Furosemide

General characteristics. Structure:

Active ingredient: 10 mg of furosemide in 1 ml of solution.

Excipients: hydroxide sodium solution 1M, sodium chloride, water for injections.

Pharmacological properties:

Pharmacodynamics. High-speed diuretic, derivative sulfonamide. Has natriuretic and hloruretichesky effects, increases removal of potassium ions, calcium, magnesium. Getting into a gleam of a renal tubule in a thick 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 (mediated by osmotically connected water) a strengthened removal of water and increase in secretion of potassium ions in a distal part of a renal tubule.

At heart failure quickly leads to decrease in preload of heart by means of expansion of large veins. 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 volume of the circulating blood.

At intravenous administration effect of furosemide develops in 15 minutes and continues within 3 hours.

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 "ricochet" 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.

Pharmacokinetics. Time of achievement of the maximum concentration at intravenous administration - 30 minutes. The relative volume of distribution - 0,1-0,2 l/kg and considerably varies depending on a basic disease. Furosemide for 98% contacts proteins of a blood plasma, generally albumine. The final elimination half-life (T1/2) of furosemide after intravenous administration makes from 1 to 1,5 hours.

It is removed preferential (88%) by kidneys in not changed look and mainly by secretion in proximal tubules. After intravenous administration of furosemide of 60-70% of the entered dose it is removed this way, Glyukuronirovanny metabolites of furosemide make 10-20% of the drug which is removed kidneys. Other part is removed through intestines - 12%. Clearance - 1,5-3 ml/min.

Gets through a placental barrier, it is allocated with breast milk. Its concentration at a fruit and the newborn same, as well as at mother.

At a renal failure removal of furosemide is slowed down, and T1/2 increases; at the expressed renal failure final T1/2 can increase till 24 o'clock.

At a hemodialysis and peritoneal dialysis furosemide is removed slightly.

At a liver failure of T1/2 of furosemide increases by 30-90% mainly owing to increase in volume of distribution. Pharmacokinetic indicators at this category of patients can strongly vary. At chronic 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.

At premature and full-term children removal of furosemide can be slowed down that depends on degree of a maturity of kidneys, metabolism of drug at babies can be also slowed down as at them glyukuruniruyushchy ability of a liver is defective. At children whose age after conception exceeds 33 weeks, final T1/2 does not exceed 12 hours. At babies at the age of two months removal of furosemide is also more senior does not differ from that at adults.

Indications to use:

Edematous syndrome at chronic heart failure, an edematous syndrome at an acute heart failure, an edematous syndrome at a chronic renal failure, an acute renal failure, an edematous syndrome at a nephrotic syndrome (at nephrotic a syndrome in the forefront there is a treatment of a basic disease); an edematous syndrome at liver diseases, wet brain; hypertensive crisis; maintenance of an artificial diuresis at poisonings with chemical compounds, the removed kidneys in not changed look.

Route of administration and doses:

Furosemide is appointed intravenously (slowly - struyno), at impossibility - intramusculary (when intravenous administration or use of drug inside is impossible). It is recommended to apply the smallest doses of drug sufficient for achievement of necessary therapeutic effect.

Intravenous administration of Furosemide is carried out when administration of drug is inside impossible or there is a disturbance of absorption of drug in a small intestine or in urgentny situations. The issue of duration of treatment is resolved by the doctor, considering character and severity of a disease. After approach of necessary effect pass to administration of drug inside.

At intravenous administration the drug should be administered slowly. Speed of intravenous administration should not exceed 4 mg a minute. At patients with a heavy renal failure (blood serum creatinine more than 5 mg/dl) it is recommended that rate of administering did not exceed 2,5 mg a minute.

The drug is administered in doses 20-40 mg by 1-2 times a day; in the absence of the diuretic answer each 2 h enter in the dose increased by 50% before achievement of an adequate diuresis.

The patient with reduced glomerular filtering and the low diuretic answer appoint in high doses - 1-1,5 g.

At children the initial single dose of drug makes 1 mg/kg (0,1 ml/kg) of body weight slowly within 1-2 minutes (0,5 ml/kg a minute). The maximum daily dose at intravenous administration at children makes 6 mg/kg.

Features of use:

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

Furosemide suppresses a lactation. In the period of a lactation reception of furosemide is contraindicated.

Before therapy by Furosemide it is necessary to exclude existence of sharply expressed urine outflow disturbances including unilateral.

Patients with partial disturbance of outflow of urine need careful observation, especially at the beginning of therapy by Furosemide.

At patients in unconsciousness, with a benign hyperplasia of a prostate, narrowing of ureters or a hydronephrosis, control of a diuresis, in connection with a possibility of an acute ischuria is necessary.

Against the background of treatment it is necessary to control periodically the ABP, the content of electrolytes of a blood plasma, acid-base state, residual nitrogen, creatinine, uric acid, function of a liver and to carry out, if necessary, the corresponding correction of treatment (owing to vomiting, diarrhea, intensive sweating and against the background of parenterally entered liquids), control of the emitted urine.

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 of a hyponatremia and a metabolic alkalosis it is inexpedient to limit consumption of table salt. For prevention of a hypopotassemia co-administration of drugs of potassium and kaliysberegayushchy diuretics is recommended (first of all Spironolactonum), and also to adhere to the diet rich with potassium (low-fat meat, potatoes, bananas, tomatoes, a cauliflower, spinach, dried fruits, etc.).

The increased risk of development of disturbances of water and electrolytic balance is noted at patients with a renal failure.

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

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

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

The drug Furosemide should not mix up in one syringe with other medicines.

