• ACRONYMS AND DEFINITIONS

• AASLD - American Association for the Study of Liver Diseases
• AHA/ACC - American Heart Assoc / American College of Cardiology
• BP - Blood Pressure
• BMD - Bone Mineral Density
• CrCl - Creatinine clearance
• DBP - Diastolic Blood Pressure
• EASL - European Association for the Study of the Liver
• GFR - Glomerular Filtration Rate
• HCTZ - Hydrochlorothiazide
• PI - Manufacturer's Package Insert
• PTH - ParaThyroid Hormone
• SBP - Systolic Blood Pressure

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• DRUGS IN CLASS

• Loop diuretics
• Furosemide (Lasix®)
• Bumetanide (Bumex®)
• Torsemide (Demadex®)

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• MECHANISM OF ACTION

• GENERAL
• Diuretics cause the kidneys to produce more urine and therefore more fluid is removed from the body
• Fluid loss causes blood pressure to decrease and it reduces the workload on the heart
• Diuretics are used to treat a number of conditions where excess body fluid is a problem - heart failure, kidney failure, liver failure, etc.


• SPECIFIC
• The nephron is the fundamental working unit in the kidney
• The "Loop of Henle" is part of the nephron
• Loop diuretics block sodium reabsorption in the Loop of Henle


• Nephron illustration - schematic of the nephron and how diuretics work

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• EFFECTIVENESS

• HIGH BLOOD PRESSURE (HYPERTENSION)

• Loop diuretics are not commonly used as first- or second-line agents to treat hypertension
• Other classes of blood pressure medications have more favorable side effect profiles and outcome data
• They are frequently used to treat hypertension in patients with conditions that cause fluid retention ( ex. heart failure, kidney disease, and liver failure)


• Cochrane meta-analysis
• A Cochrane meta-analysis evaluated trials in which loop diuretics were used to treat hypertension
• The analysis only found 3 trials where furosemide had been compared to placebo in the treatment of hypertension (none were found for bumetanide and torsemide)
• The following results were seen:
• Systolic blood pressure (SBP)
• In two trials comparing furosemide 40 mg a day to placebo, furosemide lowered SBP by an average of 5.80 mmHg more than placebo
• In one trial comparing furosemide 60 mg a day to placebo, furosemide lowered SBP by an average of 10 mmHg more than placebo [6]
• Diastolic blood pressure (DBP)
• In two trials comparing furosemide 40 mg a day to placebo, furosemide lowered DBP by an average of 3.53 mmHg more than placebo
• In one trial comparing furosemide 60 mg a day to placebo, furosemide lowered DBP by an average of 3.00 mmHg more than placebo [6]


• StraightHealthcare analysis:
• Loop diuretics are not commonly used to treat patients with hypertension unless they also have heart, kidney, or liver failure
• Other medications have more outcome data and favorable side effect profiles than loop diuretics

• HEART FAILURE

• Loop diuretics are the preferred diuretic in most patients with heart failure
• In patients with mild heart failure who do not have significant fluid retention, thiazides may be used
• Loop diuretics are used acutely to remove large volumes of fluid in patients with decompensated heart failure
• Loop diuretics are used chronically in heart failure to prevent fluid retention and buildup
• Despite their almost universal use in patients with heart failure, there have been no long-term studies that have evaluated the effects of loop diuretics on significant clinical outcomes [19]


• Compared to thiazide diuretics, loop diuretics have the following characteristics:
• Loop diuretics increase sodium excretion by 20-25% versus 5-10% for thiazides
• Loop diuretics maintain their effectiveness once the CrCl falls below 30-40 ml/min, where thiazides tend to become ineffective


• Professional guidelines:
• The AHA/ACC recommends diuretics and salt restriction in the following heart failure patients:
• Patients with current or prior symptoms of heart failure
• Patients with a reduced ejection fraction who have evidence of fluid retention
• Loop diuretics are the preferred diuretics in most patients, however, thiazide diuretics may be preferred in hypertensive patients with mild fluid retention [19]
• StraightHealthcare analysis:
• Loop diuretics are the most effective diuretics at removing fluid in patients with heart failure
• Heart failure patients with a history of significant fluid retention should be on a loop diuretic
• Heart failure patients with a history of mild fluid retention and hypertension may be controlled with a thiazide diuretic
• Despite the lack of clinical trials, loop diuretics undoubtedly improve outcomes in heart failure patients as they are the most effective means of treating fluid retention

