Polythiazide

439.8818296

439.88

206-468-4

SWY93BD8RL

108161

DTXSID6025939

WHITE, CRYSTALLINE POWDER|CRYSTALS FROM ISOPROPANOL

C - Cardiovascular system

151.63000

4.59280

Crystals or white powder. (NTP, 1992)

1.598g/cm3

202.5 °C

580.1ºC at 760mmHg

304.7ºC

1.566

2.64e-01 g/L

...SHOULD BE STORED IN LIGHT-RESISTANT CONTAINERS...

RATE OF DECOMP INCR WITH INCR IN PH|MELTS BETWEEN 207 °C & 217 °C WITH DECOMP

Its rate of decomposition in solution increases with an increase in pH. (NTP, 1992). Insoluble in water.

Amines, Phosphines, and Pyridines

POLYTHIAZIDE is a sulfonamide derivative. With strong reducing agents will produce hydrogen sulfide gas.

COMMERCIALLY AVAIL TABLETS HAVE EXPIRATION DATE OF 5 YR FOLLOWING DATE OF MFR, WHEN STORED IN LIGHT RESISTANT CONTAINERS

P264, P270, P301+P312, P330, P501

H302

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).

Flash point data for this material are not available, but it is probably combustible. (NTP, 1992)

Fires involving this material may be controlled using a carbon dioxide, dry chemical or Halon extinguisher. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

PATIENTS RECEIVING CHLOROTHIAZIDE & RELATED DIURETICS MAY DEVELOP ELECTROLYTE DISTURBANCES (EG, PRIMARILY HYPOKALEMIA, BUT ALSO HYPOMAGNESEMIA & HYPERCALCEMIA) WHICH MAY ENHANCE THE CARDIOTOXICITY OF DIGITALIS. /THIAZIDE DIURETICS/|USE OF ENTERIC-COATED COMBINATIONS OF POTASSIUM CHLORIDE & THIAZIDE HAS BEEN ASSOC WITH HIGH INCIDENCE OF ULCERATION OF DISTAL JEJUNUM OR ILEUM. /THIAZIDE DIURETICS/|THE CONCURRENT ADMIN OF THIAZIDE DIURETICS & MONOAMINE OXIDASE INHIBITORS MAY RESULT IN HYPOTENSION. /THIAZIDE DIURETICS/|MANY DIABETIC PATIENTS REGULATED BY CHLORPROPAMIDE OR OTHER SULFONYLUREAS EXHIBIT IMPAIRED DIABETIC CONTROL WHEN ANY THIAZIDE DIURETIC IS ADDED TO THE DRUG REGIMEN. THIS EFFECT IS USUALLY, BUT NOT ALWAYS, REVERSIBLE... /THIAZIDE DIURETICS/|For more Interactions (Complete) data for POLYTHIAZIDE (22 total), please visit the HSDB record page.

LD50 Rat ip 400 mg/kg|LD50 Dog oral 450 mg/kg

THIAZIDES...APPEAR IN MILK OF NURSING MOTHER. /THIAZIDES/

Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.

Antihypertensive Agents; Diuretics, Thiazide|THIAZIDES ARE DIURETICS OF CHOICE IN MGMNT OF EDEMA DUE TO MILD-TO-MODERATE CONGESTIVE HEART FAILURE. EDEMA DUE TO CHRONIC HEPATIC OR RENAL DISEASE MAY ALSO RESPOND FAVORABLY. ...HYPERTENSIVE DISEASE... /BENZOTHIADIAZIDE DIURETICS/|ALTHOUGH THIAZIDE DIURETICS...REPORTED TO PRODUCE ELEVATION OF PLASMA RENIN ACTIVITY, CLINICAL SIGNIFICANCE OF THIS HAS NOT BEEN ESTABLISHED. ...HAVE BEEN EFFECTIVE DIURETICS IN SOME PT WITH NEPHROSIS, BUT THEIR OVERALL THERAPEUTIC USEFULNESS...UNPREDICTABLE. /THIAZIDE DIURETICS/|MOST OF THIAZIDES ARE GIVEN IN DIVIDED DAILY DOSES FOR TREATMENT OF HYPERTENSION & FOR DIURESIS. ...POLYTHIAZIDE COULD BE GIVEN LESS FREQUENTLY, SINCE...DURATION OF ACTION /IS/ LONGER THAN 24 HR.|For more Therapeutic Uses (Complete) data for POLYTHIAZIDE (12 total), please visit the HSDB record page.

