Diuretics & renal function

a) LOOP AGENTS [frusemide; ethacrynic acid]

• Most powerful of all clinically used diuretics
• Short acting agents
• Inhibit Na⁺ and Cl^- reabsorption in the thick ascending limb of the loop of Henle via Na+, K+, -ATPase-dependent pump —>

i) increased solute load in distal portions of nephron —> act as osmotic agents

ii) failure to reabsorb Na+ & Cl- at loop of Henle —> decreased osmolarity in medullary interstitial fluid —> reduced concentrating ability of kidney

• The thick ascending limb of the loop of Henle plays an important part in divalent cation handling; inhibition of active NaCl transport —> increased Ca²⁺ and Mg²⁺ excretion: —> hypomagnesemia & hypocalcaemia [useful for acute hypercalcemia]
• Owing to the large NaCl absorptive capacity of the loop of Henle, agents that act at this site produce a diuretic effect much greater than that seen with other diuretic groups
• Fast response post IV injection; lasts 2-3 hours
• Frusemide may also increase blood flow to the kidney via rein-angiotensin & PG
• Due to increased Na⁺ to more distal segments of nephron —> exchange of Na⁺ for H⁺ and K⁺ —> metabolic alkalosis and hypokalemia

b) THIAZIDES [Chlorothiazide]

• Inhibit NaCl reabsorption in the early segments of the distal convoluted tubule

‑> increased Na⁺ and Cl^- in urine

• May also stimulate Ca²⁺ reabsorption in DCT [Ca²⁺ reabsorption in DCT is modulated by PTH] —> may decrease Ca²⁺ excretion [useful for inhibiting kidney stones]

c) CARBONIC ANHYDRASE INHIBITORS [Acetazolamide(Diamox)]

• Block reabsorption of in the PCT by inhibiting carbonic anhydrase —> increased HCO₃^- in tubule acting as an osmotic diuretic
• Normally the carbonic anhydrase that lines the luminal border of the proximal convoluted tubule catalyses the association of H₂O & CO₂ into carbonic acid -> H⁺ & HCO₃^-—> reabsorption of HCO₃^-
• Note that metabolic acidosis 2° to renal HCO₃^- loss is a danger
• Na⁺ accompanies the HCO₃^-

d) POTASSIUM-SPARING DIURETICS [spironolactone]

• compete with aldosterone for receptor sites at the cortical collecting tubule—>

i) block Na⁺ reabsorption effect of aldosterone —> Na⁺ acts as a diuretic in tubules

ii) block aldosterone effect on K⁺ secretion —> maintain/increase extracellular K⁺

• Also has a direct effect in inhibiting the effect of aldosterone in stimulating H⁺ secretion —> metabolic acidosis

e) OSMOTIC DIURETICS [mannitol]

• filtered into tubular fluid —> not easily reabsorbed by tubules —> increase in osmotically active substances in tubules —> increase osmotic pressure prevents water reabsorption —> diuresis
• as mannitol is rapidly distributed in the ECF & extract water from the cells —> hyponatremia & expansion of extracellular compartment

f) ADH INHIBITION

• Anti diuretic hormone [ADH] acts on the collecting ducts to increase their permeability to water —> decrease urine volume
• narcotics, hypnotics, anaesthetics, alcohol can inhibit ADH secretion —> water fails to be reabsorbed by distal tubules —> large amounts of dilute urine

K. C. Potger
Copyright © 2001