Hydrochlorthiazidum

General characteristics. Structure:

Active agent: a hydrochlorothiazide (in terms of 100% substance) - 25 mg or 100 mg;

Excipients: cellulose microcrystallic, sugar milk (lactose), potato starch, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Thiazide diuretic of average duration of action. Has diuretic effect, breaks a reabsorption of ions of sodium, chlorine, potassium, magnesium, water in distal department of nephron. The diuretic effect develops in 1-2 hours, reaches a maximum in 4 hours and 6-12 hours proceed. Action decreases at reduction of a glomerular filtration rate and stops at size not less than 30 млмин. At patients with not diabetes mellitus has antidiuretic effect (reduces the volume of urine and increases its concentration). Has anti-hypertensive properties and it can be used for this purpose both in monotherapy, and for strengthening of anti-hypertensive effect of other drugs. The hypotensive effect develops due to expansion of arterioles. Tiazida do not exert impact on normal arterial pressure. Anti-hypertensive action comes in 3-4 days, but for achievement of optimum therapeutic effect 3-4 weeks can be required. Thiazide diuretics reduce removal of calcium with urine and by that reduce formation of nephroliths.

Pharmacokinetics. It is soaked up from digestive tract it is incomplete (60-80% of the dose accepted inside). Communication with proteins of a blood plasma makes 40%, the visible volume of distribution - 3-4 l/kg. The maximum concentration in a blood plasma is defined by 2-5 h. The elimination half-life makes 6-15 h. It is not metabolized by a liver. Also about 4% in a look гидролизата-2-амино-4-хлоро-т-бензенедисульфонамида (decreases at alkalinuria) by glomerular filtering and active canalicular secretion in proximal department of nephron are removed by kidneys of 95% in not changed look. Gets through a placental barrier and into breast milk.

Indications to use:

- arterial hypertension (it is used both in monotherapy, and in a combination with other anti-hypertensive means);
- edematous syndrome of various genesis (chronic heart failure, nephrotic syndrome, acute glomerulonephritis, chronic renal failure, portal hypertensia, treatment by corticosteroids, premenstrual syndrome);
- control of a polyuria, it is preferential at a nephrogenic not diabetes mellitus;
- prevention of formation of stones in urinary tract (reduction of a hypercalcuria).

Route of administration and doses:

Inside, after food. The dosage of drug is established individually. At constant medical control minimum effective dose is established.
Adults
As anti-hypertensive means: the usual initial daily dose of drug makes 25-50 mg once, as means of monotherapy or in a combination with other anti-hypertensive drugs. For some patients there can be sufficient an initial dose of 12,5 mg, both in the form of monotherapy or, and in a combination. It is necessary to apply minimum effective dose which is not exceeding 100 mg a day.
If the hydrochlorothiazide is combined with other hypotensive drugs, there can be a need to lower a dose of other drug to warn an excessive lowering of arterial pressure. Hypotensive action comes in 3-4 days, however for achievement of optimum therapeutic effect 3-4 weeks can be required.
After the treatment termination the hypotensive effect remains within one week.
Edematous syndrome of various etiology: the usual initial daily dose makes 25-100 mg of 1 times a day or 1 time in two days. Depending on therapeutic effect the dose can be lowered to 25-50 mg of 1 times a day or 1 time in two days. In some hard cases in an initiation of treatment doses to 200 mg a day can be required.
Premenstrual syndrome: the usual dose makes 25 mg a day and is applied from the beginning of manifestation of symptoms prior to the beginning of periods.
Nephrogenic not diabetes mellitus: the usual daily dose makes 50-150 mg in stages.
Children
Doses are established proceeding from the body weight of the child. The usual pediatric daily dose makes 1-2 mg/kg of body weight or 30-60 mg on square meter of a body surface, is appointed once a day. The general daily dose to children aged up to 2 years makes 12,5 - 37,5 mg; aged from 2 up to 12 years - on 37,5 - 100 mg.

Features of use:

To apply with care at diseases of kidneys and the expressed disturbances of their function.
With diseases of kidneys of a tiazida can cause an azotemia in patients. At patients with an impaired renal function the cumulative effect of drug can develop. If progressing of a disease of kidneys does not raise doubts, it is necessary to suspend or interrupt therapy with diuretics.
As thiazide diuretics lose the therapeutic effectiveness if the speed of glomerular filtering makes less than 39 млмин., at such patients with drugs of the choice loopback diuretics are.
Tiazida it is necessary to apply with care at patients with the broken function of a liver or the progressing liver diseases as little changes of an electrolytic or water balance can cause a hepatic coma.
Allergic reactions are more probable at patients with an allergy or bronchial asthma in the anamnesis.
The possibility of an aggravation of a current of general diseases of connecting fabric (system lupus erythematosus) is described.
At prolonged use of drug it is regularly necessary to control the level of electrolytes of blood and clearance of creatinine. During use of drug it is necessary to recommend to patients the diet enriched with potassium. At emergence of signs of deficit of potassium, and also at simultaneous use of cardiac glycosides, glucocorticosteroids and adrenocorticotropic hormone purpose of drugs of potassium or kaliysberegayushchy diuretics is shown.
Anti-hypertensive effect of drug can be strengthened at patients after a sympathectomy.
Removal of calcium decreases tiazidam. At some patients at prolonged treatment of a tiazidama pathological changes of epithelial bodies were observed.
Concentration of bilirubin in serum can increase at use of Hydrochlorthiazidum because of replacement from places of linkng with albumine.
Levels of cholesterol and triglycerides can increase.
For prevention of deficit of potassium and magnesium appoint a diet with the increased maintenance of these microelements, kaliysberegayushchy diuretics, salts of potassium and magnesium.
Regular control of contents in a blood plasma of potassium, glucose, uric acid, lipids, creatinine is necessary.
During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From water and electrolytic exchange and acid-base balance arise more often at long reception in high doses:

