Hydroflumethiazide

331.29

331.29

205-173-8

501CFL162R

757071|44627

DTXSID3023132

C47557

CRYSTALS|White to cream colored, finely divided, crystalline powder

C - Cardiovascular system

2935904000

135

-0.2

Solid

1.5955 (estimate)

272-273 °C

531.6±60.0 °C(Predicted)

275.3ºC

1.55

>49.7 [ug/mL]

Refrigerator

2.2E-11mmHg at 25°C

LD50 in mice (mg/kg): >8000 orally, 750 i.v., 6280 i.p. (Piala)

ODORLESS

1 IN 100 DISPERSION IN WATER: BETWEEN 4.5-7.5

8.9None

8.9|PK1 8.9; PK2 10.7

FORMS WATER-SOL SALTS WITH BASES

NONH for all modes of transport

2

42/43

36

DK9625000

Xn,Xi

UNSTABLE IN ALKALINE SOLN

P261-P280-P284-P304 + P340-P342 + P311

H317-H334

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]|P261, P272, P280, P285, P302+P352, P304+P341, P321, P333+P313, P342+P311, P363, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Overdoses lead to diuresis, lethargy progressing to coma, with minimal cardiorespiratory depression and with or without significant serum electrolyte changes or dehydration.

...DISRUPTION OF URICOSURIC THERAPY BY ADMIN OF DIURETIC WHICH INCR PLASMA URIC ACID LEVELS (THIAZIDES)... /THIAZIDE DIURETICS/|CONCURRENT ADMIN OF THIAZIDE DIURETICS & MONOAMINE OXIDASE INHIBITORS MAY INCR HYPOTENSION. /THIAZIDE DIURETICS/|ELECTROLYTE DISTURBANCES PRODUCED BY /HYDROFLUMETHIAZIDE/ PREDISPOSE PATIENT TO...TOXICITY /OF DIGITALIS GLYCOSIDES/. SEVERE POTASSIUM DEPLETION MAY OCCUR /WITH CONCOMITANT CORTICOSTEROIDS, CORTICOTROPIN & AMPHOTERICIN B/. MAY ANTAGONIZE EFFECTS OF ORAL ANTICOAGULANTS.|/HYDROFLUMETHIAZIDE MAY PROLONG/ NEUROMUSCULAR BLOCKADE /OF/ NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS...TUBOCURARINE CHLORIDE OR GALLAMINE TRIETHIODIDE...RENAL CLEARANCE OF LITHIUM...DECREASED...SERUM LITHIUM /MAY INCREASE IN PATIENTS RECEIVING LITHIUM CARBONATE & LONG-TERM DIURETIC/.|For more Interactions (Complete) data for HYDROFLUMETHIAZIDE (22 total), please visit the HSDB record page.

74%

Used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Also used in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.

Antihypertensive Agents; Diuretics, Thiazide|POTENT ORALLY ADMIN DIURETIC USEFUL IN MGMNT OF EDEMA ASSOC WITH CARDIAC FAILURE, HEPATIC CIRRHOSIS, PREMENSTRUAL TENSION, & STEROID ADMIN. ...ALSO RECOMMENDED FOR TREATMENT OF MILD TO MODERATE HYPERTENSION EITHER ALONE OR IN COMBINATION WITH OTHER ANTIHYPERTENSIVE AGENTS.|EXCEPT FOR FACT THAT SMALLER DOSAGE IS REQUIRED FOR HYDROFLUMETHIAZIDE...NO CONVINCING EVIDENCE OF SIGNIFICANT DIFFERENCES IN THERAPEUTIC, METABOLIC, OR TOXIC OR SENSITIZATION IN EDEMATOUS OR HYPERTENSIVE PT OVER THAT OF PARENT COMPD, FLUMETHIAZIDE, OR PROTOTYPE CHLOROTHIAZIDE.|REFRACTORY CASES MAY REQUIRE AS MUCH AS 200 MG/DAY IN DIVIDED DOSES. DOSAGE SHOULD BE ADJUSTED TO PROVIDE MIN EFFECTIVE DOSE FOR INDIVIDUAL PT.|For more Therapeutic Uses (Complete) data for HYDROFLUMETHIAZIDE (11 total), please visit the HSDB record page.