Regular control of function of kidneys and ultrasound examination of kidneys (possibility of a nephrolithiasis and nephrocalcinosis) is required from premature children.

Some side effects (for example, excessive decrease in the ABP) can break ability to concentration of attention and reaction that can be dangerous at control of motor transport or work with mechanisms. Especially it belongs to the period of the beginning of therapy or increase in a dose of drug, and also to cases of a concomitant use of antihypertensives or alcohol.

Side effects:

From cardiovascular system: an excessive lowering of arterial pressure (ABP), a collapse, tachycardia, arrhythmia, decrease in volume of the circulating blood.

From the central nervous system: dizziness, headache, muscular weakness, spasms of gastrocnemius muscles (tetany), paresthesias, apathy, adynamia, weakness, slackness, drowsiness, confusion of consciousness, thrombophlebitis.

From a sense body: hearing disorder.

From a digestive tract: anorexia, dryness in a mouth, thirst, nausea, vomiting, diarrhea, an intra hepatic cholestasia, pancreatitis (aggravation), increase in activity of "hepatic" transaminases.

From urinogenital system: an oliguria, an acute ischuria (at patients with a benign hyperplasia of a prostate, an urethrostenosis), intersticial nephrite, a hamaturia, at premature children is possible a nephrolithiasis and a nephrocalcinosis.

Allergic reactions: purpura, urticaria, exfoliative dermatitis, multiformny erythema, vasculitis, necrotizing angiitis, skin itch, fever, fever, photosensitization, acute anaphylaxis.

From bodies of a hemopoiesis: leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, aplastic or hemolitic anemia.

From water and electrolytic exchange and acid-base balance: hypovolemia, dehydration (risk of development of thrombosis and thromboembolism), hypopotassemia, hyponatremia, hypochloraemia, hypocalcemia, hypomagnesiemia, metabolic alkalosis.

Laboratory indicators: a hyperglycemia, a hypercholesterolemia, a gipertriglitseridemiya, passing increase in concentration of creatinine and urea in blood, a hyperuricemia, a glucosuria, a hypercalcuria.

At premature children within the first weeks of life furosemide can increase risk of preservation of Botallov Canal.

Local pain reaction in the place of an intramuscular injection is possible.

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 medicines, Allopyrinolum.

Pressor amines and furosemide mutually reduce efficiency.

The medicines blocking kanaltsiyevy secretion increase concentration of furosemide 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 lengthenings of an elimination half-life increases (for low-polar).

Reduces renal clearance of drugs of lithium and increases probability of development of intoxication.

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 not depolarizing muscle relaxants.

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

Purpose of inhibitors of the angiotensin-converting enzyme (ACE) or antagonists of receptors of angiotensin II to the patients who were previously receiving treatment by furosemide 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 probenitsid or methotrexate can reduce efficiency of furosemide (an identical way of secretion). On the other hand furosemide can lead to decrease in renal elimination of these medicines. Intravenously entered furosemide has slightly alkali reaction therefore it cannot be mixed with medicines with pH less than 5,5.

Contraindications:

Hypersensitivity to furosemide and other components of drug; at patients with an allergy to sulfonamides (sulfanamide antimicrobic means or drugs of sulphonylurea) the "cross" allergy to furosemide can develop; an acute glomerulonephritis, an acute renal failure with an anury (the size of glomerular filtering less than 3-5 ml/min.), a heavy liver failure, a hepatic coma and a prekoma, sharply expressed disturbances of outflow of urine of any etiology (including hemilesion of urinary tract); the expressed hypopotassemia and a hyponatremia; a hypovolemia (with arterial hypotension or without it) or dehydration; dekompensirovanny mitral or aortal stenosis, increase in the central venous pressure (over 10 mm hg), idiopathic hypertrophic subaortal stenosis, digitalis intoxication.

With care: arterial hypotension; at states at which the excessive lowering of arterial pressure is especially dangerous (the stenosing damages of coronary and/or brain arteries); at an acute myocardial infarction (the risk of development of cardiogenic shock increases); at the latent or demonstrated diabetes mellitus (decrease in tolerance to glucose); to gout; at a gepatorenalny syndrome; at a hypoproteinemia (risk of development of ototoxicity); at urine outflow disturbance (a benign hyperplasia of a prostate, an urethrostenosis or a hydronephrosis); at decrease in hearing; pancreatitis, diarrhea; at ventricular arrhythmia in the anamnesis; at a system lupus erythematosus; at premature children (a possibility of formation of kaltsiysoderzhashchy stones in kidneys (nephrolithiasis) and adjournment of salts of calcium in a parenchyma of kidneys (nephrocalcinosis) therefore regular control of function of kidneys and ultrasound examination of kidneys is necessary).

Overdose:

Symptoms: the expressed decrease in the ABP, a collapse, shock, a hypovolemia, dehydration, haemo concentration, arrhythmias (including an atrioventricular block, fibrillation of ventricles), an acute renal failure with an anury, thrombosis, a thrombembolia, drowsiness, confusion of consciousness, sluggish paralysis, apathy.

Treatment: correction of disturbances of water and electrolytic balance and an acid-base state, hematocrit, completion of volume of the circulating blood, a symptomatic treatment. There is no specific antidote.

Storage conditions:

To store in the place protected from light 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 the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and intramuscular administration of 10 mg/ml. Packaging: on 2 ml in ampoules of neutral glass. 5 ampoules in a blister strip packaging from a film and aluminum foil or without foil. 1 or 2 planimetric packagings together with the scarificator ampoule ceramic or a knife for opening of ampoules and the application instruction in a pack from a cardboard. When using ampoules with a ring of a break or a point of a break the knife or the scarificator do not put.