Loop Diuretics in Clinical PracticeDiuretics are commonly used to control edema across various clinical fields. Diuretics oral to iv lasix conversion sodium reabsorption in specific renal tubules, resulting in increased urinary sodium and water excretion. Loop diuretics are the most potent diuretics. In this article, we review five important aspects of loop diuretics, in particular furosemide, which oral to iv lasix conversion be considered when prescribing this medicine: The bioavailability of furosemide differs between oral and intravenous therapy. Additionally, the threshold and ceiling doses of furosemide differ according to the particular clinical condition of the patient, for example in patients with severe edema or chronic kidney disease.
Oral Diuretics Recommended for Use in the Treatment of Chronic Heart Failure
Diuretics are commonly used to control edema across various clinical fields. Diuretics inhibit sodium reabsorption in specific renal tubules, resulting in increased urinary sodium and water excretion.
Loop diuretics are the most potent diuretics. In this article, we review five important aspects of loop diuretics, in particular furosemide, which must be considered when prescribing this medicine: The bioavailability of furosemide differs between oral and intravenous therapy.
Additionally, the threshold and ceiling doses of furosemide differ according to the particular clinical condition of the patient, for example in patients with severe edema or chronic kidney disease. To maximize the efficiency of furosemide, a clear understanding of how the mode of delivery will impact bioavailability and the required dosage is necessary.
Diuretics are commonly used to control edema in a number of clinical fields. In this article, we review five important aspects of loop diuretics that we must be aware of when we prescribe this medicine: The bioavailability can be improved if it is taken before meals because food can disrupt its absorption 2.
Furosemide is absorbed from the gastrointestinal tract, and its peak diuretic effect occurs between 1 and 1. Protein-bound furosemide is delivered to the proximal tubule, and secreted via organic transporters that are expressed at the luminal site of action 1 , 2 , 3. Thus, patients with renal dysfunction show a decreased response and increased plasma half-life of furosemide due to the reduction of urinary excretion 1 , 2 , 3.
In patients with severe edema, the effect of furosemide may be altered due to inadequate gastrointestinal absorption. Patients unresponsive to oral furosemide should be switched to intravenous therapy or oral torsemide. The bioavailability of torsemide is predictable. Loop diuretics have a threshold dose; no diuretic effect is shown when the dose is lower than the threshold dose.
They also have a dose-responsive effect. The threshold dose of furosemide differs according to the clinical condition of the patient. For example, the threshold dose of intravenous furosemide is 10mg in a population with normal renal function. This increases to mg in patients with declining renal function 5. Therefore, furosemide doses lower than 80mg are not effective in advanced CKD patients.
Loop diuretics have a ceiling dose; this is the dose that shows the maximum fractional sodium excretion. Although loop diuretics display dose-response curves, doses above the ceiling dose are only moderately effective.
Repeated infusions with the ceiling dose are more effective than increasing the dose of furosemide 4. The ceiling dose of intravenous furosemide also varies in different diseases; this dose is mg in patients with CKD or nephrotic syndrome, and mg in patients with congestive heart failure or liver cirrhosis.
The half-life of the various loop diuretics are not the same: The half-life of furosemide is prolonged in advanced renal dysfunction, and the half-life of torsemide is doubled in hepatic dysfunction. Torsemide can be administered once daily while furosemide needs to be administered two or three times a day 4.
The bolus therapy of furosemide rapidly increases sodium excretion. However, this excretion is at its maximum for the first hours and then it progressively declines 1. Post-diuretic renal sodium and fluid retention are inevitable 6. This compensatory sodium retention occurs along the other segments of the nephron that are not related to furosemide.
To avoid this compensation, furosemide should be injected at short intervals or infused continuously. Continuous intravenous infusion is more effective than, or in some cases, similar to, intravenous bolus therapy 7 , 8 , 9.
A continuous infusion of furosemide tends to increase urine output and is associated with less ototoxicity, a significant side effect associated with furosemide, in patients with acute decompensated heart failure Recently, a randomized double-blind multicenter study was published, which reported on the comparison between bolus and continuous infusions without loading doses in patients with acute decompensated heart failure There was no difference between the groups.
However, meta-analysis showed that the continuous infusion of loop diuretics preceded by a loading dose was more diuretic than intermittent dosing The maximum diuresis occurs 3 hours after continuous infusion has begun Therefore, when furosemide is administered by continuous infusion, an intravenous loading dose of furosemide is required to increase the initial intratubular concentration of furosemide 4 , 7.
