What Are Furosemide Side Effects?

Furosemide (furosemide / INN / BAN /), frusemide (formerly BAN), also known as furanilic acid and furosemide, are widely used in the treatment of congestive heart failure and edema. It is also used to prevent nosebleeds during horse racing. Like some other diuretics, furosemide is listed as a prohibited drug by the World Anti-Doping Agency because it can be used illegally to cover up other drug tests ^[1] .

Furosemide (furosemide / INN / BAN /), frusemide (formerly BAN), also known as furanilic acid and furosemide, are widely used in the treatment of congestive heart failure and edema. It is also used to prevent nosebleeds during horse racing. Like some other diuretics, furosemide is listed as a prohibited drug by the World Anti-Doping Agency because it can be used illegally to cover up other drug tests ^[1] .

Drug Name

Furosemide

Alias

Furanilic acid

Foreign name

Furosemide, Frusemide, LAS

Whether prescription drugs

prescription

Main indications

Edema, hypertension, acute pulmonary edema, or cerebral edema

Main medication contraindications

Breastfeeding women should be used with caution

Drug type

Diuretics

Furosemide compounds

Furosemide Basic Information

Chinese name: furosemide

Chinese aliases: furosemide; diuretic acid; furosemide; diurethine; aspartate; ascites; fuluofen; furanilic acid; diurethamide

English name: furosemide

English alias: Furosemide, 5- (Aminosulfonyl) -4-chloro-2-([2-furanylmethyl] amino) benzoicacid; 4-Chloro-N-Furfuryl-5-Sulfamoylanthranilic Acid; Lasix; Frusemide '

CAS number: 54-31-9

Molecular formula: C ₁₂ H ₁₁ ClN ₂ O ₅ S

Structural formula:

Molecular weight: 330.74400

Exact mass: 330.00800

PSA: 131.01000

LogP: 3.74480

Furosemide

Appearance and properties: white powder

Density: 1.606

Melting point: 220 ° C (dec.) (Lit.)

Boiling point: 582.1ºC at 760 mmHg

Flash point: 11 ° C

Stability: Stable, but light sensitive, air sensitive and hygroscopic. Incompatible with strong oxidants.

Storage conditions: low temperature, ventilated and dry in warehouse

Furosemide Safety Information

Customs Code: 2942000000

Dangerous Goods Transport Code: UN 1230 3 / PG 2

WGK Germany: 3

Danger category code: R61

Safety instructions: S7-S16-S36 / 37-S45-S53-S36 / 37 / 39-S22

RTECS number: CB2625000

Dangerous goods mark: T ^[1]

Furosemide production method

From 2,4-dichlorobenzoic acid (see 12740) through chlorosulfonation, ammoniation, acidification to obtain 2,4-dichloro-5-sulfamoylbenzoic acid. It is then condensed with furfurylamine to produce furosemide.

Furosemide uses

This product has a strong and short diuretic effect. It is a potent diuretic, used to treat edema caused by heart, liver, kidney and other diseases, especially cases that are not effective for ketal diuretics. Acute renal failure and hypertension; together with fluid replacement, this product can promote non-draining of poisons ^[1] .

Furosemide laboratory analysis

Method name: Furosemide API-Determination of Furosemide-Neutralization Titration

Scope of application: This method uses the titration method to determine the content of furosemide in furosemide drug substances.

This method is applicable to furosemide.

Principle of the method: After the test sample is dissolved in methanol, water and a phenol red indicator solution are added, and the titration is performed with a sodium hydroxide titration solution. The titration result is corrected by a blank test, and the content of furosemide is calculated according to the amount of the titration solution.

Reagent: 1. ethanol

Thymol blue indicator liquid

Cresol Red Indicator Solution

Sodium hydroxide titration solution (0.1mol / L)

Phenolphthalein indicator

Reference potassium hydrogen phthalate

equipment:

Sample preparation:

Thymol blue indicator liquid

Take 0.1g of thymol blue, add 4.3mL of 0.05mol / L sodium hydroxide solution to dissolve, and then dilute to 200mL with water.

Cresol Red Indicator Solution

Take 0.1g of cresol red, dissolve by adding 5.3mL of 0.05mol / L sodium hydroxide solution, and dilute to 100mL with water.

