Loop Diuretic

Aka: Loop Diuretic, Furosemide, Lasix, Bumetanide, Bumex, Torsemide, Demadex, Ethacrynic Acid, Edecrin

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II. Indications

  1. Symptomatically reduce pulmonary and Peripheral Edema
    1. Congestive Heart Failure
    2. Nephrotic Syndrome
    3. Renal Insufficiency (GFR<30%)
      1. Other Diuretics (e.g. Thiazide Diuretics) are ineffective at low GFR
      2. Loop Diuretics (esp. Furosemide) may be used to prevent weight gain between Dialysis runs
  2. Emergency Management of Pulmonary Congestion (Lasix)
    1. Left Ventricular Dysfunction (CHF)

III. Contraindications

  1. Sulfonamide Allergy

IV. Precautions

  1. All Loop Diuretics except Torsemide need to be dosed twice daily for effect
  2. Loop Diuretics are associated with significant Electrolyte abnormalities and volume depletion (FDA black box warning)
  3. Loop Diuretics have a threshold dose, below which they have no effect
  4. Loop Diuretics have a ceiling dose, above which increasing dose has little effect
    1. Better in these cases to increase frequency at the ceiling dose

V. Mechanism

  1. Loop Diuretics are the most potent Diuretics
  2. Potently inhibits reabsorption of Sodium and chloride
    1. Action at ascending loop of Henle in glomerulus (Inhibits Na+/K+/Cl+ co-transporter)
    2. Results in increased urinary Sodium and water excretion
  3. Direct Venodilation in Pulmonary Edema
    1. Reduces venous return (Preload)
    2. Reduces Central Venous Pressure
    3. Synergistic effect with Morphine and Nitroglycerin
  4. Reduces Intravascular Volume
    1. Reduces Cardiac Output
    2. Beware Hypotension in Myocardial Infarction

VI. Preparations: Relative Potency (40 to 20 to 1)

  1. Furosemide (Lasix) 40 mg IV (equivalent to 80 mg oral, but variable bioavailability)
  2. Torsemide (Demadex) 20 mg IV (equivalent to 20 mg oral)
  3. Bumetanide (Bumex) 1 mg IV (equivalent to 1 mg oral)
  4. References
    1. Pham (2017) Card Fail Rev 3(2):108-122 +PMID: 29387462 [PubMed]

VII. Preparations: Bumetanide (Bumex)

  1. Oral dosing (adults)
    1. Start: 0.5 to 1 mg orally twice daily
    2. Maximum: 10 mg/day
    3. Duration: 4-6 hours
  2. Intravenous dosing (adults)
    1. Start: 1 mg IV/dose (Max: 4-8 mg/dose)
  3. Intravenous Infusion (adults)
    1. Load: 1 mg IV
    2. Rate: 0.5 to 2 mg/hour IV

VIII. Preparations: Furosemide (Lasix)

  1. Precautions
    1. Lasix (named for LAst SIX) is only effective for 6 hours
    2. Optimal dosing is given at least twice daily (patient otherwise is Sodium avid 18 hours/day)
    3. Half-life: 1 to 1.5 hours
    4. Highly variable bioavailability on oral ingestion (varies between 10 and 90%)
      1. Increased bioavailability when taken with meals
      2. Gastrointestinal absorption is markedly decreased in severe edema
      3. Contrast with Torsemide which has excellent and consistent bioavailability
    5. Higher doses (2-3x) required for Nephrotic Syndrome
    6. Renal dysfunction results in decreased response and increased half-life
      1. Only 15-20% of Furosemide dose is delivered to the renal tubule in stage 5 CKD
  2. Oral Dosing (adults)
    1. Start: 20-40 mg orally daily to twice daily
    2. Maximum: 600 mg/day (rare to exceed 400 mg/day)
    3. Peak effect at 1 to 1.5 hours after oral dose
    4. Duration: 6-8 hours
  3. Intravenous Dosing
    1. Intravenous dose is typically one half of oral dose (in exacerbations, the oral dose is often used IV)
    2. Administer slowly over 1-2 minutes
      1. Doses higher than 80 mg should infuse slowly to avoid Ototoxicity
    3. Bolus: 20-40 mg IV (0.5-1.0 mg/kg, max 2 mg/kg)
    4. Infusion: 0.25 to 0.75 mg/kg/hour
    5. Onset: Diuresis starts within 10 minutes
    6. Peak effect in 10-30 minutes
    7. Duration: 6 hours
    8. Peak Diuretic effect of repeat dosing is 25% of the first dose
      1. Compensatory Sodium retention may be overcome by frequent IV doses or continuous infusion
    9. Maximum effective dose (ceiling dose)
      1. Chronic Kidney Disease or Nephrotic Syndrome: 80 to 200 mg
      2. Congestive Heart Failure or Cirrhosis: 40-80 mg
  4. Intravenous Infusion
    1. Background
      1. More effective at maintaining a constant increased Urine Output with less adverse effects (e.g. Ototoxicity)
      2. Maximum diuresis at 3 hours after continuous infusion started
    2. Loading dose: 40-200 mg
      1. Loading doses higher than 80 mg should infuse slowly to avoid Ototoxicity
    3. Infusion dose
      1. Start: 10-20 mg/hour IV
      2. Maximum: 40 mg/hour IV
      3. Very high dose Furosemide infusions (4 mg/min) risk Ototoxicity