The recommended loading dose of furosemide is mg according to renal function. The natriuretic response to furosemide is also reduced in patients with CKD 4. This diminished tubular secretion is due to the elevated level of endogenous organic anions that interfere with furosemide secretion via organic acid transporters in the proximal tubule 4 , Therefore, to achieve the desired effect, higher doses or an increased frequency of furosemide treatment is required to increase tubular secretion.
Patients with nephrotic syndrome also experience decreased furosemide activity. The tubular secretion of furosemide is reduced in patients with hypoalbuminemia, because the delivery of furosemide is dependent on the level of plasma albumin 1 , 2 , 3. Additionally, furosemide can bind to albumin within the tubular lumen, which reduces the level of active and unbound drug that is capable of binding to the tubular receptor 2.
Consequently, a furosemide dose two to three times greater than the usual dose is required to maintain an effective concentration of free drug at the action site. Angiotensin-converting enzyme inhibitor or angiotensin II receptor blockade reduces renal albumin excretion. Salt and water intake must be limited to prevent post-diuretic sodium retention.
In patients with severe hypoalbuminemia, albumin infusion may be considered, although the efficacy of this approach is, to date, undetermined Excessive weight gain between dialysis sessions induces high blood pressure and edema.
Such patients can be considered for furosemide administration if residual renal function remdevelop allergic reactions,ains. Large doses or combination therapy are essential to attain the desired effect in dialysis patients. In one study, furosemide ,mg daily increased urine volume in hemodialysis patients, however, this response gradually declined during the one year follow-up period.
Patients with residual renal function who receive diuretic therapy are twice as likely to have sustained residual renal function one year later, compared with patients without diuretics Therefore, it is not necessary to change the dosing strategy in patients undergoing hemodialysis There are three major types of adverse events associated with furosemide: Excessive diuresis due to high doses of the drug can induce extracellular fluid volume contraction, resulting in contraction alkalosis.
Furosemide induces various electrolyte imbalances including hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia, and hyperuricemia 3 , Hypokalemia is caused by the increased distal delivery of potassium and secondary mineralocorticoid excess Caution should be taken when prescribing furosemide to patients taking digoxin.
Although furosemide does not change the plasma level of digoxin, furosemide-induced hypokalemia increases the risk of digitalis-induced arrhythmias Furosemide is a sulfonamide, and can therefore induce hypersensitivity reactions such as rash or acute interstitial nephritis. In patients who develop allergic reactions, furosemide can be replaced with ethacrynic acid, which is a loop diuretic but not a sulfonamide 3 , However, ethacrynic acid has been shown to be more ototoxic Furosemide can lead to reversible ototoxicity, although permanent deafness had also been reported.
Ototoxicity is related to both the peak serum drug concentration and the rate of infusion. However, lower doses can also cause ototoxicity in patients with renal dysfunction or those undergoing concurrent aminoglycoside therapy Therefore, one must be cautious when considering a bolus infusion of a high furosemide dose.
To avoid an abrupt increase in peak serum concentration, doses higher than 80mg of furosemide need to be infused slowly. Finally, furosemide can displace warfarin from its binding sites on blood proteins. Therefore, a lower dose of warfarin may be needed when warfarin is administered with furosemide. Furosemide increases the risk of gout when co-administered with cyclosporine, which reduces renal urate excretion Loop diuretics, especially furosemide, are widely used in various conditions.
The threshold and ceiling doses of furosemide differ according to the clinical condition. Furosemide also has several side effects, especially in CKD patients.
To maximize the efficiency of furosemide, a solid understanding of its bioavailability and dose adjustment kinetics associated with each route of administration is necessary.
National Center for Biotechnology Information , U. Journal List Electrolyte Blood Press v. Published online Jun Find articles by Se Won Oh. Find articles by Sang Youb Han. Sang Youb Han, M. Received Jun 25; Accepted Jun This article has been cited by other articles in PMC. Abstract Diuretics are commonly used to control edema across various clinical fields. Loop diuretics, Furosemide, Chronic kidney disease.
Introduction Diuretics are commonly used to control edema in a number of clinical fields. Dosage of Loop Diuretics Loop diuretics have a threshold dose; no diuretic effect is shown when the dose is lower than the threshold dose.
Continuous versus Bolus Infusion The bolus therapy of furosemide rapidly increases sodium excretion. Adverse Events There are three major types of adverse events associated with furosemide: Conclusion Loop diuretics, especially furosemide, are widely used in various conditions. N Engl J Med. Am J Physiol Renal Physiol. Diuretic use in renal disease. Update in diuretic therapy: New insights into diuretic use in patients with chronic renal disease.