8_HST110 Diuretics 2017 Flashcards
What are diuretics good for?
Increased urine output
Both solute and water excretion are increased
Decreased ECF volume
All diuretics inhibit Na+ reabsorption by the nephron
Increase urinary excretion of (X) (natriuresis)
Decrease (Y) volume
X = Na+ Y = ECF
Diuretics are useful in the treatment of what 2 conditions?
volume overload and hypertension
The site of action of a diuretic determines how much (X) excretion will be achieved
Depends partly on how much (X) are reabsorbed at the site
Determines what effects on other solutes (K+, Ca2+, HCO3-) will be seen
X = sodium and water
Effect on other nephron segments: Inhibition of Na+ reabsorption at one site of the nephron (X) delivery of Na+ and water to more distal segments. The ability of distal segments to handle the increased solute and water load determines the overall effect of the diuretic
X = increases
Action of diuretics depends on delivery in sufficient quantities to the site of action. Most diuretics act at the (X)
X = lumen of the tubule (filtered or secreted by PT)
Name 5 classes of diuretics
- Carbonic anhydrase inhibitors
- Osmotic diuretics
- Loop diuretics
- Thiazide diuretics
- Potassium-sparing diuretics (Aldosterone antagonists, Na+ channel blockers)
Carbonic Anhydrase Inhibitors:
Site of action:
(X)
Prototype:
(Y)
Mechanism:
Inhibit carbonic anhydrase
Rationale for use:
~1/3 of Na+ reabsorbed in PCT is via (Z) antiporter, which depends on CA
Rarely used as a diuretic
X = Proximal tubule Y = Acetazolamide Z = Na+-H+
Net effect of Carbonic Anhydrase Inhibitors on Na+
Downstream nephron segments increase Na+ reabsorption (aka not super effective)
Only 5-10% of filtered Na+ excreted
Osmotic Diuretics:
Site of action:
(X)
Prototype:
Mannitol
Mechanism: Freely filtered by glomerulus, not reabsorbed Increase luminal (Y) and inhibit reabsorption of (Z)
Rationale for use: bulk of fluid and ion reabsorption takes place in PCT
X = Proximal tubule, TDL Y = osmolality Z = water
Net effect of Osmotic agents on Na+
Downstream nephron segments increase Na+ reabsorption
Only 10% of filtered Na+ excreted
Bottom line:
Rarely used as a diuretic
Loop Diuretics
Site of action:
(X)
Prototype:
(Y)
Mechanism:
Inhibit (Z) symporter
Abolishes medullary interstitial gradient
Blocks tubuloglomerular feedback at (A)
Rationale for use:
Loop of Henle is vital to urinary concentration
X = Thick ascending limb Y = Furosemide Z = Na+-K+-2Cl- A = macula densa
Net effect of Loop Diuretics on Na+
Downstream segments have limited ability to absorb Na+
Up to 25% of filtered Na+ excreted
Bottom line:
Most potent diuretic
Thiazide Diuretics
Site of action:
(X)
Prototype:
Hydrochlorothiazide (HCTZ)
Mechanism:
Inhibit (Y) symporter
Rationale for use:
Increased urinary Na+ loss
X = Distal convoluted tubule Y = Na+-Cl-
Net effect of Thiazie Diuretics on Na+
Downstream segments have limited ability to absorb Na+
5-10% of filtered Na+ excreted
Bottom line:
Used for treatment of hypertension and edema
K+sparing diuretics
Site of action:
Sites of K+ secretion: (X)
Prototype:
Aldosterone antagonist: (Y)
Na+ channel blocker: amiloride
Mechanism:
Aldosterone antagonists: block mineralocorticoid receptor and decrease activity and number of (Z) channels
Na+ channel blockers: block (Z)
Rationale for use:
Avoid (A)
X = late distal tubule, cortical collecting duct Y = spironolactone Z = ENaC A = hypokalemia
Net effect of K+ sparing diuretics on Na+
3-5% of filtered Na+ excreted
Bottom line:
Weak diuretics
Can be used with other diuretics for HTN and edema
Can be used to prevent/treat hypokalemia caused by other diuretics
Diuretics: Effects on K+
- Blocking Na+ reabsorption increases delivery of Na+ and water to the (X) nephron
- K+ secretion increases due to:
* Increased Na+ reabsorption (via (Y))
* Increased tubular flow (via (Z) K+ channels)
* Increased (A) (stimulated by volume depletion)
X = distal Y = ROMK Z = flow-sensitive A = aldosterone
Diuretics: Effects on Ca+
Ca2+ reabsorption (paracellular) is normally coupled to Na+ reabsorption in the (X)
Thus, diuretics that impair (Y) reabsorption at these sites also inhibit Ca2+ reabsorption
X = proximal tubule and thick ascending limb Y = Na+
What is the 1 exception for diuretics effects on Ca2+?
Thiazide diuretics STIMULATE Ca2+ reabsorption at the distal tubule
Diuretics: Effects on HCO3-
Primary sites of HCO3- reabsorption and H+ secretion
- Proximal tubule: HCO3- reabsorption coupled to (X) reabsorption
- CCD: (Y) secretion coupled to (X) reabsorption
X = Na+ Y = H+
Diuretics: Effects on HCO3-
Carbonic anhydrase inhibitors
*Directly inhibit HCO3- reabsorption -> increase HCO3- excretion -> metabolic (X)
X = acidosis
Diuretics: Effects on HCO3-
Loop and thiazide diuretics decrease ECF volume and cause (X)
Stimulate proximal Na+ reabsorption and H+ secretion (via (Y)) -> more HCO3- reabsorbed
Stimulate (Z) activity -> increase H+ secretion in CCD -> increase (A) reabsorption
X = metabolic alkalosis Y = NHE3 Z = aldosterone A = HCO3-
Diuretics: Effects on HCO3-
K+-sparing diuretics:
Inhibit Na+ reabsorption in distal tubule and CCD -> decrease H+ secretion -> (X)
X = metabolic acidosis
