What Is Chlorothiazide?

Hydrochlorothiazide is a diuretic and antihypertensive drug. Mainly applicable to cardiogenic edema, hepatogenic edema and renal edema: such as nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and edema caused by excessive adrenal cortex hormones and estrogen; hypertension; diabetes insipidus disease. Potassium salts should be appropriately added during long-term application.

Hydrochlorothiazide is a diuretic and antihypertensive drug. Mainly applicable to cardiogenic edema, hepatogenic edema and renal edema: such as nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and edema caused by excessive adrenal cortex hormones and estrogen; hypertension; diabetes insipidus disease. Potassium salts should be appropriately added during long-term application.
In major international and domestic events, diuretics such as hydrochlorothiazide are important detection objects. This medicine does not have an excitatory effect itself, but it can increase urine output by using such drugs, can reduce body weight or dilute illegal drugs in urine before the game, so it is also included in the banned list.
Chinese name
Hydrochlorothiazide
Foreign name
HYDROCHLOROTHIAZIDE
Pinyin name
qng l saì qín
Molecular formula
C7H8ClN3O4S2
Molecular weight
297.74
specification
10mg 25mg

Hydrochlorothiazide compounds

Hydrochlorothiazide Basic Information

Chinese name: Hydrochlorothiazide
Chinese alias: 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide; hydroquineline; dihydrochlorothiazide; double Hydrochlorothiazide; hexachloro-1,1 dioxo-1,2,3,4-4H-1,2,4-benzothiadiazine-7-sulfamine;
English name: hydrochlorothiazide
English alias: 6-Chloro-3,4-Dihydro- (2H) -1,2,4-Benzothiadiazine-7-Sulfonamide 1,1-Dioxide; Hydrochlorothiazide; 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-, 1,1-dioxide;
CAS number: 58-93-5
Molecular formula: C 7 H 8 ClN 3 O 4 S 2
Molecular weight: 297.73900
Exact mass: 296.96400
PSA: 135.12000
LogP: 2.97740

Hydrochlorothiazide physicochemical properties

Appearance and properties: white crystalline powder
Density: 1.693g / cm 3
Melting point: 273 ° C
Boiling point: 577ºC at 760mmHg
Flash point: 302.7ºC
Refractive index: 1.632
Stability: Stable, but incompatible with strong oxidants.
Storage conditions: low temperature, ventilated and dry in warehouse

Hydrochlorothiazide Safety Information

Customs Code: 29350009090
Dangerous Goods Transport Code: UN 1230 3 / PG 2
Danger category code: R22
Safety instructions: S22-S24-S36 / 37-S45-S33-S16-S7
RTECS number: DK9100000
Dangerous goods mark: Xi; T; F [1]
Safety term: S22: Do not inhale dust. S24 / 25: Avoid contact with skin and eyes.

Hydrochlorothiazide production method

5-Chloro-2,4-chlorosulfanilide was obtained from m-chloroaniline by chlorosulfonation, and then reacted with ammonia to produce 5-chloro-2,4-aminosulfanilide, which was finally obtained by distorting formaldehyde [1] .

Hydrochlorothiazide uses

Diuretics can lower blood pressure and diuretic effect, often combined with other antihypertensive drugs. Mainly applicable to cardiogenic edema, hepatogenic edema and renal edema: such as nephrotic syndrome, acute glomerulonephritis, chronic renal failure, and edema caused by excessive adrenal cortex hormones and estrogen; hypertension; diabetes insipidus disease. Potassium salts should be appropriately supplemented during long-term application [1] .

