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Sodium chloride
Secretion of:
H+ (via Na+/H+ exchanger)
6. Collecting Duct
Reabsorption of:
Na+ (aldosterone dependent)
H2o (ADH dependent)
Secretion of:
H+
K+
REGULATION OF RENAL FUNCTION BY SELECTED HORMONES
MAJOR DIURETIC CLASSES
♠ thiazide diuretics:
♪ hydrochlorothiazide, chlorothiazide
♠ loop diuretics:
♪ furosemide, torsemide, indapamide
♠ K+ sparing diuretics:
♪ amiloride, triamterene,
♪ spironolactone,eplerenone
♠ osmotic diuretics:
♪ mannitol, urea
♠ carbonic anhydrase inhibitors:
♪ acetazolamide
SITE OF ACTION OF DIURETICS
LOOP DIURETIC
BUMETANIDE, INDAPAMIDE, FRUSEMIDE,
TOLBUTAMIDE
Mechanism of action:
♣ inhibit the Na+/ K+/ 2Cl- cotransport system in
the thick ascending limb of Henle's loop .
♣ Inhibiting the kidney's ability to reabsorb
sodium, thus enhancing the loss of sodium in
the urine. And when sodium is lost in the
urine, water goes with it.
♣ This type of diuretic is called a high-ceiling
diuretic or a loop diuretic.
THERAPEUTIC EFFECT
Equivalent Dose, mg 1 40 20
0.5 - 2.0 mg 20 - 80 mg 10 - 40 mg
Usual Adult Oral Dosage
qd -bid qd - bid qd - bid
THIAZIDE DIURETIC
HYDROCHLOROTHIAZIDE,
CHLORTALIDONE, CHLOROTHIAZIDE
Mechanism of action:
♣ Thiazide diuretics are secreted into the tubular fluid by
proximal tubule cells. These agents act in the distal
convoluted tubule and block a Na+, Cl- symporter that is
associated with the luminal membrane.
♣ ↑ plasma urate concentration:
-compete with the urate for secretion by the organic acid
secretory system at the proximal tubules
♣ ↓ GFR ( direct effetc on renal vasculature)
♣ ↓ ca2+ secretion due to direct effect at the early portion of the
distal tubules hypercalcemia
THERAPEUTIC EFFECTS
treat edema associated with a variety of
pathophysiologic conditions including
congestive heart failure, cirrhosis, renal
insufficiency and the nephrotic syndrome,
therapy of hypertension
Not metabolised
Eliminated by secretion at proximal tubules
ADVERSE EFFECTS
POTASIUM SPARING DIURETICS
ALDOSTERONE VS, NA+ CHANNEL
VS
Blocking the exchange of sodium for potassium,
resulting in excretion of sodium and
potassium but relatively little loss of
potassium…
♣ Aldosterone antagonist:
◙ eg: spironolactone, eplerenone
◙ competitive inhibitor of aldosterone at the
mineralocorticoid receptors
◙ act at the distal portion of distal tubule &
the collecting duct
♣ Aldosterone effect:
↑ Na+, H2o reabsorption,
↑ K+ secretion & Ca2+ excretion
ADVERSE EFFECT
POTASSIUM SPARING DIURETIC
ADVERSE EFFECT
THERAPEUTIC USES
Use in combination with loop & thiazide
diuretic
Enhances natriuresis caused by other diuretics
Prevents hypokalemia
Block aldosterone
Tx of primary hyperaldosteronism
Tx of edema of liver cirrhosis
Tx of hypertension
Tx for heart failure
CONTRAINDICATION/ DRUG
INTERACTION
Hypersensitivity
Anuria
Hyperkalemia
Pregnancy (spironolactone)
↓ blood viscocity
iv 100-500mg/day