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At least 19 recordsLinked to original sources
PubMed1997

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group.

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. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone. DESIGN/METHODS: A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4). SETTING: Twenty-five centers, with most patients evaluated in referral centers. MAIN OUTCOME MEASURES: The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately). RESULTS: Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2, 3, 4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension. CONCLUSIONS: Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.

Activities of Daily Living↗
PubMed1976

Pharmacodynamic actions of midodrine, a new alpha-adrenergic stimulating agent, and its main metabolite, ST 1059.

Pharmacodynamic actions of alpha-(2,5-dimethoxyphenyl)-beta-glycinamido-ethanol-hydrochloride (midodrine, Gutron) and alpha-(2,5-dimethoxy-phenyl)-beta-aminoethanol (ST 1059), the main metabolite of midodrine, were investigated in various experimental procedures. Midodrine raises arterial blood pressure both after parenteral and enteral administration in animal experiments. Midodrine increases peripheral vascular tone when given in doses still ineffective in raising blood pressure. The d(+)-isomer of midodrine is by far less effective than the racemic mixture. Pretreatment with atropine, reserpine, guanethidine or hexamethonium has no influence on midodrine activity. Midodrine effects are greatly reduced by phentolamine but rather enhanced by propranolol pretreatment. Midodrine raises blood pressure in pithed rats, too; in the experiments performed the drug is devoid of central effects even when high doses are given. Chronic pretreatment with midodrine over a longer period reduces the effect of a subsequent single injection of this substance. Because of the results cited above midodrine may be classified as a direct peripheral alpha-adrenergic stimulating agent. alpha-Adrenergic receptor stimulation induced by midodrine can be demonstrated in various smooth muscle organs (blood vessels, nictitating membrane, intestine, pupil, urinary bladder, bronchi). In contrast to other pressor sympathomimetic agents, midodrine is of long duration of action and good efficacy after enteral administration. ST 1059, the main metabolite of midodrine, is an active alpha-adrenergic stimulating agent with a shorter duration of action than midodrine. It is suggested that midodrine is the well-absorbed "transport form", from which ST 1059, the actural pressor agent, is formed enzymatically in organism.

Adrenergic alpha-Agonists↗
PubMed2007

In vivo pharmacodynamic interactions between two drugs used in orthostatic hypotension--midodrine and dihydroergotamine.

A combination of midodrine and dihydroergotamine (DHE) is frequently used clinically in patients suffering from severe orthostatic hypotension (OH). Whereas midodrine acts as a selective, peripheral alpha1-receptor agonist, DHE displays complex pharmacology and can behave as an alpha-adrenergic receptor agonist or antagonist. Surprisingly, the consequences of such a combination on blood pressure have never been investigated. The present study was performed in order to evaluate the pressor effects induced by the administration of both midodrine and DHE in old conscious dogs (n = 6) in experimental condition reproducing autonomic failure-related baroreflex dysfunction (atropine 0.1 mg/kg). For this purpose, we first studied the relative potency and intrinsic activity of each agonist and noradrenaline (NA) for the alpha1-adrenergic receptor. The orders of potency obtained in our study were 0.35, 11 and 400 microg/kg for NA, DHE and midodrine, and intrinsic activity: NA > midodrine > DHE. These results strongly suggest that DHE really acts in vivo as an alpha1-adrenoceptor partial agonist. Afterwards, the pressor effects of coadministration of midodrine (0.4 mg/kg) and DHE (15 microg/kg) were investigated: in one setting, midodrine was first administered, followed by DHE; in another, DHE was first administered, followed by midodrine. Our results show that in conscious dogs, the combination of midodrine and DHE leads to near-complete abolition of the pressor effect induced by the first administered drug. This in vivo proof of such antagonistic effects on blood pressure could explain clinical observations of worsening of OH in humans administered midodrine plus DHE. Although in vivo results obtained in conscious healthy dogs need to be experimentally and clinically confirmed in humans suffering from OH, these results strongly suggest that a midodrine-DHE combined treatment should be avoided in clinical practice.

Adrenergic alpha-1 Receptor Agonists↗
PubMed2006

[Comparative efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes].

