Renal - Diuretics

Front 1

Proximal tubule

-solute reabsorption

Back 1

--70% of filtered Na reabsorbed here
--85% of filtered bicarbonate reabsorbed here
--80% of filtered phosphate reabsorbed here
--80% of filtered K reabsorbed here

Hint 1

pg 69

Front 2

Proximal tubule

-diuretics

Back 2

--carbonic anhydrase inhibitors
1. Acetazolamide
2. Methazolamide*
--osmotic diuretics

Hint 2

pg 75

Front 3

Medullary portion of TALH

-solute reabsorption
-reabsorptive capacity
-contribution to gradient

Back 3

--active Na, Cl, and K reabsorption here (Na/K/2Cl transporter)
--reabsorptive capacity can be increased to 50% of the filtered Na load when proximal reabsorption is decreased
--NaCl reabsorption increases medullary osmotic gradient

Hint 3

pg 70

Front 4

Cortical portion of TALH

-solute reabsorption
-reabsorptive capacity
-contribution to gradient

Back 4

--active Na, Cl, and K reabsorption here (Na/K/2Cl transporter)
--reabsorptive capacity can be increased to 50% of the filtered Na load when proximal reabsorption is decreased
--does NOT contribute to the medullary osmotic gradient

Hint 4

pg 70

Front 5

Medullary portion of TALH

-diuretics

Back 5

Na/K/2Cl co-transporter blockers
1. Furosemide
2. Bumetanide
3. Torsemide

Hint 5

pg 76

Front 6

Cortical portion of TALH

-diuretics

Back 6

Na/K/2Cl co-transporter blockers
1. Furosemide
2. Bumetanide
3. Torsemide

Hint 6

pg 76

Front 7

Distal tubule

-solute reabsorption
-reabsorptive capacity

Back 7

--5% of filtered NaCl reabsorbed (thiazide sensitive Na/Cl transporter)
--most of remaining bicarbonate is reabsorbed between here and the late distal tubule (8%)
--limited capacity for further increasing NaCl reabsorption

Hint 7

pg 70

Front 8

Distal tubule

-diuretics

Back 8

1. Thiazides
2. Chlorthalidone
3. Metolazone
4. Indapamide
5. Osmotic diuretics

Hint 8

pg 76

Front 9

Cortical collecting tubule

-solute reabsorption
-reabsorptive capacity

Back 9

**important site for control of K secretion into final urine
--3% of filtered Na reabsorbed here
--fixed reabsorptive capacity
--site of aldosterone dependent Na reabsorption

Hint 9

pg 70

Front 10

Cortical collecting tubule

-diuretics

Back 10

K sparing diuretics
1. Spironolactone -- aldosterone antagonist
2. Eplerenone
3. Triamterene -- blocks epithelial Na channel
4. Amiloride -- blocks epithelial Na channel

Hint 10

pg 76

Front 11

Proximal tubular diuretics (acetazolamide)

-MOA

Back 11

MOA: inhibition of luminal and intracellular carbonic anhydrase --> inhibition of Na/H exchange at apical membrane and basolateral bicarbonate reabsorption

Hint 11

pg 77

Front 12

Proximal tubular diuretics (acetazolamide)

-diuretic potency

Back 12

mild potency

--sites downstream reabsorb Na and H2O
--the blocking of carbonic anhydrase is incomplete
--only 30% of Na is reabsorbed with bicarb, most is reabsorbed as NaCl
--development of hyperchloremic metabolic acidosis changes physical properties of carbonic anhydrase, rendering the diuretic ineffective

Hint 12

pg 78

Front 13

Proximal tubular diuretics (acetazolamide)

-effects on urine and plasma composition (3)

Back 13

1. Increased urinary excretion of bicarb (alkaline urine)

2. normal anion gap metabolic acidosis (loss of bicarb and inhibition of proximal H secretion)

3. increased K excretion

Hint 13

pg 78

Front 14

Proximal tubular diuretics (acetazolamide)

-use in non-edematous states (2)