CLINICAL TOXICITY IS RELATIVELY RARE & USUALLY RESULTS FROM UNEXPECTED HYPERSENSITIVITY. /BENZOTHIADIAZIDE DIURETICS/|...NUMBER OF HYPERSENSITIVITY REACTIONS HAVE BEEN REPORTED /ONE OF SUCH IS/ PANCREATITIS...|...IF PATIENTS DEVELOPS HYPOKALEMIA WHILE TAKING THIAZIDE FOR HYPERTENSION, CLINICIAN SHOULD CONSIDER DECR DOSAGE...RATHER THAN ADDING POTASSIUM SUPPLEMENT. SPECIAL CARE IS NECESSARY TO ENSURE ADEQUATE DIETARY INTAKE OF POTASSIUM BY PATIENTS RECEIVING THIAZIDE & DIGITALIS CONCURRENTLY. /THIAZIDE DIURETICS/|IN PATIENTS, PARTICULARLY THOSE WITH HYPOTENSIVE DISEASE & DECR RENAL RESERVE, MANIFESTATIONS OF RENAL INSUFFICIENCY MAY BE AGGRAVATED AFTER INTENSIVE OR PROLONGED COURSES OF THIAZIDES THAT LEAD TO EXCESSIVE DEPLETION OF FLUID & ELECTROLYTE. /BENZOTHIADIAZIDE DIURETICS/|For more Drug Warnings (Complete) data for POLYTHIAZIDE (15 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 (OR 1 LB). /BENZOTHIADIAZIDE DIURETICS/

As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure

Agents that promote the excretion of urine through their effects on kidney function. (See all compounds classified as Diuretics.)|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 inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA. (See all compounds classified as Sodium Chloride Symporter Inhibitors.)

THIAZIDES ARE RAPIDLY ABSORBED FROM GI TRACT... IN GENERAL, THIAZIDES WITH RELATIVELY LONG DURATIONS OF ACTION SHOW...HIGH DEGREES OF BOTH BINDING TO PLASMA PROTEINS & ARE REABSORBED TO GREATER EXTENT BY RENAL TUBULES. ... POLYTHIAZIDE.../HAS/ LONGER DURATION OF ACTION THAT IS CORRELATED WITH SLOWER EXCRETION.|IN DOGS...ABOUT 30% OF DRUG IS METABOLIZED & ITS METABOLITES ARE EXCRETED PRIMARILY IN URINE. ABOUT 60 TO 90% OF DRUG & METABOLITE ARE EXCRETED WITHIN 24 HR IN DOG; PRIMARILY IN URINE, BUT UP TO 20% MAY BE EXCRETED IN FECES.|THIAZIDES CROSS PLACENTA & APPEAR IN CORD BLOOD. /THIAZIDE DIURETICS/|THIAZIDES...APPEAR IN MILK OF NURSING MOTHER. /THIAZIDES/|STUDY OF NORMAL HUMAN SUBJECTS RECEIVING SINGLE 1 MG ORAL DOSES REVEALED MEAN PLASMA T/2 FOR ABSORPTION & ELIMINATION OF 1.2 & 25.7 HR, RESPECTIVELY. APPROX 25% OF DRUG WAS EXCRETED UNCHANGED IN THE URINE.

