Hydrochlorothiazide

General characteristics. Structure:

Active ingredient: 25 mg of a hydrochlorothiazide in 1 tablet.

Excipients: lactoses monohydrate, talc, gelatin, calcium stearate, potato starch.

Pharmacological properties:

Pharmacodynamics. Thiazide diuretic of average force. Reduces a reabsorption of ions of sodium at the level of a cortical segment of a Henle's loop, without influencing its site passing in a kidney medulla that defines weaker diuretic effect in comparison with furosemide. Blocks a karboangidraza in proximal department of gyrose tubules, strengthens removal with urine of potassium ions (in distal tubules the ion of sodium exchanges on a potassium ion), hydrocarbonates and phosphates. Practically does not influence an acid-base state (the ion of sodium is removed or together with a chlorine ion, or with a hydrocarbonate therefore at an alkalosis removal of hydrocarbonates amplifies, at acidosis - chlorides). Increases removal of ions of magnesium; detains in an organism calcium ions and removal of urates.

The diuretic effect develops in 1 - 2 h, reaches a maximum in 4 h, proceeds 10-12 h. Action decreases at reduction of a glomerular filtration rate and stops at the size of its less than 30 ml/min. At patients with not diabetes mellitus has antidiuretic effect (reduces the volume of urine and increases its concentration). Lowers arterial pressure due to reduction of volume of the circulating blood, change of reactivity of a vascular wall, decrease in pressor influence of vasoconstrictive medicines (Epinephrinum, Norepinephrinum) and strengthening of depressor influence on a ganglion. In some cases lowers intraocular pressure at glaucoma.

Pharmacokinetics. Absorption – 80%, bystry. Communication with proteins of plasma – 60-80%. Bioavailability – 70%, TCmax – 2-5 h. The average size AUC increases in the therapeutic range of doses in direct ratio to increase in a dose, at purpose of 1 times a day cumulation is insignificant. Gets through a gematoplatsentarny barrier and into breast milk.

T1/2 is 6 - 15 h. It is not metabolized by a liver. It is removed by kidneys: 95% in not changed look and about 4% in a look гидролизата-2-амино-4-хлоро-m-бензенедисульфонамида (decreases at alkalinuria) - by glomerular filtering and active canalicular secretion in proximal department of nephron.

Indications to use:

Arterial hypertension; an edematous syndrome of various genesis (chronic heart failure, portal hypertensia, a nephrotic syndrome, a chronic renal failure, a liquid delay at obesity), not diabetes mellitus; the subcompensated glaucoma forms.

Route of administration and doses:

At arterial hypertension: inside, 25-50 mg/days, at the same time an insignificant diuresis and a natriuresis are noted only in the first day of reception (appoint it is long in a complex with other hypotensive medicines: vazodilatator, angiotensin-converting enzyme inhibitors, sympatholytics, beta adrenoblockers). At increase in a dose from 25 to 100 mg proportional increase in a diuresis, a natriuresis and a lowering of arterial pressure are observed. In a single dose over 100 mg - increase of a diuresis and a further lowering of arterial pressure are insignificant, disproportionately increasing loss of electrolytes, especially potassium ions and magnesium is observed. Increase in a dose over 200 mg is inexpedient since strengthening of a diuresis does not happen.

At an edematous syndrome (depending on a state and reaction of the patient) appoint 25 - 100 mg in a daily dose, accept once (morning) or in 2 receptions (in the first half of day).

To elderly people – 12,5 mg of 1 - 2 time a day.

To children aged from 3 up to 14 years - on 1 mg/kg/days. After 3 - 5 days of treatment it is recommended to take a break for 3 - 5 days. As a maintenance therapy in the specified dose appoint 2 times a week. When using a discontinuous course of treatment with reception in 1 - 3 day or within 2 - 3 days with the subsequent break decrease in efficiency is expressed to a lesser extent and side effects develop less often.

For decrease in intraocular pressure appoint on 25 mg of 1 times in 1 - 6 days; the effect occurs in 24 - 48 h.

At not diabetes mellitus - 25 mg of 1 - 2 time a day with gradual increase in a dose (a daily dose - 100 mg) before achievement of medical effect (reduction of thirst and a polyuria), the dose decline is possible further.

Features of use:

At prolonged treatment it is necessary to control carefully clinical symptoms of disturbance of water and electrolytic balance, first of all, at patients of group of the increased risk: patients with diseases of cardiovascular system and abnormal liver functions.

The hypopotassemia can avoid use of K+ - the containing drugs or food, rich K+ (fruit, vegetables), especially in case of the strengthened loss of K+ (the expressed diuresis, long treatment) or simultaneous treatment by cardiac glycosides or glucocorticosteroids.

Increases removal of magnesium with urine that can lead to a hypomagnesiemia.