PERIODIC SERUM ELECTROLYTE DETERMINATION SHOULD BE DONE ON ALL PATIENTS IN ORDER TO DETECT ELECTROLYTE IMBALANCE SUCH AS HYPONATREMIA, HYPOCHLOREMIC ALKALOSIS, & HYPOKALEMIA. /THIAZIDE DIURETICS/|THIAZIDE DIURETICS ARE CONTRAINDICATED IN ANURIA, PATIENTS HYPERSENSITIVE TO THESE & OTHER SULFONAMIDE DRUGS, & IN OTHERWISE HEALTHY PREGNANT WOMEN WITH OR WITHOUT MILD EDEMA. ...SHOULD BE USED WITH CAUTION IN PATIENTS WITH RENAL DISEASE, SINCE THEY MAY PPT AZOTEMIA. /THIAZIDE DIURETICS/|One of the most common adverse effects of the thiazides is potassium depletion which occurs in most patients. Potassium depletion may cause cardiac arrhythmias and is particularly important in patients receiving cardiac glycosides because hypokalemia potentiates the cardiac toxicity (e.g., increased ventricular irritability) of these agents. Potassium concentrations may be especially low in patients with primary or secondary aldosteronism, in patients with a low potassium intake, in those receiving other potassium-depleting drugs, and in patients with other losses of potassium, as in vomiting and diarrhea. Intermittent rather than continuous administration of the thiazides and/or ingestion of potassium-rich foods may reduce or prevent potassium depletion; however, prophylactic administration of a potassium supplement such as potassium chloride solution or a potassium-sparing diuretic may be necessary in patients whose serum potassium concentration is less than about 3 mEq/L. Enteric-coated potassium-containing tablets should not be used because of the possibility of GI ulceration. /Thiazides/|Hypercalcemia may also occur infrequently in patients receiving thiazides, especially in patients receiving vitamin D or having mild hyperparathyroidism. Hypomagnesemia may also occur. /Thiazides/|For more Drug Warnings (Complete) data for HYDROFLUMETHIAZIDE (24 total), please visit the HSDB record page.

3. 3= MODERATELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT FOR 70 KG PERSON (150 LB). /BENZOTHIADIAZIDE DIURETICS/

Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)|Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)|Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA. (See all compounds classified as Sodium Chloride Symporter Inhibitors.)

Hydroflumethiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract|THIAZIDES ARE ABSORBED FROM GI TRACT & OWE THEIR USEFULNESS LARGELY TO THEIR EFFECTIVENESS BY ORAL ROUTE. ABSORPTION IS RELATIVELY RAPID. MOST AGENTS SHOW DEMONSTRABLE DIURETIC EFFECT WITHIN HR AFTER ORAL ADMIN. /THIAZIDE DIURETICS/|IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW PROPORTIONATELY HIGH DEGREE OF BINDING TO PLASMA PROTEINS & ARE REABSORBED BY RENAL TUBULES. ... DRUG PASSES READILY THROUGH PLACENTAL BARRIER TO FETUS. ALL THIAZIDES PROBABLY UNDERGO ACTIVE SECRETION IN PROXIMAL TUBULE. /THIAZIDE DIURETICS/|AFTER IV INFUSION OF HYDROFLUMETHIAZIDE, 2 DISTRIBUTION PHASES, T/2 OF 0.26 & 0.85 HR. AFTER SINGLE ORAL DOSE OF 2 UMOL/KG, T/2 BETA SHORTER THAN AFTER DOSE OF 6 UMOL/KG, WITH MEAN T/2 BETA OF 8.7 & 17.9 HR.|AFTER ORAL ADMIN OF HYDROFLUMETHIAZIDE EVERY 24 HR FOR 7 DAYS, MEAN BIOL T/2 OF 6.85 HR; MEAN T/2 OF METABOLITE WAS 17.7 HR. 0.652 OF DOSE EXCRETED UNCHANGED IN URINE, 0.049 AS METABOLITE. MEAN RENAL PLASMA CLEARANCE OF DRUG WAS 0.356 L/HR/KG.|For more Absorption, Distribution and Excretion (Complete) data for HYDROFLUMETHIAZIDE (8 total), please visit the HSDB record page.

