Diuretics Flashcards
loop diuretic effects on acid/base
thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr
thiazide diuretic effects on acid/base
thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr
osmotic diuretic effects on acid/base
osmotic diuretics induce metabolic acidosis (bicarb excreted via solvent drag?)
CA inhibitor effects on acid/base
CA inhibitors induce metabolic acidosis (more bicarb excretion)
K-sparing diuretics effects on acid/base
K-sparing diuretics induce metabolic acidosis (Na not reabsorbed, therefore lumen not negative, therefore H+ not excreted)
effects on acid-base by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics
thiazide and loop diuretics induce metabolic alkalosis in three ways: 1. hypovolemia -> incr Na reabs in PT via Na-H exchanger due to incr AgII (leading to more bicarb reabs), 2. hypovolemia -> hyperaldo -> three mechs -> alkalosis, 3. these diuretics cause more Na in distal tubule, where Na enters principal cell and causes negative lumen V which incr H+/K+ secr; CA inhibitors induce metabolic acidosis (more bicarb excretion); osmotic diuretics induce metabolic acidosis (bicarb excreted via solvent drag?); K-sparing diuretics induce metabolic acidosis (Na not reabsorbed, therefore lumen not negative, therefore H+ not excreted)
loop diuretic effects on K
loop/thiazide diuretic cause V depletion (-> aldo) and incr distal Na delivery (inhibit TAL/DCT Na reabs) -> incr K secretion -> hypokalemia; also cause alkalosis -> hypokalemia; thiazide are more kaliuretic than loop b/c they have longer DOA and thus less likely to have K conserving time periods
thiazide diuretic effects on K
loop/thiazide diuretic cause V depletion (-> aldo) and incr distal Na delivery (inhibit TAL/DCT Na reabs) -> incr K secretion -> hypokalemia; also cause alkalosis -> hypokalemia; thiazide are more kaliuretic than loop b/c they have longer DOA and thus less likely to have K conserving time periods
osmotic diuretic effects on K
osmotic diuretics cause V depletion and incr distal NaCl delivery -> hypokalemia
Ca inhibitor effects on K
acetazolamide causes V depletion (-> aldo) and incr distal Na delivery (w/ NaHCO3) and poorly resorbable anion (HCO3-) delivery -> hypokalemia
mannitol
osmotic diuresis
acetazolamide
CA inhibitors
furosemide
inhibits NKCC2 by substituting for chloride on transporter
how do most diuretics get into tubule?
most via tubular secretion rather than glomerular filtration (protein-bound)
mechs of “braking phenomenon”
neural (SNS), endocrine (RAAS), physical hypertrophy of unaffected nephron segments (chronic diuretic resistance)
conditions associated w/ decreased diuretic action (4)
bowel wall edema (no GI abs of drug); hypoalbuminemia (no proteins to bind drugs); ECV depletion (decr RPF); CKD
CA inhibitors lost from PT, lost in urine
lost from PT: bicarb, Na (b/c NaH has no gradient so Na not reabs), water; however, Na reabs in distal nephron, so instead lost in urine: bicarb, K (due to distal delivery of NaHCO3)
clinical use of CA inhibitors (4)
limited use as natriuretic; correction of metabolic alkalosis (be careful b/c alkalotic pts are already hypokalemic and CA inhibitor will worsen it); altitude sickness; glaucoma
loop diuretics lost in urine
chlorine, K, Na, water, Ca, Mg; these diuretics also block uric acid secretion so less uric acid lost; more water than Na lost (hypotonic urine -> can use to correct hyponatremia)
clinical use of loop diuretics (4)
correction of edematous disorders (CHF, pulm edema, nephrotic syndrome, renal failure); hyperkalemia; hypercalcemia; severe HTN (rarely used due to short half life)
loop vs thiazide half life
thiazide longer half life (better to tx HTN, more likely to cause kaliuresis)
loop diuretic side effects (7)