Hydrochlorothiazide Drug Analysis

Method name:
Determination of hydrochlorothiazide-neutralization titration method
Application:
This method uses a titration method to determine the hydrochlorothiazide content.
This method is applicable to the determination of hydrochlorothiazide.
Method principle:
After the test product was dissolved by adding dimethylformamide, an azo violet indicator solution was added, and the solution was titrated with a sodium methoxide titration solution (0.1mol / L) in a nitrogen flow until the solution was just blue. Read the amount of sodium methoxide titrant used, and correct the titration result with a blank test.
Reagent:
Water (newly boiled to room temperature)
Sodium methoxide titration solution (0.1mol / L)
Azo violet indicator liquid
Anhydrous methanol
Base benzoic acid
Dimethylformamide
equipment:
Sample preparation:
Sodium methoxide titration solution (0.1mol / L)
Preparation: Take 150mL of anhydrous methanol (water content below 0.2%), put it in a container cooled by ice water, add 2.5g of freshly cut metal sodium in portions, and completely dissolve, then add anhydrous benzene (water content below 0.02%) ) Moderate to 1000mL, shake well.
Calibration: Take about 0.4g of standard benzoic acid dried in a phosphorus pentoxide dryer under reduced pressure, accurately weigh, add 15mL of anhydrous methanol to dissolve, add 5mL of anhydrous benzene and 1% thymol blue One drop of aqueous methanol solution was titrated to blue with this solution, and the result of the titration was corrected by a blank test. Each 1mL of sodium methoxide titration solution (0.1mol / L) is equivalent to 12.21mg of benzoic acid. Calculate the concentration of the solution based on the consumption of the solution and the amount of benzoic acid taken, that is, obtained.
During the calibration of this liquid, care should be taken to prevent the interference of carbon dioxide and the volatilization of solvents, and it should be recalibrated before each use.
Storage: Keep in a closed container with a titration device to avoid contact with carbon dioxide and moisture in the air.
Azo violet indicator liquid
Take 0.1 g of azo violet, add 100 mL of dimethylformamide to dissolve, and obtain.
Steps:
Accurately weigh about 0.12g of the test product, add 40mL of dimethylformamide, add 3 drops of azo violet indicator solution, and titrate with sodium methoxide titration solution (0.1mol / L) until the solution appears blue. The results were corrected with a blank test. Record the volume (mL) of the sodium methoxide titration solution consumed. Each 1mL of sodium methoxide titration solution (0.1mol / L) is equivalent to 14.89mg of C7H8ClN3O4S2.
Note 1: "Precise weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision weighing" means that the accuracy of the measured volume should conform to the national standard for the volume of the pipette. Precision requirements [2] .

