Loop diuretics include-

Furosemide, Bumetamide, Ethacrynic acid, Torsemide

Refer - Furosemide 

Interacting drugs- Loop diuretics - summary

Loop diuretics +

Aminoglycosides-                                                                                                             auditory toxicity increased with concurrent use. Hearing loss of varying degree may occur

Anticoagulants-                                                                                                           anticoagulant activity enhanced

Beta blockers-                                                                                                          propranolol plasma levels and cardiovascular effects enhanced.  Atenolol was not affected with (propranol)

Chloral hydrate-                                                                                                              transcient diaphoresis, hot flushes, hypotension, tachcardia, weakness and nausea occur with concurrent use

Digitalis glycosides-                                                                                                       diuretic-induced electrolyte disturbances may predispose to digitalis-induced arrhythmias

Lithium-                                                                                                                          possible increased plasma lithium levels and toxicity

Non-depolarizing  muscle realaxing-                                                                                        actions of the muscle relaxants antagonised or potentiated,  perhaps dependent on the loop diuretic dosage

Sulfonylureas-                                                                                                                       loop diuretics decrease glucose tolerance resulting in hypoglycemia in patients prevoiusly well controlled on sulfonylureas

Theophylline                                                                                                                         actions of theophylline altered,enhanced or inhibited 

+Loop diuretics

Charcoal-                                                                                                                      charcoal reduce the absorption of furosemide, depending on the clinical situation, this will reduce its effectiveness or toxicity

Cisplatin-                                                                                                                           additive ototoxicy may occur

Clofibrate-                                                                                                                              an exaggerated diuretic action may occur

Hydantoins                                                                                                                     hyadantoins may reduce the diuretic effects of furosemide (phenytoin) )

NSAIDs-                                                                                                                           effects of the loop diuretics decreased

Probenecid-                                                                                                                             actions of the loop diuretics reduced

Salicylates-                                                                                                                            diuretic response impaired in patients with cirrhosis and ascites

Thiazide diuretics-                                                                                                                       both groups have synergistic effects that result in profound diuresis  and serious electrolyte abnormalities 

Diuretic 

Loop diuretics include- Furosemide, Bumetamide, Ethacrynic acid, Torsemide

Refer - Furosemide 

FIXED DOSE COMBINATIONS APPROVED BY DCG(I)                                                FROM JANUARY 1961 TILL NOVEMBER 2014

Furosemide, Ethacrynic acid, Bumetanide, Torsemide-

Furosemide

GI- anorexia, nausea, vomiting, diarhea, oral and gastric irritation, cramping, constipation, pancreatitis, jaundice, ischemic hepatitis

CNS- vertigo, headache, blurred vision, hearing loss, dizziness, paresthesis, xanthopsia, restlessness, fever.

Hematologic- anemia, leukopenia, purpura, aplastic anemia, thrombocytopenia, agenulocytosis

Dermatologic- photosensitivity, urticaria, pruritus, necrotizing angitis, (vaculitis, cutaneous vasculitis) interstitial nephritis,exfoliative dermatitis, erythema multiforme, rash, occasionally, local irritation, and pain with parentral use.

Cardiovascular- orthostatic hypotension, thrombophlebitis, chronic aoritis

Miscellaneous- gkycosuria, muscle spasm, weakness, urinary bladder spasm, hyperuricemia, hyperglycemia

Ethacrynic acid

GI- anorexia, nausea, voimiting, diarrhea, pancreatitis ( acute) jaundice, discomfort, pain, sudden watery profuse diarrhea, GI bleeding, dysphagia.

Hematologic- severe neutropenia has occured in a few critically ill patients also receiving agents known to produce this effect. Rare instances of Henoch-Scoenlein purpura have occured in patients with rheumatic herat diseases. Thrombocytopenia , agranulocytosis

Miscellaneous- fever,chills, hematuria, apprenhension, confusion, fatigue, malaise, acute gout, sense of fullness in the ears, abnormal liver function tests, in seriously ill patients on multiple drug therapy that included ethacrynic acid (rare) vertigo, headache, blurred vision, tinnitus, hearing loss (irreversible ) rash occassionally, local iritation.

Pain have occured in parentral use, hyperuricemia, hyperglycemia.. Acute symptomatic hypoglycemia with convusions occurred in two uremic patients who received above doses above those receommended.

