Pharmacological properties

Primary mechanism of effect of thiazide diuretics is increase in a diuresis by blocking of a reabsorption of ions of sodium and chlorine at the beginning of renal tubules. it they increase excretion of sodium, chlorides and, therefore, water. excretion of other electrolytes, namely potassium and magnesium, also increases. in the maximum therapeutic doses the diuretic/natriuretic effect of all tiazid is approximately identical. they also reduce activity of a karboangidraza by removal strengthening bicarbonate ion, but this action is usually poorly shown and does not influence on rn urine. the hydrochlorothiazide has also hypotensive properties. on normal hell thiazide diuretics do not influence.

Hydrochlorothiazide not completely, however is pretty fast soaked up in a digestive tract. Increase in removal of sodium and urine is observed already in 2 h and reaches the maximum value approximately in 4 h after reception. This action remains during 6–12 h. After intake in a dose of 100 mg the maximum concentration in blood plasma is reached in 1.5-2.5 h. At the maximum diuretic activity (approximately in 4 h after reception) concentration of a hydrochlorothiazide in blood plasma makes 2 mkg/ml. Linking with proteins of blood plasma makes 40%. Primary way of elimination — renal (filtration and secretion) in not changed look. Elimination half-life at patients with normal function of kidneys makes 6.4 h, patients with a moderate renal failure have 11.5 h, and patients with clearance of creatinine have less than 30 ml/min. — 20.7 h. The hydrochlorothiazide gets through a placental barrier and is excreted with breast milk.

Indication

For elimination of hypostases in stagnant heart failure, cirrhosis with ascites, a premenstrual syndrome, therapy gks or estrogen;

in the hypostases connected with various forms of dysfunction of kidneys, such as nephrotic syndrome, acute glomerulonephritis and HPN;

for treatment of AG in the form of monotherapy or in a combination with other antihypertensive medicaments (at more severe forms of AG);

for reduction of a polyuria (paradoxical image), mainly in nephrogenic not diabetes;

for decrease in a hypercalcuria.

Use

Dose of medicament is selected individually (under constant medical control establish a minimal effective dose).

should take the Pill after a meal.

Usual initial dose for elimination of hypostases makes 25–100 mg of 1 times a day or 1 time in 2 days. Depending on clinical performance the dose is reduced to 25–50 mg of 1 times a day or 1 time in 2 days. In hard cases it is possible to use medicament in an initial dose to 200 mg/days

In premenstrual hypostasis a usual dose makes 25 mg/days and it is applied from the beginning of manifestation of symptoms prior to the beginning of periods.

as antihypertensive medicament a hydrochlorothiazide usually appoint in an initial daily dose 25–50 mg in one step in the form of monotherapy or in a combination with other hypotensive drugs. For some patients the use in an initial dose is enough 12.5 mg both in the form of monotherapy, and in a combination with other hypotensive drugs. It is necessary to use medicament in the minimal effective dose which is not exceeding 100 mg/days. If the Hydrochlorothiazide is combined with other hypotensive drugs, there can be a need for a dose decline of other medicament to prevent excessive decrease in the ABP.

within 3–4 days, however for achievement of optimum effect can be required up to 3–4 weeks. After the end of treatment the hypotensive effect remains about 1 week

In nephrogenic not diabetes the recommended daily dose is 50–150 mg in stages.

depending on the body weight of the child. The usual daily dose makes 1–2 mg/kg of body weight or 30–60 mg on 1 m ² body surfaces and 1 time a day is accepted. The daily dose for children under 2 years makes 12.5-37.5 mg, 2–12 years — 37.5-100 mg a day.

Contraindication

Hypersensitivity to medicament or to other sulfonamides, an anury, heavy renal (the clearance of creatinine is lower than 30 ml/min.) or a liver failure, the feeding period a breast.

Side effects

Disturbance of electrolytic balance: a hypopotassemia, a hypomagnesiemia, a hypercalcemia and a gipokhloremichesky alkalosis which are shown in the form of dryness in a mouth, thirst, arrhythmia, changes of mentality, mood, spasms and myalgia, nausea, vomiting, increased fatigue or weakness. the gipokhloremichesky alkalosis can cause development of hepatic encephalopathy or hepatic coma. the hyponatremia which is shown confusion of consciousness, spasms, a soporous condition, delay of process of thinking, fatigue, hyperexcitability, spasms is possible.

Metabolic disturbances: hyperglycemia, glucosuria. With an asymptomatic course of the disease the Hydrochlorothiazide can cause development of a hyperuricemia and attack of gout in patients.

Use of the Hydrochlorothiazide can worsen tolerance of glucose owing to what the demonstration latentno of the proceeding diabetes can be observed. At use in high doses can lead to increase in level of lipids in blood serum.

from a GIT: cholecystitis or pancreatitis, cholestatic jaundice, diarrhea, sialadenitis, constipation, anorexia.

from a cardiovascular system: arrhythmia, orthostatic hypotension, vasculitis.

Neurologic manifestations: dizziness, passing illegibility of sight, headache, paresthesia.

Hematologic manifestations (very seldom): leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia.

Reaction of hypersensitivity: urticaria, a purpura, a necrotic vasculitis, Stephens's syndrome — Johnson, a respiratory distress syndrome (including a pneumonitis and not cardiogenic hypostasis of a lung), a photosensitization, anaphylactic reactions (up to shock).

Other: decrease in potency, renal failure, interstitial nephrite.

