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Furosemide 40mg
Furosemide
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Active Ingredient: Furosemide

Furosemide is used for treating fluid build-up and swelling caused by congestive heart failure, liver cirrhosis, or kidney disease. It is also used in combination with other medicines to treat fluid build-up in the lungs. Furosemide is a loop diuretic. Loop diuretics make the kidneys eliminate larger amounts of electrolytes (especially sodium and potassium salts) and water than normal (diuretic effect). Loop diuretics are useful for treating many conditions in which salt and water retention (eg, edema, swelling) is a problem.

Dosage Form

Granules for the preparation of suspension for oral administration (for children), a solution for intravenous and intramuscular administration, tablets.

Pharmacologic Effect

"Loopback" diuretic; causes a fast, strong and short-term diuresis. It has natriuretic and chloruretic effects, increases the excretion of K +, Ca2 +, Mg2 +. Penetrating into the lumen of the renal tubule in the thick segment of the ascending knee of the loop of Henle, blocks the reabsorption of Na + and Cl–. Due to an increase in the excretion of Na +, a secondary (mediated osmotically bound water) enhanced water excretion and an increase in K + secretion in the distal part of the renal tubule occurs. At the same time, excretion of Ca2 + and Mg2 + increases. It has secondary effects due to the release of intrarenal mediators and the redistribution of intrarenal blood flow. Against the background of a course of treatment, the effect does not weaken. In heart failure, it quickly leads to a decrease in preload on the heart through the expansion of large veins. It has a hypotensive effect due to an increase in NaCl excretion and a decrease in the reaction of vascular smooth muscle on vasoconstrictor effects and as a result of a decrease in the BCC. The action of furosemide after intravenous administration occurs in 5-10 minutes; after ingestion - after 30-60 minutes, the maximum action - after 1-2 hours, the duration of the effect - 2-3 hours (with reduced kidney function - up to 8 hours). During the period of validation, Na + excretion increases significantly, however, after its termination, the excretion rate decreases below the initial level (“rebound” or “cancellation” syndrome). The phenomenon is caused by a sharp activation of the renin-angiotensin and other antinatriuretic neurohumoral regulation links in response to massive diuresis; stimulates arginine-vasopressive and sympathetic systems. Reduces the level of atrial natriuretic factor in plasma, causes vasoconstriction. Due to the phenomenon of "rebound" when taken 1 time per day may not have a significant impact on the daily excretion of Na + and blood pressure.

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Pharmacokinetics

Absorption - high, TCmax when taken orally - 1-2 hours, with intravenous administration - 30 minutes. The remaining pharmacokinetic parameters for intravenous administration and ingestion are the same. Bioavailability - 60-70%. Relative volume of distribution - 0.2 l / kg. Communication with plasma proteins - 98%. Gets through a placental barrier, it is allocated with breast milk. Metabolized in the liver to form 4-chloro-5-sulphamoyl anthranilic acid. It is secreted into the lumen of the renal tubules through the anion transport system existing in the proximal nephron. T1 / 2 = 0.5–1 h. Excreted mainly (88%) by the kidneys in unchanged form and in the form of metabolites; with feces - 12%. Clearance - 1.5-3 ml / (min • kg).

Indications

Edema syndrome in CHF grade II — III, liver cirrhosis, kidney disease (including against the background of nephrotic syndrome); acute heart failure (pulmonary edema), brain edema, hypertensive crisis (alone or in combination with other antihypertensive drugs), arterial hypertension (severe), hypercalcemia; conducting forced diuresis in case of poisoning by chemical compounds excreted by the kidneys in unchanged form; eclampsia.

Contraindications

Hypersensitivity, acute renal failure with anuria (glomerular filtration rate value is less than 5.3 ml / min), severe hepatic failure, hepatic coma and precoma, stenoses of the urethra, acute glomerulonephritis, obstruction of urinary tract stone prekomatosnoe state, hyperglycemic coma, hyperuricemia, gout , decompensated mitral or aortic stenosis, GOKMP, increased central venous pressure (over 10 mm Hg), arterial hypotension, acute myocardial infarction, pancreatitis, drug shenie water-electrolyte metabolism (hypovolemia, hyponatremia, hypokalemia, hypochloremia, hypocalcemia, hypomagnesemia), digitalis intoxication.

Alert
With caution. Prostatic hyperplasia, SLE, hypoproteinemia (risk of ototoxicity), diabetes mellitus (decreased glucose tolerance), stenosing atherosclerosis of cerebral arteries, pregnancy (especially the first half, may be used for life), lactation.

