Disease relevance of metolazone

• Hypoplastic anemia associated with metolazone [1].
• Captopril/metolazone induced renal failure [2].
• Refractory ascites was defined by the absence of response after 3 months of high doses of diuretics (spironolactone 200 mg/d + furosemide 80 mg/d + metolazone 2.5 mg/d) and the need for repeated paracentesis [3].
• Eighteen patients with hepatic cirrhosis or nephrotic syndrome and having edema and/or ascites were treated during successive periods with metolazone 5 to 40 mg/day, spironolactone 100 mg/day, and with both diuretics concurrently [4].
• Metolazone and spironolactone in cirrhosis and the nephrotic syndrome [4].

High impact information on metolazone

• Metolazone for severe dilated cardiomyopathy refractory to conventional therapy [5].
• We observed that elimination of glycosylation sites in flounder NCC did not affect the affinity of the cotransporter for metolazone [6].
• Also, swapping the amino-terminal domain, the carboxyl-terminal domain, the glycosylation sites, or the entire extracellular glycosylation loop between rat and flounder NCC had no effect upon ions or metolazone affinity [6].
• The function of the Na(+):K(+):2Cl(-) cotransporter was not affected by extracellular pH or by the addition of metolazone, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), or R(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1-H-indenyl-5-yl)-oxy]acetic acid (DIOA) to the extracellular medium [7].
• Injection of 10 ng of FLAG-tagged hNCC cRNA resulted in metolazone-sensitive (22)Na(+) uptake of 3.4 +/- 0.2 nmol Na(+)/oocyte per 2 h [8].

Chemical compound and disease context of metolazone

• Median (range) maximal weight loss was -5.05 (-11.3 to 1.6) kg after the addition of bendrofluazide and -5.6 (-12.2 to 4.8) kg after the addition of metolazone (NS) [9].
• A comparison of the effects of chlorothiazide and of metolazone in the treatment of hypertension [10].
• In the following case report, a 69-year-old woman with multiple medical problems developed toxic epidermal necrolysis after treatment with metolazone and phenytoin [11].

Biological context of metolazone

• Spironolactone alone had little effect, but the addition of metolazone renewed diuresis and natriuresis and resulted in additional substantial weight losses in all patients responsive to metolazone alone [4].
• Metolazone alone produced a marked diuresis, natriuresis, and weight loss in 8 patients [4].
• Metolazone is a diuretic/antihypertensive agent, which has a therapeutic effect on blood pressure (BP) in human essential hypertension without causing a natriuresis [12].
• Higher resolution autoradiography indicated that [3H] metolazone binding sites were localized in a highly specific manner over short lengths of tubular segments, which by their morphology and distribution most likely represented distal convoluted tubules [13].
• Moreover metolazone does not affect the pharmacokinetics of furosemide [14].

Anatomical context of metolazone

• This could be explained by a direct effect of ketones on the respiratory center or a sudden increase in hydrogen ion concentration superimposed on previously chronic alkalemic pH due to the potent combination of furosemide and metolazone [15].
• To elucidate the functional implications of mutations associated with this disorder, metolazone-sensitive (22)Na(+) uptake, subcellular localization, and glycosidase-sensitive glycosylation of human NCC (hNCC) were determined in Xenopus laevis oocytes expressing FLAG-tagged wild-type or mutant hNCC [8].
• Direct effect of metolazone on sodium-dependent transport across the renal brush border membrane [16].
• Metolazone and axillary vein thrombosis [17].

Associations of metolazone with other chemical compounds

• Changes in plasma potassium, urate, bicarbonate, renin, and angiotensin II occurred during treatment with both metolazone and bendroflumethiazide; the only significant difference, however, was in changes in plasma bicarbonate [18].
• To ascertain whether diuretics have an antihypertensive effect independent of natriuresis, 12 stable patients on maintenance hemodialysis underwent a crossover evaluation with hydrochlorothiazide, 50 mg daily, metolazone, 5 mg daily, or placebo in 4-wk treatment periods for 6 mo [19].
• It is concluded that during chronic metolazone administration, the overall activity of the renin angiotensin system was diminished or unchanged [20].
• Most of them appear to lose efficacy as the glomerular filtration rate decreases, except for metolazone and indapamide [21].
• Cough frequency evaluated by the visual analog scale was significantly lower for losartan than for lisinopril and similar to that for metolazone [22].

Gene context of metolazone

• Thus, while long-term treatment with metolazone inhibited the rise in urinary calcium excretion elicited by an oral calcium load, the effect was significant only in patients who had high baseline urinary calcium and PTH values [23].
• The apparent Kd of metolazone for the renal PBR was 3.8 X 10(-7) M [24].

Analytical, diagnostic and therapeutic context of metolazone

• Determination of the diuretic agent metolazone in plasma by high-performance liquid chromatography [25].
• The plasma potassium responses to 1 week's treatment with metolazone 0.625 mg, 1.25 mg and 2.5 mg in combination with spironolactone 50 mg, and metolazone 2.5 alone were examined in a double-blind, crossover study in twelve healthy subjects [26].
• Determination of a Metolazone metabolite in human urine by high-performance liquid chromatography/diode-array detection, high-performance liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometry [27].
• Studies with clearance and micropuncture techniques indicate that metolazone inhibits transport of sodium and phosphate in the proximal tubule [16].
• A novel solid-phase on-line elution HPLC method employing fluorescence detection to measure metolazone in plasma and whole blood has been developed [28].

References