135-09-1NS(=O)(=O)c1cc2c(cc1C(F)(F)F)NCNS2(=O)=ODMDGGSIALPNSEE-UHFFFAOYSA-NHydroflumethiazide is a benzothiadiazine consisting of a 3,4-dihydro-HH-1,2,4-benzothiadiazine bicyclic system dioxygenated on sulfur and carrying trifluoromethyl and aminosulfonyl groups at positions 6 and 7 respectively. A diuretic with actions and uses similar to those of hydrochlorothiazide. It has a role as a diuretic and an antihypertensive agent. It is a thiazide and a benzothiadiazine.
135-09-1DTXSID3023132CHEMBL1763CHEBI:5784Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Cardiovascular system -> Diuretics
log Kow = 0.36
-0.2
0.36
CRYSTALS
White to cream colored, finely divided, crystalline powder
Solubility (mg/ml) at 25 °C: acetone >100; methanol 58; acetonitrile 43; water 0.3; ether 0.2; benzene <0.1.
INSOL IN ACID
Soluble in dilute alkali but unstable in alkaline solutions.
SOL IN ALC; FREELY SOL IN ACETONE
8.58e-01 g/L
Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Thiazide Diuretics
FDA approved drugs -> Active ingredient
FDA approved drugs -> Active ingredient
Pharmaceuticals
272-273
272-273 °C
272 - 273 °C
안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.
Danger
H317 (97.6%): May cause an allergic skin reaction [Warning Sensitization, Skin]
P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
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).
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.
C - Cardiovascular system
QC - Cardiovascular system
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.
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/
현재 필터 조건에 해당하는 반응 기록이 없습니다.
불러오는 중…
8.9
PK1 8.9; PK2 10.7
White Solid
...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.
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/
Drug Induced Liver Injury Rank (DILIrank 2.0)
Hydroflumethiazide
Ambiguous-DILI-concern
2
Adverse reactions
DOI:10.1016/j.drudis.2016.02.015
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).
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.
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 ... .
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.
501CFL162R
HYDROFLUMETHIAZIDE
Physiologic Effects [PE] - Increased Diuresis
Established Pharmacologic Class [EPC] - Thiazide Diuretic
Chemical Structure [CS] - Thiazides
Hydroflumethiazide is a Thiazide Diuretic. The physiologic effect of hydroflumethiazide is by means of Increased Diuresis.
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.
Agents that promote the excretion of urine through their effects on kidney function.
Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.
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.
HOLDREDGE ET AL, J AM CHEM SOC 81, 4807 (1959); CLOSE ET AL, J AM CHEM SOC 82, 1132 (1960); YALE ET AL J AM CHEM SOC 2042; NOVELLO ET AL, J ORG CHEM 25, 970 (1960). NUMEROUS PATENTS, EG, LUND ET AL, US PATENT 3,254,076 (1966 TO LOVENS).
m-Aminobenzotrifluoride + chlorosulfonic acid + ammonia + formaldehyde (chlorosulfonation/sulfonamide formation/carbonyl condensation).
MARKET PREPN (TABLETS) 50 MG.
Grade: National Formulary grade of chemical.
용도Labelled Hydroflumethiazide. Antihypertensive; diuretic.