Diuretics Flashcards
Which loop diuretic does not have a sulphonamide structure?
Ethacrynic acid
MOA of carbonic anhydrase inhibitors (CAIs)
When PCT lumen CA is inhibited, no H+ is formed in the cytosol and no Na+ and HCO3- is absorbed into the cells.
At the collecting tube, Na+ concentration is increased (because it was not absorbed at the PCT) and principle cells absorb it, while secreting K+ –> hypokalemia
The intercalated A cells of the collecting tube are unable to secrete H+ into the urine because CA is inhibited and so less NH4+ is excreted –> acidosis
On the basolateral membrane of the intercalated A cell, the bicarbonate/Cl- anti porter is inhibited, preventing Cl- excretion in the urine –> hyperchloremic acidosis
What are the uses of CAIs?
Glaucoma: oral acetazolamide or topical dorzolamide decrease aqueous humor formation
Urinary alkalization
Metabolic acidosis
Mountain sickness: above 3000m pt may have respiratory alkalosis (weak, dizziness, headache, insomnia) which can be treated with a CAI
ADR of CAIs
Hyperchloremic metabolic acidosis
Renal stones due to increased urine phosphate and Ca2+
Hypokalemia
Decreased urine NH4+ excretion, which can worsen hepatic coma
Cross-allergy with sulfonamide
When are CAIs contraindicated?
Hepatic encephalopathy
Sulfonamide allergy
MOA of loop diuretics
Na+/K+/2Cl- pump is inhibited at the thick ascending limb of LOH
Loss of 25% of Na+ in the urine
Lack of K+ in the cytosol leads to less K+ entering the lumen through leaky channels which inhibits the positive potential of the lumen that usually drives Mg2+ and Ca2+ reabsorption (via paracellular pathway) –> Mg2+ and Ca2+ are lost in urine
At the collecting tube, Na+ concentration is increased (because it was not reabsorbed at the TAL) and principle cells absorb it, while secreting K+ –> hypokalemia
The intercalated A cells of the collecting tube take back the lost K+ in exchange for H+ secretion –> blood alkalosis
Loop diuretics can be used for:
Hyperkalemia Hypercalcemia Acute renal failure Acute heart failure Hypertension emergency
Loop diuretics are contraindicated in:
Sulphonamide allergy
Acute gout
Which drugs are CAIs?
Acetazolamide
Dorzolamide
Which drugs are loop diuretics?
Furosemide
Bumetanide
Torsemide
Ethacrynic acid
ADR of loop diuretics
Hypokalemic metabolic alkalosis
Ototoxicity: worse if combined with aminoglycoside
Hyperuricemia: H+ competes with uric acid to be secreted (so increased H+ secretion leads to reduced uric acid secretion). As well, hypovolemia increases uric acid reabsorption in the PCT.
Hypomagnesemia
Cross-allergy with sulphonamide (except ethacrynic acid) –> skin rash
Thiazides MOA
Thiazides block the action of the Na+/Cl- cotransporter in the DCT –> 10% NaCl is lost in urine.
Na+ in the cytosol is reduced and so the Na+/Ca2+ anti porter on the basolateral membrane is activated by PTH leading to increased Ca2+ reabsorption.
At the collecting tube, Na+ concentration is increased (because it was not reabsorbed at the DCT) and principle cells absorb it, while secreting K+ –> hypokalemia
The intercalated A cells of the collecting tube take back the lost K+ in exchange for H+ secretion –> blood alkalosis
How can thiazides be used?
Hypertension: in the short term, they decrease BP. In the long term after about 6 months, they directly decrease vessel tension possibly due to K+ channel opening.
Kidney stone or hypercalciuria (Ca2+ is now in the blood, not the urine, so stones are less likely to form in the lumen)
Nephrogenic diabetes insipidus (unknown mechanism)
Chronic heart failure
ADR of thiazides
Hypokalemic metabolic alkalosis
Hyperuricemia: H+ competes with uric acid to be secreted (so increased H+ secretion leads to reduced uric acid secretion)
Hyperglycemia: hypokalemia decreases insulin release from the pancreas islet beta cells and impairs insulin sensitivity
Hyperlipidemia
Hyponatremia
Cross-allergy to sulphonamide
Thiazides are contraindicated in:
Sulfonamide allergy
Acute gout