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Scottish Medical Journal Feb 1988The usage of powerful diuretics, such as metolazone, may lead to thrombotic complications.
The usage of powerful diuretics, such as metolazone, may lead to thrombotic complications.
Topics: Axillary Vein; Diuretics; Female; Humans; Metolazone; Middle Aged; Thrombosis
PubMed: 3388002
DOI: 10.1177/003693308803300110 -
American Journal of Kidney Diseases :... Feb 2020Hyponatremia can complicate thiazide use in a minority of susceptible individuals and can result in significant morbidity and even mortality. Risk factors for... (Review)
Review
Hyponatremia can complicate thiazide use in a minority of susceptible individuals and can result in significant morbidity and even mortality. Risk factors for thiazide-associated hyponatremia include age, female sex, and possibly low body mass. A genetic susceptibility has recently been uncovered. Although frequently developing early after thiazide treatment initiation, many cases of hyponatremia present after months or years of use. Many cases are asymptomatic or have mild symptoms, but seizures and/or coma may develop, especially in those with acute onset. The pathophysiology is incompletely understood and includes some combination of excessive fluid intake, cation (sodium and potassium) depletion, osmotic inactivation of sodium, and reduced ability to excrete free water. Reduced distal delivery of filtrate, reduced solute load (urea), direct inhibition of the sodium-chloride cotransporter, and increased collecting duct permeability to water mediated by some combination of antidiuretic hormone, prostaglandins, and thiazides themselves may contribute to this diluting defect. The predominant pathophysiologic mechanism(s) varies from patient to patient. The cornerstone of therapy is cessation of thiazide use, cation repletion, and oral fluid restriction. If severely symptomatic, 3% saline solution may be indicated. Overly rapid correction of chronic hyponatremia must be avoided in all cases.
Topics: Biomarkers; Humans; Hypertension; Hyponatremia; Sodium; Thiazides
PubMed: 31606239
DOI: 10.1053/j.ajkd.2019.07.011 -
Upsala Journal of Medical Sciences 1987Metolazone action was studied 1) in vitro on isolated operculum of Fundulus heteroclitus (active chloride transport) using an Ussing chamber (metolazone conc 500 microM)...
Metolazone action was studied 1) in vitro on isolated operculum of Fundulus heteroclitus (active chloride transport) using an Ussing chamber (metolazone conc 500 microM) and in vivo 2) using the modified Sperber technique in the hen (metolazone infusion rate 0.75-1.2 micrograms/kg/min) and 3) in healthy volunteers using clearance techniques (metolazone infusion rate 10 mg/h). Metolazone reduced (p less than 0.05) short circuit current potential differences with 20% from average control values (p less than 0.05), while direct current resistance was unchanged. This is comparable to thiazide but much lower than loop diuretic effects. True tubular excretion fraction of metolazone before and after novobiocin (2.7 mumol/kg/min coinfusion averaged 14.1 and 4.5%, resp. (p less than 0.01; n = 8). Thus metolazone is partly eliminated by renal tubular secretion. However, the diuretic effect (sodium, chloride and potassium excretion)--and clearances of Cr51-EDTA and I125-Na-o-iodohippurate--were symmetrical, i.e. independent of metolazone urinary excretion rate, as previously shown for thiazides. Renal clearance of metolazone in healthy volunteers. (HPLC-method) averaged 173 +/- 20 ml/min (n = 8). Probenecid (1 g iv.) significantly reduced the renal clearance of metolazone to 33 +/- 7 ml/min and potassium excretion with maximum 30%, while diuretic and saluretic effects were significantly increased with maximum 30%. Thus, also in humans the diuretic effect of metolazone is not coupled to the urinary excretion rate of the drug, but suggests that its diuretic effect is elicited primarily from the peritubular side of the nephron. Probenecid apparently dissociates sodium from potassium excretion effects of metolazone. This implies a luminal, sodium-independent kaliuretic effect of the drug.