Sodium hydroxide titration solution (0.1mol / L)

Preparation: Take an appropriate amount of sodium hydroxide, add water and shake to dissolve it into a saturated solution. After cooling, place it in a polyethylene plastic bottle and let it stand for several days. Take 5.6mL of a clear saturated sodium hydroxide solution, add freshly boiled cold water to 1000mL, and shake well.

Calibration: Take about 0.6g of standard potassium hydrogen phthalate dried to constant weight at 105 ° C, weigh it accurately, add 50mL of freshly boiled cold water, shake it to dissolve it as much as possible, add 2 drops of phenolphthalein indicator solution, When this solution is titrated, when the end point is reached, potassium hydrogen phthalate should be completely dissolved and titrated until the solution becomes pink. Each 1mL of sodium hydroxide titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.

Storage: Put it in a polyethylene plastic bottle and keep it in a sealed container. There are 2 holes in the plug. One glass tube is inserted into the hole. One tube is connected to the soda lime tube. One tube is used to suck out the liquid.

Phenolphthalein indicator liquid

Take 1 g of phenolphthalein and add 100 mL of ethanol to dissolve.

Operation steps: Precisely weigh about 0.5g of the test sample, add 30mL of ethanol, dissolve at low temperature, let cool, add 4 drops of cresol red indicator liquid and 1 drop of thymol blue indicator liquid, and use sodium hydroxide titration solution (0.1 mol / L) Titrate until the solution becomes purple-red, and correct the result of the titration with a blank test. Each 1mL of sodium hydroxide titration solution (0.1mol / L) is equivalent to 33.07mg of C12H11ClN2O5S.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards ^[2] .

Furosemide pharmacopoeia standard

Furosemide source (name), content (potency)

This product is 2-[(2-furanmethyl) amino] -5- (sulfamoyl) -4-chlorobenzoic acid. Calculated on dry basis, containing C ₁₂ H ₁₁ ClN ₂ O ₅ S shall not be less than 99.0%.

Furosemide traits

This product is white or almost white crystalline powder; odorless, almost odorless.

This product is soluble in acetone, slightly soluble in ethanol, and insoluble in water.

Melting point

This product has a melting point (Appendix VIC to the second edition of the Pharmacopoeia of 2010 Edition) of 208 to 213 ° C. It decomposes simultaneously when melted.

Absorption coefficient

Take this product, weigh it accurately, add 0.4% sodium hydroxide solution to dissolve and quantitatively dilute it to make a solution containing about 10 g per 1 ml. According to UV-Vis spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 Edition) The absorbance was measured at the wavelength, and the absorption coefficient () was 565 to 595.

Furosemide identification

(1) Take about 25mg of this product, add 5ml of water, add sodium hydroxide test solution dropwise to dissolve it, add 1 to 2 drops of copper sulfate test solution, and a green precipitate is formed.

(2) Take 25mg of this product, put it in a test tube, add 2.5ml of ethanol to dissolve it, and then add 2ml of p-dimethylaminobenzaldehyde test solution along the wall of the tube.

(3) Take this product, add 0.4% sodium hydroxide solution to make a solution containing about 5g per 1ml, and measure it at 228nm, 271nm, and 333nm by UV-visible spectrophotometry (Appendix IV A of Pharmacopoeia Part II of 2010 Edition). There is maximum absorption at the wavelength of.

(4) The infrared light absorption spectrum of this product should be consistent with the control spectrum ("Infrared Spectra of Drugs" 184).

Furosemide check

Clarity and color of alkaline solution

Take 0.50g of this product, add 5ml of sodium hydroxide test solution to dissolve, add 5ml of water, the solution should be clear and colorless; if it is turbid, compare with No. 2 turbidity standard solution (Appendix B of Part II of the Pharmacopoeia of the 2010 edition), it must not be more concentrated ; If the color is developed, it must not be deeper compared with the yellow standard colorimetric solution No. 3 (Appendix A of the 2010 Pharmacopoeia Part II Method A).

chloride

Take 2.0g of this product, add 100ml of water, shake it thoroughly, and filter; take 25ml of the filtrate and check it according to law (Appendix A of Part Two of the 2010 Pharmacopoeia). Compare with the control solution made of 7.0ml of standard sodium chloride solution. Thick (0.014%).