Hydrochlorothiazide Pharmacopoeia Standard

[Source (name), content (potency)]
This product is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide. Calculated on dry basis, C 7 H 8 ClN 3 O 4 S 2 should be 98.0% 102.0%.
[Character]
This product is a white crystalline powder; odorless and slightly bitter.
This product is soluble in acetone, slightly soluble in ethanol, insoluble in water, chloroform or ether; soluble in sodium hydroxide test solution.
[Identification]
(1) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
(2) Take 50mg of this product, put it in a 100ml measuring bottle, add 10ml of 0.1mol / L sodium hydroxide solution to dissolve, dilute with water to the mark, shake well, take 2ml precisely, put it in a 100ml measuring bottle, use 0.01mol / L sodium hydroxide solution was diluted to the mark, shaken, and measured according to the ultraviolet-visible spectrophotometry (Appendix IVA of the Pharmacopoeia Part II of the 2010 edition). It had the maximum absorption at the wavelengths of 273nm and 323nm, the absorbance at the wavelength of 273nm and the The absorbance ratio is 5.4 to 5.7.
(3) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 285).
[Inspection] Take 1.0g of the chloride, add 20ml of water, shake, filter, and separate 10ml of the filtrate. Check according to law (Appendix A). Compare with the control solution made of 5.0ml of standard sodium chloride solution. Thick (0.01%).
The ignition residue shall not exceed 0.1% (Appendix N).
[Content determination] Determination according to high performance liquid chromatography (Appendix V D).
Chromatographic conditions and system suitability tests use octadecylsilane bonded silica as a filler; 0.1 mol / L sodium dihydrogen phosphate-acetonitrile (9: 1) (pH adjusted to 3.0 ± 0.1 with phosphoric acid) as the mobile phase; The detection wavelength was 271 nm, the flow rate was 1.5 ml per minute, and the column temperature was 30 ° C. Take hydrochlorothiazide and chlorothiazide reference substance, dissolve and dilute with mobile phase to make a solution containing 0.04mg per 1ml, and use it as a system suitability test solution. The resolution of the hydrochlorothiazide and chlorothiazide peaks should be greater than 2.0.
Take about 20mg of the product by measurement, weigh it accurately, place it in a 100ml measuring bottle, add 5ml of methanol-acetonitrile (1: 1), shake to dissolve, dilute to the mark with mobile phase, shake well, take 5ml precisely and place In a 25ml volumetric flask, dilute to the mark with mobile phase, shake well, and use it as the test solution. Take 10ml into the liquid chromatograph and record the chromatogram; also take an appropriate amount of hydrochlorothiazide reference substance, accurately weigh it, and make a solution containing about 0.04mg per 1ml by the same method as the reference solution. The same method is used to calculate the peak area according to the external standard method.
[Identification]
Take 50mg of this product, put it in a 100ml measuring flask, dissolve it with 10ml of 0.1mol / L sodium hydroxide solution, dilute with water to the mark, shake well, take 2ml of this solution, put it in a 100ml measuring bottle, and use 0.01mol / L hydrogen Dilute the sodium oxide solution to the mark, shake well, and measure the absorbance in the wavelength range of 250nm to 350nm according to the UV-visible spectrophotometry (Appendix IV A). It has the maximum absorption at the wavelengths of 273nm and 323nm. The absorbance ratio is 5.4 to 5.7.
In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
[Inspection] Take 0.5g of this product, add 25ml of water, shake for 2 minutes, filter, take 10ml of the filtrate, add 0.01ml / L sodium hydroxide solution 0.2ml and methyl red indicator solution 0.15ml, the solution should be yellow . Add 0.4ml of 0.01mol / L hydrochloric acid solution, the solution should be red.
Take about 15mg of this substance, add an equal volume of 2.5ml of methanol and acetonitrile solution to dissolve, and dilute to 10ml with 0.02mol / L potassium dihydrogen phosphate solution (adjust the pH value to 3.2 with phosphoric acid) as the test solution. Accurately measure the appropriate amount of the test solution, add the solvent solution [take an equal volume of 50ml of methanol and acetonitrile mixed with 0.02mol / L potassium dihydrogen phosphate solution (adjust the pH value to 3.2 with phosphoric acid) to 200ml] and make 1ml The solution containing 7.5 g was used as a control solution. Another approximately 15 mg of hydrochlorothiazide and chlorothiazide reference substance were dissolved in 25 ml of a mixed solution of methanol and acetonitrile, and then diluted to 100 ml with a 0.02 mol / L potassium dihydrogen phosphate solution (pH adjusted to 3.2 with phosphoric acid). 5ml of this solution was precisely and evenly measured, and diluted to 100ml with a solvent solution as a system suitability test solution. According to high performance liquid chromatography (Appendix VD). Octadecylsilane-bonded silica gel was used as the filler; mobile phase A was: 0.02 mol / L potassium dihydrogen phosphate solution (pH adjusted to 3.2 with phosphoric acid)-methanol-tetrahydrofuran (940: 60: 10), mobile phase B is: methanol-0.02mol / L potassium dihydrogen phosphate solution (pH adjusted to 3.2 with phosphoric acid)-tetrahydrofuran (500: 500: 50); flow rate is 1.0ml per minute, linear gradient elution; detection wavelength is 224nm. The resolution of the hydrochlorothiazide and chlorothiazide peaks should be greater than 2.5.
Time (minutes)
Mobile phase A (%)
Mobile phase B (%)
0
100
0
22.5
55
45
45
55
45
52.5
100
0
75
100
0
Take 10 ml of the control solution and inject it into the liquid chromatograph, and adjust the detection sensitivity so that the peak height of the main component peak is about 20% to 25% of the full scale. Precisely measure 10 ml each of the solvent solution, test solution and control solution, and inject them into the liquid chromatograph respectively to record the chromatogram. If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak must not be greater than the area of the main peak of the control solution (0.5%), and the sum of the areas of the peaks of each impurity must not be more than twice the area of the main peak of the control solution (1.0%). Peaks smaller than 0.1 times (0.05%) of the main peak area of the control solution may be disregarded.
An appropriate amount of isopropyl alcohol was used for methanol and ethanol, and accurately weighed, and a solution containing about 0.2 mg per 1 ml of water was used as an internal standard solution. Take about 0.25g of this product, weigh it accurately, place it in a 20ml headspace bottle, add 2ml of N, N-dimethylformamide, shake to dissolve, add 1ml of internal standard solution, add water to 10ml, and seal with a lid. , Shake to dissolve, as a sample solution. Appropriate amounts of methanol and ethanol were weighed, accurately weighed, and water was used to make solutions containing about 0.15 mg and 0.25 mg of methanol and ethanol per 1 ml, respectively. 5ml was accurately measured, placed in a 20ml headspace bottle, 2ml of N, N-dimethylformamide was added, 1ml of an internal standard solution was precisely added, and then water was added to 10ml, which was sealed with a cap and used as a reference solution. According to the residual solvent measurement method (Appendix P) test, a chromatographic column (30m × 0.32mm, 1.0m) with an open capillary column and an inner capillary coated with 6% cyanopropyl and 94% methylpolysiloxane was used as the column. Program temperature increase: The initial temperature is 40 ° C. After 8 minutes of holding, the temperature is raised to 45 ° C to 200 ° C for 3 minutes. The detector is FID, the temperature is 250 ° C; the inlet temperature is 200 ° C; the carrier gas is nitrogen, and the flow rate is 2 ml per minute. For headspace injection, the equilibrium temperature of the headspace vial was 80 ° C, the equilibration time was 30 minutes, and the injection volume was 1.0ml. Take the headspace sample test of the reference solution and the test solution, record the chromatogram, and calculate the peak area by the internal standard method. The methanol and ethanol should meet the requirements [3] .