• CHRONIC KIDNEY DISEASE

• Patients with chronic kidney disease tend to retain sodium and fluid, and this causes their blood pressure to rise
• Loop and thiazide diuretics help to alleviate this effect
• Thiazide diuretics tend to become less effective as kidney function decreases where loop diuretics tend to maintain their effectiveness
• Professional guidelines:
• The National Kidney Foundation recommends the following in chronic kidney disease:
• Thiazide diuretics can be used in patients with a GFR > 30 ml/min/1.73m²
• Loop diuretics can be used in all patients with chronic kidney disease, and should be used in patients with a GFR < 30 ml/min/1.73m²
• Potassium-sparing diuretics should be used with great caution because of their potential to raise potassium levels [90]

• LIVER FAILURE (CIRRHOSIS)

• Liver failure causes arterial dilation which can stimulate the renin-angiotensin-aldosterone system (RAAS)
• RAAS illustration
• Increases in aldosterone can lead to fluid and sodium retention
• Patients with liver failure often develop severe swelling and water retention around the abdomen (a condition called ascites)
• Loop diuretics and aldosterone antagonists block the effect of increased aldosterone (spironolactone has been studied in clinical trials, but eplerenone has not, and therefore eplerenone is not recommended)


• Professional guidelines:
• The EASL and the AASLD give the following general guidelines for diuretics in patients with liver failure (ascites):
• Mild ascites (detectable on a physical exam)
• Mild ascites may be treated with spironolactone alone
• Starting dose of 100 mg a day, titrated up 100 mg every 7 days as needed (max 400 mg a day)
• Monitor weight, potassium levels, and kidney function closely
• If weight loss is not ≥ 2 kg a week, or high potassium levels develop, furosemide may be needed [91]
• Moderate or recurrent ascites
• Moderate or recurrent ascites is typically treated with spironolactone and furosemide combined
• Starting doses are spironolactone 100 mg a day + furosemide 40 mg a day
• Dosing in a 100:40 ratio of spironolactone to furosemide typically keeps potassium levels normal
• Dosing may be increased every 3-5 days depending on response and level of edema
• Doses may be titrated up as needed to a maximum of spironolactone 400 mg a day + furosemide 160 mg a day
• Maximum recommended weight loss is 1 kg/day in patients with edema and 0.5kg/day in patients without edema (AASLD states there is no weight loss limit in patients with "massive edema")
• Diuretic therapy should be stopped and reassessed if:
• Hepatic encephalopathy develops
• Sodium levels < 120 mEq/L
• Serum creatinine > 2.0 mg/dl
• Potassium levels are too high or low
• Severe muscle cramps develop [91,92]

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• COMBINING THIAZIDE AND LOOP DIURETICS

• COMBINATION THERAPY
• Over time, the effectiveness of loop diuretics can wane as the kidneys adapt to chronic diuretic therapy
• Patients with obvious fluid overload who do not respond to optimal doses of loop diuretics may benefit from the addition of a thiazide diuretic


• Effectiveness
• In studies, combination therapy has yielded a significant diuretic response in > 90% of patients
• Fluid loss (measured as weight loss) of 1kg a day is common, but 3-5kg loss over 24 hours has been seen
• Adverse effects
• Low potassium (hypokalemia) is a major concern with combination diuretic therapy
• Serum potassium reductions of 0.4 - 0.8 meq/L are common even with potassium supplements
• Increases in serum creatinine, sodium loss (hyponatremia), and dehydration are also a concern
• Thiazide choice
• Metolazone has been studied the most in combination therapy, but other thiazides (HCTZ, chlorothiazide) have also been shown to be effective [20]
• Dosing
• Recommended dosing:
• Metolazone 2.5 - 10 mg once a day, or 2.5 - 10 mg two to three times a week
• HCTZ 25 - 100 mg once a day
• Intravenous chlorothiazide 500 - 1000 mg given once or twice a day or intermittently [19,20]


