Diuretics Flashcards
What are diuretics
A drug or substance that increases the rate of urine secretion
What is the primary mechanism of Na+ transport in the proximal convoluted tubule
Na+/ H+ exchange
What are the classes of diuretics that work at the PCT
Carbonic anhydrase inhibitor
Osmotic diuretics
What is the prototypic agent of carbonic anhydrase inhibitors
Acetazolamide
MOA of acetazolamide
Inhibit of carbonic anhydrase in the brush border and cytoplasm
How is acetazolamide administered
Orally
Effects of acetazolamide
Metabolic acidosis
Potassium wasting (hypokalemia)
Acidosis of the cerebrospinal fluid causing hyperventilation
Clinical uses of acetazolamide
- Treatment of severe acute glaucoma
- Prevent acute mountain “high altitude” sickness
- Diuretic effect only if the edema is accompanied by metabolic alkalosis
Topical analogs for carbonic anhydrase inhibitors
- Dorzolamide
- Brinzolamide
Mention osmotic diuretics
- Mannitol
- Glycerol
- Isosorbide
How is Mannitol administered
Intravenously
MOA of mannitol
Increase concentration of solute in the tubular lumen and thus via osmosis promote excretion of water and electrolytes
Therapeutic use of mannitol
- Reduce raised intracranial pressure
- Reduce raised intraocular pressure in acute congestive glaucoma
- Maintain osmolarity of extracellular fluid during dialysis
Adverse reactions of Mannitol
Hyponatremia
Pulmonary edema
Headache, nausea, and vomiting
Mention loop diuretics
Furosemide
Bumetanide
Tiracemide
Ethacrynic acid
Which part of the nephron do loop diuretics work on
Thick ascending limb
How much sodium is filtered by the TAL
25%
What cotransporter is found on the TAL
Na+/K+/2Cl-
Clinical uses of loop diuretics
- Congestive heart failure
- Cirrhosis of the liver
- Renal disease (nephrotic syndrome)
Short term management of ascites due to:
- Malignancy
- Idiopathic edema
- Lymphedema
Short term management of hospitalised pediatric patients
How are loop diuretics used to treat disorders causing hypercalcaemia
By reducing the lumen voltage gradient that drives cation reabsorption in the loop, loop diuretics increase the excretion of divalent cations (Ca and Mg) and this can be useful in treating hypercalcaemia
How are loop diuretics administered
Oral
Parenteral
Adverse effects of loop diuretics
- Hypokalemia, hyponatremia, hypocalcemia
- Hyperglycaemia and hyperuricemia
- Ototoxicity
Important drug-drug interaction of loop diuretics
-Combinations with thiazide diuretics leads to potassium conservation and improved diuretic response
What diuretics work at the distal convoluted tubule
Thiazide diuretics (hydrochlorothiazide)
How much sodium is reabsorbed at the DCT
6 to 8%
What happens in the body when it is in a hypertonic state
Anti diuretic hormone (ADH) is released by the posterior pituitary and increases the permeability and water reabsorption by the DCT.
MOA of hydrochlorothiazide
To inhibit sodium chloride transport in the early segment of the DCT
Increases Na+/Cl- secretion
Why are thiazides used to treat hypercalcinuria
When Na+ excretion is increased, Ca+ excretion is decreased
Clinical uses of thiazides
- Hypertension
- Heart failure (reduce blood volume)
- Treatment of kidney stones caused by hypercalcinuria
- Nephrogenic diabetes insupidus
How are thiazides administered
Orally
Adverse reactions of thiazides
- Hypokalemic metabolic alkalosis
- Hyperuricemia caution in gout
- Hyperglycaemia
- Electrolyte imbalance
Mention drugs under potassium sparing diuretics
- Aldosterone antagonists: Spironolactone
- Non steroidal potassium sparing drugs: triamterene and amiloride
Function of aldosterone
Stimulates the rates of Na+ reabsorption and K+ secretion
