Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties:

Pharmacotherapeutic Group: High-ceiling diuretic sulfonamides, loop diuretics; ATC code: C03CA01 

Mechanism of action:

The principle renal action of furosemide is to inhibit active chloride transport in the thick ascending limb. Re-absorption of  sodium, chloride from the nephron is reduced and a hypotonic or isotonic urine produced. Pharmacodynamic effects: 
The evidence from many experimental studies suggests that furosemide acts along the entire nephron with the exception of the distal exchange site. The main effect is on the ascending limb of the loop of Henley with a complex effect on renal circulation. Blood-flow is diverted from the juxta-medullary region to the outer cortex. It has been established that prostaglandin (PG) biosynthesis and the renin-angiotensin system are affected by furosemide administration and that furosemide alters the renal permeability of the glomerulus to serum proteins.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties

Absorption:
Approximately 65% of the dose is absorbed after oral administration. The plasma half-life is biphasic with a terminal elimination phase of about 1½ hours.                                                                                         1 Furosemide is a weak carboxylic acid which exists mainly in the dissociated form in the gastrointestinal tract.
Furosemide is rapidly but incompletely absorbed (60-70%) on oral administration and its effect is largely over within 4 hours. The optimal absorption site is the upper duodenum at pH 5.0.


Distribution:
Furosemide is up to 99% bound to plasma proteins. Biotransformation:

Furosemide is bound to plasma albumin and little biotransformation takes place Elimination: 
Regardless of route of administration 69-97% of activity from a radio-labelled dose is excreted in the first 4 hours after the drug is given. Furosemide is mainly eliminated via the kidneys (80-90%) mainly excreted in the urine, largely unchanged; but also excreted in the bile, non-renal elimination being considerably increased in renal failure.
Furosemide crosses the placental barrier and is excreted in the milk.

A small fraction of the dose undergoes biliary elimination and 10-15% of the activity can be recovered from the faeces.

Hepatic impairment

Where liver disease is present, biliary elimination is reduced up to 50%. Renal impairment 
Renal impairment has little effect on the elimination rate of furosemide, but less than 20% residual renal function increases the elimination time.

Elderly

The elimination of furosemide is delayed in the elderly where a certain degree of renal impairment is present.
Pediatric population
A sustained diuretic effect is seen in the newborn, possibly due to immature tubular function.