denopamine and Hypotension

In 1993, we reported the pathophysiology of postprandial hypotension (PPH) in patients with sympathetic dysfunction: a fall of BP resulted from both excess systemic vasodilation and lack of compensatory increase of cardiac output and vascular resistance in the leg arteries. In that article, we showed the beneficial results of combined oral administration of denopamine (a selective beta 1-agonist) and midodrine HCI (a selective alpha 1-agonist) on this condition. The present study was undertaken to further evaluate the efficacy and safety of this agonist combination in autonomic failure (AF) patients with PPH. This was a one-month trial. A total of 13 chronic AF patients received orally 30 mg of denopamine and 12 mg of midodrine three times a day, 30 minutes before each meal. We measured brachial BP every 10 min in the daytime and every 15 min in the nighttime, using a 24-h indirect BP recorder. The combined use of these agonists produced a significant improvement in PPH and maintained a near-normal BP level. In conclusion, the combined administration of denopamine and midodrine three times a day is a well-tolerated and efficacious treatment for PPH.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Aged; Autonomic Nervous System Diseases; Chronic Disease; Drug Therapy, Combination; Ethanolamines; Female; Humans; Hypotension; Male; Middle Aged; Midodrine; Postprandial Period; Treatment Outcome

Food ingestion increases mesenteric blood flow, and then results in a decrease of total vascular resistance (VR). Postprandial hypotension (PPH) may be caused by a lack of compensatory increase in cardiac output (CO) together with a lack of reflex peripheral vasoconstriction to the decrease in total VR. In order to increase CO and VR, we orally administered both denopamine 10 mg (a selective beta 1-adrenergic agonist) and midodrine HCl 4 mg (a selective alpha 1-adrenergic agonist) to six patients with progressive autonomic failure (AF). PPH was well prevented by concomitant administration of both denopamine and midodrine HCl 30 min before oral ingestion of 75 g of glucose, i.e., CO and portal blood flow as well as VR in the lower legs increased. These hemodynamic reactions after oral ingestion of 75 g of glucose were very similar to those in the control subjects. The marked increase in heart rate after drug administration may be the result of cardiac supersensitivity in patients with AF. Combined oral administration of both denopamine and midodrine HCl is a safe and useful management of PPH in patients with AF.

Topics: Administration, Oral; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Adult; Autonomic Nervous System Diseases; Drug Therapy, Combination; Eating; Ethanolamines; Female; Hemodynamics; Humans; Hypotension; Male; Middle Aged; Midodrine

In order to treat postprandial hypotension (PPH), we orally administered a combination of denopamine (10 mg, a selective beta 1-adrenergic agonist) and midodrine-HCl (4 mg, a selective alpha 1-adrenergic agonist) to eight patients with autonomic failure (AF) prior to and after eating. When the patients were given 75 g glucose with 225 ml water without drugs, blood pressure fell subsequently, cardiac output (CO) was unchanged, and vascular resistance of the lower legs (LVR) decreased. However, concomitant administration of denopamine and midodrine-HCl prevented PPH and increased CO and LVR. The portal blood flow was not indifferent to the drugs. A marked increase in heart rate after drug administration was seen in some patients with AF, which reflects the supersensitivity to denopamine. Combined oral administration of denopamine and midodrine-HCl is a safe and useful therapy for PPH in patients with AF.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Aged; Blood Pressure; Cardiac Output; Drug Therapy, Combination; Eating; Ethanolamines; Female; Heart Rate; Humans; Hypotension; Male; Middle Aged; Midodrine; Plethysmography; Receptors, Adrenergic, alpha-1; Receptors, Adrenergic, beta-1; Regional Blood Flow; Vascular Resistance

The pharmacokinetics of denopamine on a hemodialysis day and on an interdialysis day was evaluated in 11 hemodialysis patients. Tmax was the only pharmacokinetical parameter that differed significantly between healthy volunteers and hemodialysis patients. It is suggested that denopamine can be administered to hemodialysis both on hemodialysis days and on interdialysis days without dosage adjustments.

Topics: Adrenergic beta-Agonists; Adult; Ethanolamines; Humans; Hypotension; Male; Regression Analysis; Renal Dialysis

Topics: Acid-Base Equilibrium; Autonomic Nervous System; Calcium; Catecholamines; Droxidopa; Ethanolamines; Female; Humans; Hypotension; Middle Aged; Renal Dialysis; Saline Solution, Hypertonic