Effects of metolazone: A Synthesis of Findings from 24 Studies

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Original Abstract of the Article

Major Research Findings

Metolazone is a diuretic, saluretic, and antihypertensive drug that belongs to the quinazoline class and has similar medicinal properties to other thiazide diuretics. 9 , 3 , 12 , 17 , , 24 , 11 , 8 , , 4 , 19 , , 20 , 16 , 2 , 18 , 22 , 13 , 15 , , 6 , 7 , 5 , 21 , 1 , 23 , 14 , 10 A number of studies have investigated the diuretic, antihypertensive, and safety profiles of metolazone. The studies have examined the effects of metolazone on urine production, blood pressure, and overall patient tolerability.

The pharmacokinetic properties of metolazone, including its absorption, distribution, metabolism, and elimination, have been investigated in various populations. 9 , 19 These studies have shown that metolazone pharmacokinetics may be influenced by factors such as gender and food intake, highlighting the importance of individual patient characteristics when considering drug dosages.

Benefits and Risks

Benefit Summary

Metolazone has been reported to provide several benefits, including:

  • Diuretic effect, which helps reduce fluid retention and alleviate swelling.
  • Antihypertensive effect, which can help control high blood pressure.
  • In some studies, metolazone has been shown to potentially alleviate coughing associated with ACE inhibitors.

Risk Summary

Metolazone is associated with potential risks, including:

  • Electrolyte imbalances, such as low potassium (hypokalemia) and low sodium (hyponatremia).
  • Potential for kidney function impairment.
  • Risk of pancreatitis in some individuals.

Comparison Across Studies

Commonalities Across Studies

A consistent finding across numerous studies is that metolazone is effective as a diuretic and antihypertensive agent. 9 , 3 , 12 , 17 , , 24 , 11 , 8 , , 4 , 19 , , 20 , 16 , 2 , 18 , 22 , 13 , 15 , , 6 , 7 , 5 , 21 , 1 , 23 , 14 , 10 These studies provide evidence for its therapeutic potential in managing fluid retention and high blood pressure.

Differences Across Studies

Variations exist in the reported effects and side effects of metolazone across different research studies. For instance, metolazone's pharmacokinetics have been shown to vary based on gender and food consumption. Moreover, while electrolyte imbalances, kidney dysfunction, and pancreatitis have been reported as potential side effects, their severity and frequency can differ between studies. 9 , 19 , 6 , 23 , 14

Consistency and Inconsistencies in Results

While metolazone's effectiveness has been confirmed in multiple studies, discrepancies exist in the degree of its effects and the risk of adverse events. These inconsistencies may be attributed to differences in study populations, dosages, treatment durations, or other variables.

Important Considerations for Real-World Applications

Although metolazone offers potential benefits, it is crucial to acknowledge its associated risks. When using metolazone, following a doctor's instructions and adhering to prescribed dosages is paramount. Promptly seeking medical advice if any unusual symptoms arise while taking metolazone is essential.

Limitations of Current Research

There are ongoing gaps in our understanding of metolazone's long-term effects and its impact on various patient groups. Research on long-term metolazone use is limited, and the long-term consequences are not fully understood.

Future Research Directions

Further research is needed to comprehensively evaluate the long-term effects of metolazone and to investigate the relationship between its efficacy and side effects in greater detail. Studies focusing on identifying optimal patient populations for metolazone therapy and determining appropriate dosages are crucial.

Conclusion

Metolazone offers promise for managing fluid retention and high blood pressure, but it is essential to be aware of its potential risks. Close monitoring by a healthcare professional is critical to ensure safe and effective use of this medication.

Given the limitations in current research, further investigation into metolazone's long-term effects and its impact on diverse patient groups is necessary. Continued research will provide valuable insights to optimize the use of metolazone for individual patients.

Literature analysis of 24 papers
Positive Content
16
Neutral Content
3
Negative Content
5
Article Type
3
0
1
3
23
1.

The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone.

Author: RipleyE B, GehrT W, WallaceH, WadeJ, KishC, SicaD A

Blunted sodium excretion
Decreased potassium excretion

Indomethacin or sulindac significantly attenuated the natriuretic response to metolazone, a distal tubular diuretic, likely due to NSAID-induced sodium reabsorption. Indomethacin also significantly decreased urinary potassium excretion.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

2.

Effect of thiazides on colonic NaCl absorption: role of carbonic anhydrase.

Author: GoldfarbD S, ChanA J, HernandezD, CharneyA N

Thiazide side effects

Thiazide diuretics inhibit electroneutral NaCl absorption in the distal colon by inhibiting mucosal carbonic anhydrase.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

3.

The evaluation of the diuretic action of parenteral formulations of metolazone.

Author: CvetanovicIvana, RanadeVasant, MolnarJanos, WheltonAndrew, SombergJohn

Diuretic effect
Natriuretic effect
Furosemide use
Metolazone use

This study aimed to compare the diuretic and natriuretic effects of two parenteral formulations of metolazone and their combination with furosemide. Metolazone, an anthracrene acid derivative, has a dual diuretic effect on the proximal and distal tubule, making it a potential treatment option for critically ill patients who require parenteral diuretic therapy.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Dietary NaCl and KCl do not regulate renal density of the thiazide diuretic receptor.

Author: FanestilD D, VaughnD A, BlakelyP

This study investigated whether the renal density of the thiazide receptor (TZR) is modulated by changes in dietary intake of NaCl or KCl. The study found no evidence that renal TZR density is regulated in response to changes in dietary salt intake.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

BRASH syndrome.

Author: SrivastavaShaurya, KemnicTyler, HildebrandtKyle R

BRASH syndrome

This case report describes a 62-year-old woman with chronic kidney disease stage 4, sleep apnea, and heart failure who presented to the emergency room with weakness and bradycardia due to hyperkalemia and beta-blockers. The patient was diagnosed with BRASH syndrome and treated with potassium-lowering agents, fluids, and dopamine.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction.