Essentially unchanged|AFTER REPEATED ORAL ADMIN OF 100 MG EVERY 24 HR FOR 7 DAYS TO HEALTHY MALES, METABOLITE 2,4-DISULFAMYL-5-TRIFLUOROMETHYLANILINE DETERMINED.

It appears to have a biphasic biological half-life with an estimated alpha-phase of about 2 hours and an estimated beta-phase of about 17 hours|Half-life is 12-27 hr. /From table/|/Hydroflumethiazide has a/ estimated distribution half-life of approximately 2 hours and an estimated terminal elimination half-life of approximately 17 hours ... .

Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.|...BENZOTHIADIAZIDES HAVE DIRECT EFFECT ON RENAL TUBULAR TRANSPORT OF SODIUM & CHLORIDE...INDEPENDENT OF ANY EFFECT ON CARBONIC ANHYDRASE. /THIAZIDE DIURETICS/|NATURE OF CHEM INTERACTION BETWEEN THIAZIDES & SPECIFIC RENAL RECEPTORS RESPONSIBLE FOR CHLORURETIC EFFECT IS NOT KNOWN; NO CRITICAL ENZYMATIC REACTIONS HAVE BEEN IDENTIFIED. /THIAZIDES/|THIAZIDES INHIBIT REABSORPTION OF SODIUM &...CHLORIDE IN DISTAL SEGMENT. ... AS CLASS...HAVE IMPORTANT ACTION ON EXCRETION OF POTASSIUM THAT RESULTS FROM INCR SECRETION OF CATION BY DISTAL TUBULE. ... GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES, PARTICULARLY WITH IV ADMIN FOR EXPTL PURPOSES. /THIAZIDES/|THIAZIDES MAY DECR EXCRETION OF URIC ACID IN MAN, THUS INCR ITS CONCN IN PLASMA. HYPERURICEMIC EFFECT RESULTS PRIMARILY FROM INHIBITION OF TUBULAR SECRETION OF URATE. ... UNLIKE MOST OTHER NATRIURETIC AGENTS...DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM... /ENHANCE/ EXCRETION OF MAGNESIUM... /THIAZIDES/|For more Mechanism of Action (Complete) data for HYDROFLUMETHIAZIDE (11 total), please visit the HSDB record page.

Thiazide diuretic overdose should be treated by immediate evacuation of the stomach followed by supportive symptomatic treatment and monitoring of serum electrolyte concentrations and renal function. /Thiazide diuretic/

In addition to diuresis and resultant dehydration, overdosage of thiazides may produce lethargy, nausea, weakness, and electrolyte imbalance; lethargy may progress to coma within a few hours with minimal depression of respiratory and cardiovascular function and without evidence of dehydration or serum electryolye change. The mechanism of thiazide-induced CNS depression is unknown. GI irritation and hypermotility may occur, and temporary elevation of the BUN has been reported. Serum electrolyte changes (e.g., hypokalemia, hypochloremia, hyponatremia) may occur, especially in patients with impaired renal function. /Thiazides/|May suppress lactation, but compatible /SRP: with breast feeding/. /Thiazide diuretics, from table/

Diucardin

MARKET PREPN (TABLETS) 50 MG.|Grade: National Formulary grade of chemical.

SOLUBILITY VALUES OF HYDROFLUMETHIAZIDE INCR BY RAISING TEMP IN PRESENCE OF VARIOUS TWEENS.

DETERMINATION OF 2,4-DISULFAMYL-5-TRIFLUOROMETHYLANILINE IN HYDROFLUMETHIAZIDE USING HPLC.|AOAC Method 973.74. Thiazide in Drugs. Spectrophotometric Method. Applicable to benzthiazide, chlorothiazide, methylclothiazide, hydrochlorothiazide, and hydroflumethiazide.

SPECTROFLUOROMETRIC METHOD TO DETERMINE HYDROFLUMETHIAZIDE IN HUMAN PLASMA AND URINE IS DESCRIBED.|LIQUID-CHROMATOGRAPHIC DETECTION OF THIAZIDE DIURETICS IN URINE. ASSAY BY REVERSED-PHASE CHROMATOGRAPHY WITH DETECTION BY UV ABSORPTION.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals