sodium excretion was observed in patients [5].

Chemical compound and disease context of midodrine

• BACKGROUND: Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension [10].
• Current practice patterns suggest that beta blockers, fludrocortisone, and midodrine, are commonly used to treat patients with vasovagal syncope, and patients with the dysautonomic response are generally treated with fludrocortisone and midodrine [11].
• This led to successfully oral treatment of the orthostatic hypotension with clonidine 150 micrograms bd and midodrine 10 mg bd [12].
• A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily [13].
• Several vasoconstrictors including the alpha-adrenergic agonists, midodrine and noradrenalin, and the vasopressor analogues, ornipressin and terlipressin, have all been associated with a significant improvement in renal function in 57 to 100% of cases and even reversal of hepatorenal syndrome in 42 to 100% of cases [14].

Biological context of midodrine

• OBJECTIVE: To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension [15].
• Ephedrine significantly increased (P < 0.05) the pulse rate as compared with placebo and midodrine, whereas midodrine produced a statistically significant (P < 0.05) but clinically minimal decrease in pulse rate compared with placebo [16].
• DESIGN/METHODS: Midodrine dose-blood pressure response, pharmacokinetics, and duration of action were examined in a double-blind, placebo-controlled, four-way crossover trial [17].
• Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine [18].
• Additionally, midodrine appears to cause less frequent and severe adverse effects associated with alpha-receptor agonism such as piloerection and urinary hesitancy [18].

Anatomical context of midodrine

• Conversely, in patients with markedly impaired baroreceptor mechanisms, treatment with midodrine may produce extracellular fluid volume depletion and exacerbate orthostatic hypotension [19].
• The therapeutic efficacy of midodrine, an alpha-adrenergic agonist that does not cross the blood-brain barrier, was investigated in a double-blind crossover trial in seven patients with orthostatic hypotension due to autonomic failure [19].
• An in vivo dog model showed 1 to be more selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the active metabolite of midodrine), and phenylpropanolamine (4) [20].
• A 20 h continuous treatment of rats with catecholamines, using subcutaneously implantable retard tablets, had either no (adrenaline, isoproterenol, midodrine) or a slight (noradrenaline) suppressive effect on the in vitro responsiveness of peripheral blood T-lymphocytes [21].
• Midodrine uptake by Caco-2 cells was saturable and was inhibited by various PEPT1 substrates [22].

Associations of midodrine with other chemical compounds

• PURPOSE: In this double-blind study, the authors compared the safety and efficacy of the investigational oral agent midodrine, a specific alpha 1-sympathomimetic agent, with ephedrine, a nonspecific alpha- and beta-adrenergic receptor agonist [16].
• Agents such as fludrocortisone, midodrine, and epoetin alfa offer successful pharmacologic interventions [23].
• Before and after 4 administrations of alpha 1-adrenoceptor agonist (midodrine hydrochloride 0.03, 0.1, 0.3 and 1.0 mg./kg. intravenously), cystometry, urethral pressure profilometry and external urethral sphincter electromyography were performed [24].
• These findings indicate that PEPT1 can transport midodrine and contributes to the high bioavailability of this drug and that Gly modification of DMAE is desirable for a prodrug of DMAE [22].
• Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects) [25].

Gene context of midodrine

• The human cytochrome P450 (CYP) isoforms catalyzing the oxidation metabolism of desglymidodrine (DMAE), an active metabolite of midodrine, were studied [26].
• The uptake of midodrine, but not DMAE, was markedly increased in PEPT1-expressing oocytes compared with water-injected oocytes [22].
• We report the use of midodrine, an alpha agonist, in an 18-year-old man with Bardet-Biedl syndrome and recurrent intradialytic hypotension [27].
• To clarify the effect of a long-acting selective alpha 1-adrenoceptive sympathomimetic agent on sympathetic outflow to muscles (muscle sympathetic activity, MSA) in humans, 5 mg of midodrine hydrochloride was injected intravenously in ten healthy male subjects aged 19-25 [28].
• Ischemic calf exercise evoked similar peak CBF in both trials, but midodrine reduced the hyperemic response over 5 min of recovery (P < 0.02) [29].

Analytical, diagnostic and therapeutic context of midodrine

• Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group [15].
• Midodrine decreased both supine and upright HR (all HR values are given as bpm) at 2 hours (from 78+/-2 supine to 108+/-5 upright before treatment and from 69+/-2 supine to 95+/-5 upright after treatment, P<.005 for supine and P<.01 for upright) [2].
• The double-blind titration period with either midodrine or ephedrine was 3 to 5 days; the titration end point was to increase standing systolic blood pressure to > or = 80 mm Hg and to maintain a supine pressure below 180/100 mm Hg [16].
• Midodrine, a peripheral alpha-adrenergic agonist, finds use in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies [18].
• The patients were given a dose of midodrine (mean dose, 5.5 mg; range, 5 to 10 mg) 30 minutes before each hemodialysis session [30].

References