Sulfate

Take 25ml of the remaining filtrate under the above chloride and check it according to law (Appendix B of Part II of the Pharmacopoeia 2010), compared with the control solution made of 2.0ml of standard potassium sulfate solution, it must not be more concentrated (0.04%).

relative substance

Protect from light. Take this product, add a mixed solvent (take 22ml of glacial acetic acid, add acetonitrile-water (1: 1) to 1000ml, mix well) and dissolve and dilute to make a solution containing about 1mg per 1ml, as the test solution; precise amount Take an appropriate amount, add the above mixed solvent to quantitatively dilute to make a solution containing 10 g per 1 ml, and use it as a control solution. According to the high performance liquid chromatography (2010 edition Pharmacopoeia Part II Appendix VD) test, use octadecylsilane bonded silica gel as Filler, using water-tetrahydrofuran-glacial acetic acid (70: 30: 1) as the mobile phase, the detection wavelength is 272nm. The theoretical number of plates based on furosemide peak is not lower than 4000. 20l of the control solution is injected into the liquid chromatograph, Adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 20% of the full scale. Then accurately measure 20 l each of the test solution and the reference solution, and inject them into the liquid chromatograph respectively, and record the chromatogram to the main component peak retention time. If the impurity peak in the chromatogram of the test solution, the area of a single impurity peak should not be greater than 0.2 times (0.2%) of the main peak area of the control solution, and the sum of the peak areas of each impurity should not be greater than the main peak area of the control solution (1.0%). ).

Loss on drying

Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (Appendix L of Pharmacopoeia Part II of 2010 Edition).

Residue on ignition

Must not exceed 0.1% (Appendix N of Part Two of the 2010 Pharmacopoeia).

Heavy metal

Take 0.50g of this product and check it according to law (Appendix H of the 2010 edition of Pharmacopoeia, the third method), containing no more than 20 parts per million of heavy metals.

Arsenic salt

Take 1.0g of this product, add 1g of calcium hydroxide, add a small amount of water, stir well, first heat on a low fire, and then burn to complete ashing, let cool, add 5ml of hydrochloric acid and 23ml of water, check according to law (2010 Pharmacopoeia II (Appendix J First Law), should meet the requirements (0.0002%).

Determination of furosemide

Take about 0.5g of this product, accurately weigh, add 30ml of ethanol, dissolve at a slight temperature, let cool, add 4 drops of cresol red indicator solution and 1 drop of thymol blue indicator solution, and use sodium hydroxide titration solution (0.1mol / L) Titrate until the solution becomes purple-red, and correct the result of the titration with a blank test. Each 1ml of sodium hydroxide titration solution (0.1mol / L) is equivalent to 33.07mg of C ₁₂ H ₁₁ ClN ₂ O ₅ S ^[3] .

Furosemide Categories

Diuretics.

Furosemide storage

Shaded and sealed.

Furosemide

(1) Furosemide tablets (2) Furosemide injection (3) Compound furosemide tablets

Furosemide

The 2010 Edition of the Pharmacopoeia of the People's Republic of China ^[3]

Furosemide drug description

Furosemide Classification

Circulatory Drugs> Antihypertensive Drugs> Diuretic Antihypertensive Drugs

Furosemide

1. Tablets: 20mg each; 40mg

2. Injection: 20mg (2ml)

Furosemide pharmacodynamics

The effect of radon on water and electrolyte excretion. Can increase the excretion of water, sodium, chlorine, potassium, calcium, magnesium, phosphorus, etc. Unlike thiazide diuretics, furosemide and other diuretics have a clear dose-response relationship. With the increase of the dose, the diuretic effect is obviously enhanced, and the drug dosage range is larger. This class of drugs mainly inhibits the active reabsorption of NaCl in the thick walled section of the renal tubular myelin. As a result, the concentration of Na ⁺ and Cl ^{-in the} lumen fluid increases, while the concentration of Na ⁺ and Cl ^{-in the} medullary fluid decreases, which makes the osmotic pressure gradient The difference is reduced, and the renal tubular condensing function is reduced, resulting in increased excretion of water, Na ⁺ , and Cl-. As Na ⁺ reabsorption decreases, the Na ⁺ concentration of the distal tubule increases. As for the mechanism by which furosemide inhibits Cl ^- reabsorption in the thick wall of the ascending branch of renal tubular pulp, it is believed that there is a chlorine pump at this site. Studies have shown that Na ⁺ and Cl related to Na ⁺ -K ⁺ ATPase are present outside the basement membrane at this site. -Paired transport system, furosemide reduces Na ⁺ , Cl- reabsorption by inhibiting the function of this system. In addition, furosemide may still inhibit the reabsorption of Na ⁺ and Cl by the proximal tubule and the distal tubule, and promote the secretion of K ^{+ by the} distal tubule. Furosemide increases Ca ²⁺ and Mg ²⁺ excretion by inhibiting the reabsorption of Ca ²⁺ and Mg ²⁺ by Heinz thurium. Short-term medication can increase uric acid excretion, while long-term medication can cause hyperuricemia.