• StraightHealthcare analysis:
• When optimal doses of loop diuretics become ineffective, adding a thiazide diuretic can have a profound effect
• Electrolytes and fluid balance must be monitored closely when loop diuretics are combined with thiazides

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• SIDE EFFECTS

• LOW POTASSIUM (HYPOKALEMIA)
• Loop diuretics cause potassium loss
• The overall effect is not well-defined
• We found one review article from 1980 that looked at potassium loss with loop diuretics
• The review lacked many details, but we included it since it was all we could find
• BMJ review article
• A review from the British Medical Journal from 1980 looked at trials involving furosemide that measured changes in potassium levels
• Out of 11 studies involving 181 patients, the following effects of furosemide on potassium levels was seen:
• At an average dose of 75 mg, furosemide caused an average decrease in potassium levels of 0.30 meq/L [35]


• StraightHealthcare analysis:
• Loop diuretics cause potassium loss
• The degree of potassium loss will vary greatly among patients, and will be affected by factors such as kidney function, other medications taken, diuretic dose, diet, and medical conditions
• In practice, loop diuretics are often prescribed with potassium supplements
• Potassium levels should be checked frequently when starting a loop diuretic or during dose adjustments
• In chronic, stable therapy, potassium levels should be checked periodically

• INCREASED URINATION
• Because diuretics promote fluid loss by the kidneys, they all can cause increased urination
• This effect is greatest with loop diuretics and less with thiazides and potassium-sparing diuretics


• LOW SODIUM (HYPONATREMIA)
• Because loop diuretics promote sodium excretion, they may cause low sodium (hyponatremia)
• The risk for low sodium will vary greatly among patients, and will be affected by factors such as diet, diuretic dose, other medications, and medical conditions
• Patients on chronic loop diuretic therapy should have their sodium levels checked periodically


• INCREASED URIC ACID (GOUT RISK)
• Loop diuretics cause the kidneys to retain uric acid which can lead to higher blood uric acid levels
• High uric acid levels can precipitate or worsen gout, an inflammatory joint disease
• A number of case-control and cohort studies have found that the risk of gout is elevated in patients who take loop diuretics [39]
• We could find no well-done studies that measured changes in uric acid levels with loop diuretic therapy
• The Demadex® PI cites the following study with limited details:
• In a study of hypertensive patients taking Demadex® 10 mg a day for 6 weeks, the average uric acid level increased by 1.2 mg/dl [36]
• StraightHealthcare analysis:
• If possible, patients with uncontrolled gout may want to avoid loop diuretics
• If loop diuretics are necessary, then uric acid levels should be monitored closely and treated appropriately


• CALCIUM LOSS (HYPOCALCEMIA)
• Loop diuretics cause the kidneys to excrete calcium
• Urinary loss of calcium can affect blood levels of calcium
• Randomized trial
• In a randomized trial where participants took bumetanide or placebo for a year (see osteoporosis below), urinary calcium excretion was increased by 44% from baseline in bumetanide-treated patients and by 26% in placebo-treated patients. Plasma calcium levels were not affected by bumetanide.
• Participants in both groups took calcium supplements and vitamin D throughout the trial [44]
• Cross-sectional study
• A cross-sectional study looked at the association of loop diuretic use and calcium levels
• Compared to nonusers, loop diuretic users had slightly lower average blood calcium levels (9.11 mg/dl vs 9.21 mg/dl) [102]
• Torsemide PI
• The Torsemide PI cites one study in heart failure patients that showed an average decrease in calcium levels of 0.10 mg/dl after one year of torsemide therapy [36]
• StraightHealthcare analysis:
• Loop diuretics increase calcium excretion in the kidneys. To compensate for the loss, PTH levels rise and calcium is sequestered from bones. In long-term use, this may adversely affect bone health.