IX. Preparations: Torsemide (Demadex)

  1. Background
    1. Oral Bioavailability 80-90% consistently, even in severe edema (contrast with Furosemide)
    2. Once daily dosing (contrast with all other Loop Diuretics)
    3. Half-life: 3 to 4 hours (doubled in hepatic dysfunction)
  2. Oral Dosing (adults)
    1. Start: 10-20 mg orally daily
    2. Maximum: 200 mg/day
    3. Duration: 12-16 hours
  3. Intravenous Dosing (adults)
    1. Start: 10 mg IV
    2. Maximum: 100-200 mg/day
  4. Intravenous Infusion (adults)
    1. Load: 20 mg
    2. Rate: 5-20 mg/hour

X. Preparations: Ethacrynic Acid (Edecrin)

  1. Oral Dosing
    1. Start: 25 mg orally daily
    2. Maximum: 200-400 mg divided 2-3 times daily
  2. Intravenous Dosing
    1. Start: 0.5 to 1 mg/kg IV up to 100 mg/dose

XI. Adverse Effects

  1. Risk of central volume depletion (Dehydration, Hypotension and contraction alkalosis)
  2. Renal dysfunction
    1. Minimize dosage when starting an ACE Inhibitor
    2. Avoid NSAIDs
  3. Hypersensitivity (esp. Sulfonamide)
    1. Ethacrynic Acid is the only non-sulfonamide Loop Diuretic
  4. Electrolyte abnormalities
    1. Metabolic Alkalosis
    2. Hypokalemia
    3. Hypomagnesemia
    4. Hypocalcemia
    5. Hyponatremia
    6. Hyperosmolality
  5. Ototoxocity
    1. Typically reversible (but permanent Deafness may occur)
    2. Risk Factors
      1. Higher Loop Diuretic serum concentrations (esp. high dose Furosemide)
      2. Renal dysfunction
      3. Concurrent Aminoglycoside use
      4. More common with Ethacrynic Acid

XII. Mechanism: Loop Diuretic Resistance

  1. Renal Insufficiency
    1. Renal Toxin (e.g. NSAID) decreases GFR
    2. NSAIDs
  2. Decreased Diuretic oral absorption
  3. Structural changes in the Kidney
    1. Normal aging
    2. Distal tubular hypertrophy (long term use)
      1. Consider adding a Thiazide Diuretic
      2. Counters distal tubular reabsorption
      3. Significantly boosts Loop Diuretic effect
  4. Increased Dietary Sodium intake
    1. CHF patient is an avid Sodium retainer
    2. Sodium is common in most foods
      1. Chicken Noodle soup = 1200 meq
      2. Milk 122 meq
      3. Big Mac 1010 meq
      4. Canned Spinach 910 meq

XIII. Drug Interactions

  1. Warfarin
    1. Furosemide displaces Warfarin from Protein binding and increases Warfarin levels and INR
  2. Cyclosporine
    1. Cyclosporine decreases Uric Acid excretion, and increased gout risk when used with Furosemide

