Hydrochlorthiazidum

General characteristics. Structure:

Active ingredient: 25 mg and 100 mg of a hydrochlorothiazide.

Excipients: potato starch, calcium stearate, lactose monohydrate.

Diuretics are applied to therapy of supertension, congestive heart failure, and other diseases at which in an organism too large amount of liquid collects.

Pharmacological properties:

Pharmakozhinamika. Thiazide diuretic. Breaks a reabsorption of ions of sodium, chlorine and water in distal tubules of nephron. Increases removal of potassium ions, magnesium, bicarbonate; detains in an organism calcium ions. The diuretic effect occurs in 2 h, reaches a maximum in 4 h and proceeds to 12 h. Promotes decrease in the raised ABP. Besides, reduces a polyuria at patients with not diabetes mellitus (the action mechanism is finally not found out). In some cases lowers intraocular pressure at glaucoma.

Pharmacokinetics. After intake of 60-80% of a dose it is absorbed from a GIT. Time of achievement of Cmax in plasma - 1.5-3 h. The hydrochlorothiazide collects in erythrocytes. In a removal phase its concentration in erythrocytes in 3-9 times more, than in plasma. Linkng with proteins of plasma - 40-70%. Vd in a terminal phase of removal makes 3-6 l/kg (that is equivalent to 210-420 l at the body weight of 70 kg).

The hydrochlorothiazide is metabolized in very small degree. Its only thing the metabolite found in trace quantities is 2-amino-4-hloro-M-benzendisulfonamid.

Removal of a hydrochlorothiazide from plasma has two-phase character: T1/2 in an initial phase makes 2 h, in a terminal phase - about 10 h. At patients with normal function of kidneys removal is carried out almost only by kidneys. In general 50-75% of the dose accepted inside are removed with urine in not changed look.

At patients of advanced age and at renal failures the clearance of a hydrochlorothiazide significantly decreases that leads to significant increase in its concentration in a blood plasma. The decrease in clearance noted at elderly patients, apparently, is connected with deterioration in function of kidneys. At patients with cirrhosis of changes of pharmacokinetics of a hydrochlorothiazide it is not noted.

Indications to use:

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

Route of administration and doses:

For intake. A pill should be taken after food, swallowing entirely, washing down with enough liquid.

Duration of treatment depends on type and disease severity. Dosing is selected individually and demands constant medical control.

At arterial hypertension the initial dose usually makes 25 mg of drug once a day.

At treatment of hypostases of a cordial, hepatic or renal etiology the initial dose makes 25-50 mg of drug of times a day (that there correspond to 1 tablet 25 mg or ½ tablets of 100 mg). The maintenance dose makes 25 mg – 50 mg – 100 mg of a hydrochlorothiazide a day (1 tablet of 25 mg – 2 tablets on 25 mg or ½ tablets of 100 mg – 1 tablet of 100 mg respectively).

Extra care should be observed at patients with heart failure, patients with the broken function of a liver or kidneys.

Features of use:

With care apply at patients with gout and a diabetes mellitus.

At patients with a renal failure systematic control of concentration in plasma of electrolytes and KK is necessary.

At emergence of signs of deficit of potassium, and also at simultaneous use of cardiac glycosides, GKS and AKTG is shown purpose of drugs of potassium or kaliysberegayushchy diuretics.

At prolonged use it is necessary to adhere to the diet rich with potassium.

Simultaneous use of diuretics with NPVS is not recommended.

Adequate and well controlled clinical trials of safety of a hydrochlorothiazide at pregnancy were not conducted. In pilot studies signs of adverse action on a fruit were not observed. Considering it, use at pregnancy is possible only according to vital indications and only in that case when the estimated advantage for mother surpasses potential risk for a fruit.

The hydrochlorothiazide gets into breast milk. It is recommended to avoid use of a hydrochlorothiazide in the first month of breastfeeding as there are messages on suppression of a lactation.

Side effects:

Frequency of undesirable reactions which were observed or during conduct of clinical trials or were received from spontaneous messages on development of undesirable reactions is defined as follows: often (> 1/100 - <1/10); infrequently (> 1/1000 - <1/100); seldom (> 1/10 000 - <1/1000); very seldom (<1/10 000), it is unknown (frequency cannot be determined by the data which are available for today).

From bodies of a hemopoiesis and lymphatic system. Infrequently: leykotsitopeniya; seldom: thrombocytopenia; very seldom: hemolitic anemia, aplastic anemia, agranulocytosis. Fever with a fever, a pharyngalgia and changes in mucous membranes can be signs of an agranulocytosis. At a concomitant use of a hydrochlorothiazide and Methyldopums immunohemolitic anemia can develop.