Effect on hemodynamics. Furosemide can inhibit the activity of prostaglandin degrading enzymes, increase the content of prostaglandin E2, and thus have a vasodilator effect. Dilatation of renal blood vessels, reduction of renal blood vessel resistance, increase of renal blood flow, especially deep renal cortex blood flow, is of great significance in the diuretic effect of furosemide, and it is also the theoretical basis for its prevention of acute renal failure. In addition, unlike other diuretics, -type diuretics do not decrease the glomerular filtration rate while the renal tubular fluid flow increases, which may be related to the reduction of chlorine flowing through dense plaques, thereby weakening or blocking the bulb-tube balance . Furosemide can expand the volume of the veins in the lungs, reduce the permeability of pulmonary capillaries, and its diuretic effect can reduce the amount of return to the heart, reduce the right end ventricular diastolic pressure, and help the treatment of acute right heart failure. Since furosemide can reduce pulmonary capillary permeability, it provides a theoretical basis for the treatment of adult respiratory distress syndrome.

Furosemide pharmacokinetics

The oral absorption rate is 60 to 70%, and eating can slow absorption, but it does not affect the absorption rate and its efficacy. The oral absorption rate in patients with end-stage renal disease decreased to 43 to 46%. In edema diseases such as congestive heart failure and nephrotic syndrome, due to intestinal wall edema, the oral absorption rate also decreases, so the drug should be administered parenterally in the above cases. It is mainly distributed in extracellular fluid, with an average distribution volume of 11.4% of body weight and a plasma protein binding rate of 91-97%, almost all of which bind to albumin. The drug can pass through the placental barrier and can be secreted into milk. After oral and intravenous administration, the onset time was 30 to 60 minutes and 5 minutes, respectively, and the peak time was 1 to 2 hours and 0.33 to 1 hour. The duration of action was 6 to 8 hours and 2 hours, respectively. There is a large individual difference in half-life , which is 30 to 60 minutes in normal people, 75 to 155 minutes in patients without urine, and 11 to 20 hours in patients with severely impaired liver and kidney function. Due to poor liver and kidney clearance ability, the half-life is prolonged in 4-8 hours. 88% of this drug is excreted by the kidney in its original form, 12% is excreted by the bile by the liver, and the liver metabolism is increased in those with impaired renal function. This medicine is not cleared by dialysis.

Furosemide indications

Edema diseases include congestive heart failure, liver cirrhosis, kidney disease (nephritis, nephropathy, and acute and chronic renal failure due to various causes

Furosemide injection

Exhaustion), especially when other diuretics are not effective, the use of this class of drugs may still be effective. Combined with other drugs to treat acute pulmonary edema and acute brain edema.

Hypertension is not the drug of choice for the treatment of essential hypertension in the ladder therapy of hypertension, but when thiazide drugs are not effective, especially when accompanied by renal insufficiency or hypertension crisis Drugs are particularly suitable.

Prevention of acute renal failure is used for various reasons leading to insufficient renal blood perfusion, such as water loss, shock, poisoning, accidental anesthesia, and circulatory insufficiency. Timely application can reduce the chance of acute tubular necrosis.

Hyperkalemia and hypercalcemia.

Dilute hyponatremia, especially when the blood sodium concentration is below 120mmol / L.

Antidiuretic hypersecretion (SIADH).

Acute drug poisoning, such as barbiturate poisoning.

Furosemide dosage

oral

Usual Adult:

Edema disease: The initial dose is 20-40 mg once a day, and 20-40 mg is added after 6-8 hours if necessary until a satisfactory diuretic effect appears. The maximum daily dose can reach 600mg, but generally should be controlled within 100mg, divided into 2 to 3 times. Some patients can reduce to 20-40mg once a day, or once every other day (or 20-40mg a day, continuous medication for 2 to 4 days a week).

Hypertension: The starting dose is 40 to 80 mg per day, divided into two doses, and the dose is adjusted as appropriate.

