Furosemide

General characteristics. Structure:

Active ingredient: 40 mg of furosemide in 1 tablet.

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

Pharmacological properties:

Pharmacodynamics. "Loopback" diuretic; causes quickly coming, severe and short-term diuresis. Has natriuretic and hloruretichesky effects, increases removal of potassium ions, calcium, magnesium. Getting into a gleam of a renal tubule in a tolyosty segment of the ascending Henle's loop knee, blocks a reabsorption of ions of sodium and chlorine. Owing to increase in allocation of ions of sodium there is secondary (oposredoyovanny osmotically connected water) a strengthened release of water and increase in secretion of potassium ions in a distal part of a renal tubule. At the same time allocation of calcium ions and magnesium increases. Has the secondary effects caused by release of intra renal mediators and redistribution of an intra renal blood-groove. Against the background of course treatment there is no easing of effect.

At heart failure quickly reduces preloading (at the expense of a phlebectasia), reduces the pulmonary pressure and filling pressure of a left ventricle. This quickly developing effect, apparently, is mediated through effects of prostaglandins and therefore a condition for its development is lack of disturbances in synthesis of prostaglandins in addition to what implementation of this effect also requires dostatochyony safety of renal function.

Has hypotensive effect owing to increase in removal of sodium of chloride and decrease in reaction of smooth muscles of vessels to vasopressor influences, and as a result of reduction of the volume of the circulating blood (VCB).

Effect of furosemide after intake comes in 30-60 min., at most a deystyoviya - in 1-2 h, effect duration - 3-6 h.

During action removal of ions of sodium considerably increases, however after its termination, the speed of removal decreases below the initial level (a syndrome of "rikoyoshet", or "cancellation"). The phenomenon is caused by sharp activation a renin-angiotenzinovogo and other anti-natriuretic neurohumoral links of regulation in response to a massive diuresis; stimulates arginine-vazopressivnuyu and sympathetic system. Reduces the level of an atrial natriuretic factor in a blood plasma, causes vasoconstriction. Owing to a phenomenon of "ricochet" at reception of 1 times a day furosemide can not have significant effect on daily removal of ions of sodium and arteyorialny pressure.

Pharmacokinetics. Absorption - high, bioavailability - 50-70%. Time of achievement of the maximum konyotsentration at intake - 1-1,5 hours. The relative volume of distribution - 0,1-0,2 l/kg of body weight. Communication with proteins of a blood plasma - 98% (generally from an albuminayoma). Gets through a placental barrier, it is allocated with breast milk. Clearance - 1,5-3 ml/min.

It is metabolized with formation of 4-chlorine-5-sulfamoylanthranilic acid. Cosecretes in a gleam of renal tubules through the system of transport of anions existing in proximal department of nephron. An elimination half-life - 0,5-1 hour. It is removed preyoimushchestvenno (88%) by kidneys in not changed look and in the form of metabolites; through a kishechyonik - 12%. At a renal failure removal of furosemide is slowed down, and the elimination half-life increases; at the expressed renal failure the final elimination half-life can increase till 24 o'clock.

At a hemodialysis and peritoneal dialysis and continuous out-patient peritoneal dialysis furosemide is removed slightly. At a liver failure the elimination half-life of furosemide increases by 30-90%, mainly owing to increase in volume a raspredeleyoniya. The pharmacokinetics at such patients is variable. At heart failure, heavy degree of arterial hypertension and at patients of advanced age removal of furosemide is slowed down owing to depression of function of kidneys.

Indications to use:

Edematous syndrome of various genesis, including at chronic heart failure, cirrhosis (a syndrome of portal hypertensia); an edematous syndrome of renal genesis (at a nephrotic syndrome in the forefront there is a treatment of a basic disease); arterial hypertension.

Route of administration and doses:

Appoint inside, in the morning, on an empty stomach, without chewing and washing down with enough liquid.

The mode of dosing is set individually, depending on indications, a kliniyochesky situation, age of the patient, size of the diuretic answer and dynamics of a soyotoyaniye of the patient.

Duration of therapy is defined by the doctor individually.

Average single initial dose for adults - 20-80 mg; in the absence of the diuretic answer the dose is increased by 20-40 mg in each 6-8 h before obtaining the adequate diuyoretichesky answer. It is recommended that the daily dose was divided into 2-3 receptions. The single dose, if necessary, can be increased to 600 mg and more (it is required at a snizheyoniya of size of glomerular filtering and a hypoproteinemia).

At arterial hypertension appoint 20-40 mg, in the absence of sufficient a snizheyoniya of the arterial pressure (AP), it is necessary to attach other antihypertensives to treatment. At addition of Furosemide to already appointed hypotensive drugs, their dose has to be reduced twice.