• OSTEOPOROSIS / FRACTURE RISK
• Loop diuretics cause the kidneys to excrete (lose) calcium
• Calcium loss can increase the risk of osteoporosis
• We found several studies that evaluated the effects of loop diuretics on bone health


• Randomized controlled trial with bumetanide, J of Bone and Mineral Res (2006)
• A small trial enrolled 87 postmenopausal women with osteopenia
• Main inclusion criteria: > 50 years old; > 12 months since last menses; osteopenia at lumbar spine or total hip
• Main exclusion criteria: hypo- or hyperthyroidism within last 5 years; diuretic treatment within last 3 months; received treatment with corticosteroids, anticonvulsants, NSAIDs, bisphosphonates, estrogen, or raloxifene in last 2 years
• Baseline characteristics: average age 66 years; median T-score lumbar spine -1.7; median T-score total hip -1.4; taking calcium supplements ∼ 41%
• Patients were randomized to 1 of 2 groups:
• Group 1 (46 patients) - Bumetanide 2 mg once daily
• Group 2 (41 patients) - Placebo once daily
• All patients took calcium 800 mg + cholecalciferol 10 mcg throughout the study
• Bumetanide 2 mg is considered equivalent to furosemide 80 mg
• PRIMARY OUTCOME: percentage change at week 52 from baseline in BMD at the lumbar spine and total hip
• At 52 weeks, the following was seen:
• Primary outcome (lumbar spine): Group 1 -0.69%, Group 2 +0.26% (p=0.08)
• Primary outcome (total hip): Group 1 -1.61%, Group 2 +0.32% (p=0.003)
• Plasma PTH levels (% change): Group 1 +5.6%, Group 2 -3.0% (p=0.003)
• Urinary calcium excretion (% change): Group 1 +44%, Group 2 +26% (p<0.01) [44]


• Archives of IM study 1
• A cohort study in the Archives of Internal Medicine compared changes in bone mineral density (BMD) between men who took loop diuretics and those who did not
• The study found the following results:
• Men who took loop diuretics regularly had twice the annual decline in bone mineral density at the hip as those who did not take loop diuretics:
• Loop diuretic users - average decrease of 0.78% hip BMD annually
• Nonusers - average decrease of 0.33% hip BMD annually


• Archives of IM study 2
• Another cohort study in the Archives of Internal Medicine looked at the risk of fracture and BMD changes in women who took loop diuretics compared to those who did not
• The study found the following results:
• There was no significant difference between loop diuretic users and nonusers for risk of hip fractures, vertebral fractures, or lower arm and wrist fractures
• There was no significant difference in BMD changes between loop diuretic users and nonusers [101]


• StraightHealthcare analysis:
• Based on the available evidence, loop diuretic therapy likely decreases BMD and increases osteoporosis risk in long-term users
• There is currently no evidence that loop diuretics increase fracture risk
• Patients with osteoporosis or those who are at high risk for osteoporosis may want to avoid loop diuretics, although in many cases, this will not be an option
• Patients at risk for osteoporosis who need long-term loop diuretic therapy should be screened periodically for osteoporosis


• PARATHYROID HORMONE (PTH) LEVELS
• Parathyroid hormone is a hormone that increases blood levels of calcium by stimulating calcium release from bones and by promoting calcium reabsorption from the kidneys and intestines
• Because loop diuretics cause calcium loss in the urine, parathyroid hormone excretion is often increased to counteract this effect
• Randomized trial
• In a randomized trial where participants took bumetanide or placebo for a year (study detailed under osteoporosis above), parathyroid levels were higher in the bumetanide group
• Placebo group had a decrease in PTH levels of 3% where PTH levels were increased by 5.6% in the bumetanide group
• Both groups received calcium and vitamin D supplements throughout the study [44]
• Cross-sectional study
• A cross-sectional study looked at the association of loop diuretic use and PTH levels
• Compared to nonusers, loop diuretic users had higher average levels of PTH
• Compared to nonusers, loop diuretic users had a higher risk for secondary hyperparathyroidism [102]
• StraightHealthcare analysis:
• Loop diuretics cause calcium loss and the body compensates for this by increasing parathyroid hormone secretion


