Pharm of Diuretics Flashcards
Diuretic definiton
Agent that increases urinary excretion of Na and water
2 main ways Na is reabsorbed in PCT
Na symporter (Na and glucose/Cl/amino acid)
Na-H antiporter
The concentration gradient of Na is kept low due to basolateral Na/K ATPase
Renal tubular Na and water transport:
Proximal tubule
Permeable to water
2/3 of Na is reabsorbed here (via channels, symporters, antiporters, and carbonic anhydrase)
Renal tubular Na and water transport:
Descending limb
Permeable to water
Water moves from tubule to the hyperosmotic renal medulla
Renal tubular Na and water transport:
Ascending limb
Impermeable to water
25% of Na is reabsorbed via NKCC symporter
Causes a dilution of the filtrate and increases the medullary osmolality
Renal tubular Na and water transport:
Distal tubule
Impermeable to water
5-10% of Na is reabsorbed (Na-Cl symporter)
Further dilutes the filtrate
Renal tubular Na and water transport:
Collecting duct
2-5% of Na reabsorbed
Aldosterone: causes Na to be reabsorbed and K/H to be secreted
ADH causes insertion of aquaporin 2 and the concentration of urine
2 places in the nephron that are permeable to water
Proximal tubule
Descending limb
4 major classes of diuretics
Carbonic anhydrase inhibitors (acetazolamide)
Loop diuretics (furosemide)
Thiazide diuretics (hydrochlorothiazide)
Potassium sparing diuretics (spironolactone, amiloride)
Why does blocking carbonic anhydrase cause a diuretic effect?
No carbonic anhydrase means H2CO3 (from bicarb and H) isnt converter to water and CO2
This decreases the intracellular concentration of bicarb and H (because water and CO2 can cross the membrane and reform them)
Less H means less Na/H antiporter activity
More Na, bicarb, and also water is left in filtrate
Acetazolamide
Carbonic anhydrase inhibitor at the proximal tubule
Loss of Na and bicarb (causes metabolic acidosis)
Limited use as a diuretic because tolerance develops after 3 days (body starts making more CA)
Adverse effects and main uses for acetazolamide
CA inhibitor
Adverse effects: alkaline urine can cause precipitation of calcium phosphate (renal stones)
Uses: acute mountain sickness, open-angle glaucoma
Mechanism of action for furosemide
It’s a loop diuretic
- At ascending loop of Henle, they inhibit NKCC (eliminate the countercurrent multiplier system)
- At macula densa cells they inhibit the detection of Na concentration
- Dilate veins (reduce venous pressure)
Loop diuretic effect on renin
Furosemide inhibits absorption of Na, K and Cl which stimualtes rennin release
3 stimuli for the secretion of renin
Decrease in renal arterial pressure
Decrease in NaCl at macula densa cells (at DCT)
Decrease in blood pressure (increase in sympathetic discharge)
Aldosterone causes…
Na renal reabsorption
K and H secretion
Loop diuretics effects on ions
Inhibit NKCC (lose those ions) Loss of K causes loss of lumen positive potential, causes loss of Mg and Ca Stimulation of renin release and increases aldosterone causes loss of K and H
3 conditions where you would use loop diuretics
CHF
Acute pulmonary edema
Peripheral edema
Adverse effects of loop diuretics
Hyponatremia, hypovolemia and hypotension from Na loss
Hypokalemia and metabolic alkalosis due to aldosterone secretion
Hyperuricemia (uric acid crystals deposit in joints) from the diuretics competing with uric acid secretion at proximal tubule (need to be secreted at proximal tubule so they can work on luminal LoH)
Ototoxicity (damage of auditory nerves)
Mechanism of action of thiazide diuretics
Block Na/Cl symporter at distal tubule (increase Na excretion and decrease blood volume)
Dilation of arterioles (decrease blood pressure)
3 main uses for thiazide diuretics
Hypertension (decrease BP from arteriole dilation and decrease in bv)
Edema (decrease bv and decrease venous pressure and capillary filtration)
Nephrogenic diabetes insipidus (reduces max dilution of the filtrate to deal with the excessive excretion of very dilute urine)
Adverse effects of thiazide diuretics
Hyponatremia (from prevention of maximal dilution of urine at the DT)
Hypokalemia and metabolic alkalosis (from aldosterone secretion)
Hyperuricemia (thiazides compete with uric acid secretion)
Hyperglycemia (interference with release/action of insulin)
Aldosterone activates the mineralcorticoid receptor to cause…
Increases synthesis of Na/K ATPase (high K in cells allows K to flow down its gradient into lumen - loss)
Increased synthesis of luminal Na channel (Na absorption)
Spironolactone
K sparing diuretic
Competitive antagonist of aldosterone
Blocks synthesis of mineralcorticoid receptor
Blocks synthesis of luminal Na channels
Amiloride
K spring diuretic
Blocks Na flow through luminal Na channels
3 uses for K sparing diuretics
Edema
Heart failure
Primary hyperaldosteronism
2 adverse effects of K sparing diuretics
Hyperkalemia (esp when used with K supplements)
Reversible gynecomastia with spironolactone