- emergence of a hypopotassemia and gipokhloremichesky alkalosis is possible: dryness in a mouth, strengthening of thirst, disturbance of a heart rhythm, change of mood and mentality, a spasm or muscle pain, nausea, vomiting, unusual fatigue and weakness. The Gipokhloremichesky alkalosis can cause hepatic encephalopathy or a hepatic coma;
- hyponatremia: confusion of consciousness, spasm, apathy, delay of process of thinking, fatigue, irritability;
- hypomagnesiemia: arrhythmias;

- From system of a hemopoiesis: agranulocytosis, thrombocytopenia and hemolitic and aplastic anemia, leykotsitopeniya;
- From cardiovascular system: arrhythmia, tachycardia, orthostatic hypotension, thrombosis, thromboembolism.
- From urinogenital system: acute intersticial nephrite, a vasculitis, a hypercreatinemia, decrease in a potentiality is in rare instances possible.
- From digestive tract: cholecystitis or pancreatitis, jaundice, diarrhea, a sialadenitis, a lock, anorexia, pains in epigastriums;
- From a nervous system: dizziness, temporary vagueness of sight, headaches, paresthesias, xanthopsia;
- Metabolic: hyperglycemia, glucosuria, hyperuricemia and exacerbation of gout, hypercalcemia, lipidemia;
- Other: allergic reactions.

Interaction with other medicines:

At combined use of drug with glycosides of a foxglove the possibility of manifestations of toxicity of drugs of the foxglove (for example, a hyperexcitability of a ventricle) connected with a hypopotassemia and a hypomagnesiemia can increase.
Strengthens action of not depolarizing muscle relaxants.
Combined use of Amiodaronum with thiazide diuretics can increase risk of developing of the arrhythmias connected with a hypopotassemia.
Effect of anti-hypertensive drugs can be strengthened if they are applied along with tiazida.
At combined use with corticosteroids or a calcitonin the risk of development of a hypopotassemia increases.
At simultaneous use reduces efficiency of peroral hypoglycemic drugs.
Non-steroidal anti-inflammatory drugs, in particular indometacin, reduce anti-hypertensive effect of tiazid.
Simultaneous use of a diflunizal with a hydrochlorothiazide causes substantial increase of level of the last in plasma and reduces its giperurikemichesky action.
Tiazida can reduce action of noradrenaline by arterial pressure.
Thiazide means can increase sensitivity to tubocurarine.
Ethanol and phenobarbital, diazepam can increase anti-hypertensive effect of thiazide diuretics.
Colestyraminum can suppress absorption of thiazide diuretics in a gastro intestinal path (reducing absorption by 85%).
At simultaneous use can increase in blood concentration of salts of lithium to toxic level. It is necessary to avoid combined use of these drugs.

Contraindications:

- hypersensitivity to drug or other sulfonamides;
- anury;
- heavy renal (the clearance of creatinine is lower than 30 ml/min.) or a liver failure;
- unmanageable diabetes mellitus;
- Addison's disease;
- refractory hypopotassemia, hyponatremia, hypercalcemia.
With care to apply at a hypopotassemia, a hyponatremia, a hypercalcemia, at patients with coronary heart disease, cirrhosis, at elderly people, at the patients having a lactose intolerance at reception of cardiac glycosides, at gout.

Pregnancy and period of a lactation
The hydrochlorothiazide gets through a placental barrier and into breast milk. Use of drug in the first trimester of pregnancy is contraindicated. In the second and third trimesters of pregnancy drug can be appointed only in case of emergency when the advantage for mother exceeds potential risk for a fruit and/or the child (there is a danger of development of jaundice of a fruit or the newborn, thrombocytopenia and other effects). In need of purpose of drug in the period of a lactation feeding by a breast should be stopped.

Overdose:

Symptoms: A hypopotassemia (an adynamia, paralysis, locks, arrhythmias), drowsiness, decrease in the ABP dryness in a mouth, an oliguria, tachycardia.

Treatment: To wash out a stomach, to accept absorbent carbon, to administer the potassium drugs, infusion of solutions of electrolytes. A symptomatic treatment, there is no specific antidote.

Storage conditions:

List B. In dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Tablets on 25 mg and 100 mg. On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. 2 blister strip packagings together with the application instruction place in a pack from a cardboard.