YIELDS 5-CHLORO-2-METHYLSULFAMYL-4-SULFAMYLANILINE IN DOG. /FROM TABLE/

Half-life is approx 25 hr. /From table/

As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide 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 polythiazide 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.|DOMINANT ACTION OF THIAZIDES IS TO INCR RENAL EXCRETION OF SODIUM & CHLORIDE & ACCOMPANYING VOL OF WATER. THIS EFFECT IS VIRTUALLY INDEPENDENT OF ACID-BASE BALANCE. /BENZOTHIADIAZIDE DIURETICS/|RENAL ACTIONS OF THIAZIDE DIURETICS DECR EXTRACELLULAR FLUIDS & PLASMA VOL, CARDIAC OUTPUT, & TOTAL EXCHANGEABLE SODIUM IN INDIVIDUALS WITHOUT ANY EVIDENCE OF CARDIAC FAILURE. AT THIS STAGE, SODIUM & WATER DEPLETION APPEARS TO PROVIDE ADEQUATE BASIS FOR ANTIHYPERTENSIVE EFFECT... /BENZOTHIADIAZIDE DIURETICS/|GLOMERULAR FILTRATION RATE MAY BE REDUCED BY THIAZIDES... THIS IS PRESUMABLY RESULT OF DIRECT ACTION ON RENAL VASCULATURE. ...THIAZIDES DECR RENAL EXCRETION OF CALCIUM RELATIVE TO THAT OF SODIUM, SINCE ITS REABSORPTION IS UNAFFECTED IN DISTAL NEPHRON WHEREAS THAT OF SODIUM IS BLOCKED. /BENZOTHIADIAZIDE DIURETICS/|BECAUSE HEMODYNAMIC MEASUREMENTS INDICATE THAT PERIPHERAL VASCULAR RESISTANCE IS DECR BY THIAZIDES, DIRECT ACTION OF THESE DRUGS ON ARTERIOLAR SMOOTH MUSCLE HAS BEEN SUGGESTED. /BENZOTHIADIAZIDE DIURETICS/|For more Mechanism of Action (Complete) data for POLYTHIAZIDE (8 total), please visit the HSDB record page.

SYMPTOMS: Symptoms of exposure to related compounds include lethargy, muscle cramps, acidosis, gastric upset, skin rash, salivary gland obstruction, psychosis, convulsions, hyperuricemia, leukopenia, jaundice, increased hepatic decompensation in hepatic cirrhosis; photosensitization, precipitation or aggravation of diabetes mellitus; ulceration of small intestine from combined therapy with potassium chloride; hypercalcemia, and rarely glomerulonephritis, pancreatitis, thrombocytopenic pupura or agranulocytosis. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits very toxic fumes. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

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/

...HAS CAUSED ACUTE TRANSITORY MYOPIA IN THIRTY-ONE-YR-OLD WOMAN WHO TOOK DRUG AS DIURETIC SEVERAL MO AFTER NORMAL PREGNANCY IN HOPES OF LOSING WT, & NEXT DAY HAD BLURRED VISION... INTRAOCULAR PRESSURE...SUBNORMAL...|ONE HUNDRED MOTHERS HAD RECEIVED ORAL DIURETICS FOR AT LEAST 3 WK PRIOR TO ADMISSION & CONTROLS RECEIVED NONE. NO EFFECTS WERE OBSERVED IN PLATELET COUNTS IN EITHER.|A SINGLE DOSE OF POLYTHIAZIDE UNDER CONDITIONS OF MAXIMAL WATER DIURESIS INCREASED RENAL EXCRETION OF MAGNESIUM.|May suppress lactation, but compatible /SRP: with breast feeding/. /Thiazide diuretics, from table/

Polythiazide

PRODUCT ANALYSIS: ...UV SPECTROPHOTOMETRY.|AOAC Method 974.41. Polythiazide in Drugs. Spectrophotometric Method.|HPLC CHROMATOGRAPHIC ANALYSIS OF POLYTHIAZIDE IN PHARMACEUTICAL TABLET FORMULATIONS.|HPLC DETERMINATION OF POLYTHIAZIDE IN PHARMACEUTICAL DOSAGE FORMS.|For more Analytic Laboratory Methods (Complete) data for POLYTHIAZIDE (7 total), please visit the HSDB record page.

LIQ CHROMATOGRAPHIC DETECTION OF THIAZIDE DIURETICS IN URINE.|ELECTRON-CAPTURE GAS CHROMATOGRAPHIC PROCEDURE FOR MEASURING PLASMA CONCN OF POLYTHIAZIDE DESCRIBED. SENSITIVITY DOWN TO 0.2 NG/ML WAS ACHIEVED.|HPLC DETERMINATION OF POLYTHIAZIDE IN HUMAN PLASMA.|A ASSAY WAS DEVELOPED FOR BENZTHIAZIDE IN PLASMA, URINE, & FECES, USING HIGH PERFORMANCE LIQ CHROMATOGRAPHY. A REVERSE-PHASE COLUMN WAS EMPLOYED USING POLYTHIAZIDE AS AN INTERNAL STD.

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