Diuretics Flashcards
Renal Vasodilators Action
Increase renal blood flow without reducing GFR
FF (GFR/RBF) decreases so protein concentration and hydro osmotic forces in peritubular capillaries decrease
Decrease in osmotic forces allow sodium and water to leak back into tubule so increased sodium excretion
Weak diuretic because compensatory sodium reabsorption in more distal nephron segments
Pharmacological use is limited–> dopamine used to increase RBF in shock
Osmotic Diuretic Drugs
Mannitol
Osmotic Diuretic Actions/Properties
Freely filtered, limited reabsorption, not metabolized by kidney, inert, works mainly at PT, Intravenos
Limits water reabsorption and sodium reabsorbed without water so Na concentration in tubule falls–> Net sodium reabsorption falls because because unfavorable concentration gradient
Urine volume and sodium excretion increase proportional to osmotic load
Enhance potassium, sodium, chloride, water, and mannitol excretion
Enhance potassium excretion in distal tubule because more sodium available for exchange
Osmotic Diuretic (Mannitol) Uses
Edema
Glaucoma to reduce intraocular pressure
Acute renal failure
Intracranial pressure reduction
Mannitol toxicity
Extracellular volume expansion –>Mannitol distributed to extracellular compartments and extracts water from cells which leads to EXPANSION OF EXTRACELLULAR VOLUME AND HYPONATREMIA
Complicates heart failure and produce pulmonary edema
Dehydration, Hyperkalemia, Hypernatremia–> without adequate water replacement leads to severe dehydration and Hypernatremia. Water extracted from cells, intracellular K increases and K then leaves the cells to extracellular compartment resulting in hyperkalemia
HYPONATREMIA–> if severe renal impairment then mannitol not excreted and retained in plasma so osmotic extraction of water results in hyponatremia
Carbonic Anyhdrase Inhibitor Drugs
Acetazolamide
Carbonic Anydrase Mechanism of Action
Secrete into PT by organic acid transporter (OAT)
CA usually catalyze so carbonic acid formation which produces H for bicarb reabsorption
Block CA decrese bicarb reabsorption and Na reabsorption in PT–> Urine pH alkali nixed
Loop of Henle not permeable to bicarb so can’t compensate for increase Na load
K secretion in distal tubule increases
Urine volume increases along with Na, K, and bicarb and chloride excretion falls
Carbonic anyhdrase therapeutic use
Glaucoma to reduce aqueous humor formation
Alkalinize urine to decrease drug toxicity
Metabolic alkalosis
Treat symptoms of acute altitude sickness
Diuresis is apparent 30 min after admin, max at 2 hours and persist for 2 hours
Carbonic Anyhdrase Inhibitor Toxicity and Contraindications
Hyperchloremic Metabolic Acidosis–> from chronic reduction of bicarb by CA inhibitor and this limits diuretic efficacy for 2-3 days
Renal stones–> phosphaturia and hypercalciuria occurs during bicarbonaturic response and these calcium phosphate salts are relatively insoluble in tubular fluid alkaline pH
Renal Potassium Wasting–> increase Na presented to collecting tubule is partially reabsorbed which increases lumen negative electrical potential in that segment and enhancing K secretion (K sparing diuretics counteract this effect)
Generally safe
Contraindication: contribute to development of hyperammonemia and hepatic encephalopathy in patients with cirrhosis
Renal Vasodilators Drugs
Fenoldopam
Dopamine
Atriopeptins (atrial natriuretic peptides)
Loop Diuretic Drugs
Furosemide, Bumetanide, Ethacrynic Acid
Loop Diuretic Mechanism of Action
Na/K/2Cl symport inhibitor
Secreted into PT by OAT
Act on cortical and medullary segment of ascending limb of LOH to inhibit Cl reabsorption–> reduced reabsorption of both Na and CL by inhibiting Na/k/2Cl symporter
High doses of furosemide and Bumetanide to inhibit CA for PT effect
Most powerful diuretic short acting and short time of action
Hyperuremia because of increased urate reabsorption in PT
Enhanced excretion of Na, K, CL, and H20, and Ca
K excretion increased because increased Na delivery to distal tubule which increases Na/K exchange
Loop Diuretic Therapeutic Uses
Loop diuretics rapidly absorbed and eliminated by GFR and tubular secretion in the kidney
Absorption of furosemide within 2-3 hours
Diuresis is rapid onset and short in duration
Acute pulmonary edema
Hypertension
Management of edema due to cardiac, hepatic, or renal disease
Loop Diuretics Toxicity and Side Effects
Hypokalemia–> inhibit salt reabsorption in thin ascending loop (TAL), loop diuretics increase Na delivery to collecting duct and increased Na delivery causes increase secretion of K and H in collecting duct leading to hypokalemia and metabolic acidosis
Hyperuricemia–>loop diuretics cause hypovolemia and increased uria acid reabsorption
Hyperglycemia- furosemide only
Ototoxicity–> deafness with high doses and Ethacrynic acid>furosemide>Bumetanide (more common in patients with diminished renal function)
Volume depletion
Thiazide Diuretics
Chlorothiazide
Hydrochlorothiazide
Metolazone
Thiazide Diuretics Mechanism of Action
Secreted in PT by OAT
Orally available, moderate onset of activity (60 min), longer duration of action, intermediate in activity (8-10% of filtered load)
Act on cortical diluting segment of ascending limb of loop of Henle to inhibit the NaCl reabsorption (cotransporter)
Higher doses it can inhibit CA in PT
Reduced GFR
K secretion increases due to increased Na deliver to distal tubule (Na/K exchange)
Can’t dilute urine and enhance urate reabsorption in PT
Urine volume increases along with excretion of Na, Cl and K (hypertonic urine)
Decrease excretion of Ca
Thiazide Diuretic Therapeutic Use
Diuresis is rapid onset and long in duration
Management of edema due to CHF
Hypertension
Management of hypercalciuria in patients with renal calculi
Thiazide Diuretic Toxicity
Hypokalemia
Hyperuricemia
Hyperglycemia–> decreased insulin secretion
Should not be used if GFR
Potassium sparing diuretics
Aldosterone antagonist (spironolactone, Eplerenone) Sodium Channel Inhibitors (Triamterene, Amiloride)
Aldosterone Antagonist Mechanism of Action
Acts on distal tubule as a competitive antagonist of aldosterone
Urine volume increases with increase excretion of Na and CL and no change in K
Weak as diuretic because only 2-3% filtered sodium load excreted
Aldosterone Antagonist Therapeutic Uses
Hypertension Refractory edema Primary aldosteronism Use with thiazides or loop diuretic to enhance diuretic effect and reduce K loss Long duration of action Improve survival in heart failure
Aldosterone Toxicity
Hyperkalemia Gynecomastia (spironolactone >>> Eplerenone)
Ca channel inhibitors Mechanism of action
Inhibit entry of Na into principal cells so Na/K exchanger doesn’t occur (Amiloride blocks Na/H exchanger in higher concentrations)
Independent of aldosterone effects
Urine volume increases and Na excretion increases with no change in K
High doses the Triamterene reduces GFR
Weak as diuretic–> 2-3% of filtered sodium load excreted
Sodium Channel inhibitors Therapeutic use
Use with thiazides or loop diuretics to enhance diuretic effect and reduce K loss
Treat edema or hypertension
Sodium Channel inhibitors Toxicity
Hyperkalemia
Azotemia- Triamterene
Choice of Diuretic
Intrinsic activity- loop>thiazides> potassium-sparing
Cost- thiazides thiazides
Risk to benefit ratio
Effect on renal hemodynamics