Hypercalcemia: 80 to 120 mg a day, divided into 1 to 3 times.

Common amount for children

The initial dose of edema disease is 2 mg / kg, and if necessary, it is added by 1 to 2 mg / kg every 4 to 6 hours. Newborns should prolong the interval between medications.

Intravenous injection

Usual Adult:

Edema disease:

a. General dosage: The initial dosage is 20 40mg, if necessary, the dosage should be increased every 2 hours until satisfactory curative effect appears. It can be administered in divided doses during the maintenance period.

b. Acute left heart failure: the initial dose is 40 mg, and if necessary, an additional 80 mg per hour until a satisfactory effect appears.

c. Chronic renal insufficiency: The daily dose is generally 40 120mg.

Hypertension crisis: the initial dose is 40 to 80 mg, with acute left heart failure or acute renal failure, the dosage can be increased as appropriate.

Hypercalcemia: 20 80mg at a time.

Common amount for children:

Edema disease: The initial dose is 1mg / kg, and 1mg / kg is added every 2 hours if necessary. The maximum daily dose can reach 6mg / kg. ^[4]

Furosemide is contraindicated

Cross-allergies. People who are allergic to sulfa drugs and thiazide diuretics may also be allergic to this drug.

This medicine can pass through the placental barrier and should be avoided as far as possible in pregnant women, especially in the first 3 months of pregnancy. No prevention for pregnancy-induced hypertension syndrome

Furosemide

use. Animal experiments have shown that this product can cause placenta hydronephrosis, miscarriage and increased fetal mortality.

This medicine can be secreted by breast milk. Women who are breastfeeding should use it with caution.

The half-life of the drug in the newborn is significantly prolonged, so the interval between medications for the newborn should be prolonged.

The elderly have an increased chance of hypotension, electrolyte disturbances, thrombosis and impaired renal function.

Be cautious in the following situations: People who have no urine or severe renal impairment, the latter need to increase the dose, so the interval between medications should be extended to avoid side effects such as ototoxicity; Diabetes; Hyperuricemia or history of gout severe liver function impairment, which can induce liver coma due to water and electrolyte disturbance; acute myocardial infarction, excessive diuresis can trigger shock; pancreatitis or history of this disease; those with a tendency to hypokalemia, especially Application of digitalis or ventricular arrhythmia; lupus erythematosus, this drug can aggravate the disease or induce activity; prostate hypertrophy. Hypokalemia, overdose of digitalis, disabled in patients with liver coma, and used with caution in advanced liver cirrhosis. High doses are extremely toxic to the eyes of hyperuricemia.

The product can penetrate the placenta, increase the formation of fetal urine, and increase the acid concentration in maternal, fetal serum and amniotic fluid. Therefore, for pregnant women, it is necessary to take this product only in the case of heart failure.

Furosemide adverse reactions

Commonly related to water and electrolyte disorders, especially when used in high doses or for long periods of time, such as orthostatic hypotension, shock, hypokalemia, hypochloremia, hypochlorine alkalosis, hyponatremia, hypocalcemia And related thirst, fatigue, muscle soreness, arrhythmia, etc.

Rare people have allergic reactions (including rash, interstitial nephritis, and even cardiac arrest), blurred vision, yellow vision, light sensitivity, dizziness, headache, anorexia, nausea, vomiting, abdominal pain, diarrhea, pancreatitis, muscle rigidity Etc., myelosuppression leads to granulocytopenia, thrombocytopenic purpura and aplastic anemia, liver function impairment, abnormal finger and toe sensation, hyperglycemia, positive urine glucose, exacerbation of pre-existing diabetes, and hyperuricemia. tinnitus

Furosemide

Hearing impairment is more common when high-dose intravenous rapid injection (dose greater than 4-15 mg per minute) is mostly temporary, and a few are irreversible, especially when used concurrently with other ototoxic drugs. In hypercalcemia, it can cause kidney stones. It has been reported that this drug can aggravate idiopathic edema. Can cause hypokalemia, hypochloremia, decreased blood magnesium, nausea, vomiting, diarrhea, rash, pruritus, muscle cramps, dizziness, fatigue, lethargy, dry mouth, excessive injection can cause temporary deafness. Individual cases have leukocytopenia, thrombocytopenia, erythema polymorphism, orthostatic hypotension. Long-term use can cause gastric and duodenal ulcers, produce hyperuricemia, can cause gastrointestinal irritation or discomfort, acute pancreatitis, jaundice, and phantom vision in individual cases. Intravenous injection can cause cardiac arrest and even death. Cardiovascular system: In addition to diuretic effects, furosemide also has a transient but sure vasodilator effect. The product changes the venous blood volume and peripheral vascular resistance in patients with renal impairment, orthostatic hypotension and fainting, and the symptoms are more severe when used in combination with other antihypertensive drugs.

