Diuretics

Front 1

Most important use of diuretics

Back 1

Mobilization and excretion of fluid causing edema

Front 2

Other uses of diuretics

Back 2

1) Tx of HTN
2) Drug overdose
3) Hypercalcemia
4) Hypercalciuria
5) Nephrogenic DI

Front 3

Where does acetazolamide work? What does it do?

Back 3

Carbonic anhydrase inhibitor; works in early proximal tubule

Front 4

Most important pharmacokinetic principle of diuretics

Back 4

They act from the luminal side of the renal epithelial cells (because transport mechs that are inhibited by diuretics are in luminal membrane). Therefore, they need to be in high enough concentration in the tubular fluid to work.

Front 5

What mechanism does probenecid inhibit?

Back 5

Organic acid secretory mechanism (Acetazolamide, loop, and thiazide diuretics use this)

Front 6

Acetazolamide, loop, and thiazide diuretics are weak _____

Back 6

acids

Front 7

Amiloride and triamterene are weak _____

Back 7

bases

Front 8

How are Amiloride and triamterene secreted?

Back 8

By organic base secretory mechanism in the late proximal tubule

Front 9

T/F Mannitol is filtered and secreted.

Back 9

F. Just secreted. Its diuretic activity is based on property as non-reabsorbable solute.

Front 10

Where does spironolactone work?

Back 10

It is a steroid that interferes with translocation of aldosterone to the nucleus

Front 11

Where do the ADH antagonists work?

Back 11

basolateral side of collecting duct cells

Front 12

T/F Diuretics are rapidly excreted.

Back 12

T. This is a consequence of the fact that the concentration of them is high in the tubular lumen fluid

Front 13

How and when does glucose act as an osmotic diuretic?

Back 13

Uncontrolled DM, the filtered load of glucose exceeds ability of prox tubule to reabsorb it.

Front 14

T/F Mannitol causes increased excretion of both Na and H20

Back 14

T

Front 15

Why aren't osmotic diuretics used for mobilizing edema fluid?

Back 15

Because they INCREASE blood osmolarity which draws water from ICF to ECF, expanding ECF further. Can cause heart failure or pulmonary edema.

Front 16

What are osmotic diuretics used for?

Back 16

Reducing ICP (or intraocular pressure)

Front 17

Mech of Action of acetazolamide

Back 17

In proximal tubule, it inhibits the reabsorption of filtered bicarb by inhibiting carbonic anhydrase.

(Also inhibits reabsorption of filtered Na and H2O, because they accompany bicarb)

Front 18

Why doesn't acetazolamide have a stronger diuretic action/prevent more Na from getting reabsorbed since it works in the proximal tubule?

Back 18

Because the other parts of nephron can act in a load - dept fashion - the more Na they get, the more they'll absorb.

Front 19

Clinical indications of acetazolamide (CA inhibitors) - 3

Back 19

1) Glaucoma - reduces aqueous humor formation and IOP

2) Alkalinization of the urine (incr solubility of certain substances to allow excretion. Also to tx drug overdose.)

3) Altitude sickness - which is accompanied by respiratory alkalosis (hypoxemia causes hyperventilation)

Front 20

Why are CA inhibitors used to alkalinize the urine?

Back 20

Cystine, uric acid, and methotrexate are more soluble in alkaline rather than acid urine, so it helps excrete.

Also treats drug overdose of lipid-soluble organic acids. "Traps" them in the A- form which won't get reabsorbed.

Front 21

Toxicity of CA inhibitors (acetazolamide)

Back 21

Hyperchloremic metabolic acidosis with normal anion gap.

They do NOT increase secretion of Cl-, so its concentration decreases. Anion gap is normal because Cl- is a "measured" ion


Also causes Hypokalemia because it increases flow rate thru distal tubule.

Front 22

Contraindications of CA inhibitors

Back 22

Hepatic cirrhosis. Because alkalinization decreases excretion of NH4 by shifting equilibrium to NH3, which does into blood.

Front 23

Bumetanide and ethacrynic acid are what types of diuretics?

Back 23

Loop

Front 24

How do loop diuretics (furosemide) produce diuresis?

Back 24

Inhibits Na/K/2Cl cotransporter in TALH.