AIM: To compare efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes (VVS). MATERIAL AND METHODS: The trial included 35 patients with recurrent VVS confirmed at long passive head-up tilt table test (HTTT) or maximal load bicycle exercise test (MET). These tests were also used for assessing efficacy of atenolol and midodrine in cases when syncopes occur in repeated tests. If recurrent induction of VVS was absent, efficacy of the drugs was assessed by long-term (up to 12 months) clinical observation. Long-term administration of atenolol and midodrine was continued in patients with effect by HTTT and/or MET. Eighteen patients were randomized to take atenolol in a daily dose up to 50 mg, seventeen--to take midodrine in a daily dose up to 15 mg. RESULTS: Efficacy of atenolol by HTTT and MET was 8%, midodrine--57% (p = 0.01). All the patients benefited from the drugs in their long-term regimen. Long-term administration of atenolol induced remission of VVS in 82% cases, midodrine--in 89% (insignificant). Overall efficacy of atenolol was 44%, of midodrine--70% (insignificant). In 5 of 6 patients resistant to atenolol and midodrine monotherapy, combined use of the drugs was effective. Treatment with atenolol, midodrine and their combination prevented VVS in 89% patients. Both short- and long-term courses of atenolol and midodrine were safe in terms of side effects. CONCLUSION: Atenolol and midodrine as well as their combination were highly effective and well tolerated in the treatment of VVS patients.

Adolescent↗
PubMed2025

Real-World Experience of Midodrine in Hospital Setting in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), a progressive disease, is characterized by increased pulmonary vascular resistance (PVR) and leads to right ventricular failure and premature death. PAH therapies aim to reduce PVR; however, these treatments as vasodilators may also result in reduced systemic vascular resistance and mean arterial pressure (MAP), leading to clinical or symptomatic hypotension. Low MAP can limit the administration of optimal dosage of PAH drugs. Midodrine, an oral alpha-1 adrenergic agonist, as a promising intervention, can potentially increase mean MAP and improve tolerance to PAH therapies. RESEARCH QUESTION: Does the use of midodrine improve MAP and allow for simultaneous uptitration of PAH therapy while hospitalized? STUDY DESIGN AND METHODS: A retrospective analysis of 433 patients treated at Houston Methodist Lung Center was undertaken between January 2005 and September 2022. Of these, 57 patients were prescribed midodrine during their hospital stay. We matched 57 patients 1:1 with propensity score matching between patients with PAH not given midodrine (control patients) based on age, sex, World Health Organization functional class, B-type natriuretic peptide, and 6-minute walk distance. RESULTS: Among hospitalized patients with PAH, those receiving midodrine were more likely to undergo uptitration of their PAH medications compared with those not receiving midodrine (n = 30 vs n = 17, respectively; P < .05). Patients on midodrine during hospitalization received higher doses of epoprostenol (P < .001), treprostinil (P < .05), and selexipag (P < .05). Additionally, no adverse effects attributable to midodrine were reported. INTERPRETATION: This study, to our knowledge the first large-scale analysis of PAH data, investigated the use of midodrine in hospitalized patients with PAH. In this single-center study, we share real-world experience of using midodrine to mitigate systemic hypotension, thereby facilitating the uptitration of PAH-targeted therapies.

B-type natriuretic peptide (BNP)↗
PubMed1998

Midodrine: a role in the management of neurocardiogenic syncope.

OBJECTIVE: To determine the benefit of midodrine, an alpha agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope. SETTING: Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope). PATIENTS: 16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt. DESIGN AND INTERVENTION: Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation. RESULTS: Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo (p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects. CONCLUSIONS: Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms.

Adrenergic alpha-Agonists↗
PubMed1998

A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension.

OBJECTIVE: To determine the best therapeutic strategy for the use of midodrine in patients with neurogenic orthostatic hypotension (NOH). BACKGROUND: Midodrine is a peripherally acting alpha-adrenergic agonist useful in the treatment of NOH. However, neither the most effective dosage of midodrine nor the required frequency of administration is established. DESIGN/METHODS: Midodrine dose-blood pressure response, pharmacokinetics, and duration of action were examined in a double-blind, placebo-controlled, four-way crossover trial. Twenty-five patients with NOH were randomized to receive on successive days placebo or midodrine 2.5, 10, or 20 mg. Blood pressures of patients in the supine and standing positions were measured sequentially. A global assessment of the patient's overall symptom improvement after each leg of the study was performed. Blood levels of midodrine and its active metabolite, desglymidodrine, were assayed. RESULTS: Midodrine significantly increased standing systolic blood pressure, with the increase peaking at 1 hour. There was a significant linear relation between midodrine dosage and mean systolic blood pressure. The mean score for global improvement of symptoms was significantly higher for midodrine (10 and 20 mg) compared with placebo. The half-life of desglymidodrine was approximately 4 hours. CONCLUSION: A 10-mg dose of midodrine prescribed two to three times daily is effective in increasing orthostatic blood pressure and ameliorating symptoms in patients with NOH.