Endocrinology and metabolism: The effect of this product on lipid metabolism is similar to that of thiazide drugs. Furosemide can cause antidiuretic hormone disorder syndrome (IADHS). Patients' plasma antidiuretic hormone (ADH) concentration increases, the body's total sodium is normal, and the total potassium level decreases significantly. If you use this product quickly, it will cause a sharp increase in hyperprotease and aldosterone secretion. Animal experiments show that long-term use of this product causes thiamine deficiency and damages heart function. Therefore, for patients who use the product for a long time, the concentration of thiamine in the blood should be paid attention to. Similar to thiazide drugs, this product can also cause hyperuricemia and gout, and the frequency and degree of seizures are even worse. In elderly patients, gout may occur after taking 3 months.

Electrolyte and body fluid balance: Similar to thiazide drugs, myelin diuretics also cause changes in electrolyte balance.

The characteristics and degree of action are different. The incidence is about 23%.

Calcium metabolism is different from thiazide drugs. Furosemide does not promote calcium reabsorption in distal renal tubules, but can cause transient hypercalcemia. This product can cause secondary parathyroidism in newborns, causing bone calcium loss. The excretion rate of calcium is 10 to 20 times greater than that of normal children, and there is a risk of kidney stones. There is also the possibility of secondary sepsis.

Low blood magnesium, although this product can increase the renal clearance of magnesium, but it does not necessarily affect the concentration of magnesium in plasma.

Liver: Furoxime is very toxic to the liver of animals. Clinically, for patients with a history of liver cirrhosis, even taking a low dose of this product will accelerate the onset of hepatic encephalopathy. It is best to use spironolactone.

Digestive system: The incidence of nausea, vomiting, and diarrhea is less than 1% at conventional doses. However, the incidence is significantly higher at high doses or with uremia.

Urinary system: This product is a strong diuretic. Excessive diuresis and dehydration can cause a temporary decrease in glomerular filtration rate and an increase in BUN in the blood, accounting for 8% of adverse reactions. Elderly patients with enlarged prostates will experience acute urinary retention, overflow urinary incontinence, and interstitial nephritis. Long-term use of this product to treat spontaneous edema will gradually damage kidney function and cause acute renal failure.

Skin: Rash is more common. In renal failure, with large doses of this product, squamous dermatitis and multiple erythroderma may occur, which is rare among other diuretics.

Sensory organs: When the blood concentration of this product exceeds 50 g / ml, it can cause eye and ear poisoning reactions. Such as glaucoma, dizziness, and hearing loss are sometimes irreversible. Hypercalcemia and the formation of stones in the fetus have also been reported. The product may also cause anaphylactic shock.

Furosemide drug interactions

Adrenal sugar, mineralocorticoids, adrenocorticotropic hormones and estrogen can reduce the diuretic effect of this medicine and increase electrolyte disorders, especially

Furosemide

Chance of hypokalemia.

Non-steroidal anti-inflammatory analgesics can reduce the diuretic effect of this drug, and increase the chance of kidney damage, which is related to the former's inhibition of prostaglandin synthesis and reduction of renal blood flow.

Combined with sympathomimetic drugs and anticonvulsant drugs, diuretic effect weakened.

Rhenium is used in combination with clobetin (amtoxamine), the effects of both drugs are enhanced, and muscle soreness and rigidity can occur.

Combined with dopamine, the diuretic effect is strengthened.

Drinking and alcohol-containing preparations and drugs that can cause blood pressure can enhance the diuretic and hypotensive effects of this drug; combined with barbiturates and anesthetics, it can easily cause orthostatic hypotension.

This medicine can reduce the excretion of uric acid and increase the blood uric acid. Therefore, when it is used in combination with drugs for treating gout, the dosage of the latter should be adjusted appropriately.

Reduce the efficacy of hypoglycemic drugs.