Author: MonroyA, PlataC, HebertS C, GambaG

The thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) is the primary pathway for salt reabsorption in the mammalian distal convoluted tubule. When expressed in Xenopus laevis oocytes, rat TSC exhibits high affinity for both cotransported ions. Thiazides affect the affinity of both Na(+) and Cl(-) and their inhibitory effects are influenced by extracellular Na(+) and Cl(-) concentrations. rTSC function is affected by extracellular osmolarity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

9.

Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

Author: LiXueqing, WangRutao, LiuYang, LiuYun, ZhengHeng, FengYabo, ZhaoNa, GengHongbin, ZhangWanzhi, WenAidong

Treat hypertension

This study examined the pharmacokinetic characteristics, safety, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally. It also assessed the effects of food and gender on oral metolazone pharmacokinetic parameters.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

10.

Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide.

Author: SchaefferP, VigneP, FrelinC, LazdunskiM

Antihypertensive effect

Indapamide, a drug used to treat high blood pressure, was found to bind to a membrane form of carbonic anhydrase in pig renal cortex membranes. This binding was inhibited by acetazolamide and thiazide diuretics, suggesting that indapamide's antihypertensive effect may be related to its inhibition of carbonic anhydrase.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension.

Author: KasaiTakatoshi, BradleyT Douglas, FriedmanOded, LoganAlexander G

Lower blood pressure
Reduce apnea-hypopnea

This study investigates the relationship between fluid displacement during sleep and obstructive sleep apnea in hypertensive patients. The researchers hypothesize that intensified diuretic therapy will reduce sleep apnea severity and blood pressure in proportion to the reduction in overnight leg fluid volume.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Tamm-Horsfall protein/uromodulin deficiency elicits tubular compensatory responses leading to hypertension and hyperuricemia.

Author: LiuYan, GoldfarbDavid S, El-AchkarTarek M, LieskeJohn C, WuXue-Ru

Renal dysfunction

Tamm-Horsfall protein (THP) deficiency can cause progressive disturbances in renal functions, resulting in prolonged activation of the renin-angiotensin-aldosterone axis and hyperuricemia.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

13.

Amylin, calcitonin gene-related peptide, and adrenomedullin: effects on thiazide receptor and calcium.

Author: BlakelyP, VaughnD A, FanestilD D

Renal calcium control

Amylin, but not rat calcitonin, increased renal thiazide receptor density and decreased renal calcium excretion in rats. Adrenomedullin increased TZR density modestly but without effect on U(Caex). CGRP did not alter TZR density and tended to increase U(Caex).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

15.

Comparison of metolazone versus chlorothiazide in acute decompensated heart failure with diuretic resistance.

Author: MoranvilleMichael P, ChoiSuji, HoggJennifer, AndersonAllen S, RichJonathan D

Diuretic resistance

The study compared the effectiveness of oral metolazone versus intravenous chlorothiazide as add-on therapy to loop diuretics in hospitalized patients with acute decompensated heart failure (ADHF) and renal dysfunction.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Thiazide-like diuretic drug metolazone activates human pregnane X receptor to induce cytochrome 3A4 and multidrug-resistance protein 1.

Author: BanerjeeMonimoy, ChenTaosheng

Drug metabolism regulation
Drug-drug interactions

This study identified metolazone, a diuretic drug, as an activator of human pregnane X receptor (hPXR). Metolazone activated hPXR-mediated expression of CYP3A4 and MDR1, which could lead to drug-drug interactions. The study recommends caution when using metolazone in patients undergoing combination therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough.

Author: ChanP, TomlinsonB, HuangT Y, KoJ T, LinT S, LeeY S

Hypertension treatment
Reduced cough risk
Cough

Losartan is associated with a decrease in the incidence of cough in patients with previous ACE inhibitor-induced cough. The incidence of cough with losartan (18%) was significantly lower than with lisinopril (97%) and similar to that for metolazone (21%).

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

21.

Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease.

Author: BrionL P, PrimhakR A, Ambrosio-PerezI

Oxygen reduction
Ventilatory support reduction
Complications

This review assessed the risks and benefits of diuretics in preterm infants with chronic lung disease (CLD). The review found that diuretics can reduce the need for oxygen and ventilatory support, but they can also cause complications such as electrolyte disturbances.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

22.

Possible protein binding displacement interaction between glibenclamide and metolazone.

Author: GeorgeS, McBurneyA, ColeA

No significant interaction

Metolazone did not significantly affect the protein binding of glibenclamide. This suggests that metolazone is unlikely to cause a clinically significant increase in the free fraction of glibenclamide in patients receiving both drugs.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

23.

Thiazide Diuretics in Chronic Kidney Disease.

Author: SinhaArjun D, AgarwalRajiv

Hypertension Treatment
Electrolyte Abnormalities

Thiazide diuretics are a type of blood pressure medication. They have been traditionally avoided in people with advanced chronic kidney disease (CKD). This review discusses recent findings that suggest thiazides may be effective in treating hypertension in people with advanced CKD.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

24.

[Diuretics and antihypertensive agents in chronic kidney insufficiency: comparison of the effects of metolazone and furosemide].

Author: GrothH, VetterH, AchermannR, KuhlmannU, SiegenthalerW, VetterW

Lower blood pressure
Difficult to manage
Low potassium

Metolazone and furosemide, two potent diuretic agents, had comparable antihypertensive potency in patients with hypertension and chronic renal failure. However, diuretic monotherapy was successful in only 25% of patients, with the majority requiring additional antihypertensive agents, such as beta-blockers or hydralazine.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : German

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