Hydrochlorothiazide Drug Description

Hydrochlorothiazide classification

Urinary System Drugs> Diuretics> Medium Diuretics

Hydrochlorothiazide dosage form

Tablets: 10mg, 25mg, 50mg each.

Hydrochlorothiazide Pharmacology and Toxicology

Effects on water and electrolyte excretion
Hydrochlorothiazide
Diuretic effect, the excretion of urinary sodium, potassium, chlorine, phosphorus and magnesium is increased, while the excretion of urinary calcium is decreased. The action mechanism of this class of drugs mainly inhibits the reabsorption of sodium chloride in the anterior segment of the distal tubule and the proximal tubule (lighter), thereby increasing the Na + -K + exchange in the distal tubule and the collecting duct and increasing K + secretion. Its mechanism of action is not fully understood. This class of drugs can inhibit carbonic anhydrase activity to varying degrees, so it can explain its effect on proximal tubules. This class of drugs can also inhibit phosphodiesterase activity, reduce fatty acid uptake and mitochondrial oxygen consumption in the renal tubules, thereby inhibiting the active reabsorption of Na + and Cl- by the renal tubules.
Antihypertensive effect. In addition to the diuretic and sodium-releasing effects, there may also be extra-renal action mechanisms involved in lowering blood pressure, which may increase the excretion of Na + by the gastrointestinal tract.
Effects on renal hemodynamics and glomerular filtration function
As the renal tubules reduce water and Na + reabsorption, the pressure in the renal tubules increases, and the water and Na + flowing through the distally curved tubules increase, stimulating dense plaques through the tube-bulb reflex, which increases the secretion of renin and angiotensin in the kidney , Cause renal vasoconstriction, renal blood flow decreased, glomerular in and out of the arterioles contraction, glomerular filtration rate also decreased. Decreased renal blood flow and glomerular filtration rate, and no effect on Heinz tincture, are the main reasons for the diuretic effect of this class of drugs is far inferior to tincture diuretics.

Hydrochlorothiazide pharmacokinetics

Oral absorption is rapid but incomplete, bioavailability is 60% to 80%, and eating can increase absorption, which may be related to prolonged drug retention in the small intestine. After 2 hours of oral administration, a diuretic effect is produced, the peak time is 4 hours, and the hypotensive effect is produced after 3 to 6 hours, and the duration of the effect is 6 to 12 hours. Part of this drug binds to plasma proteins, the protein binding rate is 40%, and the other part enters red blood cells and placenta.
After the absorption of the drug, the blood concentration of the elimination phase begins to decrease rapidly, and the blood concentration decrease significantly slows down in the later stage, possibly due to the drug entering the red blood cells in the later stage. Excreted mainly by the urine in its original form. This product has a half-life T1 / 2 of 15 hours and prolonged congestive heart failure and impaired renal function. 50% to 70% of this product is excreted from the urine in its original form and can also be secreted through milk.

