Pharmacology: Pharmacodynamics: Mechanism of Action: Furosemide is a potent diuretic. It is an anthranilic acid derivative and chemically it is 4-chloro-N-furfuryl-5-sulphamoylanthranilic acid. Furosemide inhibits the reabsorption of sodium and chloride in the loop of Henle as well as in the proximal and distal tubules; its action is independent of any inhibitory effect on carbonic anhydrase. The urinary excretion of potassium, calcium and magnesium is increased by Furosemide.
Hyperuricaemia may occur and is presumed to result from a competitive inhibition of urate secretion in the proximal tubules. Furosemide has a steep dose-response curve and is designated a high-ceiling diuretic. Following intravenous administration, the onset of diuresis is within 5 minutes and the duration of diuretic effect is approximately two hours.
Pharmacokinetics: Furosemide is extensively bound to plasma proteins and is mainly excreted in the urine, largely unchanged. Significantly more Furosemide is excreted in urine following intravenous injection than after the tablet form. Furosemide glucuronide is the main biotransformation product. Furosemide has a biphasic half-life in plasma with a terminal elimination phase of approximately 1.5 hours. Although mainly excreted in the urine, variable amounts are also excreted in bile and non-renal elimination may be considerably increased in renal failure.
In renal/hepatic impairment: Where liver disease is present, biliary elimination is reduced up to 50%. Renal impairment has little effect on the elimination rate of Hydro-ren, but less than 20% residual renal function increases the elimination time.
The elderly: The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.
Neonates: A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.