Adrenergic alpha-Agonists↗
PubMed1993

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine.

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Adult↗
PubMed2004

Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure.

We tested the hypothesis that the oral alpha1-adrenergic agonist, midodrine, would limit the fall in arterial pressure observed during exercise in patients with pure autonomic failure (PAF). Fourteen subjects with PAF underwent a stand test, incremental supine cycling exercise (25, 50, and 75 W), and ischemic calf exercise, before (control) and 1 h after ingesting 10 mg midodrine. Heart rate (ECG), beat-to-beat blood pressure (MAP, arterial catheter), cardiac output (Q, open-circuit acetylene breathing), forearm blood flow (FBF, Doppler ultrasound), and calf blood flow (CBF, venous occlusion plethysmography) were measured. The fall in MAP after standing for 2 min was similar ( approximately 60 mmHg; P = 0.62). Supine MAP immediately before cycling was greater after midodrine (124 +/- 6 vs 117 +/- 6 mmHg; P < 0.03), but cycling caused a workload-dependent hypotension (P < 0.001), whereas increases in Q were modest but similar. Midodrine increased MAP and total peripheral resistance (TPR) during exercise (P < 0.04), but the exercise-induced fall in MAP and TPR were similar during control and midodrine (P = 0.27 and 0.14). FBF during cycling was not significantly reduced by midodrine (P > 0.2). By contrast, recovery of MAP after cycling was faster (P < 0.04) after midodrine ( approximately 25 mmHg higher after 5 min). Ischemic calf exercise evoked similar peak CBF in both trials, but midodrine reduced the hyperemic response over 5 min of recovery (P < 0.02). We conclude midodrine improves blood pressure and TPR during exercise and dramatically improves the recovery of MAP after exercise.

Adrenergic alpha-Agonists↗
PubMed2006

Treatment of postural tachycardia syndrome: a comparison of octreotide and midodrine.

We assessed the potency of octreotide and midodrine, and their combination, in the treatment of the postural tachycardia syndrome (POTS) and orthostatic intolerance (OI). Nine patients with POTS and six patients with OI stood for up to 1 hour while their HR and BP were monitored. Patients received on separate days, midodrine 10 mg 1 hour before testing, octreotide 0.9 micro g/kg 8 minutes before testing or combination therapy. Standing time in the patients with POTS was 41.2 +/- 8.4 minutes and not improved by midodrine or octreotide, but increased to 56.3 +/- 2.7 (P < 0.01) minutes following combination therapy. The standing heart rate in POTS, 114 +/- 0.7 bpm, was suppressed by midodrine 92.8 +/- 0.7 (P < 0.001), octreotide 90.6 +/- 0.78 (P < 0.001), and combination therapy 84.7 +/- 0.7 (P < 0.001). Combination therapy was better than monotherapy (P < 0.001) but only for the first 10 minutes of standing. Standing time of 36.3 +/- 3.5 minutes in the patients with OI improved with midodrine, octreotide and combination therapy (55.5 +/- 3.1, 56.5 +/- 3.5, and 56.6 +/- 3.3, respectively, P < 0.05 for each). Standing heart rate in OI was 100 +/- .76 bpm; following midodrine it was 80.3 +/- .69 (P < 0.05), following octreotide it was 84.8 +/- .86, and following combination therapy it was 71.2 +/- .9 (P < 0.01). The RR interval versus time area under the curve (The Orthostatic Index) was 21.1 +/- 4 in patients with OI. After midodrine it was 41.4 +/- 3.5 (P < 0.01), after octreotide 40.3 +/- 3.8 (P < 0.01) and after the combination it was 47.3 +/- 4.6 (P < 0.001). Midodrine and octreotide suppressed tachycardia in POTS and improved standing times in OI. The two drugs had similar potencies; combination therapy was not significantly better than monotherapy.

Adult↗
PubMed2001

Usefulness of midodrine in patients with severely symptomatic neurocardiogenic syncope: a randomized control study.