Dosing regimen

Intravenous (rarely intramuscularly), parenteral administration is advisable to carry out in cases where it is not possible to take it inside - in emergency situations or with a pronounced edematous syndrome. Edema syndrome: the initial dose is 40 mg. Intravenous administration is carried out within 1-2 minutes; in the absence of a diuretic response, it is administered every 2 h in a dose increased by 50% until adequate diuresis is achieved. The average daily dose for intravenous administration in children is 0.5-1.5 mg / kg, the maximum is 6 mg / kg. Patients with reduced glomerular filtration and low diuretic response are prescribed in large doses - 1–1.5 g. The maximum single dose is 2 g. Inside, in the morning, before meals, the average single initial dose is 20–80 mg; in the absence of a diuretic response, the dose is increased by 20-40 mg every 6-8 hours until an adequate diuretic response is obtained. A single dose, if necessary, can be increased to 600 mg or more (required when reducing the glomerular filtration and hypoproteinemia). In hypertension, 20-40 mg is prescribed, in the absence of a sufficient reduction in blood pressure, other antihypertensive drugs must be added to the treatment. When furosemide is added to already prescribed antihypertensive drugs, their dose should be reduced by 2 times. The initial single dose in children is 2 mg / kg, the maximum - 6 mg / kg.

Side effects

Since the cardiovascular system

Decrease in arterial pressure, orthostatic hypotension, collapse, tachycardia, arrhythmias, decrease in circulating blood volume.

The nervous system

Dizziness, headache, myasthenia, calf muscle cramps (tetany), paresthesia, apathy, weakness, weakness, lethargy, drowsiness, confusion.

From the senses

Impaired vision and hearing.

From the digestive system

Decreased appetite, anorexia, dry mouth, thirst, nausea, vomiting, constipation or diarrhea, cholestatic jaundice, pancreatitis (exacerbation).

From the genitourinary system

Oliguria, acute urinary retention (in patients with prostatic hypertrophy), interstitial nephritis, hematuria, reduced potency.

Allergic reactions

Purpura, urticaria, exfoliative dermatitis, erythema multiforme exudative, vasculitis, necrotizing angiitis, pruritus, chills, fever, photosensitization, anaphylactic shock.

From the side of blood formation organs

Leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia.

From the water and electrolyte exchange

Hypovolemia, dehydration (risk of thrombosis and thromboembolism), hypokalemia, hyponatremia, hypochloremia, hypocalcemia, hypomagnesemia, metabolic alkalosis.

Laboratory values

Hyperglycemia, hypercholesterolemia, hyperuricemia, glycosuria, hypercalciuria. When administered intravenously (optional) - thrombophlebitis, renal calcification in premature babies.

Overdose

Symptoms: reduction in blood pressure, collapse, shock, hypovolemia, dehydration, hemoconcentration, arrhythmias (including AV block, ventricular fibrillation), acute renal failure with anuria, thrombosis, thromboembolism, drowsiness, confusion, flaccid paralysis, apathy. Treatment: correction of water-salt balance and KOS, replenishment of BCC, symptomatic treatment. There is no specific antidote.

Special instructions

Against the background of a course of treatment, it is necessary to periodically monitor blood pressure, plasma electrolyte concentration (including Na +, Ca2 +, K +, Mg2 +), KOS, residual nitrogen, creatinine, uric acid, liver function, and, if necessary, appropriate correction of treatment (with more frequency in patients with frequent vomiting and on the background of parenterally injected fluids). Patients with hypersensitivity to sulfonamides and sulfonylurea derivatives may have a cross-sensitivity to furosemide. Patients receiving high doses of furosemide, in order to avoid the development of hyponatremia and metabolic alkalosis, it is impractical to limit salt intake. For the prevention of hypokalemia, the simultaneous administration of K + and potassium-sparing diuretics (primarily spironolactone) is recommended, as well as a diet rich in K +. An increased risk of developing disorders of water and electrolyte balance is observed in patients with renal insufficiency. Selection of the dosing regimen for patients with ascites on the background of cirrhosis should be carried out in stationary conditions (violations of water and electrolyte balance may lead to the development of hepatic coma). This category of patients shows regular plasma electrolyte monitoring. It is recommended to suspend treatment when the onset or increase of azotemia and oliguria in patients with severe progressive kidney disease. Provided with milk in women during lactation, and therefore it is advisable to stop feeding. Patients with diabetes mellitus or with reduced glucose tolerance require periodic monitoring of the concentration of glucose in the blood and urine. In patients with unconsciousness, with hypertrophy of the prostate gland, narrowing of the ureters or hydronephrosis, monitoring of urine output is necessary due to the possibility of acute urinary retention. During the period of treatment should be avoided classes of potentially hazardous activities that require increased attention and speed of psychomotor reactions.

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Dope

Although furosemide itself is not doping, it is used in sports medicine for removing banned substances and, as a result, is itself equated with doping drugs and is banned for use in athletes by the World Anti-Doping Agency (WADA). In addition, in some non-power sports such as rhythmic gymnastics or synchronized swimming, where the weight of an athlete is fundamental, furosemide is used as a means of losing weight, which is also regarded as doping.