XIV. References

  1. Won Oh (2015) Electrolyte Blood Press 13(1):17-21 +PMID: 26240596 [PubMed]

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Related Studies

Cost: Medications

Furosemide (on 6/18/2017 at Walmart.com)
Furosemide 20mg #30 tablets for $4.00 $0.13 each
Furosemide 20mg #90 tablets for $10.00 $0.11 each
Furosemide 40mg #30 tablets for $4.00 $0.13 each
Furosemide 40mg #90 tablets for $10.00 $0.11 each
Furosemide 80mg #30 tablets for $4.00 $0.13 each
Furosemide 80mg #90 tablets for $10.00 $0.11 each
furosemide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
FUROSEMIDE 10 MG/ML SOLUTION Generic $0.10 per ml
FUROSEMIDE 20 MG TABLET Generic $0.02 each
FUROSEMIDE 40 MG TABLET Generic $0.02 each
FUROSEMIDE 80 MG TABLET Generic $0.04 each
lasix (on 3/8/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
LASIX 20 MG TABLET Generic $0.02 each
LASIX 40 MG TABLET Generic $0.02 each
bumetanide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
BUMETANIDE 0.5 MG TABLET Generic $0.66 each
BUMETANIDE 1 MG TABLET Generic $0.61 each
BUMETANIDE 2 MG TABLET Generic $1.12 each
torsemide (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
TORSEMIDE 10 MG TABLET Generic $0.08 each
TORSEMIDE 100 MG TABLET Generic $0.28 each
TORSEMIDE 20 MG TABLET Generic $0.09 each
TORSEMIDE 5 MG TABLET Generic $0.06 each
edecrin (on 5/18/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
EDECRIN 25 MG TABLET $21.72 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

Ontology: Bumetanide (C0006376)

Definition (NCI) A potent sulfamoylanthranilic acid derivative belonging to the class of loop diuretics. In the brain, bumetanide may prevent seizures in neonates by blocking the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC1), thereby inhibiting chloride uptake thus, decreasing the internal chloride concentration in neurons and may block the excitatory effect of GABA in neonates.
Definition (CSP) 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid.
Definition (MSH) A sulfamyl diuretic.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002034
SnomedCT 387498005, 86647004
LNC LP16052-0, MTHU006833
English Bumetanide, Bumethanide, Benzoic acid, 3-(aminosulfonyl)-5-(butylamino)-4-phenoxy-, bumetanide, bumetanide (medication), BUMETANIDE, Bumetanide [Chemical/Ingredient], Bumetanide (product), Bumetanide (substance)
Swedish Bumetanid
Czech bumetanid
Finnish Bumetaniidi
Russian BUMETANID, БУМЕТАНИД
Japanese ブメタニド
Polish Bumetanid
Spanish bumetanida (producto), bumetanida (sustancia), bumetanida, Bumetanida
French Bumétanide
German Bumetanid
Italian Bumetanide
Portuguese Bumetanida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Ethacrynic Acid (C0014963)

Definition (NCI) An unsaturated ketone derivative of aryloxyacetic acid without a sulfonamide substituent belonging to the class of loop diuretics. Ethacrynic acid is extensively bound to plasma proteins; both ethacrynic acid in its unchanged form as well as its metabolites are excreted in bile and urine.
Definition (MSH) A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.
Definition (PDQ) An aryloxy-acetic acid derivative belonging to the class of loop diuretics. Ethacrynic acid interferes with the chloride binding site of the Na+, K+, Cl- cotransporter system in the thick ascending loop of Henle, thereby inhibiting the reabsorption of sodium, potassium, and chloride ions. This leads to an increase in the excretion of sodium, potassium, chloride, calcium, and water. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41163&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41163&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C485" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D004976
SnomedCT 373536004, 81947000
English Acid, Etacrynic, Acid, Ethacrynic, Etacrynic Acid, Acetic acid, (2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxy)-, Acid, Ethacrinic, Ethacrinic Acid, [2,3-Dichloro-4-(2-methylene-1-oxobutyl)phenoxy]acetic Acid, ethacrynic acid, EA, ethacrynic acid (medication), Ethacrynic Acid, Ethacrynic Acid [Chemical/Ingredient], ethacrinic acid, etacrynic acid, Ethacrynic acid, Ethacrynic acid product, Etacrynic acid, Ethacrynic acid (product), Ethacrynic acid (substance), Etacrynic acid product, ETHACRYNIC ACID
Swedish Etakrynsyra
Czech kyselina ethakrynová
Finnish Etakryynihappo
Russian ETAKRINOVAIA KISLOTA, ЭТАКРИНОВАЯ КИСЛОТА
Japanese エタクリン酸
Croatian ETAKRINSKA KISELINA
Polish Kwas etakrynowy
Spanish ácido etacrínico (producto), ácido etacrínico (sustancia), ácido etacrínico, Ácido Etacrínico
French Acide étacrynique
German Etacrynsäure
Italian Acido etacrinico
Portuguese Ácido Etacrínico
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Furosemide (C0016860)