Bumetanide-

CNS- asterixis, encephalopathy with pre-esisting liver disease,impaired hearing, ear discomfort, vertigo, headache, dizziness.

GI- upset stomach, dry mouth, nasusea, vomiting, diarrhea, pain

GU- premature ejaculation, difficulty in maintaining erection, renal failure

Musculoskeletal- weakness, arthiritic pain, pain, muscle cramps, fatigue

Cardiovascular- hypotension, ECG changes, chest pain Miscellaneous- hives, pruritus, itching, dehydration, sweating, hyperventilation, nipple tenderness, rash, thrombocytopenia

Lab test abnormalities- Diuresis rarely accompanied by changes in LDH , total serum bilirubin, serum proteins, AST, ALT, alkaline phosphatase, cholesterol and creatinine clearance, deviations in hemoglobin, prothrombin time, hematocrit, WBC, platelet counts, and differential counts, 

Torsemide-

CNS- headache, dizziness, asthenia, insomnia, nervousness, syncope

GI- diarrhea, constipation, nausea, dyspepsia, edema, GI hemorrhage, rectal bleeding

Cardiovascular- ECG abnormality, sore throat, chest pain, artial fibrillation, hypotension, ventricular tachycardia, shunt thrombosis Respiratory- rhinitis, cough increase

Musculoskeletal- arthalgia, myalgia Lab test abnormalities- hyperglycemia, hyperuricemia, hypokalemia,hypovolumia

Miscellaneous- excessive urination.

Hypersensitive to sulphonamides,hypovalemia with or without hypertension, hypokalemia, hyponatraemia, precomatose stage associated with liver cirrhosis. Additions disease.

Special precautions:

Hepatic or renal impairment, pregancy, lactation, gout, diabetes, impaired micturition. Potassium supplements may be needed.

Monitoring- observe blood dyscrasis, liver or kidney damage or idiosyncratic reactions. Perform frequent serum electrolyte,calcium, glucose uric acid, CO2, creatinine and BUN determinations during the first few monthsof therapy and periodiclly thereafter.

Cardiovascular effects- too vigorous a diuresis, as evidenced by rapid and excessive weight loss, may induce an acute hypotensive episode

Electrolyte imbalance- when excessive diuresis occurs, withdraw the drugs until homestatis is restored. If excessive loss occurs, reduce dosage or withdraw the drug temporarily.

Hypokalemia- prevention requires particular attention to the following- patients receiving digitalis for CHF, hepatic cirrhosis, and ascites, innaldosterone excess with normal renal function potassium -losing nephropathy, certain diarrheal states or where hypokalemia is an added risk to the patient (eg history of ventricular arrhythmias)

Possible drug related deaths occurred with ethacrynic acid in critically ill patients refractory to other diuretics.

Hypomagnesiumia- loop diuretics increase the urinary excretion of magnesium

Hypocalcemia- serum calcium levels may be lowered

Gastric hemorrhage- ethacrynic acid may increase the risk of gastric hemorrhage associated with corticosteroid treatment.

Hyperuricemia- asymptomatic hyperuricemia can occur and rarely gout may be precipitated Reversible elevation of BUN may be seen.

Glucose- increases in blood glucose and alterations in glucose tolerance tests (fasting and 2 hour postprandial ) have been associated.

Lipids- increases in LDL and total cholesterol and triglycerides with minor decreases in HDL cholesterol may occur.

Photosentivity- photosentisitization may ocur. Use protective measures.

Drug/Food interactions- bioavailability of furosemide is decreased and its degree of diuresis reduced when administered with food.

Warnings-

Dehydration- excessive diuresis may result in dehydration and reduction of blood volume with circulatory collapse and the possibility of vascular thrombosis and embolism, particularly in elderely patients.

Hepatic cirrhosis and ascites- supplemental potassium chloride and if required an aldosterone antagonist help to prevent hypokalemia and metabolic alkalosis.

Oxytoxicity- usually oxytoxicity is associated with rapid injection with severe renal impairment, with doses several times the usual dose and concurent use of other otoxic drugs.

Systemic lupus erythematous- may be exacerbated or activated.

Diarrhea- because of amount of sorbitol in the frusemide solution vehicle, thepossibility of diarrhea,especially in children exists when higher dosages are given.

Hypersentivity- patients with known sulfonamide sensitivity may show allergic reactions to furosemide ,torsemide or bumetanide.