• KIDNEY STONE RISK
• Because loop diuretics promote calcium excretion into the urine, they could theoretically be associated with kidney stone formation
• In sick newborns that need furosemide, this is a known issue
• We found no studies in adults that evaluated kidney stone risk with loop diuretics


• LOW MAGNESIUM (HYPOMAGNESEMIA)
• Loop diuretics cause the kidneys to excrete (lose) magnesium
• Low magnesium levels may be a particular concern in heart failure patients since they have been associated with heart arrhythmias
• A handful of cohort studies have come to differing conclusions on the long-term effects of low magnesium levels in heart failure patients [47]
• We could find no good, randomized trials that have evaluated the benefit of monitoring and treating magnesium levels in patients taking loop diuretics
• Professional guidelines:
• The AHA/ACC recommends that magnesium levels be checked on hospitalized heart failure patients, but makes no recommendation for outpatient or chronic care [19]
• StraightHealthcare analysis:
• The clinical significance of magnesium loss caused by loop diuretics is unclear
• Currently, there is no conclusive evidence that routine monitoring of magnesium levels is beneficial


• PHOTOSENSITIVITY
• Loop diuretics may cause the skin to become more sensitive to the sun and reactions may occur
• Limiting sun exposure and using sunscreen can help prevent reactions [85]


• CHOLESTEROL (LIPID PARAMETERS)
• Loop diuretics appear to cause a small, acute increase in total cholesterol, LDL cholesterol, and triglycerides [49,50,36]
• This effect may be related to hemoconcentration (increased concentration of blood products due to free water loss)
• In chronic therapy, loop diuretics do not appear to have a significant effect on lipid parameters [36]


• ELEVATED BLOOD SUGARS / DIABETES RISK
• The effect of loop diuretics on blood sugar levels and diabetes risk is not well-defined
• Studies evaluating an effect have been mixed and inconsistent
• In long-term therapy, the effect does not appear to be significant [36, 52, 56, 57]


• HEARING LOSS / EAR RINGING (OTOTOXICITY)
• On rare occasions, loop diuretics can cause hearing loss or ear ringing (tinnitus)


• The risk appears to be higher in the following circumstances:
• Very high doses
• Severe kidney disease
• Intravenous (IV) dosing
• Low protein levels (hypoproteinemia)
• When given with certain medications - aminoglycoside antibiotics, cisplatin, ethacrynic acid, salicylates [56,57]

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• TOLERANCE TO LOOP DIURETICS

• Over time, the kidneys can adapt to chronic loop diuretic therapy and the effectiveness can wane


• To overcome tolerance, several strategies can be tried:
• Increasing the dose of diuretic
• Increasing the frequency of the dosing
• Restricting dietary sodium intake
• Adding a thiazide diuretic (see combination therapy above) [19]

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• CONTRAINDICATIONS

• Bumetanide (Bumex®)
• Hypersensitivity to bumetanide
• Anuria (no urine output)
• Hepatic coma
• Severe electrolyte depletion


• Furosemide (Lasix®)
• Hypersensitivity to furosemide
• Anuria (no urine output)


• Torsemide (Demadex®)
• Hypersensitivity to torsemide
• Hypersensitivity to sulfonylureas (see sulfa allergy below)
• Anuria (no urine output)
• Hepatic coma
• Severe electrolyte depletion

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• PRECAUTIONS

• KIDNEY DISEASE
• Patients with significant kidney disease need diuretics to help increase fluid elimination
• Loop diuretics are the most effective class of diuretics for eliminating fluid
• Loop diuretics maintain their effectiveness once the CrCl falls below 30 ml/min, where thiazide diuretics lose their effectiveness


• LIVER DISEASE
• Cirrhosis
• Patients with cirrhosis often need diuretics to control fluid retention
• Loop diuretics and spironolactone are preferred in these patients
• See liver failure above
• Mild to moderate liver disease
• dosage adjustments are not typically needed


• SULFA ALLERGY
• Loop and thiazide diuretics contain a sulfonamide group in their structure
• The sulfonamide group is different from the one that is found in sulfa-based antibiotics
• Patients with a history of allergy to sulfa-based antibiotics may have a slight increase in risk of an allergic reaction to thiazide and loop diuretics


