Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Diuretics with a major diuretic action. ATC code: C03CA01 Furosemide, a synthesis saluretic agent, causes an increase in the water and sodium elimination, even in cases in which the glomerular filtration is very limited.
The natriuretic effect is dose-dependent, therefore, furosemide allows to obtain a guided diuresis; the urinary excretion of potassium is, instead, significantly limited. As a result, the sodium-potassium ratio is extremely favourable. The diuretic effect following an oral administration begins within the first hour and lasts 4-6 hours; by intravenous administration the effect occurs within few minutes and lasts for about 2 hours, while by intramuscular administration the effect occurs a few minutes later, but the duration of the action is longer.

Pharmacokinetic Properties

5.2. Pharmacokinetic properties
Furosemide is rapidly absorbed from the gastrointestinal tract. The t max for the tablets is about 1-1.5 hours, while for the oral solution is 0.6 hours. The absorption of the drug shows a marked inter- and intra-individual variability. The bioavailability in healthy volunteers is approximately 50 % - 70 % for tablets and about 80 % for the oral solution. In patients, the bioavailability of the drug is affected by various factors including the underlying pathologies and it can be reduced to 30% (e.g. nephrotic syndrome).
Furosemide has a high plasma protein binding (98%), mainly to albumin.
Furosemide is mainly excreted in an unchanged form, through secretion in the proximal tubule. After intravenous administration, approximately 60% - 70 % of the drug is eliminated by this route. There is a metabolite glucuronized for about 10-20% of the total amount excreted in the urine. The remaining amount is excreted in the faeces, probably due to biliary secretion. The terminal half-life of furosemide after intravenous administration is approximately 1 - 1.5 hours.
Furosemide is excreted in breast milk. In addition, it crosses the placental barrier and passes slowly to the fetus. In the fetus and newborn infant it reaches the same concentrations found in the mother.

Renal disorders
The elimination of furosemide is slowed in patients with impaired renal function and its half-life is prolonged up to 24 hours in patients with severe renal insufficiency.
In the nephrotic syndrome the reduced concentrations of plasma proteins lead to a higher concentration of free furosemide (unbound). On the other hand, however, the effectiveness of furosemide is reduced in these patients because of the intratubular albumin binding and the reduced tubular secretion.
Furosemide is poorly removed by haemodialysis in patients undergoing haemodialysis, peritoneal dialysis and CAPD.

Hepatic failure
In patients with hepatic failure, the half-life of furosemide is increased from 30% to 90 %, primarily due to a larger volume of distribution. Moreover, in these patients there is a wide variation in all pharmacokinetic parameters.