Renal function impairment- if high dose-parentral furosemide therapy is used controlled IV infusion is advisable.

Pregnancy- use caution when administering before delivery.

Lactation- decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- safety and efficacy for use in children have not been established

Indication:

Diuretic

Dosage-

Edema- 20 to 80mg/day as a single dose. Prompt diuresis ensues. Based on the response administer a second dose 6 to 8 hours later. If response is not satisfactory, increase by increments of 20 or 40mg, no sooner than 6 to 8 hours. Hypertension- 40mg twice daily; adjust according to response.

Overdosage-

Symptoms-

Acute profound water loss, volume and electrolyte depletion, dehydration, reuction of blood volume, and circulatory collapse, with a possibility of vascular thrombosis and embolism. Electrlyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps.

Treatment

1. Replace fluid and electrolyte losses by careful monitoring of urine and electrolyte output and serum electrolyte levels.

2. Assure adequate drainage in urinary bladder outlet bstruction (such as prostatic hypertrophy)

3. Hemodialysis does not accelerate furosemide or torsemide eliminaton.

4. Induce emesis or perform gastric lavage

5. If required, givre oxygen or artificial respiration.

6. Treatment includes supportive measures 

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Intestitial nephritis- ( 1285 )

Acute nephritis can occur during the course of viral infections with the deposition of bacterial and viral infections with the deposition of immune complexes again believed to be responsible for the transient renal damage that occurs.

Drugs causing adverse reactions- ( 385 )

1. Penicillins 2. Sulfonamides 3. Phenidione 4. Furosemide 5. Thiazides 

Deafness-

Drugs causing adverse reactions- ( 388 ) 

1. Aminoglycosides 2. Ethacrynic acid 3. Furosemide 4. Quinine 5. Bleomycin 6. Chloroquin 7. Mustine 8. Aspirin 9. Northriptyline

Loop diuretics

1. May cause GI upset, take with food or milk

2. Drug will increase urination, take early in the day

3. Notify physician if muscle weakness , cramps, nausea, or dizziness occur

4. Orthostatic hypotension may occur, get up slowly

5. Diabetes mellitus patients- may increase blood glucose levels, affecting urine glucose tests.

6. Photosentivity may occur in some patients. Cution patients to take protective measures (ie Sunscreens, protective clothing) against exposure to ultraviolet light or sunlight

7. Hypersensitivity patients should avoid medications that may increase blood pressure, including OTC products for ppetite suppression and cold symptoms

8. Drug will increase urination; take early in the day.

9. Orthostatic hypotension may occur; get up slowly.

10. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to butetanide, ethacrynic acid, furosemide, sulfonamide or thiazide diuretics or other related medicines. Also tell your doctor if your are allergic to any other substances such as foods, preservatives or dyes.

11. Pregnancy- diuretics should not be taken during pregnancy unless recommended by your doctor.

12. Breast feeding- furosemide passes into breast milk, it is not known whether bumetanide or ethacrynic acid passes into breast milk.

13. Children- no specific information available comparing the use of diuretics in children other age groups, these medicines are not expected to cause differnt side effects in children than they do in adults.

14. Elderly- dizziness, lightheadedness or signs of too much potassium loss more likely to occur in elderly. Elderly patients are more likely to develop blood clots.

15. Other medicines- tell your doctor- when you are loop diuretics it is especially important that your doctor know if you are taking any other medicines.

16.Other medical problems- tell your doctor if you have any other medical problems- Diabetes mellitus or - loop diurtetics may increase the amount of sugar in the blood. Gout or Hearing problems or Pancreatitis - loop diuretics may make these conditons worse Heart attack- use ofloop diuretics after a recent heart attack may increase the chance of side effects. Kidney disease or Liver disease - higher blood levels of loop diuretic may occur which may increase the chance of side effects Lupus erythematous - ethacrynic acid and furosemide may make this condition worse

17. Missed dose- If you miss a dose of this medicine take it as soon as possible. However if it is almost time for your next dose go back to your regular dosing schedule. Do not double doses.

Drug/Food interactions-

Bioavailability of furosemide is decreased and its degree of diuresis reduced when administered with food.

Pregnancy-

Use caution when administering before delivery.

Lactation-

Decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children-

Safety and efficacy for use in children have not been established