Back 14

1. Glaucoma -- decreases formation of aqueous humor by blocking carbonic anhydrase in the ciliary body (methazolamide is perferred)

2. to alkalinize the urine -- treat renal stones or metabolic alkalosis

Hint 14

pg 78

Front 15

Loop diuretics

-MOA

Back 15

MOA: block active Na/K/2Cl co-transport in the TALH
--secreted into the proximal tubule via organic acid pathway and transported to site of action
--potency dependent on urinary concentration of diuretic, not plasma concentration
--tubular secretion is potentiated by albumin; hypoalbuminemia decreases potency

Hint 15

pg 80

Front 16

Loop diuretics

-potency

Back 16

--HIGH

Hint 16

pg 80

Front 17

Loop diuretics

-effects on urine and plasma composition (5)

Back 17

1. Increase Na, K and Cl excretion
2. Increase fractional excretion of Ca by 30%
3. Increase fractional Mg excretion by 60%
4. may increase or decrease uric acid excretion
5. decrease free H2O reabsorption and free H2O clearance by impairing the medullary gradient

Hint 17

pg 80

Front 18

Loop diuretics

-use in edematous states (3)

Back 18

*Diuretic of choice for:
1. pulmonary edema
2. edema in patients with renal failure
3. nephrotic syndrome

Hint 18

pg 81

Front 19

Loop diuretics

-use in non-edematous states (5)

Back 19

1. HTN
2. hypercalcemia
3. acute renal failure (treatment of oliguria)
4. acure hyperuricemia
5. severe hyponatremia

Hint 19

pg 81

Front 20

Loop diuretics

-adverse effects (7)

Back 20

1. volume depletion
2. hypokalemia
3. metabolic acidosis
4. hypocalcemia
5. hypomagnesemia
6. acute interstitial nephritis (allergic)
7. **deafness in patients with renal fail

Hint 20

pg 81

Front 21

Osmotic diuretics (mannitol, glucose, urea)

-MOA and site of action

Back 21

MOA:
--proximal tubule: decreased Na reabsorption due to decreased H2O reabsorption
--descending loop of henle: decreased H2O reabsorption secondary to osmotic effect
--**desecnding thin limb of loop: major effect here, decreased tubular fluid osmolality results in greater passive influx of Na from the interstitium and increased Na excretion and tubular fluid flow rate -- disrupts gradient
--collecting tubule: decreased urea reabsorption from collecting tubule which further decreases interstitial osmolality
--vasa recta: increased vasa recta blood flow dissipates gradient -- may account for majority of diuretic effect

Hint 21

pg 82

Front 22

Osmotic diuretics (mannitol, glucose, urea)

-potency

Back 22

--highest peak urine flow of all diuretics
--Na excretion greater than thiazides and less than loop diuretics

Hint 22

pg 83

Front 23

Osmotic diuretics (mannitol, glucose, urea)

-effect on plasma and urine composition

Back 23

1. increase Na excretion
2. increase K excretion
3. increase bicarb excretion
4. increase free H2O excretion

Hint 23

pg 83

Front 24

Osmotic diuretics (mannitol, glucose, urea)

-uses (5)

Back 24

***NOT used to treat edeam because they expand ECF

1. acute renal failure
2. cerebral edema*
3. severe hyperuricemia
4. dialysis disequilibrium syndrome (prevents #2)
5. intoxications*

Hint 24

pg 83

Front 25

Osmotic diuretics (mannitol, glucose, urea)

-adverse effects (5)

Back 25

1. volume depletion
2. hypernatremia (enhances free H2O loss)
3. hyponatremia (dilutes Na present in the ECF by enhancing H20 movement from ICF)
4. hypokalemia
5. acute renal failure

Hint 25

pg 83

Front 26

Coritcal TALH and early distal tubule diuretics (Thiazides)

-MOA
-potency

Back 26

MOA: inhibit active NaCl transport in the cortical thick ascending limb and early distal tubule (major site of action)

--blocks 40% of NaCl reabsorption

--moderate potency

Hint 26

pg 83/84

Front 27

Coritcal TALH and early distal tubule diuretics (Thiazides)

