Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Thiazide diuretic (saluretic) of medium strength and duration of action. It has a weaker diuretic effect compared to furosemide. Reduces the reabsorption of sodium, chlorine and water from primary urine into the blood in the proximal part of the tubules. Removes K+, Mg2+, bicarbonates and phosphates, retains Ca2+. The diuretic effect begins to appear after 2 hours, maximum after 4 hours, the duration of the diuretic effect is 10-12 hours. Due to the expansion of arterioles and a decrease in the volume of blood volume, it lowers blood pressure. The hypertensive effect appears after 4 days. In diabetes insipidus, it reduces the volume of urine while increasing its concentration.
Pharmacokinetics
60-80% absorbed from the gastrointestinal tract. 40% binds to blood proteins, where its maximum concentration is determined after 2-5 hours. The half-life is 6-15 hours. Most (95%) are excreted unchanged by the kidneys. Penetration of the drug through the placental barrier was noted.
Contraindications
- severe forms of diabetes mellitus ;
- hypersensitivity to the drug or to sulfonamides ;
- severe renal failure;
- children's age (up to 2 years);
- anuria;
- pregnancy in the first trimester;
- Addison's disease;
- gout.
It is prescribed with caution when the level of potassium and sodium decreases and calcium in the blood increases, with ischemic heart disease, liver cirrhosis, when taking cardiac glycosides, and in the elderly.
Special instructions for the use of the drug Hydrochlorothiazide
During long-term treatment, you should follow a diet rich in potassium. Caution must be exercised when selecting dosages for patients with gout, as hydrochlorothiazide may cause an increase in uric acid levels. In diabetes mellitus, hyperglycemia may occur during treatment with hydrochlorothiazide, especially against the background of hypokalemia. In case of renal failure, it is necessary to carefully monitor electrolyte balance and creatinine clearance. Severe loss of water and electrolytes during long-term treatment with high-dose diuretics may exacerbate symptoms of renal failure. Hydrochlorothiazide penetrates the placental barrier. During pregnancy, indications for use must be carefully substantiated. A diuretic should not be prescribed for eclampsia, preeclampsia, or edema of any origin during pregnancy. Hydrochlorothiazide may pass into breast milk, so you should avoid breastfeeding during treatment.
Side effects
- A decrease in the level of potassium, magnesium, an increase in calcium in the blood is manifested by thirst and dry mouth , muscle cramps , heart rhythm disturbances, mental changes, severe fatigue ;
- hyponatremia , which is manifested by confusion , slower thinking, increased excitability, convulsions and muscle cramps ;
- an increase in blood sugar levels and its appearance in the urine. Thiazides reduce glucose tolerance, so latent diabetes mellitus manifests itself;
- increased lipids and uric acid in the blood (with long-term use of high doses);
- cholecystitis, cholestatic jaundice, inflammation of the salivary glands, constipation;
- arrhythmias and orthostatic hypotension ;
- dizziness, headache, blurred vision (blurredness), paresthesia ;
- urticaria, purpura, Stevens-Johnson syndrome , necrotizing vasculitis, anaphylactic shock ;
- interstitial nephritis with impaired renal function;
- decreased potency .
Hydrochlorothiazide
Renal dysfunction
In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.
In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal dysfunction progresses and/or oligonuria (anuria) occurs, hydrochlorothiazide should be discontinued.
Liver dysfunction
When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.
Water-electrolyte balance and metabolic disorders
Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in the volume of circulating fluid (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis).
Clinical symptoms of fluid and electrolyte imbalance are dry mouth, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of water-electrolyte imbalance should be identified and blood electrolyte levels should be regularly monitored.
Sodium
All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking hydrochlorothiazide.
Potassium
When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (potassium concentration less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.
Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary heart disease , chronic heart failure. In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs.
In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood must be carried out within the first week from the start of treatment.
If hypokalemia occurs, appropriate treatment should be prescribed.
Hypokalemia can be corrected by using potassium-containing medications or eating foods rich in potassium (dried fruits, fruits, vegetables).
Calcium
Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer).
Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.
Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.
Magnesium
Thiazides have been found to increase renal excretion of magnesium, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.
Glucose
Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood. Dosage adjustment of hypoglycemic medications may be required.
Uric acid
In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.
Lipids
When using hydrochlorothiazide, the concentration of cholesterol and triglycerides in the blood plasma may increase.
Acute myopia/secondary closed glaucoma
Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include a sudden decrease in visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms occur, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required.
Risk factors for the development of acute angle-closure glaucoma are: a history of an allergic reaction to sulfonamides or penicillin.
Immune system disorders
There are reports that thiazide diuretics (including hydrochlorothiazide) may cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.
In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.
Photosensitivity
There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of the diuretic is necessary, the skin should be protected from exposure to sunlight or artificial ultraviolet rays.
Non-melanoma skin cancer
Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of non-melanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide. Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.
Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.
To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.
In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide.
Alcohol
During treatment with hydrochlorothiazide, it is not recommended to drink alcoholic beverages, because ethanol enhances the antihypertensive effect of thiazide diuretics.