INTRODUCTION: The efficacy of midodrine for the management of patients with neurocardiogenic syncope was assessed prospectively in a randomized control study. METHODS AND RESULTS: Patients who had at least monthly occurrences of syncope and a positive tilt-table test were included in the study. A total of 61 patients were randomly allocated to treatment either with midodrine or with fluid, salt tablets, and counseling. Midodrine was given at a starting dose of 5 mg three times a day and increased up to a dose of 15 mg three times a day when required. Midodrine was given during the daytime every 6 hours. Thirty-one patients were assigned to treatment with midodrine; the other 30 patients were advised to increase their fluid intake and were instructed to recognize their prodromes and abort the progression to syncope. Patients were followed-up for at least 6 months. A quality-of-life questionnaire was administered at the time of randomization and 6 months after. At the 6-month follow-up, 25 (81%) of 31 midodrine-treated patients and 4 (13%) of the 30 fluid-therapy patients had remained asymptomatic (P < 0.001). One patient had to discontinue taking midodrine due to severe side effects and another six patients experienced minor side effects that did not require drug discontinuation. CONCLUSION: 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.

Adrenergic alpha-Agonists↗
PubMed2006

Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives.

Midodrine is an oral drug for orthostatic hypotension. This drug is almost completely absorbed after oral administration and converted into its active form, 1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (DMAE), by the cleavage of a glycine residue. The intestinal H+-coupled peptide transporter 1 (PEPT1) transports various peptide-like drugs and has been used as a target molecule for improving the intestinal absorption of poorly absorbed drugs through amino acid modifications. Because midodrine meets these requirements, we examined whether midodrine can be a substrate for PEPT1. The uptake of midodrine, but not DMAE, was markedly increased in PEPT1-expressing oocytes compared with water-injected oocytes. Midodrine uptake by Caco-2 cells was saturable and was inhibited by various PEPT1 substrates. Midodrine absorption from the rat intestine was very rapid and was significantly inhibited by the high-affinity PEPT1 substrate cyclacillin, assessed by the alteration of the area under the blood concentration-time curve for 30 min and the maximal concentration. Some amino acid derivatives of DMAE were transported by PEPT1, and their transport was dependent on the amino acids modified. In contrast to neutral substrates, cationic midodrine was taken up extensively at alkaline pH, and this pH profile was reproduced by a 14-state model of PEPT1, which we recently reported. 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.

Amino Acids↗
PubMed2004

Taste and smell disturbance with the alpha-adrenoceptor agonist midodrine.

OBJECTIVE: To report a case of a disturbance of taste and smell associated with the alpha-adrenoceptor agonist midodrine. CASE SUMMARY: A 64-year-old white man with autonomic failure was started on midodrine 5 mg/day as treatment for orthostatic hypotension. After 3 months, the dose was increased to 12.5 mg/day, whereupon he noted a new onset of taste and smell disturbance. These symptoms made eating so unpleasant that the man greatly reduced his food intake, leading to significant weight loss. In addition, he experienced well-recognized adverse effects of midodrine, such as scalp pruritus, after the dose increase. All symptoms resolved with a dose reduction of midodrine (to 5 mg/day), and the patient increased his food intake, resulting in a return to his initial body weight. DISCUSSION: Midodrine is commonly associated with dose-dependent adverse effects, such as scalp pruritus and cutis anserina. Disorders of taste and smell have not been previously reported with midodrine, although it has been suggested that other sympathomimetic drugs may have effects on the olfactory threshold. Severe disorders of taste and smell may impact not only on a patient's quality of life, but also on their physical well-being, with significant weight loss being reported in this case. According to the Naranjo probability scale, this patient's taste and smell disturbance was probably associated with midodrine. CONCLUSIONS: The use of midodrine may be associated with taste and smell disturbance. This case suggests that such an association is likely to be dose dependent.

Adrenergic alpha-Antagonists↗
PubMed1993

Pharmacokinetic parameters and haemodynamic actions of midodrine in young volunteers.