The effect of reducing anticoagulant drugs and antifibrinolytic drugs is mainly related to the decrease in blood volume after diuresis, the increase of blood coagulation factor concentration, and the improvement of liver blood supply and increased synthesis of coagulation factors in the liver by diuresis.

This medicine strengthens the effect of non-depolarizing muscle relaxant, which is related to the decrease of blood potassium.

Combined with antibiotics such as amphotericin, cephalosporin, and aminoglycosides, renal toxicity and ototoxicity increase, especially when the original kidney is damaged.

When combined with antihistamines, ototoxicity increases, and tinnitus, dizziness, and dizziness are easy to occur.

The nephrotoxicity of thallium combined with lithium has increased significantly and should be avoided as much as possible.

Intravenous injection of this drug after taking chloral hydrate can cause sweating, flushing, and increased blood pressure, which is related to the increase in thyroxine from the bound state to the free state, which leads to enhanced catabolism.

Chlorine alkalosis increased with the combined use of sodium carbonate and sodium carbonate.

The combined use of thiazines and myelin diuretics often causes severe deterioration of renal function.

This product reduces the clearance of aminoglycosides by about 35%, which will increase eye toxicity and the risk of permanent deafness.

The combination of this product with cephalosporins can enhance renal toxicity.

Combining this product with mannitol will cause kidney failure and strengthen the effect of arrow poison. This product can inhibit the secretion of lithium ions by renal tubules, which may cause lithium poisoning.

Combining this product with spironolactone or ACE inhibitor captopril can cause acute renal toxicity and severe hyponatremia.

Furosemide notes

Side effects such as slight nausea, diarrhea, drug rash, pruritus, and blurred vision may occur. Sometimes, orthostatic dizziness, fatigue, and fatigue may occur.

Furosemide

, Muscle spasm, thirst, leukopenia in a few cases, thrombocytopenia, erythema polymorphism, orthostatic hypotension in some cases. Long-term application can cause gastric and duodenal ulcers.

As it can reduce uric acid excretion, it can produce hyperuricemia after repeated application, and individual patients can produce acute gout after long-term application. Use with caution in patients with gout.

After application, diabetic patients can increase blood glucose; diabetic patients should be used with caution. Although its blood glucose is much weaker than that of thiazide diuretics, it may still increase blood glucose when used in combination with hypoglycemic drugs.

Because the diuretic effect is fast and powerful, pay attention to the starting dose to prevent excessive diuresis, causing dehydration and electrolyte imbalance.

After taking hepatitis patients, liver coma is easily caused by excessive loss of electrolytes (especially K +). Use with caution in patients with severe liver dysfunction.

When long-term heavy medication, check the electrolyte concentration in the blood. Patients with refractory edema are particularly prone to hypokalemia. When using digitalis or potassium-releasing steroid hormones, more attention should be paid to potassium salts.

At the same time as dehydration, a reversible increase in blood urea nitrogen levels may occur. If the creatinine level does not increase significantly and renal function is not damaged, the product can be continued. Use with caution in patients with severe renal insufficiency.

During the first month of use, check the serum electrolytes, carbon dioxide and blood urea nitrogen levels regularly. As with other diuretics, medication should be stopped immediately when there is an increase in serum urea nitrogen and oliguria in the treatment of kidney disease in progress.

can enhance the effect of antihypertensive drugs, so when combined use, the amount of antihypertensive drugs should be appropriately reduced.

Because of its structural similarity to chlorothiazide, sulfonamide compounds can reduce the arterial response to vasopressin (such as norepinephrine), and can increase the muscle relaxation and paralysis effects of tuberculin. It should be disabled for one week.

Patients with hypokalemia, overdose of digitalis, and liver coma are contraindicated. Use with caution in patients with advanced liver cirrhosis.

When the high-dose intravenous injection is too fast, hearing loss or temporary deafness may occur. It should not be used in combination with aminoglycoside antibiotics, because it is more likely to cause hearing loss.

Pregnant women are prohibited. Use with caution in children.