• Cross-reactivity between sulfa-based antibiotics and sulfonamide nonantibiotics, NEJM (2003) [PubMed abstract]
• A cohort study in the NEJM looked at the risk of an allergic reaction to nonantibiotic sulfonamides in patients who had a previous reaction to a sulfa-based antibiotic
• The study found the following:
• Patients with a history of sulfa-based antibiotic allergy who subsequently took nonantibiotic sulfonamides (including thiazide and loop diuretics) had a 10% risk of having a reaction to the nonantibiotic sulfonamide
• In patients without a history of allergic reaction to a sulfa-based antibiotic, 1.6% had a reaction to a nonantibiotic sulfonamide
• In addition, patients with a history of sulfa-based antibiotic allergy had a 14% chance of having a reaction to a penicillin antibiotic. This finding led researchers to conclude that a history of allergic reactions in general may be more predictive of a reaction than reactions to any specific medication [84]


• StraightHealthcare analysis:
• Loop and thiazide diuretics may be prescribed to patients with a history of sulfa-based antibiotic allergy
• Patients should be aware that a cross-sensitivity reaction may occur with a risk of around 10%
• Patients with a history of severe reactions to sulfa-based antibiotics should avoid nonantibiotic sulfonamides if they can. If not, then the initial dosing should be done under medical supervision.


• GOUT
• Loop diuretics can increase uric acid levels
• Patients with uncontrolled gout should avoid loop diuretics if possible
• See uric acid above


• PROLONGED QT INTERVAL
• Loop diuretics may cause hypokalemia which can increase the risk of Torsades de pointes in patients with prolonged QT interval
• Loop diuretics should be avoided in patients with congenital long QT syndrome

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• DRUG INTERACTIONS

• NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.

• HIGH ALERT INTERACTIONS
• NOTE: High alert interactions are interactions that are known to be significant and occur between two medications that are likely to be prescribed together


• Lithium - Loop diuretics may reduce the clearance of lithium. Loop diuretics should not be taken with lithium if possible. Lithium levels should be monitored closely in patients taking loop diuretics.
• Thyroid hormone (Synthroid®, levothyroxine, etc.) - high doses of furosemide (> 80 mg) may inhibit binding of thyroid hormone to thyroxine-binding globulin (TBG). This can increase free levels of thyroid hormone and subsequently lead to a decrease in total (free and bound) thyroid.


• METABOLISM
• NOTE: Drugs can be metabolized by more than one enzyme. Drugs may be metabolized by an enzyme and inhibit/induce the enzyme at the same time. Drug transporters (ex. p-glycoprotein) can play a role in drug metabolism. Not all drug interactions are clinically significant. Consult your physician or pharmacist if you are taking medications together and are concerned about a possible interaction.


• Furosemide
• Furosemide does not undergo extensive liver metabolism
• Bumetanide
• The liver metabolism of bumetanide is not well-defined
• Torsemide (Demadex®)
• CYP2C9 - substrate
• CYP2C8 - substrate


• OTHER
• Aminoglycoside antibiotics (gentamicin, etc) - Loop diuretics and aminoglycoside antibiotics both have the potential to cause ototoxicity (hearing loss). The risk may be increased when they are taken together.
• Bile Acid Sequestrants (Questran®, Welchol®, etc) - Bile acid sequestrants may decrease the absorption of loop diuretics. Loop diuretics should be taken one hour before or 4 hours after bile acid sequestrants.
• Cephalosporin antibiotics (Keflex®, Rocephin®, etc) - Furosemide may potentiate the risk of cephalosporin-induced kidney damage
• Cisplatin - Loop diuretics and cisplatin both have the potential to cause ototoxicity (hearing loss). The risk may be increased when they are taken together. Loop diuretics may also increase the risk of kidney damage from cisplatin.
• Cyclosporine - Loop diuretics and cyclosporine both increase the risk of gout. When taken together, the risk may be compounded.
• Ethacrynic acid - Loop diuretics and ethacrynic acid both have the potential to cause ototoxicity (hearing loss). The risk may be increased when they are taken together.
• Methotrexate - Loop diuretics may increase blood levels of methotrexate and vice versa.
• NSAIDS (Advil®, ibuprofen, naprosyn, etc.) - NSAIDS can block the therapeutic effect of all diuretics. Patients should monitor for decreased effectiveness of diuretics when taking NSAIDS for extended periods.
• Phenytoin (Dilantin®) - Phenytoin may inhibit the diuretic effect of furosemide
• Probenecid - Probenecid may inhibit the action of loop diuretics
• Salicylates (Aspirin, etc.) - In patients receiving high doses of salicylates, loop diuretics may block their clearance and increase the risk of salicylate toxicity.
• Sucralfate (Carafate®) - Sucralfate may inhibit the effects of furosemide. Intake should be separated by 2 hours.

