Bendroflumethiazide

Synonyms :
+–3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, 6-Trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide, Bendrofluazide, Bendroflumethiazid, Bendrofluméthiazide, Bendroflumethiazidum, Bendroflumetiazida, Benzhydroflumethiazide

Status : approved

Category

Antihypertensive Agents

Therapeutic Classification

LOW-CEILING DIURETICS, THIAZIDES

CARDIOVASCULAR SYSTEM
DIURETICS
LOW-CEILING DIURETICS, THIAZIDES
Diuretics

Description

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. It has been used in the treatment of familial hyperkalemia, hypertension, edema, and urinary tract disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p810)

Used

For the treatment of high blood pressure and management of edema related to heart failure.

Mechanism Of Action

As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.

Dosage

Form Route Strength
Tablet oral 40 mg
Tablet oral 80 mg
Tablet oral 40; 5 mg/1; mg
Tablet oral 80; 5 mg/1; mg
Tablet oral 5 mg

Pharmacodynamics

Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits 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.

Absorption

Absorbed relatively rapidly after oral administration

Half Life

8.5 hours

Protein Binding

96%

Chemical Classification

This compound belongs to the class of organic compounds known as benzothiadiazines. These are organic compounds containing a benzene fused to a thiadiazine ring (a six-member ring with two nitrogen atoms and a sulfur atom).

Benzothiadiazines

Organic compounds

Organoheterocyclic compounds

Thiadiazines

Benzothiadiazines

Chemical Name

+–3-Benzyl-3,4-dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Brands

name Dosage form Country
Corzide tablet US
Corzide tablet US
Corzide Tab W Nadolol 40mg tablet Canada
Corzide Tab W Nadolol 80mg tablet Canada
Nadolol and Bendroflumethiazide tablet US
Nadolol and Bendroflumethiazide tablet US
Naturetin 5mg tablet Canada