Furosemide poisoning

Furosemide (fast urine) mainly inhibits the reabsorption of Cl- and Na + by the medullary medulla and cortex of the kidney, promotes the large-scale excretion of Cl-, Na +, K +, and water and diuresis. It is clinically used to treat cardiac edema, renal edema, ascites due to cirrhosis of the liver, and peripheral edema caused by pulmonary edema, cerebral edema, acute renal failure or vascular wall disorders. Drug poisoning can be used to accelerate the excretion of poisons. The drug is rapidly absorbed orally, with a plasma half-life of 30 to 70 minutes, and about 10% is metabolized in the body, mainly excreted through the kidneys in the original form. Excretion is rapid, and no significant retention in the tissues is observed after 24 hours. Oral LD50 was 2g / kg in dogs, 0.8g / kg in rabbits, and 4.6g / kg in rats. The usual amount is 20mg each time, intramuscularly or intravenously. Oral 40mg / d. Mainly affect water and salt metabolism, leading to imbalance of water and electrolyte balance and disturbance of acid-base balance.

Clinical manifestation

Adverse reactions are as follows:

Metabolic abnormality

The diuretic effect of this medicine is rapid and powerful, and it is easy to cause water and electrolyte imbalance, and dehydration, hyponatremia, hypokalemia, hypochloremia, hypomagnesemia, and hypochlorine alkalosis.

2. Digestive system

Nausea, vomiting, burning sensation in the mouth and stomach, anorexia, abdominal pain, diarrhea, constipation. Large doses can cause gastric and duodenal ulcers and bleeding, acute pancreatitis, and jaundice. It can induce hepatic encephalopathy in patients with liver cirrhosis.

3. Circulatory system

Orthostatic hypotension, syncope, arrhythmia (individual reports of atrioventricular block), embolic vasculitis, etc.

4. Urinary system

Low back pain, frequent urination, hematuria, oliguria, elevated blood urea nitrogen, urine glucose, hyperuricemia, acute renal failure, etc.

5. Central nervous system and ototoxicity

May have headache, dizziness, dizziness, paresthesia, tinnitus, hearing loss or temporary deafness, hearing loss.

6. Allergic reactions

Itchy skin, urticaria, erythema polymorpha, purpura, photosensitivity, exfoliative dermatitis, occasionally bullous hemorrhagic dermatitis, allergic asthma, anaphylactic shock, etc.

7. Other

Weakness, tiredness, thirst, muscle cramps, hyperglycemia, acute gout, lupus erythematosus, etc. Occasionally feminization of male breasts.

treatment

The main points of furosemide poisoning treatment are:

1. Patients with large doses of oral poisoning should immediately induce vomiting and gastric lavage.

2. Replenish liquids and potassium salts to correct water and electrolyte imbalances.

3. Symptomatic treatment ^[5] .

Furosemide expert reviews

According to domestic reports, 11 cases of glaucoma filtering surgery did not form in the anterior chamber. After ineffective treatment with mydriatic, acetochloramide, mannitol and other pressure bandages at the follicle, 50% glucose was added to 20-40 mg of furosemide. 60ml of intravenous injection, once a day, anterior chamber formed 2 to 5 days after administration and soon returned to normal. In another report, for transient hyperglycemia in newborns, when the diuretic effect is poor, it can be increased daily by up to 160 mg per day by intravenous injection or orally, which can achieve good results. 50 cases of severe pneumonia in children were treated with furosemide intramuscular injection and antibiotics, and the hospitalization time of sick children was shortened by 3 days. The use of large doses of furosemide 60 to 100 mg intravenously every 1 to 2 hours successively doubled to the occurrence of diuretic reactions in 13 cases of leptospirosis and acute renal failure, with a total dose (1.5 ± 0.2) g in 24 hours, and 10 cases were cured without adverse effects. reaction. A large dose of 2.5 to 3.5 mg / kg is added to a 40% intravenous injection of 10% glucose injection each time to rescue acute cerebral edema and acute pulmonary edema, repeated once every 2 to 4 hours, a total of 2 to 4 times, about 15 to after the first administration Patients urinate a lot in 20 minutes, and symptoms begin to improve in 5 ± 1 minutes. They are characterized by fast action, significant curative effect, few adverse reactions, and will not cause hypokalemia. Concomitant diuretics are currently the most potent diuretics in clinical applications, and they are fast and reliable. They are suitable for edema caused by various causes and are the first choice for acute pulmonary edema. The adverse reactions of furosemide in tincture diuretics are relatively mild and relatively safe, and are favored by the majority of clinicians. The biggest adverse reaction of this drug is to cause water and electrolyte disorders, especially hypokalemia, and we should try our best to prevent it. Hypokalemia can often cause severe ventricular arrhythmias, which is particularly dangerous in patients with organic heart disease ^[6] .