Diuretics

Question 1

What is diuresis?

Answer 1

Increased production of urine by the kidney

Question 2

What is a diuretic?

Answer 2

Drug that causes diuresis

Question 3

How do all diuretics basically work?

Answer 3

Decrease reabsorption of sodium ions
so more sodium ions are excreted
water follows sodium ions
so more water is excreted too

Question 4

What is the proportion of filtered sodium ions normally excreted by the kidney?

Answer 4

Less than 1%

Question 5

How are diuretics classified into different groups?

Answer 5

Based on the part of the nephron tubule that they act on

Based on the transporter or channel that they block

Question 6

How do diuretics reach the nephron and the transporter or channel that they act on?

Answer 6

They are secreted into the tubular lumen of the proximal convoluted tubule
travel through the nephron to the region they act on
they block their specific transporter or channel from the inside of the tubular lumen

Question 7

What are the different groups of diuretics?

Answer 7

Loop diuretics

Thiazide diuretics

Potassium ion sparing diuretics

Question 8

What are the different groups of diuretics in order of potency?

Answer 8

Loop diuretics

Thiazide diuretics

Potassium-sparing diuretics

Question 9

Why are loop diuretics more potent than thiazide diuretics?

Answer 9

Because 25% of sodium ions are reabsorbed in the thick ascending limb of the loop of Henle
Whilst only 5% of sodium ions are reabsorbed in the distal convoluted tubule
So loop diuretics cause excretion of more sodium ions than thiazide diuretics, and hence more water excretion

Question 10

What region of the nephron do loop diuretics act on?

Answer 10

Thick ascending limb of loop of Henle

Question 11

What transporter or channel do loop diuretics act on?

Answer 11

NKCC2 transporter

Question 12

What are the effects of loop diuretics?

Answer 12

Reduced sodium ion reabsorption

Reduced calcium ion reabsorption

Reduced water reabsorption in the later distal convoluted tubule and collecting duct

Question 13

How do loop diuretics reduce calcium ion reabsorption?

Answer 13

Sodium, chloride and potassium ions do not move from tubular lumen into epithelial cell
Potassium ions do not move back into tubular lumen through ROMK channel making tubular lumen more positively charged
Reduced electrical gradient for calcium ions to move from tubular lumen into interstitial fluid by paracellular route

Question 14

How do loop diuretics reduce water reabsorption in the later distal convoluted tubule and the collecting duct?

Answer 14

Fewer sodium and chloride ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality of interstitial fluid in medulla
Less of an osmotic gradient for water to move into it through Aquaporins from the tubular lumen

Question 15

What are some examples of loop diuretics?

Answer 15

Furosemide

Bumetanide

Question 16

What region of the nephron do thiazide diuretics act on?

Answer 16

The distal convoluted tubule

Question 17

What transporter or channel do thiazide diuretics act on?

Answer 17

The NCC transporter

Question 18

What are the effects of thiazides?

Answer 18

Reduced sodium ion reabsorption

Reduced chloride ion reabsorption

Reduced water reabsorption in later distal convoluted tubule and collecting duct

Increased calcium ion reabsorption

Question 19

How do thiazides reduce water reabsorption in the later distal convoluted tubule and the collecting duct?

Answer 19

Fewer sodium and chloride ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality of interstitial fluid in medulla
Less of an osmotic gradient for water to move into it through Aquaporins from the tubular lumen

Question 20

How do thiazides increase calcium ion reabsorption?

Answer 20

Sodium ions do not move from tubular lumen into epithelial cell
reduced concentration of sodium ions in the epithelial cell
more of a concentration gradient for sodium ions to move from interstitial fluid into epithelial cell
increased activity of NCX on basolateral domain of epithelial cell
more calcium ions are moved from epithelial cell into interstitial fluid
so more calcium ions move from tubular lumen into epithelial cell through calcium ion uniporter on apical domain of epithelail cell

Question 21

What region of the nephron do potassium-sparing diuretics act on?

Answer 21

Later distal convoluted tubule and collecting duct

Question 22

What type of cell in the later collecting duct and distal convoluted tubule do potassium-sparing diuretics act on?

Answer 22

Principal cells

Question 23

What are the different types of potassium-sparing diuretics?

Answer 23

ENaC inhibitors

Aldosterone antagonists

Question 24

How do ENaC inhibitors reduce water reabsorption?