Definition (CHV) a drug used as a diuretic
Definition (CHV) a drug used as a diuretic
Definition (CHV) a drug used as a diuretic
Definition (NCI) A sulfamoylanthranilic acid derivative, also known as frusemide, and potent loop diuretic. Furosemide is widely used to treat hypertension and edema. This agent is highly bound to albumin and is largely excreted unchanged in the urine.
Definition (CSP) sulfamyl saluretic and diuretic; has a fast onset and short duration of action and is used in edema and chronic renal insufficiency.
Definition (MSH) A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
Definition (PDQ) An anthranilic derivative and loop diuretic with antihypertensive effect. Furosemide blocks the Na-K-Cl cotransporter (NKCC) in the luminal membrane of the thick ascending limb of the loop of Henle in the kidney, by binding to the Cl-binding site located in the cotransporter's transmembrane domain, thereby inhibiting reabsorption of sodium, chloride, potassium ions and water. This agent reduces plasma and extracellular fluid volume resulting in decreased blood pressure and cardiac output. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39247&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39247&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C515" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D005665
SnomedCT 387475002, 81609008
LNC LP32693-1, LP16155-1, MTHU016795
English Frusemid, Frusemide, Fursemide, Benzoic acid, 5-(aminosulfonyl)-4-chloro-2-((2-furanylmethyl)amino)-, Furosemide, furosemide, FRS, FUROSEMIDE, furosemide (medication), Furosemide [Chemical/Ingredient], frusemide, fursemide, Furosemide (product), Furosemide (substance)
Swedish Furosemid
Czech furosemid
Finnish Furosemidi
Russian FRUSEMID, FUROSEMID, FURSEMID, ФРУСЕМИД, ФУРОСЕМИД, ФУРСЕМИД
Italian Fursemide, Frusemide, Furosemide
Croatian FUROSEMID
Spanish frusemida, furosemida (producto), furosemida (sustancia), furosemida, Frusemida, Furosemida, Fursemida
Polish Furosemid, Lasix
Japanese フルセミド, フロセミド
French Furosémide
German Frusemid, Furosemid, Fursemid
Portuguese Frusemida, Furosemida, Fursemida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: torsemide (C0076840)

Definition (NCI) An anilinopyridine sulfonylurea belonging to the class of loop diuretics. Torsemide has a prolonged duration of action compared to other loop diuretics, is extensively protein bound in plasma and has a relatively long half-life.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C026116
SnomedCT 318034005, 108476002
English 1-isopropyl-3-((4-m-toluidino-3-pyridyl)sulfonyl)urea, torasemide, torsemide, 1-isopropyl-3-((4-(3-methylphenylamino)pyridine)-3-sulfonyl)urea, torsemide (medication), TORSEMIDE, torsemide [Chemical/Ingredient], Torasemide, Torsemide, Torasemide (product), Torsemide (substance), Torasemide (substance)
Spanish torasemida (sustancia), torsemida, torsemida (sustancia), torasemida (producto), torasemida
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Demadex (C0243946)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C026116
English Demadex, demadex
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Loop Diuretics (C0354100)

Definition (NCI) Any agent belonging to the class of loop diuretics. Loop diuretics block and inhibit the function of the sodium-potassium-chloride (Na+, K+, Cl-) cotransporter system in the thick ascending limb of the loop of Henle, thereby inhibiting the reabsorption of sodium, potassium, and chloride ions. This leads to an increase in the excretion of sodium, potassium, chloride, calcium, magnesium, ammonium and water.
Concepts Pharmacologic Substance (T121)
MSH D049994
SnomedCT 371334009, 372691009, 29051009
English Loop Diuretic, LOOP DIURETICS, loop-acting diuretics (medication), loop-acting diuretics, [CV702] LOOP DIURETICS, diuretics loop, loop diuretics, loop diuretic, Loop Diuretics, Loop diuretic product (product), Loop diuretic, Loop diuretic (substance), Loop diuretic (product), Loop diuretic product, Diuretics, Loop
French Diurétiques de l'anse, Diurétiques de l'anse de Henle
Czech kličková diuretika
German Schleifendiuretika
Spanish producto con diurético de asa, producto con diurético de asa (producto), diurético de asa (sustancia), diurético de asa, diurético de asa (producto)
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Edecrin (C0591434)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D004976
English edecrin, Edecrin
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Lasix (C0699992)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D005665
English lasix, Lasix
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Bumex (C0701009)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D002034
English bumex, Bumetanide Roche Brand, Roche Brand of Bumetanide, Bumex
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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