Diuretics

Question 1

Diuretics all work by causing the kidneys to waste __, causing them to also waste water.

Answer 1

Diuretics all work by causing the kidneys to waste sodium, causing them to also waste water.

Question 2

4 classes of diuretics

Answer 2

carbonic anhydrase inhibitors

loop diuretics

potassium sparing diuretics

thiazide diuretics

Question 3

site of carbonic anhydrase inhibitor MOA

Answer 3

PCT;

Question 4

site of nephron where most re-absorption happens

Answer 4

PCT: 60-65%

Question 5

site where thiazides MOA

Answer 5

DCT

Question 6

cite of loop diuretics MOA

Answer 6

loop diuretics

Question 7

site of postassium sparing diuetics MOA

Answer 7

CCD/collecting duct

Question 8

example of carbonic anhydrase inhibitor. outline the site and MAO

Answer 8

site; PCT– site of most sodium reabsorption

example: aetazolamide

MOA; NORMALLY, carbonic anhydrase on the lumen of the PCT cell converts bicarbonate to H2O and water. this H2O and water enters the cell, where it is buffered to H+ and HCO3-. the H+ gets transported back OUT of the cell into the urine, with Na+ being pumped into the cell through the Na/H+ transporter. Bicarb from the carbonic anhydrase buffering and Na+ get co transported back into blood, causing Na+ reabsorption and water follows. However, when CA is BLOCKED by acetazolamide, there is no bicarb to cotransport with Na+, leaving Na+ in the diltrate. there is sodium wasting and thus promotes diuresis

Question 9

3 indicatiosn for carbonic anhydrase inhibitors

Answer 9

1. altitude sickness; bicarb wasting causes a state of metabolic acisosis– shifts Hb-O2 curve and increases the o2 delivery to tissues
2. galucaoma
3. seizures

Question 10

side effects of CAHs and why

Answer 10

1. metabolic acidosis; less bicarb is being transported back into the blood (because it goes through the HCo3-/Na+ transporter in the PCT)
2. hyponatremia; sodium wasting– sodium also not transported because CA inhibited
3. hypokalemia– due to sodium delivery to distal nephron, in combo with RAS activation.

Question 11

Carbonic anhydrase inhibitors lead to __ and ___ wasting

The most common indication is __ sickness

The most common electrolyte side effect is __

Answer 11

Question 12

example of a loop diuretic, site, and MOA

Answer 12

ex/ lasix/furosemide.

site; THICK ascending loop of henle

MOA; normally in the ascending loop, Na+ is reabsorbed but it is impermeable to water. the 2NKCC transporter transports Cl, K, and Na from the filtrate back to the cell/. K+ is pumped back out, but Cl- is shuttled into the blood. the Na+ is reabsorbed through the 3Na+in/2K+out exchanger. FUROSEMIDE INHIBITS the 2NKCC channel, preventing any reabsorption of K+, Cl or Na+. Thus, Na+ accumulates in the ascending loop, causing interstitial washout.

Question 13

indications for furosemide

Answer 13

edema and pulmonary edema. it is a strong diuretic.

Question 14

electrolyte side effects of loop diuretics/furosemide

Answer 14

hypokalameia; deactivation of NKCC prevents K+ reabsorption, causing distal wasting of K+

hypernatremia: due to interstitial wash out and large H2O diuresis

Hypomagnesemia

Metabolic ALKALOSIS; loops impair Mg2+ reabsorption.

Question 15

Loop diuretics block the __

Potent salt and water diruresis Used for volume reduction

Most common electrolyte side effect it __ and __

__ is a common side effect

Answer 15

Loop diuretics block the NKCC

Potent salt and water diruresis Used for volume reduction

Most common electrolyte side effect it hypokalemia and hypernatremia Hypovolemia is a common side effect

Question 16

thiazide diuretics act on the ___. Example, and MOA

Answer 16

act on the DCT. ex/ hydrochlorothiazise, indapamide, chlorthalidone.

MOA: Normally, DCT reabsorbs Na+ and Cl- through Na+/Cl co transporter, and also reabsorbs Mg2+ and Ca2+ through channels. thiazide blocks the Na+/Cl- channel at the DCT, preventing Na+ reabsorption.

Question 17

indications and electrolyte side effects of thiazide diuretics that work at the DCT

Answer 17

indications; hypertension

electrolyte side effects; hyponatremia, hypokalemmia, hypomagnesemia, hypercalcemia

Question 18

why is gout a major side effect of thiazide diuretics

Answer 18

Thiazide diuretics are associated with elevated serum uric acid (SUA) levels. They increase direct urate reabsorption in the proximal renal tubules [3]

Question 19

type of cancer associated with hydrochlorothiazide

Answer 19

squamous cell skin cancer– causes photosensitivity.

Question 20

Loop diuretics block the __ at the ___

Thiazide diuretics block the __ at the ___

Answer 20

Loop diuretics block the NKCC (Na+K+2Cl- channel)

thiazide diuretics Block the NCCT (Na/Cl- co transport channel)

Question 21

two broad categories of potassium sparing diuretics and give an example

Answer 21

1. mineralcorticoid antagonists– spironolactone and eplerenone
2. ENaC blockers– amiloride, triamterine. (epithelial sodium chennal blockers)

Question 22

Outline the MOA of Mineralcorticoid antagonists and ENACblockers (potassium sparing diuretics)

Answer 22

normally, the principle cell of the collecting tubule reabsorbs Na+ through ENAC, creating a negative luminal charge, which is neutralized by the secretion of K+ removed by the renal outer medullary K+ channel. Aldosterone turns on this function, resulting in increased Na+ absorption and K+ excretion

When MNAs inhibit aldosterone/block its binding, it shuts down the principle cell and prevents na+ reabsorption, causing salt wasting.

• ENACblockers directly inhibit ENaC, so Na+ can’t be reabsorbed even if aldosterone is there.

Question 23

indications to use diuretics, and electrolyte and non electrolyte side effects

Answer 23

1. hypertension
2. Conn Syndrome: aldosterone excess syndrome: PSDs can offset aldosterone effects
3. left ventricular dysfunction
4. ascites from cirrhosis

**KEY NON-ELECTROLYTE side effect is that they are anti-androgens

Question 25

most common side effect of potassium sparing diuretics

Answer 25

hyperkalemia-- recall that Na+ is absorbed from the cell to the blood using Na+/K+ channel, and K+ is pumped out to maintain normal charge. if no Na+ is coming in, K+ doesn't need to leave. results in K+ hoarding and thus hyperkalemia