hypokalemia, hypocalcemia, hypercalcuria (stones), hypomagnesemia, hyperuricemia (block uric acid secretion), ototoxicity (usually reversible, worse w/ ethacrynic acid, b/c NKCC also in ear), sulfa allergy (use ethacrynic acid b/c no sulfa group)
ethacrynic acid
loop diuretic used for ppl w/ sulfa allergies, has side effect of ototoxicity (so don’t use unless severe sulfa allergy)
thiazide diuretics: onset of action timeline, natriuretic effect timeline, potency, effects on ions (Na, Cl, Ca, K, Mg)
onset of action 2-3 hrs, natriuretic effect < 6 hrs; less potent than loop diuretics b/c less Na reabs in DCT: loss of NaCl in urine (through NCC), increased calcium reabs (used to prevent stones and tx hypercalcuria), and loss of K and Mg in urine
clinical use of thiazides (4)
1st line therapy in HTN (anti-HTN effects actually continue after braking phenomenon) along w/ low salt diet; combo w/ loop diuretic to prevent braking phenomenon in chronic edematous states (beware of hypokalemia and hypomagnesemia); prevention of stones (1st line therapy due to hypocalcuric effects); tx of hyperkalemia
side effects of thiazides (7)
hypokalemia; hypomagnesiumia; hyponatremia; hyperuricemia (block uric acid secretion); incr Ca reabs; carb intolerance (impaired insulin release); sulfa allergy
amiloride
blocks ENaC
spironolactone
aldo receptor antagonist
eplerenone
aldo receptor antagonist
clinical uses of K sparing diuretics (4)
not very good natriuretics, but used w/ other diuretics to prevent hypokalemia; spironolactone doesn’t req tubular secretion and so works well at low EABV -> use to improve survival in CHF, cirrhosis, and for its anti-proteinuric effects (anti RAAS)
side effects of K sparing diuretics (2)
hyperkalemia in pts prone to it (CKD, CHF -> balance w/ loop diuretic in these pts); painful gynecomastia w/ spironolactone
osmotic diuretics (4)
mannitol, radiocontrast dye, glucose (in hyperglycemia), urea (after relief from obstructive uropathy or high-protein tube feedings)
osmotic diuretics clinical uses (2)
lead to Na and water losses, but lose more water than Na (hypotonic fluid loss) -> can lead to hyperosmolarity of blood (use to tx incr intracranial P due to hypotonicity); exogenous osmotic agents act as volume expanders in vasculature -> don’t use in edematous states, but good for dialysis pts who are hypotensive
how is Na loss w/ osmotic diuretics?
Na abs but water is not due to effective osmole (like mannitol) in tubule, thus as Na is absorbed more than water, [Na] in tubule decreases so that there is no concentration gradient remaining to drive reabsorption; so while Na and water are thus both lost in urine, there is still more water lost than sodium -> leads to hypertonicity of blood
Na excretion (as % of filtered load) for: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics
osmotic: 10%, CAI: 5-10%, loop: 25%, thiazide: 5-10%, K-sparing: 3-5%
effects on Ca excretion by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics
osmotic diuretics incr Ca excretion (solvent drag); CAI incr Ca excretion (solvent drag) - incr calciuresis along w/ alkaline urine = stones; loop diuretics incr Ca excretion (no positive lumen to push reabs of Ca) -> can cause stones; thiazide diuretics decr Ca excretion -> tx stones; K sparing diuretics don’t affect Ca excretion
effects on free water excretion by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics
osmotic diuretics and CAI incr water excretion (incr NaCl delivery to DCT allows increased dilution); loop and thiazide diuretics decr water excretion b/c can’t dilute w/ NCC and NK2Cl blocked; K sparing diuretics don’t affect dilution ability
effects on free water reabs by: osmotic diuretics, CAI, loop diuretics, thiazides, K sparing diuretics
osmotic diuretics and CAI incr water reabs; loop diuretics decr water reabs (can’t concentrate b/c gradient is dissipated); thiazide and K sparing diuretics don’t affect water reabs