Answer 24

Fewer sodium ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality in medulla
Less of an osmotic gradient for water to move into it through Aquaporin channels from the tubular lumen

Question 25

How do ENaC inhibitors reduce potassium ion secretion?

Answer 25

Sodium ions do not move from tubular lumen into epithelial cell Tubular lumen becomes more positively charged Less of an electrical gradient for potassium ions to move from epithelial cell through ROMK channels into tubular lumen Fewer potassium ions move

Question 26

What is an example of an ENaC inhibitor?

Answer 26

Amiloride

Question 27

How do aldosterone antagonists bind to the aldosterone receptors?

Answer 27

Competitive inhibition

Question 28

What is an example of an aldosterone antagonist?

Answer 28

Spironolactone

Question 29

What is a side effect of loop diuretics and thiazides?

Answer 29

Hypokalaemia

Question 30

How do loop diuretics and thiazides cause hypokalaemia?

Answer 30

Increase potassium ion secretion

Question 31

How do loop diuretics and thiazides cause increased potassium ion secretion?

Answer 31

More sodium ions and water in later distal convoluted tubule and collecting duct More sodium ions move from tubular lumen through ENaC into epithelial cell more negatively charged tubular lumen more of an electrical gradient for to potassium ions move from epithelial cell through ROMK channels into tubular lumen Tubular fluid flows through later distal convoluted tubule and collecting duct faster Removes potassium ions from tubular lumen reducing their concentration in the tubular lumen More potassium ions move from epithelial cell through ROMK channels into tubular lumen Increases activity of BK channels More potassium ions move from epithelial cell through BK channels into tubular lumen Reducing blood volume and blood pressure Activation of RAAS Aldosterone results in increased potassium secretion

Question 32

Do loop diuretics or thiazides cause hypokalaemia more often?

Answer 32

Thiazides cause hypokalaemia more often

Question 33

How can the side effect of loop diuretics and thiazides be overcome?

Answer 33

Given in combination with potassium-sparing diuretic Given with potassium ion supplements

Question 34

What is a side effect of potassium-sparing diuretics?

Answer 34

Hyperkalaemia

Question 35

How do potassium-sparing diuretics cause hyperkalaemia?

Answer 35

Decrease potassium ion secretion

Question 36

How do potassium-sparing diuretics decrease potassium ion secretion?

Answer 36

Sodium ions do not move from tubular lumen through ENaC into epithelial cell tubular lumen is more positively charged less of an electrical gradient for potassium ions to move from epithelial cell through ROMK channels into tubular lumen by facilitated diffusion

Question 37

What are loop diuretics used to treat?

Answer 37

Hypertension Oedema Hypercalcaemia

Question 38

How do loop diuretics treat hypertension?

Answer 38

Increase production of prostaglandins give vasodilation and venodilation reducing total peripheral resistance, afterload, preload

Question 39

How do loop diuretics treat oedema?

Answer 39

Reduce extracellular fluid volume

Question 40

What are thiazide diuretics used to treat?

Answer 40

Hypertension Oedema

Question 41

How do thiazide diuretics treat hypertension?

Answer 41

Cause vasodilation | reducing total peripheral resistance, afterload

Question 42

What are some examples of conditions that cause oedema?

Answer 42

Heart failure Nephrotic syndrome Renal failure Liver cirrhosis

Question 43

What is spironolactone used to treat?

Answer 43

Hypertension Oedema

Question 44

Which diuretic is preferably used to treat hypertension?

Answer 44

Thiazide If this doesn't work, or if the hypertension is caused by primary hyperaldosteronism then spironolactone is used

Question 45

Which diuretic is preferably used to treat heart failure? Why?

Answer 45

Spironoloactone | because it reduces mortality

Question 46

Which diuretic is preferably used to treat oedema caused by liver cirrhosis?

Answer 46

Spironoloctone

Question 47

What are the side effects of diuretics in general?

Answer 47

May cause hyponatraemia May cause hypovolaemia May cause gout

Question 48

What are the effects of aldosterone antagonists?

Answer 48

Reduced sodium ion reabsorption Reduces water reabsorption Reduced potassium ion secretion

Question 49

How may diuretics cause gout?

Answer 49

Diuretics compete with uric acid for secretion into the proximal convoluted tubule less uric acid secreted more uric acid in the blood precipitates out as urate crystals causing gout