Hydrochlorothiazide indications

Edema disease: excrete excess sodium and water in the body, reduce extracellular fluid volume, and eliminate edema. Common ones include congestive heart failure, cirrhotic ascites, nephrotic syndrome, acute and chronic nephritis edema, early chronic renal failure, sodium and water retention caused by adrenal corticosteroids and estrogen treatment.
Hypertension: Can be used alone or in combination with other antihypertensive drugs, mainly for the treatment of essential hypertension.
Central or renal diabetes insipidus.
Nephrolithiasis: It is mainly used to prevent the formation of stones containing calcium salts.
Rhenium can also be used to relieve symptoms of frequent urination, urgency, and dysuria caused by urinary system infections.

Hydrochlorothiazide usage dosage

Commonly used in adults: oral. For edema disease, 25 ~ 50mg each time, once or twice a day, or every other day, or 3 to 5 days a week. For the treatment of hypertension, take 25 ~ 100mg daily, divided into 1-2 times, and adjust the dosage according to the antihypertensive effect.
commonly used in children: oral. Take 1 to 2 mg / kg of body weight or 30 to 60 mg / m2 of body surface area each day, and take it 1 or 2 times, and adjust the dose according to the effect. Infants less than 6 months can reach a daily dose of 3 mg / kg.

Hydrochlorothiazide adverse reactions

Endocrine metabolism
Water and electrolyte disorders are more common, manifested as dry mouth, nausea, vomiting and extreme fatigue, muscle spasm, myalgia, and disappearance of tendon reflexes.
Hyperglycemia. This product can reduce glucose tolerance and increase blood sugar and urine glucose, which may be related to inhibiting insulin release. Generally, patients can recover after stopping the drug, but the condition of diabetic patients can be aggravated.
Hyperuricemia. This product can interfere with renal tubular excretion of uric acid, a few can induce gout attacks. Because there is usually no joint pain, hyperuricemia is easily overlooked. You can recover after stopping the medicine.
Long-term medication can increase blood cholesterol, triacylglycerol, low-density lipoprotein, and very low-density lipoprotein levels, reduce high-density lipoprotein, and possibly promote atherosclerosis.
Cardiovascular System
Diminished organ blood flow due to diuresis often causes dizziness. The elderly may have ischemia, such as mesenteric infarction or transient cerebral ischemia. Rare orthostatic hypotension.
Blood system
Hemolytic anemia, aplastic anemia, thrombocytopenia, bone marrow dysplasia, and granulocytopenia are rare.
Allergic reaction
Visible skin rash, urticaria, and photosensitive dermatitis, the latter symptoms can be expressed as a chronic photosensitive state, will continue for six months after stopping the drug. This photosensitivity is cross-reactive with sulfa drugs or phenothiazines.
Other adverse reactions
Cholecystitis, pancreatitis, sexual dysfunction, light sensitivity, and color vision disorders are rare. Long-term application of this product can appear symptoms of fatigue, burnout, dizziness, lack of appetite, nausea, vomiting, diarrhea, and decreased blood pressure. The symptoms can disappear after reducing or adjusting the electrolyte imbalance.

Hydrochlorothiazide precautions

Cross-allergy: Cross-reactions with sulfa drugs, furosemide, bumetanib, and carbonic anhydrase inhibitors.
Interference to diagnosis: can cause impaired glucose tolerance, blood glucose, urine glucose, blood bilirubin, blood calcium, blood uric acid, blood cholesterol, triglycerides, increased low-density lipoprotein concentration, blood magnesium, potassium, sodium, and Reduced urine calcium.
(3) Use with caution when:
Those who have no urine or severe renal dysfunction, because of the poor effect of this class of drugs, can cause drug accumulation and increased toxicity when used in large doses;
diabetes;
Hyperuricemia or history of gout;
For patients with severe liver damage, water and electrolyte disorders can induce liver coma;
Hypercalcemia;
Hypokalemia;
Lupus erythematosus, which can aggravate the condition or induce activity;
pancreatitis;
Sympathectomy (hypertensive effect);
Babies with jaundice.
Follow-up inspection:
blood electrolyte;
blood sugar;
blood uric acid;
blood muscle enzymes, urea nitrogen;
Blood pressure.
Medication should be started from the minimum effective dose to reduce the occurrence of side effects and reduce reflex renin and aldosterone secretion.
Patients with a tendency to hypokalemia should, as appropriate, supplement potassium or combine it with potassium-preserving diuretics.
Medication for pregnant and lactating women
can pass through the placental barrier. No preventive effect on hypertension syndrome. Therefore, pregnant women should be used with caution.
Not suitable for lactating women.

