Loop Diuretics

Question 1

What are some of the drugs that are found in this class of medications?

Answer 1

1. Sulfanamide Derivatives:
   Furosemide, bumetanide, torsemide
2. Phenoxyacetic acid derivatives:
   Ethacryonic acid

Question 2

What is their MOA?

Answer 2

They work by:
1. blocking the Na/K/2Cl symporter found in the luminal surface of the tubular cells in the thick ascending limb of the loop of Henle which leads to the excretion of about 15-25% of filtered sodium and other electrolytes like chloride, magnesium and calcium.

2. Stimulating the release of PG’s in the kidney which leads to vasodilation and increased renal blood flow.

Question 3

What are their pharmacokinetics?

Answer 3

1. They are well absorbed after being administered orally
2. They have a half life of around 2 hours.
3. They are secreted in urine

Question 4

What are their indications?

Answer 4

1. They are used in the treatment of edematous states like pulmonary edema due to heart failure (drug of choice), ascites due to hepatic failure and edema due to nephrotic syndrome.
2. They are used in the treatment of acute renal failure; since they increase the GFR and decrease fluid overload.
3. They are used to correct certain electrolyte imbalances like hypercalcemia and hyperkalemia
4. They increase PG synthesis.

Question 5

What are their adverse effects?

Answer 5

1. Ototoxicity; this can occur when the drugs are given in high doses or when given in combination with certain antibiotics like aminoglycosides, the damage could be irreversible if the drugs are continued. Ethacryonic acid is a more common cause than sulfanamide derivatives.
2. Hyperurecemia; low plasma volume caused by the drug can lead to increased uric acid reabsorption which can lead to hyperuricemia, which can lead to gout attacks.
3. Electrolyte imbalances:
   A. Hypokalemia: can be corrected by giving in combination with potassium sparing diuretics or dietary supplementation of K
   B. Hypocalcemia: will be mild because calcium is reabsorbed again in the distal convoluted tubule.
   C. Hypomagnesaemia: particularly in elderly, can be corrected by oral supplementation.

Question 6

What is the prototype drug of this class and its pharmacokinetics and dosing?

Answer 6

The prototype drug is furosemide.

Pharmacokinetics:
- it has highly successful in treatment pulmonary edema
- when taken orally it can work within an hour and lasts for 6 hours.
- overdose can lead to hypovolemia —> circulatory collapse

Dose:
Orally: 20-120mg daily
IV or IM: 20-40mg at 6 or 8 hour intervals (the first dose is given preferably in the morning to prevent the patient from going to the bathroom all night)