At a long course of treatment the regular control of emergence of clinical symptoms of disturbance of water and electrolytic balance is necessary for

, first of all patients have groups of the increased risk — patients with the broken function of heart and liver. clinical symptoms of disturbance of water and electrolytic balance are: severe vomiting, dryness in a mouth, thirst, weakness, drowsiness, concern, myalgia, spasms, muscle weakness, arterial hypotension, an oliguria, tachycardia, disturbances from a GIT.

Due to the strengthened loss of potassium and magnesium during treatment (potassium level in blood serum can decrease lower than 3.0 mmol/l) the need for compensation of loss of potassium and magnesium arises. The extra care should be observed at patients with the heart failure broken by function of a liver or at the patients receiving treatment by foxglove glycosides. The hypopotassemia can be avoided, applying kaliysoderzhashchy additives or recommending to the patient the diet rich with potassium (fruit, vegetables), especially in case of the increased potassium loss (profound diuresis, long treatment) or simultaneous treatment by glycosides of a foxglove or medicaments GKS.

Hydrochlorothiazide increases removal of magnesium with urine that can lead to development of a hypomagnesiemia.

control of clearance of creatinine is necessary for

At reduced function of kidneys. With diseases of kidneys medicament can cause an azotemia, development of cumulative effects in patients. If the renal failure is obvious, at development of an oliguria it is necessary to weigh a possibility of medicament withdrawal. Patients from the liver broken by function or with the progressing liver diseases should appoint the Hydrochlorothiazide with care as even insignificant disturbance of water and electrolytic balance and also ammonium level in blood serum can cause development of a hepatic coma.

in case of heavy atherosclerosis of brain and coronary arteries the use of medicament demands extra care.

Treatment by the Hydrochlorothiazide can break tolerance of glucose. During a long course of treatment in manifest and latent diabetes the systematic control of metabolism of carbohydrates is necessary; there can be a need for change of a dose of gipoglikemiziruyushchy drugs.

needs to control regularly a condition of patients with the broken metabolism of uric acid. Alcohol, barbiturates, medicaments enhance orthostatic hypotensive effect of the Hydrochlorothiazide.

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At long therapy in rare instances observed the pathological change of function of an epithelial body which is followed by a hypercalcemia and a hypophosphatemia. The hydrochlorothiazide can reduce amount of the iodine contacting proteins of blood plasma without manifestation of symptoms of disorders of function of a thyroid gland.

Use of the Hydrochlorothiazide can cause gastrointestinal disorders in patients with a lactose intolerance in connection with presence of lactose as a part of drug.

In the first days of administration of medicament (duration of this period is defined individually) is forbidden to run vehicles and to perform the works requiring special attention.

during pregnancy medicament can be appointed only in urgent cases, at careful weighing of the expected therapeutic effect for mother and potential risk for the child as medicament reduces the volume of blood plasma and blood supply of a placenta and also gets through a placental barrier. Thus, there is a danger of developing of jaundice of a fruit or the newborn, thrombocytopenia and other negative consequences.

Drug gets into breast milk therefore if use of medicament is absolutely necessary, feeding by a breast should be stopped.

Use of the Hydrochlorothiazide can affect results of laboratory researches: to reduce the level of the iodine connected with proteins in blood plasma; to increase concentration of bilirubin in blood serum.

Before carrying out analyses on function of an epithelial body the Hydrochlorothiazide should be cancelled.

Interaction

Should avoid simultaneous use of medicament with lithium salts (the renal clearance of lithium decreases therefore its toxicity increases).

needs to apply with care the Hydrochlorothiazide with such drugs:

antihypertensive medicaments (their action is exponentiated, dose adjustment can be required);

cardiac glycosides (the hypopotassemia and a hypomagnesiemia connected with effect of thiazide diuretics can increase toxicity of medicaments of a foxglove);

Amiodaronum (its simultaneous use with thiazide diuretics can lead to increase in risk of the arrhythmias connected with a hypopotassemia);

oral anti-diabetic medicaments (their efficiency decreases, the hyperglycemia can develop);

GKS, calcitonin (increase expressiveness of a hypopotassemia);

NPVP (can weaken diuretic and hypotensive effect of the Hydrochlorothiazide);

not depolarizing muscle relaxants (the effect of the last can amplify);

amantadiny (the clearance of an amantadin can decrease that leads to increase in its concentration in blood plasma and to increase in toxicity);

Colestyraminum (absorption of the Hydrochlorothiazide in a GIT can oppress);

alcohol, barbiturates and medicaments which enhance severity of orthostatic hypotension.

Overdose

is the Main consequence of overdose of a hydrochlorothiazide acute dehydration and loss of electrolytes which are shown by the following symptoms: tachycardia, hypotension, shock; weakness, dizziness and systremmas, paresthesia, consciousness disturbances, fatigue; nausea, vomiting, thirst; a polyuria, an oliguria or an anury (because of haemo concentration); a hypopotassemia, a hyponatremia, a hypochloraemia, an alkalosis, the increased urea nitrogen level in blood (especially at patients with a renal failure).

Specific antidote. Gastric lavage and use of activated carbon for medicament absorption reduction is recommended. In case of arterial hypotension or shock it is necessary to fill OCK and shortage of electrolytes (potassium, sodium). It is necessary to control water and electrolytic balance (especially potassium level in blood serum) and function of kidneys before normalization of indicators.

Storage conditions

B the place protected from light at a temperature of 15-25 °C.