Interaction

Combinations not recommended

Chloral hydrate - intravenous infusion of furosemide for a 24-hour period after the use of chloral hydrate can lead to hyperemia of the skin, heavy sweating, anxiety, nausea, high blood pressure and tachycardia. Therefore, the use of furosemide together with chloral hydrate is not recommended.

Aminoglycosides - slowing the excretion of aminoglycosides by the kidneys, while their simultaneous use with furosemide and increasing the risk of the development of ototoxic and nephrotoxic effects of aminoglycosides. For this reason, the use of this combination of drugs should be avoided, unless it is necessary for health reasons, and in this case, correction (decrease) of maintenance doses of aminoglycosides is required.

Careful combinations

Ototoxic drugs - furosemide potentiates their ototoxicity. Such drugs can be used simultaneously with the drug Furosemide only under strict medical indications, as the combined use can lead to irreversible damage to the organ of hearing.

Cisplatin - when used simultaneously with furosemide, there is a risk of ototoxic action. In addition, it is possible to increase the nephrotoxic effect of cisplatin when using furosemide for conducting forced diuresis during treatment with cisplatin, if furosemide is not used in a low dose (for example, 40 mg in patients with normal kidney function) and without the corresponding hydration of the patient.

Sucralfate - reducing the absorption of furosemide when taken orally and weakening its effect (furosemide when taken orally and sucralfate should be applied at least two hours apart).

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists - the use of ACE inhibitors or angiotensin II receptor antagonists in patients previously treated with furosemide may lead to an excessive decrease in renal function, and in some cases, the development of acute kidney disease failure, therefore, three days before the start of treatment or an increase in the dose of ACE inhibitors or angiotensin II receptor antagonists, the abolition of furosemide is recommended, or as minimum dose reduction.

Lithium salts - under the influence of furosemide, lithium excretion is reduced, thereby increasing the serum concentration of lithium, which increases the risk of developing toxic effects, including its damaging effects on the heart and nervous system. Therefore, the use of this combination requires monitoring of the lithium content in the blood serum.

Risperidone - care must be taken to carefully weigh the risk-benefit ratio before deciding to use a combination of risperidone with furosemide or other strong diuretics, since an increase in mortality was observed in elderly patients with dementia who received both treatment with risperidone and furosemide).

Levothyroxine - high-dose furosemide can inhibit the binding of thyroid hormones to carrier proteins and, thus, lead first to a transient increase in the concentration of free thyroid hormones, and then, in general, to a decrease in the total concentration of thyroid hormones. When using this combination, you should control the concentration of thyroid hormones.

Interactions that should be taken into account

Cardiac glycosides, drugs that cause lengthening of the QT interval in the event of a disturbance of water and electrolyte balance (hypokalemia or hypomagnemia) with the use of furosemide increases the toxic effect of cardiac glycosides and means causing a prolongation of the QT interval (increased risk of developing heart rhythm disturbances).

Glucocorticosteroids, carbenoxolone, licorice preparations in large quantities and prolonged use of laxatives when combined with furosemide increase the risk of hypokalemia.

Drugs with nephrotoxic action when combined with furosemide increases the risk of their nephrotoxic action.

Non-steroidal anti-inflammatory drugs (NSAIDs) - NSAIDs, including acetylsalicylic acid, can reduce the diuretic effect of furosemide.

In patients with hypovolemia and dehydration (including against the background of taking furosemide), NSAIDs can cause the development of acute renal failure.

Furosemide may increase salicylate toxicity.

Phenytoin - reducing the diuretic action of furosemide.

Antihypertensive drugs, diuretics, or other drugs that can lower blood pressure - when combined with furosemide, a more pronounced decrease in blood pressure is possible.

Probenecid, methotrexate or other drugs that, like furosemide, are excreted in the renal tubules, can reduce the effects of furosemide (the same path of renal excretion); on the other hand, furosemide can lead to a decrease in kidney excretion of these drugs. All this increases the risk of side effects of both the drug Furosemide, and the above-mentioned drugs taken simultaneously with it.

Hypoglycemic agents (both for oral administration and insulin preparations), pressor amines (epinephrine, norepinephrine) - weakening effects when combined with furosemide.

Theophylline, diazoxide, curare-like muscle relaxants - increased effects when combined with furosemide.

High doses of some cephalosporins (excreted mainly by the kidneys) - in combination with furosemide, they increase the risk of nephrotoxic action of cephalosporins.

Cyclosporin A - when combined with furosemide increases the risk of developing gouty arthritis due to hyperuricemia caused by furosemide, and violation of urate excretion of urates by the kidneys under the influence of cyclosporine.

Radiocontrast agents - in patients with a high risk of developing nephropathy due to the introduction of radiopaque substances treated with furosemide, there was a higher incidence of development of renal impairment after administration of radiopaque drugs, compared with patients with a high risk of nephropathy due to the administration of radiopaque drugs, which before administration radiopaque preparation was carried out only intravenous fluid (hydration).

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