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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)
d) Methazolamide


Loop diuretics

a) Bumetanide
b) * Ethacrynic acid
c) * Furosemide (Lasix)
d) Torsemide


Thiazide Diuretics

a) Bendroflumethiazide
b) Chlorothiazide
c) * Chlorthalidone
d) * Hydrochlorothiazide
e) Hydroflumethiazide
f) Indapamide
g) Methyclothiazide
h) Metolazone
i) Polythiazide
j) Trichlormethiazide


Potassium-Sparing Diuretics

a) Mineralocorticoid Antagonists (Aldosterone Antagonists)
i) Eplerenone
ii) * Spironolactone (Aldactone)
b) Inhibitors of Renal Sodium Channels
i) * Amiloride
ii) Triamterene


Osmotic Diuretics

i) Mannitol
ii) Isosorbide


Antidiuretic Hormone Antagonists

i) Conivaptan
ii) Tolvaptan

"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)).


What happens in the collecting tubule?

i) Responsible for 2-5% of NaCl reabsorption through an epithelial sodium channel (ENaC).
ii) The most important site of K+ secretion by the kidney and the site at which virtually all diuretic-induced changes in K+ balance occur.
iii) Diuretics that act upstream of the CCT will increase Na+ delivery, which will enhance K+ secretion.
iv) The basolateral Na+/K+ ATPase pumps Na+ out of the cell and into the interstitium/blood while pumping K+ into the cell, where it can exit down the concentration gradient into the lumen/urine.
v) Aldosterone increases the expression of both the ENaC and the basolateral Na+/K+ ATPase, leading to an increase in Na+ reabsorption and K+ secretion (which causes retention of water, an increase in blood volume, and an increase in blood pressure).
vi) H+ is secreted by proton pumps (H+-ATPases) into the lumen and increases urine acidity.
vii) Antidiuretic Hormone (ADH, aka vasopressin or arginine vasopressin, AVP) controls the permeability of the CCT to water by controlling the expression levels of functional aquaporin-2 (AQP2) water channels that insert into the apical membrane.
(1) In the absence of ADH, the CCT (and collecting duct) is impermeable to water and high volumes of dilute urine are produced.
(2) ADH levels are regulated by serum osmolality and volume status.
(3) Alcohol decreases ADH release and increases urine production.