Athletes
Hydrochlorothiazide may give a positive result during doping control in athletes.
Other
In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.
Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without causing signs of thyroid dysfunction.
Hydrochlorothiazide, instructions for use (Method and dosage)
The tablets are taken orally after meals.
As an antihypertensive agent: SD 25-50 mg. Hydrochlorothiazide is used as a monotherapy or in combination with other antihypertensive drugs (ACE inhibitors, vasodilators, beta-blockers, sympatholytics). Increasing the dose to 100 mg proportionally leads to an increase in diuresis, a decrease and loss of sodium. If the dose is more than 100 mg, the increase in diuresis and decrease in blood pressure are very small, but the loss of electrolytes K+ and Mg2+ increases. It is not advisable to increase the dose to 200 mg, since no increase in diuresis is observed. The hypotensive effect appears after 3-4 days, and sometimes it takes 3-4 weeks for a lasting effect.
If hydrochlorothiazide is combined with other antihypertensive drugs, the dose of the other drug may sometimes need to be reduced to avoid excessive decrease in blood pressure.
Edema syndrome : 25-100 mg in the morning (can be divided into 2 doses until 11 o’clock in the afternoon). Sometimes, in severe cases, up to 200 mg per day is prescribed first. After 3 days, take a break for 5 days. For maintenance therapy 25-50 mg - twice a week. With such an intermittent course of treatment, side effects develop less frequently.
Nephrogenic diabetes insipidus : 25 mg per day, gradually increasing to 50-150 mg, divided into 2 doses. When the effect is achieved (reduction of polyuria and thirst), the dose is reduced.
Premenstrual syndrome : 25 mg from the onset of symptoms until the onset of menstruation.
For children, doses are calculated based on the child's weight. Pediatric dose - 1-2 mg/kg body weight 1 time per day.
To reduce intraocular pressure, the instructions for use of Hydrochlorothiazide include 25 mg once every 3-6 days.
Use of the drug Hydrochlorothiazide
For maintenance therapy, the minimum effective dose should be selected individually. It is preferable to take tablets after meals. For hypertension (arterial hypertension), as a rule, at the beginning of treatment, a daily dose of 25–50 mg, taken once in the morning or in 2 divided doses, then 25 mg per day is sufficient. If the hypotensive effect is insufficient, it is recommended to use hydrochlorothiazide in combination with other antihypertensive drugs. For edema, the daily dose is usually 25–75 mg, in exceptional cases - 100 mg. As a rule, it is enough to take hydrochlorothiazide intermittently, for example every 2nd or 3rd day of the week. Children are prescribed 12.5–25 mg per day, with breaks if possible (every 2nd or 3rd day of the week). The daily dose is best taken once in the morning. For diabetes insipidus, at the beginning of treatment - 100 mg per day in 2-4 doses, then the daily dose can be reduced. To prevent the formation of kidney stones - 50 mg 2 times a day.
Overdose
Manifested by adynamia, tachycardia and arrhythmia, constipation, drowsiness , dry mouth, decreased blood pressure , and decreased daily diuresis .
There is no specific antidote, treatment is symptomatic: gastric lavage, sorbents, infusion of electrolyte solutions.
Hydrochlorothiazide 25 mg and 100 mg, tablets
Hypotension and water-electrolyte imbalance. In large doses, hydrochlorothiazide may cause increased diuresis due to loss of fluid and sodium. This can lead to dry mouth and thirst, headache, weakness, dizziness, muscle pain or muscle spasms, nervousness, palpitations, hypotension, and orthostatic disorders. It is important to restore unwanted fluid losses due to vomiting, diarrhea, and excessive sweating. Dehydration can lead to thickening of the blood and, in rare cases, to seizures, drowsiness, confusion, loss of consciousness or coma, circulatory collapse and acute renal failure. Thrombosis and embolism are possible, especially in the presence of vascular disease or in elderly patients. In combination with reduced potassium intake and/or loss of potassium (with vomiting, diarrhea), there may be an increase in potassium loss through the kidneys and a decrease in potassium levels in the blood, manifested by increased fatigue, drowsiness, apathy, muscle weakness, paresthesia, paresis, constipation, bloating and cardiac arrhythmias. Acute potassium deficiency can lead to intestinal obstruction, loss of consciousness, and coma. There may be an increase in magnesium levels in the blood. Thiazides, including hydrochlorothiazide, reduce the excretion of calcium by the kidneys and thereby lead to an increase in serum calcium levels (even in the absence of known disorders of calcium metabolism).
Renal dysfunction, kidney transplantation. In case of renal failure (glomerular filtration rate below 30 ml/min and/or serum creatinine more than 1.8 mg/100 ml), treatment with hydrochlorothiazide is not effective, and the risk of adverse reactions is increased. In chronic renal failure, the drug can accumulate and cause the development of azotemia. There is no experience with the use of hydrochlorothiazide in patients with recent kidney transplantation. Regular monitoring of the level of serum electrolytes, especially potassium ions, creatinine and urea in the blood, is recommended.