In two groups of volunteers pharmacological parameters of the antihypotensive drug midodrine have been investigated. The first group of 12 male healthy volunteers received 2.5 mg midodrine hydrochloride intravenously, as drinking solution or as tablet according to a randomized cross-over design. Plasma and urine samples were analyzed for midodrine and its main metabolite ST 1059 by high-performance liquid chromatography. The mean maximum concentration in plasma for midodrine was 10 ng/ml 20-30 min after oral administration, for ST 1059 5 ng/ml after 1 h. Midodrine was eliminated with a terminal half-life of 0.5 h, ST 1059 with a half-life of 3 hrs. The mean area under the plasma-level vs. time curve (AUC) of ST 1059 after administration of 2.5 mg midodrine i.v. was 28.7 ng x h/ml, and similar for the other formulations which are considered to be bioequivalent. In a second group of 15 volunteers with postural hypotension midodrine (M) as alpha-sympathomimetic drug and oxilofrine (O) as beta-sympathomimetic drug was given i.v. in a randomized double blind study against placebo (P). Blood pressure (BP), heart rate (HR) and circulating catecholamines (CA) were determined before and after injections of the drugs as well as before and during 10 min of tilting. Echocardiographic parameters were obtained at rest before and after the administration of the drugs. Blood pressure remained unchanged at rest and during orthostasis after all agents injected. After oral administration of midodrine heart rate was decreased and systolic blood pressure increased significantly and dose-dependently. M lowered circulating noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Midodrine is effective and safe therapy for intradialytic hypotension over 8 months of follow-up.

Intradialytic hypotension (IDH) is a common and frustrating complication of hemodialysis. Certain end stage renal disease (ESRD) patients recurrently manifest this disabling condition. Both patient-specific factors (autonomic insufficiency, cardiac disease) and dialysis treatment-related factors (ultrafiltration, increased core body temperature) are thought to have significant causative roles. Most therapeutic interventions to date have been either unsuccessful or poorly tolerated. However, recent studies have shown that midodrine, an oral peripheral alpha-1 adrenergic agonist, is an effective and safe therapy for symptomatic IDH in the short-term. We report our experience with the predialysis use of midodrine for IDH in 13 hemodialysis (HD) patients over a 5 to 8 month period. Thirteen patients (8 male, 5 female, mean age 63.9 yrs) with recurrent symptomatic IDH were given midodrine 10 mg orally 30 min before each HD session. Blood pressures (pre-HD BP, lowest intradialytic [ID] BP, post-HD BP) and body weights were tracked for each HD treatment. Values for 10 HD sessions prior to midodrine therapy (Baseline) were compared to values (10 HD sessions each) during the 1st, 5th and 8th month of midodrine therapy. Data were analyzed using ANOVA for repeated measures and paired t-tests, with each patient serving as his/her own control. Patients were monitored for 5 months (n = 13) and 8 months (n = 8), respectively. All lowest intradialytic BPs, post-HD SBPs, and MAPs were significantly improved (p <0.05) on midodrine therapy. This effect was maintained during all periods of follow-up. There was no significant difference in mean albumin, hematocrit, Kt/V, calcium, and sodium between baseline and all periods of follow-up. Mean ultrafiltration volume per HD session was not significantly different than baseline over the course of study. A subjective improvement in hypotensive symptoms was also noted. Importantly, there were no adverse reactions to midodrine in all periods of follow-up. Midodrine appears to be an effective and safe treatment for HD patients with symptomatic IDH, and remains beneficial when used for an extended period of time.

Adrenergic alpha-Agonists↗
PubMed2004

Chiral investigation of midodrine, a long-acting alpha-adrenergic stimulating agent.

Midodrine hydrochloride is a peripheral alpha(1)-adrenoreceptor agonist that induces venous and arterial vasoconstriction. Midodrine, after oral or intravenous administration, undergoes enzymatic hydrolysis and releases deglymidodrine, a pharmacologically active metabolite. Midodrine and deglymidodrine have a chiral carbon in the 2-position. To investigate the bioactivity of racemates and enantiomers of the drug and metabolite, three chromatographic chiral stationary phases, Chiralcel OD-H, Chiralcel OD-R, and alpha(1)-AGP, were evaluated for enantiomeric resolution. Good enantioseparation of midodrine racemate was obtained using the Chiralcel OD-H column. This stationary phase was then used to collect separately the midodrine enantiomers. By alkaline hydrolysis of rac-midodrine and each separated enantiomer, rac-deglymidodrine and its enantiomers were prepared. The control of the enantiomeric purity was carried out by alpha(1)-AGP stationary phase, while the hydrolysis of rac-midodrine and its enantiomers was controlled by capillary electrophoresis using trimethyl-beta-cyclodextrin as chiral selector. The pharmacological activity of the two racemates and the two enantiomeric pairs was tested in vitro on a strip of rabbit descending thoracic aorta. The tests continued that the activity of the drug and metabolite is due only to the (-)-enantiomer because neither of the (+)-enantiomers is active.

Adrenergic alpha-Agonists↗
PubMed1997

Intradialytic hypotension: is midodrine beneficial in symptomatic hemodialysis patients?

