Diuretics

diuretics

-drugs that diminish NaCl reabsorption at different sites in the nephron, thereby increasing sodium and H2O losses

-used to treat edematous states (CHF, cirrhosis, nephrotic syndrome, advanced CKD)

-used to treat hypertension

site of action of diuretics

osmotic diuretics

acetazolamide

loop diuretics

thiazide-type diuretics

potassium-sparing diuretics

determinants of diuretic potency

-diuretic dose

-quantity of Na normally reabsorbed at the diuretic-sensitive site

-ability of more distal segments to reabsorb excess sodium

re-establishment of the steady state

re-establishment of the steady state: counter-regulatory responses

-volume depletion → increased SNS, renin, ATII, aldosterone: increased filtration fraction → increased proximal tubular reabsorption, direct stimulation of Na reabsorption in the proximal tubule and collecting duct

-nephron remodeling: hypertrophy of distal nephron

loop diuretic infusion increases

-thiazide-sensitive Na/Cl cotransporter abundance: role of aldosterone

reestablishment of steady state after administration of high-dose thiazide to normal subjects

diuretics affect…

-potassium balance

-acid-base balance

-other electrolytes (Ca2+, Na+, Mg2+)

-uric acid

understanding loop and thiazide diuretic-induced hypokalemia

understanding loop and thiazide diuretic-induced metabolic alkalosis

loop diuretics- acid/base

Bartter syndrome

-genetic disease resembling chronic furosemide use

thiazide-type diuretics- acid/base

thiazides and hypercalcemia

thiazide-associated hyponatremia

thiazide-induced hyponatremia- physiologic and genetic analysis

why is hyponatremia less common with loop diuretics?

loop and thiazide diuretics may both cause

-hyperuricemia

potassium-sparing diuretics- acid/base

acetazolamide- acid/base

effect on serum potassium

-urinary K excretion depends on distal delivery of Na and aldosterone

effect on acid-base status

loop and thiazide diuretics enter the lumen by

-proximal tubular secretion

mechanisms of diuretic resistance/refractory edema

overcoming diuretic resistance

-change to a more bioavailable drug

-increase diuretic dose

-increase diuretic frequency (BID dosing)

-attempt more rigorous dietary Na restriction

-combine different classes of diuretics (“sequential nephron blockade”)

sequential diuretic use

which diuretic class used to treat: SIADH, hypercalcemia, calcium stones, loop-diuretic-induced metabolic alkalosis, loop-diuretic-induced hypokalemia

-SIADH: loop

-hypercalcemia: loop

-calcium stones: thiazide

-loop-diuretic-induced metabolic alkalosis: acetazolamide or K-sparing diuretic

-loop-diuretic-induced hypokalemia: K-sparing diuretic

conclusions