magament of edema associated with cardiovascular, renal, and endocrine abnormalities; also in treatment of HTN, and glaucoma

work at sites in the nephron to cause diuresis inhibitng reabsorption of sodium (natriuresis), some also cause kaliuresis

most act by blocking a specific ion channel or transporter in the tubular epithelial cells

proximal tubule

what gets reabsorbed and secreted here

an important site of tubular reabsorption and secretion

almost all of the filtered glucose, AAs, and other organic solutes are reabsorbed in proximal tubule

about 40% of filtered sodium chloride is reabsorbed in proximal tubule

relatively umimportant site of diuretic action, because inhibition of sodium chloride reabsorption in proximal tubule almost always leads to increased Na chloride reabsorption in more distal segments

loop and thiazide diuretics are secreted by proximal tubular cells (which are carried in tubular fluid to their site of action in loop of henle and distal tubule)

responsible for the reabsorption of ~35% of filtered Na chloride, participates in formation of [  ]ed urine by transporting Na chloride into surround interstitium making it hypertonic, this attracks water from collecting duct (under influence of ADH)

reabsorption of NA from thick ascending limb is inhibited by loop diuretics

serves to adjust the final composition and volume of urine to regulate extracellular fluid composition and pH

responsible for reabsorption of ~3% of filtered Na chloride, coupled with K and hydrogren excretion

site of action of aldosterone (increases NA reabsorption, promoting NA retention) and ADH (increases rabsorption of wtaer from collecting duct, conserving body water, [ ]ing urine

thiazide diuretics

general information

good oral bioavailability

actively secreted into the nephron by proximal tubular cells, travel through lumen to reach site of action in distal tubule

thiazide diuretics

mechanisms

act primarily on early portion of distal tubule to inhibit Na+. Cl- symporter that participates in reabsoprtion of Na and Cl from this segment

leads to delivery of greater volume of Na-chloride enriched tubular fluid to distal tubule and collecting duct -> which stimulates exchange of Na and K at these sites

small of Na is reabsobed as K is secreted into urine

thiazides have a kaliuretic effect thatcan lead to hypokalemia

thiazide diuretics

side effects

hypokalemia -> can eventually lead to hypokalemic metbolic alkalosis (H ions enter body cells and K leaves in an attempt to correct the plasma K deficiency) -> as plasma K levels fall, more H is secreted into urine in exchange for Na which further contributes to development of metabolic alkalosis

elevated blood glucose (reduced secretion of insulin due to hypokalemia), uric acid, and lipid levels

thiazide diuretics

indications

widely used in the management of cardiovascular and renal diseases

HTN

edema with heart failure

cirrhosis

corticosteriod and estrogen therapy

renal disorders (nephrotic syndrome)

nephrolithiasis

nephrogenic diabetes insipidus (kidneys aren't responsive to ADH, excreting a LOT of urine, thiazides exert a paradoxical antidiuretic effect, reducing excessive urine vol)

indapamide -> primarily used to treat HTN and heart failure

metolazone -> poss more effective than thiazides in pts with impaired renal function

loop diuretics

mechanisms

inhibit Na+, K+, 2Cl- symporter in the ascending limb of the loop of henle -> powerful natriuretic effect

inhibit reabsorption of a greater %age of filtered NA

produce kaliuresis by increasing exchange of Na and K in the late distal tubule and collecting duct via same mechanism of thiazides

increase Ca2+ and Mg excretion by reducing their reabsorption in ascending limb (result of inhibition of Na, K, Cl sympoter)

loop diuretics

side effects

hypokalemia

hypocalcemia

hypomagnesemia

metabolic alkalosis

increase blood glucose and uric acid levels (in same manner as thiazides)

possible ototoxixity -> tinnitus, vertigo, ear pain, hearing deficits

loop diuretics

indications

used when intensive diuresis is required and cannot be achieved with other diuretics

highly effective in pulmonary edema

preferred in pts with renal impairment (bc they are effective in pts whose creatinine clearance drops below 30 mL/min)

often drug of choice with edema caused by heart failure, cirrhosis

(thiazide typically preferred more for pts with HTN)

hypercalcemia

epithelial sodium channel blockers (amiloride and triamterene)

aldosterone receptor antagonist (spironolactone)

block the entry of Na into the principal tubular cell of late distal tubule and collecting duct, preventing Na reabsorption at this site, indirectly reducing the secretion of K into tubular filtrate and urine

primarily used to treat and prevent hypokalemia induced by thiazide and loop diuretics

most common side effect -> hyperkalemia