The initial single dose at children decides at the rate of 1-2 mg/kg of body weight a day on possible increase in a dose up to the maximum 6 mg/kg/days, on condition of reception of a preyoparat not more often than in 6 hours.

Features of use:

Pregnancy and lactation. Furosemide gets through a placental barrier therefore it should not be appointed at pregnancy. If according to vital indications drug is appointed pregnant, then не­обходимо careful observation of a condition of a fruit.

During feeding by a breast reception of furosemide is contraindicated. Furosemide suppresses a lactation. In need of use of drug in the period of a lactation, breastfeeding needs to be stopped.

To apply strictly on doctor's orders.

Patients with hypersensitivity to streptocides and derivatives of sulphonylurea can have cross sensitivity to furosemide.

To the patient receiving high doses of furosemide in order to avoid development giponatriyemi-AI and a metabolic alkalosis it is inexpedient to limit consumption of table salt. For prevention of a hypopotassemia use of drugs of potassium and kaliysberegayushchy diuretics is recommended (first of all Spironolactonum), and also to keep to the diet rich with potassium.

The increased risk of development of disturbances of water and electrolytic balance is noted at patients with a renal failure. During course treatment it is necessary to control periodiyochesk concentration of electrolytes of a blood plasma (including sodium, calcium, potassium, magnesium), an acid-base state, residual nitrogen, creatinine, moyochevy acid and to carry out if necessary the corresponding correctional terayopiya (with bigger frequency rate at patients with frequent vomiting and against the background of parenterally vvodiyomy liquids).

At emergence or strengthening of an azotemia and oliguria in patients with a serious progressiyoruyushchy illness of kidneys, it is recommended to suspend treatment.

Selection of the mode of dosing by the patient with ascites against the background of cirrhosis, it is necessary to provoyodit in stationary conditions (disturbances of water and electrolytic balance can entail development of a hepatic coma). Regular control of electrolytes of a blood plasma is shown to this category of patients.

Use of furosemide can cause deterioration in a current of a system lupus erythematosus, an exacerbation of gout (especially in combination with other ototoksichny prepayorata).

Periodic control of concentration of glucose in blood and urine is required from patients with a diabetes mellitus or with reduced tolerance to glucose.

At patients in unconsciousness, with a prostate hyperplasia, suzheyoniy ureters control of a diuresis in connection with a possibility of an acute zaderzhyoka of urine is necessary.

During treatment it is necessary to avoid occupations potentially dangerous types of a deyatelnoyosta requiring special attention and speed of psychomotor reactions

Side effects:

From water and electrolytic and acid-base balance: hyponatremia, hypochloraemia, hypopotassemia, hypomagnesiemia, hypocalcemia, meyotabolichesky alkalosis. The headache, a sputanyonost of consciousness, a spasm, a tetany, muscular weakness, disturbances of a heart rhythm and dispepsichesky frustration can be the symptoms indicating development of disturbances of an elekyotrolitny and acid-base state. A hypovolemia and dehydration (is more often at patients of advanced age) which can result in haemo concentration with a tendency to development of thrombosis.

From cardiovascular system: excessive decrease in the ABP, orthostatic hypotension, a collapse, tachycardia, arityomiya, decrease in volume of the circulating blood.

From a metabolism: a hypercholesterolemia, a gipertriglitseridemiya, passing increase in concentration of creatinine and urea in blood, increase serumal concentration of uric acid that can cause or strengthen displays of gout, decrease in tolerance to glucose (manifestation latentno протекающе­го a diabetes mellitus is possible).

From an urinary system: an oliguria, an acute ischuria (for example, at a hyperplasia of a prostatic zheleyoza, an urethrostenosis, a hydronephrosis); intersticial nefyorit, a hamaturia, decrease in a potentiality.

From a digestive tract: seldom - nausea, vomiting, diarrhea, separate cases of an intra hepatic cholestasia, poyovysheny activities of "hepatic" enzymes, acute pancreatitis.

From the central nervous system, an acoustic organ: in rare instances - a hearing disorder, usually reversible, and/or a sonitus, osobenyono at patients with a renal failure or a hypoproteinemia (a nefroticheyosky syndrome), it is rare - paresthesias.

From integuments: seldom - a skin itch, a small tortoiseshell, other types of rash or violent damages of skin, a polymorphic erythema, exfoliative dermatitis, a purpura, fever, a vasculitis, an eosinophilia, a photosensitization; extremely seldom - heavy anaphylactic or anaphylactoid reactions up to shock which were described only after intravenous administration so far.

From peripheral blood: seldom - thrombocytopenia, in rare instances a leukopenia, in some cases агра­нулоцитоз, aplastic or hemolitic anemia.