Liver failure. In case of severe liver dysfunction, it is contraindicated. Use with caution in patients with impaired liver function or progressive liver disease, as they can cause cholestasis and precipitate hepatic coma against the background of any change in water and electrolyte balance.
Metabolic and endocrine disorders. Thiazide diuretic therapy may decrease glucose tolerance, which may require dose adjustment of insulin and oral antidiabetic agents in patients with diabetes mellitus. Possible manifestation of latent diabetes mellitus. Possible increase in cholesterol and triglyceride levels. Monitoring of biochemical blood parameters is recommended.
Cerebrovascular and cardiovascular insufficiency. The use of hydrochlorothiazide by patients in this category requires systematic medical supervision.
Acute myopia and angle-closure glaucoma. Acute transient myopia and transient angle-closure glaucoma may occur. Stop taking hydrochlorothiazide.
Severe heart failure. Absorption of hydrochlorothiazide may be reduced.
Effect on laboratory parameters. May reduce plasma levels of protein-bound iodine and increase the concentration of free bilirubin. Before laboratory testing of the parathyroid gland, hydrochlorothiazide is discontinued.
General information. A hypersensitivity reaction to hydrochlorothiazide and excipients is possible. Hydrochlorothiazide may intensify or activate systemic lupus erythematosus. With prolonged use, pseudo-Barter syndrome may occur, which leads to edema resulting from increased renin activity and secondary hyperaldosteronism. Not prescribed for patients with Addison's disease. Do not take in cases of congenital galactose intolerance and Lapp lactase deficiency or malabsorption of glucose and galactose (contains lactose).
With prolonged therapy with hydrochlorothiazide, regular monitoring of the levels of serum electrolytes (especially potassium, sodium, calcium, magnesium), creatinine and urea, lipids (cholesterol, triglycerides), uric acid, and blood sugar is necessary. During treatment with the drug, it is recommended to consume a sufficient amount of fluid and foods containing potassium (bananas, vegetables, nuts).
The use of hydrochlorothiazide may lead to positive results in a doping test. If the drug is abused as a doping, a health hazard cannot be ruled out.
Hydrochlorothiazide therapy should be discontinued if the following pathological conditions are detected: electrolyte imbalance resistant to therapy; violation of orthostatic regulation; hypersensitivity reaction; gastrointestinal disorders; disorders of the central nervous system; pancreatitis; changes in the blood (anemia, leukopenia, thrombocytopenia); acute cholecystitis; vasculitis; worsening of existing myopia, an increase in serum creatinine concentration above 1.8 mg/100 ml or creatinine clearance below 30 ml/min.
Interaction
Indirect anticoagulants, NSAIDs, Clofibrate enhance the diuretic effect.
Taking vasodilators, beta-blockers, tricyclic antidepressants, Diazepam, barbiturates and ethanol enhances the hypotensive effect of diuretics.
Indomethacin and other NSAIDs reduce the hypotensive effect.
Cholestyramine reduces the effect of thiazide diuretics because it inhibits their absorption.
When used simultaneously with cardiac glycosides, the risk of their toxicity (increased ventricular excitability) increases, which is associated with hypokalemia and hypomagnesemia.
The use of amiodarone and diuretics increases the risk of arrhythmias, which is associated with hypokalemia.
When used together with corticosteroids, there is a risk of developing hypokalemia.
Thiazide diuretics weaken the effect of hypoglycemic drugs and norepinephrine, reduce the effect of oral contraceptives, increase the neurotoxicity of salicylates and increase sensitivity to tubocurarine. Taking methyldopa and a diuretic can cause hemolysis.
Reviews of Hydrochlorothiazide
Analyzing the reviews of patients who used this drug, we can conclude that it is used not only as a diuretic drug, but also as an antihypertensive.
Many women periodically use it for swelling associated with premenstrual syndrome - take 1 tablet in the morning a few days before menstruation.
As an antihypertensive drug, it is part of combination drugs: Capozide, Enap N, Amprilan NL, Aritel plus, Co-Diroton . At the same time, the effect is mutually enhanced, and since the dose of the diuretic is small (almost everywhere 12.5 mg), constant use, which is recommended for hypertension, does not cause side effects. Excessive excretion of potassium by hydrochlorothiadide must be compensated with a potassium diet. If it is combined with ACE inhibitors, which retain potassium in the body, this may not be necessary.
Hydrochlorothiazide price, where to buy
You can buy it in Moscow pharmacies, which are presented on the website of the Federal Information Service www.poisklekarstv.ru. The average price of Hydrochlorothiazide 25 mg No. 20 ranges from 39 to 53 rubles, and 100 mg tablets from 43 to 70 rubles.
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- Hydrochlorothiazide tab.
25 mg 20 pcs Pranapharm LLC 53 RUR order
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- Hydrochlorothiazide 0.025 g No. 20 tablets PAT NEC "Borshchagivsky chemical and pharmaceutical plant", Kiev, Ukraine
18 UAH. order