Hydrochlorothiazide drug interactions

Adrenocorticotropic hormone, adrenocorticotropic hormone, estrogen, amphotericin B (intravenous medication) can reduce the diuretic effect of this medicine and increase the chance of electrolyte disturbances, especially hypokalemia.
Non-steroidal anti-inflammatory analgesics, especially indomethacin, can reduce the diuretic effect of this drug, which is related to the former's inhibition of prostaglandin synthesis.
(3) Combined with sympathomimetic drugs, the diuretic effect is weakened.
Cholelenide (cholestyramine) can reduce gastrointestinal absorption of this drug, so it should be taken 1 hour before or 4 hours after oral cholestyramine.
Combined with dopamine, the diuretic effect is strengthened.
When combined with antihypertensive drugs, the diuretic and antihypertensive effects are strengthened.
When combined with anti-gout drugs, the latter should be adjusted in dosage.
The weakening of anticoagulant effects is mainly due to the decrease in body plasma volume and the increase of blood coagulation factor levels after diuresis, coupled with the improvement of liver blood supply by diuresis, and increased synthesis of coagulation factors.
Reduce the effect of hypoglycemic agents.
When digitalis, amiodarone, etc. are used in combination with this drug, side effects due to hypokalemia should be carefully avoided.
Rhenium is used in combination with lithium preparations, because this drug can reduce the elimination of lithium from the kidneys and increase the renal toxicity of lithium.
Ulotropine is used in combination with this medicine, its conversion to formaldehyde is inhibited, and the efficacy is reduced.
The effect of enhancing non-depolarizing muscle relaxants is related to the decrease of serum potassium.
Combined with sodium bicarbonate, the chance of hypochlorine alkalosis increases.

Hydrochlorothiazide overdose

Gastric lavage should be performed as early as possible, support should be given symptomatically, and blood pressure, electrolytes and renal function should be closely followed.

Hydrochlorothiazide poisoning

Hydrochlorothiazide (dihydrochlorothiazide, dihydrochlorothiazide) inhibits the reabsorption of sodium and chloride ions in the ascending branch cortex of the renal tubular pulp, and promotes the excretion of chloride, sodium, and potassium ions, and produces a diuretic effect. It is mainly used for the treatment of edema caused by various reasons, such as edema, ascites and hypertension caused by diseases such as heart, liver and kidney. Oral absorption is rapid and complete, with a half-life of about 10 hours, excreted by the kidneys in its original form, and 70% excreted in 24 hours. The oral LD50 of the mouse is> 800mg / kg, and the intravenous is 590mg / kg; the oral LD50 of the rat is> 2750mg / kg. The usual amount is oral: 25 ~ 50mg each time for edema treatment, 1 ~ 2 / d; 50 ~ 75mg / d for hypertension treatment, divided into 2 morning and evening. Mainly affect water and salt metabolism, leading to hypokalemia and allergic reactions.
Clinical manifestation
Adverse reactions are as follows:
Central nervous system
Such as fatigue, dizziness, dizziness, weakness, weakness, paresthesia, disappearance of tendon reflexes, insanity, delirium, convulsions, shock, coma, etc.
2. Digestive system
Dry mouth, thirst, nausea, vomiting, anorexia, flatulence, diarrhea, acute pancreatitis, jaundice and cholestatic hepatitis, patients with liver cirrhosis can induce hepatic encephalopathy.
3. Circulatory system
Palpitations, orthostatic hypotension, arrhythmia due to hypokalemia.
4. Blood system
Granulocytosis, leukopenia, thrombocytopenia, aplastic anemia, hemolytic anemia.
5. Metabolic abnormalities
Long-term use can cause hyponatremia, hypochloremia, hypokalemia, and hyperuricemia (induced gout), hyperglycemia, urine glucose, transient hyperlipidemia, and occasionally hypercalcemia.
6. Other
Allergic reactions, such as rash, pruritus, photosensitive dermatitis, acute nephritis, blurred vision, yellow vision, muscle spasm, acute pulmonary edema, and interstitial aqueous pneumonia. Some patients have renal colic with hematuria and crystal urine.
treatment
The main points of treatment for hydrochlorothiazide poisoning are:
1. Those who take large doses of poisoning by accident should immediately induce vomiting and gastric lavage.
2. Potassium supplementation, appropriate intravenous drip potassium supplementation according to the measured blood potassium value.
3. Properly replenish fluids and correct water and electrolyte disorders.
4. Other: symptomatic treatment [4] .