They're anions that compete for the Cl- binding site on the cotransporter.

Front 25

What % of filtered load of Na can loop diuretics inhibit?

Back 25

All that is reabsorbed in TALH - 25%

Front 26

T/F Furosemide decreases Ca and Mg excretion

Back 26

F. It INCREASES their excretion because reabsorption of divalent cations is directly coupled to Na reabsorption in TALH

Front 27

Furosemide (increases, decreases) uric acid excretion.

Why?

Back 27

Decreases.

INCREASED uric acid concentration in blood

Front 28

Clinical indications for furosemide

Back 28

a) Tx of edema
b) Tx of hypercalcemia

Front 29

How does furosemide treat hypercalcemia?

Back 29

It inhibits Ca2+ reabsorption when it inhibits Na+ reabsorption.

Front 30

To prevent volume contraction when treating hypercalcemia, what must be given with furosemide?

Back 30

NaCl

Front 31

What are the toxicities of loop diuretics?

Back 31

Hypokalemic metabolic alkalosis (increased flow rate thru renal tubule)

Hyponatrenia - only in patient who is polydipsic. Ability to produce dilute urine in a patient who needs to.

Hypernatremia - in patient who's dehydrated.

Ototoxicity

Magnesium depletion

Hyperuricemia

Front 32

How does Mg depletion occur in loop diuretics?

Back 32

Mg is handled just like Ca in the thick ascending limb. Most of the Mg lost comes from the intracellular fluid and serum [Mg] may not change

Front 33

Mechanism of action of thiazide diuretics

Back 33

Inhibit NaCl cotransport in the luminal membrane of the early distal tubule cells.

Modest diuresis

Front 34

Thiazides (increase, decrease) calcium excretion. Why?

Back 34

decrease, because they increase Ca reabsorption in the distal tubule.

Front 35

Thiazides (increase, decrease) GFR.

Back 35

Decrease

Front 36

Indications for thiazide diuretics

Back 36

1) Tx HTN and edema

2) Tx idiopathic hypercalciuria (reduce likelihood of stone formation).

3) Tx nephrogenic DI

Front 37

Why are thiazide diuretics used to tx nephrogenic DI?

Back 37

Can't give ADH (this is the problem).


1) They inhibit NaCl reabsorption and so inhibit dilution of the urine, moving urine toward isotonicity.

2) They Decrease GFR and cause ECF volume contraction, esp in combo with low salt diet. Results in decreased water excretion.

Front 38

What are the toxicities of thiazide diurectics?

Back 38

1) Hypokalemic met alkalosis (same scenario as loop diuretics)

2) Hyperuricemia and hyperlipidemia

3) Hyponatremia - patient has impaired ability to dilute the urine

4) Impaired gluc tolerance

Front 39

What is the mechanism of hyponatremia in thiazide diuretics?

Back 39

3 parts:
1) Na reabsorption is inhibited in cortical diluting segment, and thus dilution of the urine is impaired.

2) If volume contraction occurs, RAA is activated. A2 stimulates drinking.

3) Volume contraction increases ADH secretion, increasing water reabsorption in the collecting ducts (bc corticopapillary gradient is intract).


Combined effect: More water comes into the body than can be excreted in the urine, and serum becomes dilute.

Front 40

Triamterene and amiloride: What type of diuretics?

Back 40

K sparing

Front 41

Competitive antagonist of aldosterone

Back 41

Spironolactone

Front 42

Inhibit processes which aldo normally stimulates

Back 42

Triamterene and amiloride

Front 43

Mech of action of K-sparing diuretics

Back 43

block aldo in the late distal tubule and collecting ducts

Front 44

Mech of action of K sparing diuretics - diuresis

Back 44

Inhibit Na reabsorption by blocking Na channels in luminal membrane. Very weak.

Front 45

Clinical indications of K sparing diuretics

Back 45

Offset K wasting and prevent hypokalemia.

May be used in patients with refractory edema

Front 46

Side effects of K sparing diuretics

Back 46

Major - hyperkalemia.

Spironolactone - gynecomastia

Front 47

What drugs are used in treatment of central DI?

Back 47

desmopressin - analog of vasopressin, with no vasopressor activity.