Drug Drug Interactions

  •  Acetohexamide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Acetylcholine  : Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction.
  •  Alfentanil  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Allopurinol  : Thiazide Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Thiazide Diuretics may increase the serum concentration of Allopurinol. Specifically, Thiazide Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol.
  •  Alogliptin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Amifostine  : Antihypertensives may enhance the hypotensive effect of Amifostine.
  •  Amiodarone  : May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers.
  •  Bretylium  : May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.
  •  Bupivacaine  : Beta-Blockers may increase the serum concentration of Bupivacaine.
  •  Buprenorphine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Butabarbital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Butethal  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Butorphanol  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Canagliflozin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Carbachol  : Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction.
  •  Carbamazepine  : Thiazide Diuretics may enhance the adverse/toxic effect of Carbamazepine. Specifically, there may be an increased risk for hyponatremia.
  •  Ceritinib  : Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib.
  •  Chlorpropamide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Codeine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Colesevelam  : May decrease the absorption of Thiazide Diuretics. The diuretic response is likewise decreased.
  •  Cyclophosphamide  : Thiazide Diuretics may enhance the adverse/toxic effect of Cyclophosphamide. Specifically, granulocytopenia may be enhanced.
  •  Diazoxide  : Thiazide Diuretics may enhance the adverse/toxic effect of Diazoxide.
  •  Diazoxide  : May enhance the hypotensive effect of Antihypertensives.
  •  Dihydrocodeine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Dipyridamole  : May enhance the bradycardic effect of Beta-Blockers.
  •  Disopyramide  : May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide.
  •  Dofetilide  : Thiazide Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide Diuretics may increase the serum concentration of Dofetilide.
  •  Dronedarone  : May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6.
  •  Duloxetine  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Duloxetine.
  •  Fentanyl  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Fingolimod  : Beta-Blockers may enhance the bradycardic effect of Fingolimod.
  •  Floctafenine  : May enhance the adverse/toxic effect of Beta-Blockers.
  •  Gliclazide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glimepiride  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Gliquidone  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Glyburide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Heptabarbital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Hexobarbital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Hydrocodone  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Hydromorphone  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Insulin Aspart  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Detemir  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glargine  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Glulisine  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Lispro  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin Regular  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Insulin, isophane  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Ivabradine  : Thiazide Diuretics may enhance the arrhythmogenic effect of Ivabradine.
  •  Ivabradine  : Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.
  •  Lacosamide  : Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.
  •  Levodopa  : Hypotensive Agents may enhance the orthostatic hypotensive effect of Levodopa.
  •  Levorphanol  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Linagliptin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Lithium  : Thiazide Diuretics may decrease the excretion of Lithium.
  •  Mecamylamine  : Sulfonamides may enhance the adverse/toxic effect of Mecamylamine.
  •  Mepivacaine  : Beta-Blockers may increase the serum concentration of Mepivacaine.
  •  Metformin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Methacholine  : Beta-Blockers may enhance the adverse/toxic effect of Methacholine.
  •  Methadone  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Methohexital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Methylphenidate  : May diminish the antihypertensive effect of Antihypertensives.
  •  Midodrine  : Beta-Blockers may enhance the bradycardic effect of Midodrine.
  •  Morphine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Nalbuphine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Nifedipine  : May enhance the hypotensive effect of Beta-Blockers. Nifedipine may enhance the negative inotropic effect of Beta-Blockers.
  •  Obinutuzumab  : Antihypertensives may enhance the hypotensive effect of Obinutuzumab.
  •  Oxcarbazepine  : Thiazide Diuretics may enhance the adverse/toxic effect of Oxcarbazepine. Specifically, there may be an increased risk for hyponatremia.
  •  Oxycodone  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Oxymorphone  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Pentazocine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Pentobarbital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Pentoxifylline  : May enhance the hypotensive effect of Antihypertensives.
  •  Pethidine  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Porfimer  : Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
  •  Primidone  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Ranolazine  : May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
  •  Regorafenib  : May enhance the bradycardic effect of Beta-Blockers.
  •  Remifentanil  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Repaglinide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Reserpine  : May enhance the hypotensive effect of Beta-Blockers.
  •  Risperidone  : Hypotensive Agents may enhance the hypotensive effect of Risperidone.
  •  Rituximab  : Antihypertensives may enhance the hypotensive effect of Rituximab.
  •  Rivastigmine  : May enhance the bradycardic effect of Beta-Blockers.
  •  Ruxolitinib  : May enhance the bradycardic effect of Bradycardia-Causing Agents.
  •  Saxagliptin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Secobarbital  : May enhance the orthostatic hypotensive effect of Thiazide Diuretics.
  •  Sufentanil  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Sulpiride  : Thiazide Diuretics may enhance the adverse/toxic effect of LevoSulpiride.
  •  Tadalafil  : May enhance the antihypertensive effect of Antihypertensives.
  •  Tapentadol  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Tofacitinib  : May enhance the bradycardic effect of Bradycardia-Causing Agents.
  •  Tolbutamide  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Topiramate  : Thiazide Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide Diuretics may increase the serum concentration of Topiramate.
  •  Toremifene  : Thiazide Diuretics may enhance the hypercalcemic effect of Toremifene.
  •  Tramadol  : Analgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
  •  Vardenafil  : May enhance the antihypertensive effect of Antihypertensives.
  •  Verteporfin  : Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
  •  Vildagliptin  : Thiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
  •  Yohimbine  : May diminish the antihypertensive effect of Antihypertensives.

Food Interactions

  • Take with food to increase bioavailability.

Calculated Property

kind Value Source
logP 1.83 ALOGPS
logS -3.3 ALOGPS
Water Solubility 2.14e-01 g/l ALOGPS
logP 1.7 ChemAxon
IUPAC Name 3-benzyl-1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide ChemAxon
Traditional IUPAC Name bendroflumethiazide ChemAxon
Molecular Weight 421.415 ChemAxon
Monoisotopic Weight 421.037781946 ChemAxon
SMILES NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F ChemAxon
Molecular Formula C15H14F3N3O4S2 ChemAxon
InChI InChI=1S/C15H14F3N3O4S2/c16-15(17,18)10-7-11-13(8-12(10)26(19,22)23)27(24,25)21-14(20-11)6-9-4-2-1-3-5-9/h1-5,7-8,14,20-21H,6H2,(H2,19,22,23) ChemAxon
InChIKey InChIKey=HDWIHXWEUNVBIY-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 118.36 ChemAxon
Refractivity 93.68 ChemAxon
Polarizability 36.92 ChemAxon
Rotatable Bond Count 4 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 9.04 ChemAxon
pKa (strongest basic) -3.1 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Solute carrier family 12 member 3 : in Human
  • Calcium-activated potassium channel subunit alpha-1 : in Human
  • Carbonic anhydrase 1 : in Human
  • Carbonic anhydrase 2 : in Human
  • Carbonic anhydrase 4 : in Human