diuretics Flashcards
proximal tubule physiology
Na REAB w/ Cl isosmotically (50-75% of filtered load)
K REAB Bicarb REAB (80-90%)
ascending limb of loop of henle
- Na and Cl REAB (20-30 %) active Cl REAB
- Impermeable to water
- May compensate for increased delivery of Na from proximal tubule by increasing REAB
- cortical and medullary segments differ in response to diuretics
Distal tubule and collecting duct
- Na REAB (8-9%)
- K secreted
- regulation of Na and K exchange by aldosterone
- Permeability to water regulated by antiduretic hormone (ADH- Vasopressin
vasodilator drugs
caffeine, fenoldopam, dopamine, atriopeptins
- increase RBF w/o reducing glomerular filtration rate
- filtration fraction (FF= GFR/RBF) decreases, which reduces the protein concentration and hydroosmotic forces in the peritubular capillaries
- decreases in osmotic forces in peritubular capillaries which allow Na and water to leak back into tubule. plasma proteins contribute to these osmotic forces, plasma proteins are not filtered so remain in capillaries
- greater back leak reduces net REAB so Na excretion increases
- weak as diuretics due to compensatory Na REAB in more distal nephron segments
- dopamine agonists may be used to increase RBF in shock
osmotic diuretics
mannitol
Freely filterable at glomerulus
limited REAB by tubule
not metabolized by kidney
Pharmacologically inert
MOA osmotic diuretics
non- REAB solute limits the REAM of water from the tubule
Na is REAB w/o water, the sodium conc. in the tubule falls
Reduced Na concentration diminishes Na REAB
Action continues in ascending limb and distal tubule to limit Na REAB
Enhanced K excretion occurs in distal tubule due to increased Na available for exchange
Urine flow increases as does excretion of Na, K, and Cl
Therapeutic uses of mannitol
mannitol is poorly absorbed by the GIT and causes osmotic diarrhea rather than diuresis, must be given IV for systemic effects. Mannitol is not metabolized and is excreted by Glomerular filtration within 30-60 minutes
Prophylaxis of acute renal failure, edematous conditions where volume load is not detrimental, glaucoma, reduce intracranial pressure
toxicity of mannitol
extracellular volume expansion: (mannitol is rapidly distributed in the extracellular compartments and extracts water from cells–> hyponatremia, can complicate heart failure and can produce pulmonary edema
Dehydration, hyperkalemia, hypernatremia: mannitol use w/o adequate water replacement can –> dehydration, hyperkalemia and hypernatremia
hyponatremia: mannitol use in patients with severe renal impairment is not effectively excreted and is retained in the plasma–> osmotic extraction of water from cells resulting in hyponatremia.
inhibitors of Carbonic anhydrase MOA
Acetazolamide
- Secreted into proximal tubule by organic acid transporter (OAT)
- Carbonic anhydrase catalyzes the formation of carbonic acid from CO2 and water, which produces the H ions necessary for bicarb REAB
- blocking the enzyme decreases bicarb REAB and thereby Na REAB in the proximal tubule, urine pH increases
- loop of henle is not permeable to bicarb so cannot compensate for increased Na load
- K secretion in distal tubule increases
- urine volume increases as does the excretion of Na, K and bicarb, urinary excretion of chloride falls
Therapeutic uses of acetazolamide
carbonic anhydrase inhibitors are well absorbed after oral admin, an increase in urine pH from HCO3- diuresis is apparent within 30 minutes, is maximal at 2 hours and persists for 12 hrs after a single dose, CA inhibitor is secreted by proximal tubule in S2 segment, dosing must be reduced in renal insufficiency
-glaucoma- reduce aqueous humor formation
-alkalinize urine to decrease drug toxicity
metabolic alkolosis- treats symptoms of acute altitude sickness
toxicity/ SE/ contraindicated of acetazolamide
hyperchloremic metabolic acidosis- acidosis results from chronic reduction of HCO3- by CA inhibitors and limits the diuretic efficacy of these drugs to 2 or 3 day
Renal stones: phosphaturia and hypercalciuria occur during the bicarbonaturic response to inhibitors of CA inhibitors. calcium phosphate salts are relatively insoluble in the tubular fluid alkaline pH, this condition enhances the poptential for renal stone formation from calcium salts
Renal K wasting: increases Na presented to the collecting tubule is partially REAB, increasing the lumen- neg electrical potential in that segment and enhancing K secretion. K sparing diuretics can counteract this effect
Generally safe
contraindicated: b/c decreased urinary excretion of NH4 contributes to the development of hyperammonemia and hepatic encephalopathy in patients with cirrhosis
loop or high ceiling diuretics MOA
furosemide, bumetanide, ethacrynic acid
MOA: Na, K 2 CL symport inhibots
Secreted into porximal tuble by organic acid transporter (OAT), act on cortical and medullary segments of ascending limb of the loop of henle to inhibit active chloride REAB–> reduced REAB of NA K and CL
in high doses, furosemide and bumetanide inhibit carbonic anhydrase and have proximal tubular effect
potent diuretics-> 20-30% of the filtered load of Na is excreted, increased RBF and often GFR
K excretion increases due to increased Na delivery to distal tubule, increases Na-K exchange
Impairs the kidneys ability to make a concentrated or diluted urine
enhance urate REAB in proximal tubule, enhance excretion of Ca, urine volume increases w/ Na Cl and K
Therapeutic uses of loop diuretics (furosemide, bumetinide, ethacrynic acid)
rapidly absorbed and eliminated by glomerular filtration and tubular secretion in the kidney. absorption of furosemide within 2-3 hours and is nearly as complete as with intravenous administration
- diuresis is rapid in onset (15 minutes) and short in duration (2-3 hours)
- management of edema due to cardiac, hepatic or renal disease. since loop diuretics tend to increase RBF and GFR, they are of value in treating edema associated with nephrotic syndrome and chronic renal failure
- acute pulmonary edema
- HTN
Toxicity or side effect of loopdiuretics
hypokalemia: by inhibiting salt REAB, loop diuretics increase Na delivery to the collecting duct, increased Na delivery leads to increased secretion of K and H in the collecting duct resulting in hypokalemic and metabolic alkolosis, can be reversed by K replacement and correction of hypovolemia
hyperuricemia: loop diuretics cause hypovolemia to increase uric acid REAB resulting in hyperuricemia and gout
hyperglycemia- for furosemide only
ototoxicity–deafness w/ high doses–ethacynic acid>furosemide> bumetianide (esp in pt w/ diminished renal function)
volume depletion
Thiazide and related diuretics
hydrochlorothiazide, metolazone
MOA: Na CL Symport inhibitors
- Secreted into proximal tubule by organic acid transporter (OAT)
- Act on the cortical diluting segement of the ascending limb of the loop of henle to inhibit to inhibit NaCl REAB. inhibit the NaCL- cotransporter or symporter
- In higher doses, some thiazides inhibit CA and have a proximal tubular effect
- intermediate in activity – 8-10% of the filtered load of NA excreted
- Reduce GFR
- K secretion increases due to increased NA delivery to distal tubule, increase NA-K exchange
- Impairs the kidneys ability to produce dilute urine
- Enhace urate REAB in proximal tubule
- Decrease Renal excretion of CA
- Urine volume increases as does the excretion of Na, Cl, and K. Excrete a hypertonic urine
