Delving into the Latest Updates on Chlorothiazide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

6-Chloro-1,1-dioxo-1,2-dihydro-1lambda*6*-benzo[1,2,4]thiadiazine-7-sulfonic acid amide, 6-chloro-7-sulfamoyl-2H-1,2,4-benzothiadiazine 1,1-dioxide, CHLOROTHIAZIDE SODIUM

+ [6]

Target

NCC

Mechanism

NCC inhibitors(Thiazide-sensitive sodium-chloride cotransporter inhibitors)

Therapeutic Areas

Cardiovascular DiseasesDigestive System DisordersUrogenital Diseases+ [1]

Active Indication

EdemaGlomerulonephritisHeart Failure+ [5]

Inactive Indication-

Originator Organization

Novartis Pharma AG

Active Organization

Salix Pharmaceuticals, Inc.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (06 Oct 1961),

EdemaGlomerulonephritisHeart Failure+ [5]

Regulation-

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Structure/Sequence

Molecular FormulaC7H6ClN3O4S2

InChIKeyJBMKAUGHUNFTOL-UHFFFAOYSA-N

CAS Registry58-94-6

Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia
Specific Aims:
Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure
Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure
Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure
The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.

Start Date01 Feb 2016

Sponsor / Collaborator

Vanderbilt University

NCT05840536

/ WithdrawnPhase 4

Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure

Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Diuretics ("water pills") are often given through an IV to accelerate the fluid removal. Furosemide is commonly used for fluid removal, however some patients do not respond well to the medication. There are other diuretics available that can work in conjunction with furosemide and increase the rate of fluid removal. The other "water pills" have slightly different mechanisms of action in the body compared to furosemide and when combined they may increase fluid removal.
The investigators hypothesize that adding chlorothiazide to furosemide will result in quicker and more effective fluid removal in heart failure patients.

Start Date01 May 2014

Sponsor / Collaborator

Ochsner Home Medical Equipment, L.L.C

100 Clinical Results associated with Chlorothiazide

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100 Translational Medicine associated with Chlorothiazide

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100 Patents (Medical) associated with Chlorothiazide

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1,385

Literatures (Medical) associated with Chlorothiazide

12 Dec 2024·JCEM Case Reports

Postprandial Hypoglycemia in a Patient With Clinical Beckwith-Wiedemann Syndrome

Article

Author: London, Bella ; Mani, Bhavapriya ; Corker, Lisa Chiu ; Deng, Lily ; Murray, Alison ; Krishnamurthy, Mansa

AbstractA male neonate exhibited hallmark features of Beckwith-Wiedemann syndrome (BWS) including large for gestational age, macroglossia, multiple ear pits, and umbilical hernia. He had neonatal hypoglycemia, requiring a glucose infusion rate of 9.7 mg/kg/min. Over time, he demonstrated persistent hypoglycemia with point-of-care glucose <60 mg/dL (<3.3 mmol/L) (70-140 mg/dL, 3.9-7.8 mmol/L) prompting a critical sample. A diagnostic fast of 13 hours revealed no hypoglycemia <50 mg/dL. However, he was found to have postprandial hypoglycemia after 2 hours to 58 mg/dL (3.2 mmol/L) (70-140 mg/dL, 3.9-7.8 mmol/L) with low β-hydroxybutyrate of <1.8 mg/dL (<0.17 mmol/L) (>3.6 mg/dL, >1.8 mmol/L) and increased insulin 3.9 μIU/mL (27 pmol/L) (2-13 μIU/mL; 14-90 pmol/L). Low-dose diazoxide (6 mg/kg/day) and chlorothiazide (10 mg/kg/day) were initiated. After 48 hours on diazoxide, all episodes of postprandial hypoglycemia resolved. A safety fast on diazoxide sustained blood glucose >70 mg/dL with a rise in serum β-hydroxybutyrate at 13 and 19 hours. Our case highlights the heterogeneity of hypoglycemia in BWS, either fasting or postprandial. This emphasizes the importance of appropriate screening for both forms of hypoglycemia in patients with BWS and that diazoxide is an effective treatment.

01 Sep 2024·The Journal of the Association of Physicians of India

Loop Diuretics: An Overview of Its History and Evolution.

Review

Author: Tiwaskar, Mangesh ; Nambirajan, Ganesan ; Kashyap, Umesh ; Bhutani, Jaikrit ; Gupta, Abhinav ; Sugumaran, Amarnath ; Khare, Avadhesh Narayan ; Singh, Ajay Pratap ; Srinivas, Sandeep ; Garg, Salil ; Patil, Sachin ; Reddy, Ranga ; Zalte, Nitin ; Pal, Jyotirmoy

The loop of Henle plays a key role in kidney function, especially in retaining solutes and concentrating urine. Diuretic agents, crucial for managing fluid overload and related conditions like hypertension and heart failure (HF), enhance water and electrolyte excretion. The history of diuretics dates back to 1775 with the discovery of Digitalis, evolving significantly with the introduction of chlorothiazide in 1957, which revolutionized diuretic therapy. Loop diuretics, developed in the 1950s and including drugs like torsemide, furosemide, and ethacrynic acid, are potent agents acting on the loop of Henle. They are vital for treating severe fluid overload conditions and require careful monitoring to manage potential side effects.

01 Sep 2024·American Heart Journal Plus: Cardiology Research and Practice

Combination diuretic therapies in heart failure: Insights from GUIDE-IT

Article

Author: Ahmed, Mustafa M ; Guo, Yi ; Al-Ani, Mohammad A. ; Patel, Sandip ; Al-Ani, Mohammad A ; Ahmed, Mustafa M. ; Aranda, Juan M. ; Vilaro, Juan R ; Aranda, Juan M ; Budweg, Jeffery ; Parker, Alex M. ; Vilaro, Juan R. ; Parker, Alex M ; Li, Ang

IntroductionDiuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT.MethodsPatients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups.ResultsThere was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009).ConclusionUse of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.

1

News (Medical) associated with Chlorothiazide

21 Oct 2009

·www.biospace.com

APP Pharmaceuticals Receives Approval for the First Generic Chlorothiazide Sodium for Injection, USP

SCHAUMBURG, Ill.--(BUSINESS WIRE)--APP Pharmaceuticals, Inc., a wholly owned subsidiary of Fresenius Kabi Pharmaceuticals Holding, Inc., (NASDAQ:APCVZ) announced today that it has received approval from the U.S. Food and Drug Administration (FDA) to market Chlorothiazide Sodium for Injection, USP. APP expects to launch Chlorothiazide Sodium for Injection, USP in the fourth quarter of 2009.

100 Deals associated with Chlorothiazide

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External Link

KEGG	Wiki	ATC	Drug Bank
D00519	Chlorothiazide	C03AA04	DB00880

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Edema	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Glomerulonephritis	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Heart Failure	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Hypertension	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Kidney Failure, Chronic	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Liver Cirrhosis	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Nephrotic Syndrome	US	Salix Pharmaceuticals, Inc.	06 Oct 1961
Renal Insufficiency	US	Salix Pharmaceuticals, Inc.	06 Oct 1961

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02606253 (3T, CTgov)	Phase 4	Heart Failure	60	Metolazone (Metolazone)	lbcibnskfo(awlyeejbat) = ofystncgbd tepknhkdgs (sgrrncnjyh, shcibwntix - zovuglildu) View more	-	08 Nov 2019
				Chlorothiazide (Chlorothiazide)	lbcibnskfo(awlyeejbat) = vryyxnlzuu tepknhkdgs (sgrrncnjyh, gkhzhtpnxc - pkvmzssfmp) View more