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• LONG-TERM SAFETY

• Loop diuretics have been in use since the 1960s
• They have been prescribed to millions of people
• They can have significant side effects
• Their use should always be accompanied with an awareness of possible side effects and appropriate monitoring

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• DOSING

• Dosing
• Loop diuretic dosing chart


• Pharmacokinetics

DRUG	PEAK EFFECT	DURATION OF EFFECT
Furosemide	1 - 2 hours	6 - 8 hours
Bumetanide	1 - 2 hours	4 - 6 hours
Torsemide	1 - 2 hours	6 - 8 hours

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• DIFFERENCES BETWEEN DRUGS IN CLASS

• Furosemide is by far the most prescribed and studied loop diuretic
• Loop diuretics vary slightly in their metabolism and potential drug interactions

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• GENERIC AVAILABILITY

• Generic available:
• Furosemide (Lasix®)
• Bumetanide (Bumex®)
• Torsemide (Demadex®)

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• BIBLIOGRAPHY

• What is PMID?
• PI = Manufacturer's Package Insert

• #     PMID
• 1 - 19940300
• 2 - 16145005
• 3 - 12759325
• 4 - 8446138
• 5 - 20821851
• 6 - 19821314
• 7 - 20091662
• 8 - 20687095
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• 11 - Eplerenone PI
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• 14 - 19821398
• 15 - 21073363
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• 25 - European Association of Urology. Guidelines on Urolithiasis. 2011
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• 30- 2344503
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• 32 - 9554680
• 33 - 17904464
• 34 - 6137813
• 35 - 7388366
• 36 - Demadex PI
• 37 - 8432162
• 38 - 21095025
• 39 - 21285714
• 40 - 16291814
• 41 - 18946066
• 42 - 11733620
• 43 - 18413556
• 44 - 16355285
• 45 - 15656876
• 46 - 19368583
• 47 - 12639869
• 48 - 10672134
• 49 - 9665357
• 50 - 9702848
• 51 - 1486908
• 52 - 5920655
• 53 - 7752176
• 54 - 4102452
• 55 - 1486906
• 56 - Bumetanide PI
• 57 - Furosemide PI
• 58 - 16036053
• 59 - 16342656
• 60 - Aldactone PI
• 61 - 19843067
• 62 - 2050832
• 63 - 3661395
• 64 - 6338681
• 65 - 3189169
• 66 - 19865106
• 67 - 10199763
• 68 - 7104176
• 69 - 3884122
• 70 - 8290411
• 71 - 6409208
• 72 - 6389077
• 73 - 6619267
• 74 - 7282751
• 75 - 3521452
• 76 - 1747638
• 77 - 7431573
• 78 - 19074530
• 79 - 16035375
• 80 - 15601807
• 81 - 12011477
• 82 - 20216123
• 83 - 21193625
• 84 - 14573734
• 85 - 12020173
• 86 - 14638621
• 87 - 20010338
• 88 - 21272751
• 89 - removed
• 90 - Natl Kidney Foundation Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease.
• 91 - 20633946
• 92 - 19475696
• 93 - 19940300
• 94 - 16801488
• 95 - 19160242
• 96 - 21975748
• 97 - 12479763
• 98 - 2318517
• 99 - 22017784
• 100 - 17101936
• 101 - 19171809
• 102 - 21382989