Chlorpropamide (enhances action of ADH on renal tubule)

Front 48

Major side effect of desmoprsesin

Back 48

Hyponatremia due to increased reabsorption of free water.

Front 49

Chlorpropamide : MOA and use

Back 49

enhances action of ADH on renal tubule by increasing Na reabsorption in TALH (increases countercurrent multiplication) and increasing H20 permeability of collecting duct.

Used for Central DI.

Side effects - hyponatremia, hypoglycemia

Front 50

Drugs that block action of ADH are used to treat _____

Back 50

SIADH

Front 51

2 drugs that block action of ADH at the level of the renal tubule.

Back 51

Li and demclocycline

Front 52

Major side effect of lithium

Back 52

Nephrogenic DI (goes away when stop drug)

Front 53

What is the mechanism by which all diuretics (except K sparing) result in hypokalemia?

Back 53

increased flow rate thru the distal tubule where K is secreted. When flow rate increases, [K] is diluted and this increases driving force for further secretion of K

Front 54

Where is reabsorption of Ca coupled to reabsorption of Na?

Back 54

Proximal tubule and loop of Henle.

Front 55

Which diuretics are used to treat hypercalcemia?

Back 55

Loop

Front 56

Where is reabsorption of Ca coupled inversely to Na reabsorption? Why?

Back 56

Distal tubule. Presence of Ca-Na exchange on basolateral membrane.

Overall effect of thiazide is to decrease Ca excretion and icnrease Na excretion

Front 57

In patients with high ADH and on loop diuretics - what happens?

Back 57

Still can't fully concentrate the urine.

Front 58

What happens during peak diuresis?

Back 58

Urine is isosmotic, since kidney can neither concentrate nor dilute the urine.

Front 59

______ diuretics inhibit ability to dilute the urine but not concentrate

Back 59

Thiazides

Front 60

Which diuretic causes metabolic acidosis/Type II RTA?

Back 60

Acetazolamide - it inhibits the reabsorption of filtered bicarb, thus incrteasing its excretion. Causes H+ to increase.

Front 61

which diuretics can cause volume contraction alkalosis?

Back 61

loop, thiazide. This is because RAA is stimulated

Front 62

Which diuretics produce type IV RTA?

Back 62

k sparing. They block aldo-stimulated H+ secretion in distal tubule and colleting ducts.

Front 63

why might renal insufficiency cause refractory edema/resistance to diuretics?

Back 63

Diuretics must be in the effective concentration in tubular fluid. If delivery of the diuretic tot he tubulur fluid is impared, they won't work.

Front 64

why might hypoalbuminemia (eg nephrotic syndrome) cause refractory edema/resistance to diuretics?

Back 64

May decrease delivery of diuretic to tubular fluid. More diuretic distributes in ISF rather than plasma because they normally bind to plasma proteins.

Also, the bound form is inactive.

Front 65

Cirrhosis is a case of (hypo, hyper)aldosteronism

Back 65

Hyper

Front 66

why might hyperaldosteronism states (eg cirrhosis)cause refractory edema/resistance to diuretics?

Back 66

The late distal tubule is using load-dept reabsorption in presence of aldosterone - reabsorbing more Na the more it sees.

Can add spironolactone.

Front 67

why might CHF cause refractory edema/resistance to diuretics?

Back 67

In CHF, GFR is decreased and prox tubule reabsorption is increased due to vascular volume contraction. Both effects decrease amount of Na delivered to Loop of Henle and distal tubule.

So there is less Na to inhibit and thus natriuresis will be reduced.

Adding corticosteroids can help with this.

Front 68

What class of diuretic:
Butmetanide

Back 68

Loop

Front 69

What class of diuretic:
Acetazolamide

Back 69

Carbonic anhydrase inhibitors

Front 70

What class of diuretic:
Chlorothiazide

Back 70

Thiazide

Front 71

What class of drug:
Chlorpropamide

Back 71

Chlorpropamide is in a class of medications called sulfonylureas. Chlorpropamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently.

Front 72

What class of diuretic:
ethacrynic acid

Back 72

Loop

Front 73

What class of diuretic:
Triamterene

Back 73

K-sparing