Furosemide (Lasix)
written by Matthew Brady, pharmacy class of 2010, Dalhousie University
Introduction
Indications
Mild to moderate hypertension, alone or in combo therapy. If hypertension not controlled with thiazide, then it’s doubtful monotherapy furosemide would.
Fluid overload/edema stemming from heart failure, renal disease, and liver cirrhosis and any other fluid retentive states.
Off-Label: hypertensive crisis, hypercalcemia? (literature controversial).
Clinical Usage and Tips
Onset: 30-60 mins for diuresis with p.o. and approx 5 mins for i.v.
Duration: 6–8 hours for p.o. and 2 hrs for i.v.
Half-Life: 0.5–2 hrs. (increased in patients with HF, renal failure and slightly greater in patients with cirrhosis
*Dose of furosemide should be individualized for each patient.
It is recommended that a 50% (at least) reduction in the dose of other antihypertension meds should be done before initiation of furosemide to avoid a severe drop in BP.
Hypertension: 20–40 mg p.o. o.d – BID. 40 mg p.o. BID is optimal dose.
20 mg, 40 mg, 80 mg p.o. b.i.d equivalent in BP reduction but higher doses increased side effects.
Edema (all causes): 20-80 mg p.o. once daily. Can repeat q6-8hrs after first dose. If diuresis does not occur, increase dose 20-40 mg po. MAX DAILY DOSE: 200 mg p.o. TYPICAL DOSE: 40-120 mg p.o. once daily. 20-40 mg I.V. once daily or twice daily admin slowly over 1-2 minutes. Repeat if no diuresis/inadequate response no sooner than 2 hrs. Can increase dose by 20 mg until result is achieved. **I.V use only when p.o. administration not possible.**
Reduction of Dose in HF: Some studies suggest reduction of dose to 1/3rd of original dose or d/c if 40 mg p.o. o.d. when HF symptoms resolve.
Renal Failure Doses of up to 3200 mg I.V. o.d. ran at rate less than 500 mg/hr has been used in severe renal failure.
Weight loss should NOT exceed 1 kg per day.
Recommend high K+ diet when long therapy is indicated and supplementation when K+ than approximately 3 mEq/L or those receiving digoxin. Use potassium chloride when trying to avoid hypokalemic and hypochloremic states.
Be wary of recommending strict no-salt diet (unless in heart failure patients who can be monitored for hyponatremia).
Can cause hyperglycemia 3-4 weeks post initiation. This is not a contraindication for use in diabetics, but requires frequent monitoring of blood glucose.
Hyperuricemia happens approximately to 40% of men. Women are affected less.Monitor for signs and symptoms of gout and encourage eating more fruits (especially pineapple and cherries) as this may prevent gout flare ups.
Expect an increase in BUN when used in those with chronic renal disease.
Treatment Failure
In situations of inadequate control, explore the following options:
- ensure the patient is adherent with medication dosing
- increase dose of furosemide
- combining with thiazide, timing dose of thiazide about 30 minutes before dose of furosemide so it has time to block the Na+/Cl-
- use an IV bolus injection or continuous infusion of a loop diuretic.
Long-term treatment with furosemide can lead to resistance. via distal upregulation of Na+/Cl- transporters. Since furosemide inhibits the Na+/K+/2Cl- transporter incompletely, excretion is counteracted by the upregulated Na+/Cl- transporters and increased sodium/water (De Bruyne, 2003).
Risk Factors
Precautions
Use in hepatic cirrhosis can cause rapid alterations in fluid/electrolytes and can precipitate hepatic precoma/coma. Liver function tests should be done periodically in those on long term.
Contraindications
- Anurina.
- Discontinue if, during severe and progressive renal disease, increasing azotemia or oliguria occurs.
- Hepatic coma
- Electrolyte depletion until corrected
- Allergy to sulfa drugs. This is controversial and is more a precaution than a contraindication. Furosemide has many benefits in heart failure patients and avoiding it because of a sulfonamide allergy (one that does not include an allergy to furosemide) may be unnecessary (Johnson et al. 2005).
Interactions
Spironolactone, triamterene, or amiloride: may reduce potassium loss; monitor serum [K].
Other diuretics may enhance electrolyte imbalance.
Digoxin: can cause digoxin toxicity.
Corticosteroids: may cause potassium loss.
Lithium: decreased renal clearance of lithium and potential toxicity. Avoid if possible, or hospitalize if treatment necessary.
NSAIDs: may cause reduced efficacy of furosemide as an antihypertensive.
Adverse Reactions
Loss of K+ and resulting hyperkalemia can cause:
- tachyarrhythmias
- rhabdomyolysis
- fatigue
- syncope
- muscle spasms/weakness
- hypokalemic nephropathy (sustained low K+)
- digoxin Poisoning – since digoxin works on a K+/Na+ pump, low levels of K+ potentiate digoxin’s effects.
- low-normal levels of K+ are often asymptomatic.
Dehydration can cause
- orthostatic hypotension (especially in elderly >65 y/o)
- dry mouth and thirst
Rash possibly due to sulfonamide
Photosensitivity
Hyperglycemia
Hyperuricemia and gout (in those who have had history of gout).
Hyperlipidemia (can increase LDL, HDL, and TGs)
Thiamine deficiency due to increased urinary excretion. May be a consideration in heart failure patients.
Permanent ototoxicity can occur in doses 2-4g/daily.
Metabolic alkalosis can occur. This may be due to extracellular volume reduction which causes an increase in [bicarbonate]. Also, aldosterone is released due to volume reduction and this increases reabsorption of sodium and encourages K+ & H+ secretion which ultimately can cause alkalosis. Compensatory hypoventilation and increased CO2 retention can follow.
Pharmacokinetics, Metabolism and Excretion
Absorption: 50-70%, food affects rate but not extent of absorption.
Distribution: highly protein bound (~99%), therefore in disease states like cirrhosis, nephritic syndrome, uremia (and any others that decrease albumin) can increase free drug (unbound) concentrations.
Metabolism: Liver (minor) but increased role with decreased renal functioning.
Excretion: Renal (~90%) as unchanged drug and/or glucuronidated.
Mechanism of Action
Furosemide is a loop-diuretic that selectively inhibits electrolyte reabsorption in the thick ascending limb of the Loop of Henle by inhibiting the Na/K/2Cl triporter. Increased Na+, Cl-, K+ concentration in tubule lumen retains water and causes increased urine excretion. Decreased blood volume decreases blood pressure.
Furosemide also increases elimination of: H+, calcium, magnesium, bicarb, ammonium (all at differing amounts).
Reduces blood volume reduces cardiac preload and afterload. May also increase ejection fraction.
Clinical Vignette 1
A person takes this treatment for this reason due to concerns re: condition
This happens.
How do you respond?
Clinical Vignette 2
Additional Resources
De Bruyne LKM. 2003. Mechanisms and management of diuretic resistance in congestive heart failure. Postgraduate Medical Journal. 79: 268-71.
Johnson KK, Green DL, Rife JP, et al. 2005. Sulfonamide Cross-Reactivity: Fact or Fiction? Annals of Pharmacotherapy. 39: 290-301.
Topic Development
created: DLP, March 2007
authors: Matthew Brady, March 2009
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