Flashcards in Diuretics DSA Deck (12):
Carbonic Anydrase Inhibitors (drugs in red have a *)
a) * Acetazolamide (Diamox)
b) Brinzolamide (topical ophthalmic)
c) Dorzolamide (topical ophthalmic)
b) * Ethacrynic acid
c) * Furosemide (Lasix)
c) * Chlorthalidone
d) * Hydrochlorothiazide
a) Mineralocorticoid Antagonists (Aldosterone Antagonists)
ii) * Spironolactone (Aldactone)
b) Inhibitors of Renal Sodium Channels
i) * Amiloride
Antidiuretic Hormone Antagonists
"ADH didn't pay the Toll to Coney island."
What do diuretics do?
a) Diuretics increase sodium excretion and the amount of urine produced by the kidney. They are used to adjust the volume and/or composition of body fluids in a variety of clinical situations (e.g., hypertension, heart and renal failure, nephrotic syndrome, and cirrhosis).
difference between a diuretic and a natriuraetic
b) Technically, a diuretic is an agent that increases urine volume, while a natriuretic causes an increase in renal sodium excretion. Natriuretics almost always increase water excretion and are therefore often called diuretics. Diuretics can exert their effects on a variety of targets, such as specific membrane transport proteins, enzymes, and hormone receptors.
What happens in the proximal tubule?
i) Sodium bicarbonate (NaHCO3), sodium chloride (NaCl), glucose, amino acids, and other organic solutes are reabsorbed into the blood via specific transport systems in the early proximal convoluted tubule (PCT).
ii) Potassium ions (K+) are reabsorbed via the paracellular pathway (between cells).
iii) Water is reabsorbed passively.
iv) In the PCT: reabsorption of approximately 65% of total sodium (Na+), K+, and water; 85% of NaHCO3; nearly 100% of glucose and amino acids.
v) NaHCO3 reabsorption in the PCT is initiated by the action of the Na+/H+ exchanger (NHE3) located in the luminal membrane of the proximal tubule epithelial cell.
vi) Membrane-bound and cytoplasmic forms of carbonic anhydrase catalyze dehydration of H2CO3 to CO2 at the luminal membrane and the rehydration of CO2 to form H2CO3 in the cytoplasm.
vii) The Na+/K+ ATPase in the basolateral membrane pumps the reabsorbed Na+ into the interstitium to maintain a low intracellular Na+ concentration (this occurs in ALL portions of the nephron).
viii) In the straight segment of the proximal tubule (the late proximal tubule), acid secretory systems secrete organic acids (e.g., uric acid, NSAIDs, diuretics, antibiotics, etc.) into the luminal fluid from the blood; diuretics are delivered to the luminal side of the tubule where most of them act.
What happens in the Loop of Henle?
i) Water is reabsorbed from the thin descending limb of the loop of Henle.
ii) The thin ascending limb of the loop of Henle is relatively water impermeable and is impermeable to other ions/solutes.
iii) The thick ascending limb of the loop of Henle functions by reabsorbing Na+ (25% of the filtered Na+) and is impermeable to water.
iv) NaCl reabsorption into the interstitial space in the thick ascending loop dilutes the tubular fluid.
v) The NaCl transport system in the luminal membrane of the thick ascending loop is a Na+/K+/2Cl- cotransporter (NKCC2 or NK2CL).
vi) The Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle establishes the ion concentration gradient in the interstitium (both renal cortex and medulla).
vii) The increase in K+ concentration in the cells causes back diffusion of K+ into the tubular lumen, allowing a lumen-positive electrical potential to drive reabsorption of cations (Mg2+, Ca2+) via the paracellular pathway (therefore, inhibition of salt transport in the thick ascending limb reduces the lumen-positive potential and causes an increase in urinary excretion of divalent cations in addition to NaCl).
What happens in the distal convoluted tubule?
i) 10% of NaCl is reabsorbed.
ii) Relatively impermeable to water; NaCl reabsorption further dilutes tubular fluid.
iii) NaCl is transported via a thiazide-sensitive Na+ and Cl- cotransporter (NCC).
iv) Ca2+ is reabsorbed by calcium channels (regulated by parathyroid hormone (PTH)).