Topics: Adult; Animals; Biological Transport, Active; Bufonidae; Chickens; Diuresis; Diuretics; Electrolytes; Electrophysiology; Epithelium; Glomerular Filtration Rate; Humans; In Vitro Techniques; Killifishes; Male; Metolazone; Urinary Bladder
PubMed: 3590397
DOI: 10.3109/03009738709178675 -
Clinical Pharmacology and Therapeutics Aug 1974
Clinical Trial Comparative Study
Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Body Weight; Chlorthalidone; Diuretics; Edema; Female; Humans; Hypertension; Hypokalemia; Male; Middle Aged; Placebos; Quinazolines
PubMed: 4850607
DOI: 10.1002/cpt1974162318 -
Lancet (London, England) Mar 1986
Topics: Aged; Blood Pressure; Captopril; Diuresis; Diuretics; Drug Interactions; Drug Therapy, Combination; Female; Humans; Kidney Diseases; Metolazone; Natriuresis
PubMed: 2869237
DOI: 10.1016/s0140-6736(86)92959-4 -
Journal of Palliative Medicine Feb 2023
Topics: Humans; Metolazone; Furosemide; Conservative Treatment; Heart Failure; Kidney Failure, Chronic
PubMed: 36724315
DOI: 10.1089/jpm.2022.0532 -
European Journal of Clinical... Oct 1985In various clinical situations a poor diuretic response to furosemide may be improved by the addition of metolazone. The mechanism of this additive effect is unclear.... (Clinical Trial)
Clinical Trial
In various clinical situations a poor diuretic response to furosemide may be improved by the addition of metolazone. The mechanism of this additive effect is unclear. The purpose of the present investigation was to establish whether metolazone changes the pharmacokinetics of furosemide and by this mechanism enhances the diuretic effect. Eight volunteers were given an intravenous infusion of 4 mg h-1 of furosemide for 12 h. After 6 h 2.5 mg metolazone were administered orally. The addition of metolazone increased diuresis, urinary excretion of sodium and chloride (P less than 0.01), but decreased urinary excretion of calcium (P less than 0.01), while furosemide excretion remained unchanged. Total body clearance and renal clearance values of furosemide were similar before and after administration of metolazone. Our data confirm the additive diuretic effect of the combination treatment metolazone-furosemide and show for the first time a distinct hypocalciuric action of metolazone, similar to thiazides. Moreover metolazone does not affect the pharmacokinetics of furosemide.
Topics: Calcium; Diuretics; Drug Synergism; Furosemide; Humans; Kinetics; Metolazone; Sodium
PubMed: 3935455
DOI: 10.1111/j.1365-2362.1985.tb00179.x -
European Heart Journal Aug 2023
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Metolazone; Heart Failure
PubMed: 37572039
DOI: 10.1093/eurheartj/ehad463 -
Journal of Clinical Pharmacology Apr 1977The effects of the new diuretic metolazone were studied in ten patients with chronic renal insufficiency and ten with nephrotic syndrome. Patients were maintained on...
The effects of the new diuretic metolazone were studied in ten patients with chronic renal insufficiency and ten with nephrotic syndrome. Patients were maintained on metolazone for up to 44 months. Beneficial effects of treatment included loss of edema and improved control of blood pressure. The natriuretic effect of metolazone facilitated the use of sodium bicarbonate to treat acidosis in several patients. Concurrent administration of metolazone and furosemide produced a dramatic diuresis in one patient resistant to either diuretic alone. Adverse effects of metolazone therapy were those characteristic of other effective diuretics, Including serum electrolyte losses and hyperuricemia. Initial treatment produced small increases in serum creatinine among patients with renal insufficiency, suggesting that GFR was decreased secondary to diuresis-induced volume depletion. The study demonstrates that metolazone is both safe and effective over long periods of time.
Topics: Adult; Aged; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Creatinine; Diuretics; Drug Evaluation; Drug Therapy, Combination; Female; Furosemide; Humans; Kidney Failure, Chronic; Male; Metolazone; Middle Aged; Nephrotic Syndrome; Time Factors
PubMed: 849998
DOI: 10.1177/009127007701700409 -
American Heart Journal Dec 1978
Topics: Benzothiadiazines; Chlorthalidone; Diuretics; Ethacrynic Acid; Furosemide; Humans; Kidney; Kidney Tubules, Distal; Loop of Henle; Metolazone; Nephrons; Sodium Chloride Symporter Inhibitors; Spironolactone; Triamterene
PubMed: 717245
DOI: 10.1016/0002-8703(78)90016-9