Hydrochlorothiazide storage

Shaded and sealed.

Hydrochlorothiazide substance toxicity

Toxicity data from literature and journals
Numbering
Toxicity type
testing method
Test object
Dosage used
Toxic effect
1
Acute toxicity
oral
Adult woman
34884 ug / kg / 30D-I
1. Behavioral toxicity-changes in exercise behavior (specific analysis)
2. Hematological toxicity-changes in serum composition (such as TP, bilirubin, cholesterol)
3. Nutrition and metabolic system toxicity-changes in potassium concentration
2
Acute toxicity
oral
Adult male
75 mg / kg / 30W-I
1. Behavioral toxicity-changes in exercise behavior (specific analysis)
2. Behavioral toxicity-muscle weakness 3. Gastrointestinal toxicity-other changes
3
Acute toxicity
oral
Adult woman
500 ug / kg
1. Lung, chest or respiratory toxicity-acute pulmonary edema 2. Lung, chest or respiratory toxicity-other changes
4
Acute toxicity
oral
Adult woman
500 ug / kg
1. Nutrition and metabolic system toxicity-elevated body temperature
5
Acute toxicity
oral
Adult woman
2500 ug / kg / 5D-I
1. Behavioral toxicity-coma 2. Nutritional and metabolic system toxicity-other changes
6
Acute toxicity
oral
Adult male
12857 ug / kg / 9D-I
1. Behavioral toxicity-convulsions or seizure thresholds affected 2. Gastrointestinal toxicity-nausea, vomiting 3. Nutrition and metabolic system toxicity-other changes
7
Acute toxicity
oral
Adult woman
500 ug / kg
1. Vascular toxicity-decreased blood pressure regulation 2. Lung, chest or respiratory toxicity-acute pulmonary edema 3. Lung, chest or respiratory toxicity-cyanosis
8
Acute toxicity
oral
Adult woman
2 mg / kg / 12H-I
1. Nutrition and metabolic system toxicity-changes in sodium concentration 2. Nutrition and metabolic system toxicity-changes in chlorine concentration
9
Acute toxicity
oral
Adult woman
500 ug / kg
1. Lung, chest or respiratory toxicity-acute pulmonary edema 2. Gastrointestinal toxicity-nausea, vomiting
10
Acute toxicity
oral
Adult woman
250 ug / kg
1. Cardiotoxicity-increased heart rate without blood pressure drop 2. Vascular toxicity-shock 3. Lung, chest or respiratory toxicity-acute pulmonary edema
11
Acute toxicity
oral
Rat
2750 mg / kg
Detailed effects are not reported other than lethal dose
12
Acute toxicity
Intraperitoneal injection
Rat
234 mg / kg
Detailed effects are not reported other than lethal dose
13
Acute toxicity
Subcutaneous injection
Rat
1270 mg / kg
Detailed effects are not reported other than lethal dose
14
Acute toxicity
Intravenous injection
Rat
990 mg / kg
Detailed effects are not reported other than lethal dose
15
Acute toxicity
oral
Mouse
1175 mg / kg
Detailed effects are not reported other than lethal dose
16
Acute toxicity
Intraperitoneal injection
Mouse
578 mg / kg
Detailed effects are not reported other than lethal dose
17
Acute toxicity
Subcutaneous injection
Mouse
1470 mg / kg
Detailed effects are not reported other than lethal dose
18
Acute toxicity
Intravenous injection
Mouse
590 mg / kg
1. Peripheral neurotoxicity-spastic paralysis or no change in sensation 2. Behavioral toxicity-convulsions or seizure thresholds affected 3. Lung, chest or respiratory toxicity-other changes
19
Acute toxicity
Not reported
Mouse
1100 mg / kg
Detailed effects are not reported other than lethal dose
20
Acute toxicity
Intravenous injection
dog
250 mg / kg
Detailed effects are not reported other than lethal dose
twenty one
Acute toxicity
Intravenous injection
rabbit
461 mg / kg
Detailed effects are not reported other than lethal dose
twenty two
Chronic toxicity
oral
Rat
18540 mg / kg / 60D-I
1. Cerebral toxicity-changes in blood circulation (such as bleeding or thrombus)
2. Hepatotoxicity-Other changes 3. Kidney, ureter and bladder toxicity-Changes in renal tubules (including acute renal failure, acute tubular necrosis)
twenty three
Chronic toxicity
oral
Rat
499 mg / kg / 26
1. Hematological toxicity-other changes 2. Biochemical toxicity-Inhibition of transaminase activity and changes in the spatial structure of transaminase 3. Chronic disease-related toxicity-changes in ovarian weight
twenty four
Chronic toxicity
oral
Rat
30 mg / kg / 30D-C
1. Kidney, ureter and bladder toxicity-hematuria present 2. Hematological toxicity-changes in white blood cell count 3. Chronic disease-related toxicity-death
25
Chronic toxicity
oral
Rat
4550 mg / kg / 13W-I
1. Liver toxicity-changes in liver weight 2. Kidney, ureter and bladder toxicity-other changes 3. Nutrition and metabolic system toxicity-weight loss or rate of weight loss
26
Chronic toxicity
oral
Mouse
273 mg / kg / 13W-I
1. Kidney, ureter and bladder toxicity-changes in renal tubules (including acute renal failure, acute tubular necrosis)
2. Chronic disease-related toxicity-death
27
Mutation toxicity

