Pharmacodynamics of midodrine, an antihypotensive agent

Zachariah, Prince K.; Bloedow, Duane C.; Moyer, Thomas P.; Sheps, Sheldon G.; Schirger, Alexander; Fealey, Robert D.

doi:10.1038/clpt.1986.101

Cited by 51 publications

(32 citation statements)

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“…Blood-brain barrier permeability and CNS effects are unknown at excessively high blood concentrations, multiple times that of the original study by Zachariah et al [5]. The same study also lists drowsiness as an adverse effect.…”

Section: Discussionmentioning

confidence: 96%

“…Its mechanism of action is to increase peripheral venous resistance and decrease venous capacity, hence increasing the supine and standing blood pressure [4,7]. Notable side effects include compensatory reflex bradycardia [5], urinary urgency or retention, pilomotor reactions [2], pruritus and supine hypertension [1] and risk of bradycardia due to an alpha mediated vagal reflex [3]. Previous studies at therapeutic doses (10 mg) showed minimal or no central nervous system (CNS) side effects as it has poor absorption across the blood-brain barrier [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Early studies measured desglymidodrine peak plasma concentrations in 60 to 90 min ranging from 25 to 56 ng/ml with a mean volume of distribution of 4 L/kg [5]. The elimination half-life of midodrine itself is 30 min whereas desglymidodrine is 3 h. Midodrine is cleared from plasma in 2 h; desglymidodrine can still be detected after 10 h [7].…”

Section: Discussionmentioning

confidence: 99%

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Severe Hypertension and Bradycardia Secondary to Midodrine Overdose

Wong

Robertson

et al. 2016

J. Med. Toxicol.

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The objective of this case is to describe the pharmacokinetics and toxicity of midodrine in overdose. A 20 year old female ingested up to 350 mg midodrine while recovering in hospital from another overdose. She developed vomiting and severe hypertension (blood pressure [BP], 210/ 100 mmHg). Remarkable findings included a heart rate with a range of 43-60 beats/min, spontaneous respirations (20 breaths/min), and oxygen saturations of >95 % on FiO2 25 %, and a GS of 8. She was admitted to intensive care and had a normal non-contrast CT brain. She was treated with a glyceryl trinitrate patch (5 mg) and observed for 36 h with subsequent BP reduction to 124/81 mmHg and improved in conscious state. Midodrine and desglymidodrine concentrations were measured with liquid chromatography tandem mass spectrometry and were detected with 2-h post-ingestion at concentrations of 158.4 and 169.7 ng/mL, respectively. The parent drug concentrations rapidly decreased with an elimination of half-life of 1.6 h, and the metabolite initially increased and then decreased. The peak in blood pressure appeared to coincide with peak metabolite concentrations. Midodrine in overdose can potentially cause severe hypertension and reflex bradycardia but given its short half-life treatment with vasodilator agents and supportive care is sufficient.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Severe Hypertension and Bradycardia Secondary to Midodrine Overdose

Wong

Robertson

et al. 2016

J. Med. Toxicol.

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“…This me tabolite induces vasoconstriction of both arterioles and venous capacitance vessels and thus preventing peripher al venous pooling [9,10], This drug does not possess direct central nervous or cardiac effects and is well absorbed after oral administration. It has been used for many years for the treatment of orthostatic hypotension due to autonomic failure such as Shy-Drager syndrome as well as Bradbury-Eggleston syndrome and has been proved to be effective [11][12][13], Recently, several previous studies [14,15] have shown the efficacy of midodrine in patients with hemodialysis-related hypotension.…”

Section: Introductionmentioning

confidence: 99%

“…M idodrine ( 1 -[2',5'-dimethoxyphenyl-1 ]-2-glycinamido-ethanol( 1 )-hydrochloride) is the prodrug of a specific ai-adrenergic agonist, desglymidodrine [8,9]. This me tabolite induces vasoconstriction of both arterioles and venous capacitance vessels and thus preventing peripher al venous pooling [9,10], This drug does not possess direct central nervous or cardiac effects and is well absorbed after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Midodrine for the Treatment of Intradialytic Hypotension

Lim

Yang²,

Li³

et al. 1997

Nephron

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Recurrent intradialytic hypotension is probably the most severely disabling feature in dialysis patients and the etiology is multifactorial. We assessed the efficacy and safety of midodrine, a selective α₁-adrenergic pressor agent in 12 patients with recurrent intradialytic hypotension. Symptomatic intradialytic hypotension was defined as hypotensive symptoms occurring with a systolic blood pressure < 100 mm Hg or with 25% decrease in systolic blood pressure in those patients with a basal systolic blood pressure of 100 mm Hg. The patients who suffered from symptomatic intradialytic hypotension and failed to improve after cautious body weight adjustment were included into the study. The lowest intradialytic and postdialysis blood pressures were monitored for 18 consecutive dialysis sessions before and after midodrine treatment. Clinical signs and symptoms were also recorded during both periods. With midodrine, the mean ( ± SE) lowest systolic and diastolic blood pressure increased significantly from 68.7 ± 3.1 and 42.8 ± 2.0 mm Hg to 84.7 ± 3.9 and 52.7 ± 2.7 mm Hg respectively during the study (p < 0.01). Midodrine treatment also significantly increased postdialysis systolic and diastolic blood pressures from baseline values of 90.8 ± 3.8 and 58.3 ± 3.0 mm Hg to 113.3 ± 7.1 and 70.6 ± 3.1 mm Hg(p < 0.01 and p < 0.01 respectively). In addition, oral administration of midodrine also significantly decreased the total volume of intravenous fluid administered during symptomatic hypotension. The clinical signs and symptoms during dialysis were improved in all patients. There were no differences in hemoglobin, serum albumin, urea, creatinine, fasting blood sugar or volume removed per dialysis between both periods of the study. In conclusion, our study has demonstrated that midodrine is a safe and effective treatment for the prevention of recurrent intradialytic hypotension if routinely premedicated before each dialysis session.

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