-effects on plasma and urinary composition (6)

Back 27

1. increase Na excretion --hyponatremia
2. increase K excretion -- large K losses may occur if combined with loop diuretic
3. increase Cl excretion
4. decrease Ca excretion*
5. decrease uric acid excretion
6. decrease in free H2O excretion

Hint 27

pg 84

Front 28

Coritcal TALH and early distal tubule diuretics (Thiazides)

-use in edematous states (3)

Back 28

1. CHF
2. edematous conditions in patients with normal renal function
3. potentiate action of loop diuretics

Hint 28

pg 85

Front 29

Coritcal TALH and early distal tubule diuretics (Thiazides)

-use in non-edematous states (3)

Back 29

1. HTN (1st line) -- volume contration and arteriolar vasodilation
2. hypercalciuria in Ca stone formers -- increase Ca absorption
3. diabetes insipidus -- impaired dilution, less free H2O loss

Hint 29

pg 85/86

Front 30

Coritcal TALH and early distal tubule diuretics (Thiazides)

-adverse effects (8)

Back 30

1. hyponatremia
2. hypokalemia
3. metabolic alkalosis
4. carbohydrate intolerance
5. hyperuricemia
6. hypercalcemia
7. hypersensitivity rxn
8. increased plasma lipids and decreased HDL

Hint 30

pg 86

Front 31

Collecting tubule diuretics (K sparing)

-aldosterone antagonists (spironolactone, eplerenone); MOA, site of action

Back 31

MOA: competitive inhibition of aldosterone at cortical collecting tubule (principal cell) -- decreased Na/K-ATPase activity, decreased luminal Na-K permeability

--effect reversed by aldosterone
--no effect in the absence of aldosterone

Hint 31

pg 88

Front 32

Collecting tubule diuretics (K sparing)

-aldosterone antagonists (spironolactone, eplerenone); effect on plasma and urine electrolytes

Back 32

1. increase Na excretion
2. decrease K excretion**
3. increase urine volume
4. increase plasma K
5. little effect on free H2O excretion or reabsorption

Hint 32

pg 88

Front 33

Collecting tubule diuretics (K sparing)

-aldosterone antagonists (spironolactone, eplerenone); uses

Back 33

1. potentiate action of other diuretics in the treatment of edema
2. patients with edema and ascites due to liver disease
3. prevent diuretic induced urine K losses**
4. diagnosis and treatment of hyperaldosteronism (non-edematous use)

Hint 33

pg 88

Front 34

Collecting tubule diuretics (K sparing)

-aldosterone antagonists (spironolactone, eplerenone); adverse effects

Back 34

1. hyperkalemia
2. man boobs

Hint 34

pg 88

Front 35

Collecting tubule diuretics (K sparing)

-aldosterone independent (triamterene, amiloride); MOA and site of action

Back 35

MOA: decrease luminal Na entry by blocking epithelial Na channel (ENaC) --> decreased gradient for basolateral Na/K ATPase --> less K lost on apical membrane

--coritcal collecting tubule (principal cell)

Hint 35

pg 88

Front 36

Collecting tubule diuretics (K sparing)

-aldosterone independent (triamterene, amiloride); adverse effects

Back 36

1. hyperkalemia
2. renal calculi (Triamterene)
3. acute renal failure when Triamterene is used with NSAIDs

Hint 36

pg 89

Front 37

Diuretic resistance

-diuretic braking effect
-prevention

Back 37

--prolonged administration of a diuretic results in a platuea in weight loss and subsequently return of weight to previous level
--results from an increased stimulus for Na retention created by diuretic induced reduction in ECF

--prevented by Na restriction diet or increased dosing

Hint 37

pg 89

Front 38

Diuretic resistance

-"other" causes (6)

Back 38

1. volume contraction
2. decreased renal blood flow
3. decreased GFR
4. inadequate dosing
5. inadequate GI absorption (NSAIDs)
6. compliance

Hint 38

pg 90