Symptomatic hypotension during hemodialysis is a disabling complication in end-stage renal disease (ESRD) patients, especially in certain groups of patients who are at higher risk for this problem. Autonomic dysfunction is thought to play a significant role. We evaluated the efficacy of midodrine, an oral agent with selective alpha-adrenergic agonist activity used in the treatment of neurogenic orthostatic hypotension, on 10 hemodialysis patients with persistent intradialytic hypotension. The patients were given a dose of midodrine (mean dose, 5.5 mg; range, 5 to 10 mg) 30 minutes before each hemodialysis session. We compared blood pressure, pulse, body weight, and laboratory values for 10 consecutive dialysis sessions off and on midodrine therapy. There was a statistically significant improvement in lowest intradialytic systolic blood pressure (from 96.6 to 114.7 mm Hg; P < 0.001), lowest intradialytic diastolic blood pressure (from 53.2 to 59.0 mm Hg; P = 0.002), lowest intradialytic mean arterial pressure (from 67.7 to 77.6 mm Hg; P < 0.001), posthemodialysis systolic blood pressure (from 116.5 to 127.1 mm Hg; P < 0.001), posthemodialysis diastolic blood pressure (from 66.6 to 69.7 mm Hg; P = 0.040), and posthemodialysis mean arterial pressure (from 83.2 to 88.8 mm Hg; P = 0.001) after patients were placed on midodrine. There also was a small but statistically significant decrease in intradialytic pulse rate (from 86.3 to 81 beats/min; P = 0.021) and posthemodialysis pulse rate (from 87.4 to 81.7 beats/min; P = 0.024) after initiation of midodrine therapy. There was no significant difference in any of the prehemodialysis blood pressure measurements or pulse rate off or on midodrine therapy. The improvements in intradialytic and posthemodialysis blood pressure were associated with a uniform subjective improvement in symptoms associated with dialysis hypotension, such as cramps, fatigue, dizziness, and weakness. Other than scalp paresthesia in one patient, no adverse effects were noted. Our results suggest that the administration of a single dose of midodrine before hemodialysis is an effective therapy for intradialytic hypotension. A prospective trial with adequate patient numbers and long-term follow-up would be useful to evaluate this drug's efficacy and safety profile in patients with ESRD.

Administration, Oral↗
PubMed1999

Midodrine and cool dialysate are effective therapies for symptomatic intradialytic hypotension.

Intradialytic hypotension (IDH) is a morbid complication of hemodialysis (HD). Both midodrine, an oral selective alpha1 agonist, and cool dialysate have been reported as useful therapies for this problem. We performed this prospective crossover study to compare the efficacy of these two therapies, alone and in combination, for IDH. The study consisted of a control phase and three treatment phases: midodrine phase (10 mg oral dose pre-HD), cool dialysate phase (35.5 degrees C), and combination therapy phase (midodrine, 10 mg, and dialysate temperature, 35.5 degrees C). Each phase consisted of nine consecutive HD treatments. Eleven patients (six men, five women; mean age, 67.5 years) with known symptomatic IDH were studied. This cohort was followed up in terms of blood pressure measurements (pre-HD blood pressure, lowest intradialytic blood pressure, post-HD blood pressure), weights, laboratory values, and interventions for IDH. The lowest intradialytic blood pressures were significantly better with midodrine and cool dialysate compared with the control phase (systolic blood pressure [SBP], 103.9 +/- 4.1 [mean +/- standard error of the mean] and 102.6 +/- 2.9 v 90.6 +/- 2.5 mm Hg, respectively; P < 0.001), as were the post-HD blood pressures (SBP, 116.9 +/- 4.0 and 118.2 +/- 3.5 v 109.0 +/- 2.1 mm Hg; P < 0.01). In addition, the lowest intradialytic blood pressures were significantly better with the combination phase compared with the control phase (SBP, 103.7 +/- 4.2 v 90.6 +/- 2.5 mm Hg; P < 0.001), as were the post-HD blood pressures (SBP, 122.1 +/- 4.6 v 109.0 +/- 2.1 mm Hg; P < 0.01). There was a significant reduction in the number of nursing interventions performed and volume of saline infused for IDH with midodrine and cool dialysate compared with control. There was a trend toward amelioration of hypotensive symptoms with both therapies. Laboratory values, including Kt/V, did not change significantly with either midodrine or cool dialysate. This prospective study shows that both midodrine and cool dialysate are effective therapies for symptomatic IDH. There does not seem to be additional benefit when these two therapies are used in combination.

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