The effects of midodrine on the natriuretic response to furosemide in cirrhotics with ascites

Abstract

SUMMARY Background Resistance to loop diuretics is common in patients with ascites. Diminished glomerular filtration rate (GFR) is thought to mediate resistance to loop diuretics. Midodrine, a commonly used alpha-1 agonist, has been shown to improve GFR in non-azotemic patients with cirrhosis. Aim To conduct a randomized, double-blind, placebo-controlled, cross-over study to test the hypothesis that midodrine significantly increases natriuretic response of IV furosemide in non-azotemic cirrhotics with ascites. Methods All subjects participated in both phases, which were (i) furosemide IV infusion + oral midodrine 15 mg administered 30 min before furosemide (ii) furosemide IV infusion + oral placebo administered 30 min before furosemide. Primary outcomes were 6-h urine sodium excretion and 6-h total urine volume. Results A total of 15 patients (men: 8; age: 52.7 ± 7.6 years; serum creatinine: 1.06 ± 0.2 mg/dL) were studied. Total 6-h urine sodium excretion was 109 ± 42 mmol in the furosemide + midodrine treatment phase and was not significantly different from that in the furosemide + placebo treatment phase (126 ± 69 mmol, P = 0.6). Similarly, mean 6-h total urine volume was not significantly different between two groups (1770 ± 262 mL vs. 1962 ± 170 mL, P = 0.25). Conclusions Oral midodrine does not increase the natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites. Orally administered midodrine does not increase natriuretic response to furosemide in non-azotemic cirrhotic patients with ascites.

Review article: prescribing medications in patients with cirrhosis – a practical guide

“…In contrast to loop diuretics, data from Dao and Villeneuve suggest that for triamterene, a potassium‐sparing diuretic, despite having markedly elevated plasma levels in cirrhotics with ascites as compared with healthy volunteers, there was no difference in the magnitude of its diuretic response …”

Pharmacokinetic and Pharmacodynamic Alterations in the Roux-en-Y Gastric Bypass Recipients

“…28 In addition, prior studies have reported timed urine sodium output after oral furosemide administration as a valid PD end point. [20][21][22] …”

“…Previous studies that evaluated drug disposition in bariatric surgery recipients have focused on individual compounds (eg, metformin, sertraline, tacrolimus, and cyclosporine), and they yielded conflicting results. [20][21][22][23][24] The drug-metabolizing profile of an individual can be evaluated by studying the catalytic activity of several CYP enzymes, all in one experimental session using probe substrates that are selective and specific for respective CYP enzymes. The term "pharmacokinetics" (PKs) is defined as the quantitative analysis of the processes of drug absorption, distribution, and elimination that determine the drug concentration achieved with time, whereas "pharmacodynamics" (PDs) deals with the relationship between the drug concentration and both the desired and adverse effects produced with time.…”

Medical management of ascites

“…That is, the more the systemic circulation became vasoconstricted, the better the renal hemodynamics and the greater the renal sodium excretion. However, when midodrine is given to patients with normal hemodynamics and normal renal function, there does not appear to be any additional beneficial effects on renal function or sodium excretion [69].…”