E.coli
5 mg / L

28
Mutation toxicity

Aspergillus nidulans
1 gm / L

29
Mutation toxicity

Mouse lymphocyte
500 mg / L

30
Mutation toxicity

Hamster lung
500 mg / L / 48H

31
Mutation toxicity

Hamster Ovary
43 mg / L

32
Carcinogenicity
oral
Mouse
309 mg / kg / 2Y-C
1. Carcinogenicity-may be carcinogenic (according to RTECS standards)
2. Liver toxicity-tumor
33
Reproductive toxicity
oral
Rat
10 mg / kg, 6-15 days after conception
1. Reproductive toxicity-affects the mother
[5-30]

Hydrochlorothiazide sports ban

Hydrochlorothiazide (qng l saì qín) is a diuretic and antihypertensive drug. It is mainly applicable to cardiogenic edema, hepatogenic edema and renal edema: such as nephrotic syndrome, acute glomerulonephritis and so on.
Hydrochlorothiazide has a diuretic effect. The clinical effect of diuretics is to increase urine output by affecting the urine production process of the kidneys, thereby alleviating or eliminating symptoms such as edema.
At present, the purpose of taking by athletes is to quickly remove water from the body and reduce weight; increase urine output to reduce other stimulant metabolites in body fluids and excretion as quickly as possible to cause false negative results of drug tests; accelerate other stimulants and other metabolism The excretion process of the product, thereby alleviating certain side effects.
This medicine does not have an excitatory effect itself, but it can increase urine output by using such drugs, can reduce body weight or dilute illegal drugs in urine before the game, so it is also included in the banned list.
The earliest drugs that athletes take to improve their performance are mostly stimulant drugs-stimulants, so although other types of drugs they later use are not all excitatory (such as diuretics), and some are even inhibitory (such as -blockers), the narcotic drugs used in sports are still used as stimulants. Nowadays, stimulants are no longer simply referring to those drugs that have an stimulating effect, but are actually a collective term for banned drugs in sports [31] .

Hydrochlorothiazide Expert Reviews

Hydrochlorothiazide is suitable for all kinds of edema. Hydrochlorothiazide should be tried first, because its diuretic effect is relieved, and it will not cause serious water and electrolyte disorders. Those who are ineffective will be replaced with other diuretics. It has a satisfactory effect on cardiogenic edema, renal edema and edema caused by liver disease [32] .

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