From immune system. Infrequently: allergic reactions of skin and mucous membranes or, in rare instances, acute intersticial nephrite, disturbance of a picture of blood, medicinal fever; seldom: anaphylactic or anaphylactoid reactions (for example, shock). The first signs of shock are included by skin reactions (reddenings or a small tortoiseshell), concern, a headache, perspiration, nausea, cyanosis, allergic reactions.

From a metabolism. Disturbances of water and electrolytic balance (hypopotassemia, hyponatremia, hypochloraemia, hypomagnesiemia, hypercalcemia). In high doses drug can cause the raised diuresis due to loss of liquid and sodium (a hyponatremia and a hypovolemia). It can lead to loss of appetite, dryness in a mouth and thirst, vomiting, a headache, weakness, dizziness, drowsiness, a vision disorder, apathy, confusion of consciousness, irritability, muscular pains or spasms of muscles (for example, spasms of gastrocnemius muscles), heartbeat, hypotension, orthostatic disturbances of regulation and faints. Therefore it is important to counterbalance undesirable losses of liquid (for example, at vomiting, diarrhea, the increased perspiration). Dehydration and hypovolemia owing to the raised diuresis can lead to a pachemia and in rare instances spasms, drowsiness, confusion of consciousness, a loss of consciousness up to a coma, a vascular collapse and an acute renal failure develop. Besides, the pachemia can lead to thrombosis and an embolism, especially in the presence of diseases of vessels or at patients of advanced age. In combination with the lowered consumption of potassium and/or increase in extrarenal loss of potassium (for example, at vomiting or chronic diarrhea) increase in renal loss of potassium and a hypopotassemia as which manifestation the following symptoms can serve can be result:
- neurologic symptoms: increased fatigue, drowsiness, apathy;
- neuromuscular symptoms: muscular weakness, paresthesias, paresis;
- GIT symptoms: nausea, vomiting, an adynamia of smooth muscles with locks, abdominal distention and a meteorism;
- renal symptoms: polyuria, polydipsia;
- cordial symptoms: disturbance of a heart rhythm, cordial conductivity, arrhythmia, changes of an ECG (bradycardia or other disturbances of a cordial rhythm) and increase in a susceptibility to glycosides.

Acute shortage of potassium can result in partial intestinal obstruction up to full intestinal impassability or a loss of consciousness up to a coma. Gipermagneziuriya meets seldom and is shown as a gipomagneziyemiya since magnesium will be mobilized from bones. As a result of losses of liquid and electrolytes the metabolic alkalosis can develop or the existing alkalosis is aggravated.

Hyperuricemia and as the result, gout attacks, often meets at treatment by a hydrochlorothiazide. Often at patients with a normal metabolism, at patients with a diabetes mellitus or a latent diabetes mellitus, and also at patients with deficit of potassium the hyperglycemia can be shown. Patients with a diabetes mellitus can have a deterioration in the metabolic status. Manifestation of a latent diabetes mellitus is possible. Frequency is unknown.

Often increase in lipids (cholesterol, triglycerides) in blood serum at treatment meets a hydrochlorothiazide.

From TsNS. Seldom: headache, dizziness, paresthesia, depression, sleeplessness.

From organs of sight. Infrequently: the temporary vision disorder (for example, the obscured sight, a xanthopsia), reduction of formation of the lacrimal liquid (it is necessary to be careful when carrying contact lenses), the existing myopia can be aggravated.

From CCC. Often: heartbeat (tachycardia); infrequently: orthostatic hypotension, vasculitis (in some cases necrotic vasculitis); seldom: arrhythmia.

From respiratory system. Infrequently: short wind, acute intersticial pneumonia; very seldom: a sudden fluid lungs with shock symptoms, allergic reactions to a hydrochlorothiazide.

From the alimentary system. Often: anorexia, nausea, vomiting, diarrhea, lock, pains and spasms in an abdominal cavity.

From a gall bladder and a liver. Infrequently: hyperamilasemia, pancreatitis; seldom: jaundice; frequency is unknown: acute cholecystitis with the previous zhelchekamenny disease.

From skin and hypodermic fabrics. Infrequently: allergic reactions of integuments and mucous membranes (for example, itch, reddening, rash, photosensitivity, purpura, small tortoiseshell); very seldom: toxic epidermal necrolysis. In some cases can arise: system lupus erythematosus, reactions, similar system lupus erythematosus or reactivation of a system lupus erythematosus.

From kidneys and urinary tract. Very often: glucosuria; often: reversible increase in concentration in blood serum and in urine of creatinine and urea; infrequently: intersticial nephrite.

From reproductive system and mammary glands. Infrequently: impotence.

General disturbances. Infrequently: medicinal fever.

Interaction with other medicines:

At simultaneous use of the anti-hypertensive means which are not depolarizing muscle relaxants their action amplifies.

At simultaneous use of barbiturates, diazepam, ethanol the risk of development of orthostatic hypotension increases.