At the chronic renal failure (CRF) periodic control of KK is necessary. At HPN drug can kumulirovat and cause development of an azotemia. At development of an oliguria it is necessary to consider the possibility of drug withdrawal.

At a slight and moderate liver failure or the progressing liver diseases drug is appointed with care as little change of water and electrolytic balance and accumulation of ammonium in serum can cause a hepatic coma.

In case of a heavy cerebral and coronary sclerosis purpose of drug demands extra care.

Can break tolerance to glucose. During a long course of treatment at a manifest and latent diabetes mellitus systematic control of metabolism of carbohydrates is necessary; dose adjustment of hypoglycemic HP can be required. During treatment periodic control of concentration of uric acid is necessary.

At long therapy the pathological change of function of epithelial bodies which is followed by a hypercalcemia and a hypophosphatemia was in rare instances observed. Can affect results of laboratory researches of function of epithelial bodies therefore before definition of function of epithelial bodies drug should be cancelled.

The hydrochlorothiazide can reduce amount of the iodine contacting proteins of serum without manifestation of signs of dysfunction of a thyroid gland.

In an initial stage of use of drug (duration of this period is defined individually) it is recommended to refrain from the driving and performance of work demanding the increased concentration of attention and speed of psychomotor reactions (owing to possible development of dizziness and drowsiness), further it is necessary to be careful.

Side effects:

Disturbance of electrolytic balance, including hyponatremia (fatigue, irritability, myotonia, confusion of consciousness, spasm), gipokhloremichesky alkalosis, hypopotassemia (dryness of a mucous membrane of an oral cavity, thirst, arrhythmia, spasm or muscle pain, nausea, vomiting, weakness), hypomagnesiemia, hypercalcemia; an agranulocytosis, thrombocytopenia, a leukopenia, hemolitic and aplastic anemia, allergic reactions (skin rash, a small tortoiseshell), a purpura, a necrotizing vasculitis, Stephens-Johnson's syndrome, a respiratory distress syndrome (including a pneumonitis and not cardiogenic hypostasis of a lung), anaphylactic reactions, up to shock; cholecystitis, pancreatitis, cholestatic jaundice, sialadenitis, lock, exacerbation of gout, hyperuricemia, glucosuria, anorexia, decrease in a potentiality, diarrhea, orthostatic hypotension, photosensitization, hyperglycemia, arrhythmias, dizziness, temporarily indistinct sight, headache, paresthesias, renal failure, intersticial nephrite.

Interaction with other medicines:

It is necessary to avoid simultaneous use of Hydrochlorthiazidum with Li salts + (the renal clearance of Li + decreases, increases its toxicity).

With care it is necessary to apply with hypotensive medicines (strengthening of their action, dose adjustment can be required), cardiac glycosides (the hypopotassemia and a hypomagnesiemia against the background of therapy by thiazide diuretics can increase toxicity of cardiac glycosides), Amiodaronum (risk of development of the arrhythmias connected with a hypopotassemia), peroral hypoglycemic HP (their efficiency, risk of development of a hyperglycemia decreases), glucocorticosteroids, a calcitonin (strengthening of a hypopotassemia), non-steroidal anti-inflammatory drugs (weaken diuretic and hypotensive action), not depolarizing muscle relaxants (their effect can amplify), amantadiny (the clearance of an amantadin can decrease that leads to increase in concentration of an amantadin in plasma and possible toxicity), Colestyraminum (reduces absorption of a hydrochlorothiazide), ethanol, barbiturates and narcotic analgetics, which strengthen risk of development of orthostatic hypotension.

Tiazida can reduce concentration of the iodine in plasma connected with proteins.

Contraindications:

Hypersensitivity (including to other sulfonamides), a diabetes mellitus (difficult controlled), a chronic renal failure (KK less than 30 ml/min.), an anury, a heavy liver failure, Addison's disease, a refractory hypopotassemia, a hypercalcemia and a hyponatremia; pregnancy (the I trimester), the lactation period, children's age (up to 3 years); patients with rare hereditary diseases, such as a lactose intolerance, deficit of lactase or glyukozo-galaktozny malabsorption (in connection with the content in lactose medicine).

With care. Coronary heart disease, a concomitant use of cardiac glycosides, gout, a slight and moderate liver failure, the progressing liver diseases (risk of development of a hepatic coma), cirrhosis (risk of development of a hypomagnesiemia), advanced age, pregnancy (the II-III trimester).

Overdose:

Symptoms: hypopotassemia (adynamia, paralyzes, locks, arrhythmias), drowsiness, lowering of arterial pressure.

Treatment: there is no specific antidote; induction of vomiting, gastric lavage, reception of absorbent carbon, infusion of electrolytic solutions; compensation of deficit of potassium ions (purpose of drugs kaliyion-and kaliysberegayushchy diuretics).

Storage conditions:

To store the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On the 2nd blister strip packagings on 10 tablets in a pack.