Interaction with other medicines:

Increases concentration and risk of development nefro-and ototoksichesky effect of cephalosporins, aminoglycosides, chloramphenicol, Acidum etacrynicum, Cisplatinum, Amphotericinum In (owing to competitive renal removal).

Increases efficiency of diazoxide and theophylline, reduces - hypoglycemic lekaryostvenny means, Allopyrinolum.

Pressor amines and furosemide mutually reduce efficiency.

The medicines blocking kanaltsiyevy secretion raise a furosemide kontsentrayotion in blood serum.

At simultaneous use of glucocorticosteroids, Amphotericinum In the risk of development of a hypopotassemia increases, with cardiac glycosides - the risk of development of digitalis intoxication owing to a hypopotassemia (for highly - and low-polar) and an elimination half-life udliyoneniya increases (for low-polar).

Reduces renal clearance of drugs of lithium and increases probability of development of an intoksiyokation.

Non-steroidal anti-inflammatory drugs, сукральфат reduce diuretic effect owing to inhibition of synthesis of prostaglandin, disturbance of level of a renin in a blood plasma and removal of Aldosteronum.

Strengthens hypotensive action of antihypertensives, neuromuscular blockade of the depolarizing muscle relaxants (succinylcholine) and (tubocurarine) weakens action of nedepolyarizuyuyoshchy muscle relaxants.

The concomitant use of high doses of salicylates against the background of therapy by furosemide uveliyochivat risk of manifestation of their toxicity (owing to competitive renal a vyvedeyoniya).

Purpose of inhibitors of an angiotensin-converting enzyme (APF) or antagonists of receptors of angiotensin II to the patients who were previously receiving treatment furosemiyody can lead to deterioration in function of kidneys, and in some cases - to development of an acute renal failure.

Furosemide cancellation, or reduction of a dose of furosemide in 3 days prior to therapy by APF inhibitors or antagonists of receptors of angiotensin II is recommended. Simultaneous use of a probenetsid or methotrexate can reduce a furosemide effekyotivnost (an identical way of secretion). On the other hand furosemide can lead to decrease in renal elimination of these medicines.

Cyclosporine A - at a combination to furosemide increases risk of development of podagricheyosky arthritis owing to the hyperuricemia caused by furosemide and disturbances by cyclosporine of excretion of urates kidneys.

Patients with high risk have development of a nephropathy on introduction of the X-ray contrast means receiving furosemide higher frequency of development of narusheyoniya of function of kidneys in comparison with patients with high risk of development of a nephropathy on introduction of X-ray contrast means which received only intravenously a gidrayotation before introduction of X-ray contrast means was observed.

Contraindications:

Hypersensitivity to furosemide or to any of drug components; at patients with an allergy to sulfonamides (sulfanamide antimicrobic means or drugs of sulphonylurea) the cross allergy to furosemide can be noted;

• a renal failure with an anury;

• hepatic coma and prekoma;

• the expressed hypopotassemia;

• the expressed hyponatremia;

• a hypovolemia (with arterial hypotension or without it) or dehydration;

• sharply expressed disturbances of outflow of urine of any etiology (including hemilesion of urinary tract);

• digitalis intoxication;

• acute glomerulonephritis;

• noncompensated aortal and mitral stenosis, hypertrophic obstruktivyony cardiomyopathy;

• increase in the central venous pressure (over 10 mm hg);

• hyperuricemia;

• age up to 3 years (a firm dosage form);

• lactation period;

• intolerance of a galactose, deficit of lactase or glyukozo-galaktozny malyabsobtion.

With care: arterial hypotension, the stenosing atherosclerosis of tserebralyyony arteries, a hypoproteinemia (risk of development of ototoxicity), urine outflow disturbances (a prostate hyperplasia, an urethrostenosis or гидро­нефроз), a system lupus erythematosus, ventricular arrhythmia in the anamnesis, an acute myocardial infarction (increase in risk of development of cardiogenic shock), diarrhea, pancreatitis, a diabetes mellitus (decrease in tolerance to glucose), a gepatorenalny syndrome, gout, a beyoremennost (especially the first half, use only on vital poyokazaniye is possible).

Overdose:

Symptoms: the expressed decrease in the ABP, drowsiness, sluggish paralysis, apathy and a sputanyonost of consciousness, a collapse, shock, thrombosis, nonsense, an acute renal failure.

Treatment: provocation of vomiting, a gastric lavage, absorbent carbon, correction of poyokazatel of water and electrolytic balance and an acid-base state under control of serumal concentration of electrolytes, a hematocrit, a symptomatic treatment.

Storage conditions:

To store in the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 40 mg. Packaging: on 10 tablets in a blister strip packaging from a film of polivinilyokhloridny and aluminum foil. On 5 blister strip packagings together with an instyoruktion on use place in a pack from a cardboard.