At simultaneous use with GKS there is a risk of development of a hypopotassemia, and also orthostatic hypotension.

At simultaneous use with APF inhibitors (including captopril, enalapril) anti-hypertensive action amplifies.

The expressed arterial hypotension, especially after reception of the first dose of a hydrochlorothiazide, apparently, at the expense of a hypovolemia which leads to tranzitorny strengthening of hypotensive effect of APF inhibitor is possible.

The risk of a renal failure increases. Development of a hypopotassemia is not excluded.

At simultaneous use of peroral hypoglycemic drugs their efficiency decreases.

At simultaneous use of drugs of calcium and/or vitamin D in high doses the hypercalcemia and risk of development of a metabolic acidosis owing to delay of removal of calcium with urine under the influence of thiazide diuretics is possible.

At simultaneous use with Allopyrinolum the risk of development of allergic reactions, especially at patients with renal failures increases.

At simultaneous use with digoxin increase in risk of development of glikozidny intoxication is possible.

At simultaneous use with indometacin, piroxicam, Naproxenum, phenylbutazone perhaps some reduction of hypotensive effect.

At simultaneous use with irbesartany development of the additive hypotensive effect is possible.

At simultaneous use with carbamazepine there are messages on development of a hyponatremia.

At simultaneous use with kolestipoly, Colestyraminum absorption and diuretic effect of a hydrochlorothiazide decreases.

At simultaneous use from lithium a carbonate increase in concentration in blood of salts of lithium to toxic level is possible.

At simultaneous use with orlistaty efficiency of a hydrochlorothiazide decreases that can lead to substantial increase of the ABP and development of hypertensive crisis.

At simultaneous use with sotaloly the hypopotassemia and development of ventricular arrhythmia like "pirouette" is possible.

Contraindications:

The expressed renal failures (the acute glomerulonephritis, an oliguria, an anury, clearance of creatinine is lower than 30 ml/min. or creatinine of serum 1,8 mg / 100 are higher than ml); heavy liver failure; severe forms of gout and diabetes mellitus; hypopotassemia, hypercalcemia, hyponatremia, obezvozhivvaniye, hypovolemia; hypersensitivity to Hydrochlorthiazidum and other tiazida, sulfonamides or other components of drug.

Overdose:

Symptoms. Clinical manifestations of acute or chronic overdose depend on extent of loss of liquid and electrolytes (a hypopotassemia, a hyponatremia, a hypochloraemia).

The overdose at strong loss of liquid and sodium is expressed in the following signs and symptoms: thirst. Weakness, dizziness, muscular pains and spasms of muscles (for example, spasms of gastrocnemius muscles), headache, tachycardia, arterial hypotension and orthostatic disturbances of regulation. The hypovolemia and dehydration can lead to a pachemia with thrombosis, convulsions, drowsiness, block, confusion of consciousness, cardiovascular insufficiency, disturbance of consciousness up to a coma or to an acute renal failure. At bystry loss of liquid and electrolytes there can come the condition of a delirium.

In rare instances there is an acute anaphylaxis (symptoms include perspiration, nausea, cyanosis, heavy arterial hypotension, a loss of consciousness up to a coma).

At a hypopotassemia such symptoms as fatigue, muscular weakness, paresthesias, paralysis, apathy, abdominal distention, locks and disturbances of a heart rhythm are shown. Acute shortage of potassium can result in acute impassability of intestines or to a loss of consciousness up to a coma. Arrhythmia at a concomitant use with cardiac glycosides can amplify (digitalis) owing to a possible hypopotassemia.

Treatment. At the first signs of overdose it is necessary to stop administration of drug immediately. Within several hours after overdose it is necessary to take general measures on primary intoxication (to cause vomiting, to wash out a stomach) or the measures for decrease in absorption of drug (reception of absorbent carbon) reducing systemic action of a hydrochlorothiazide.

In addition to monitoring of the vital parameters it is necessary to repeat check of water and electrolytic balance, acid-base balance, sugar level in blood and function of kidneys, deviations are adjusted as required.

Specific antidote for a hydrochlorothiazide it is not established.

Therapeutic measures:
- at a hypovolemia and a hyponatremia: compensation of sodium and liquid in an organism;
- at a hypopotassemia: kaliyazameshcheniye;
- at a vascular collapse: change of position of a body "the head is lower than legs", if necessary a shock therapy;
- at bradycardia, resistant to therapy: to carry out temporary therapy by means of an electrostimulator.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 10 or 20  tablets in   a blister strip packaging. On  the 2nd   blister strip packagings on 10 tablets a dosage of 25 mg together with the application instruction in a pack from a cardboard. On 1 or 2 strip packagings on 20 tablets a dosage of 25 mg. On 2 or 4 strip packagings on 10 tablets a dosage of 100 mg.