Renal pharmacology

Question 1

What are diuretics?

Answer 1

Drugs that increase the rate of urine flow
and excretion of Na+ and water from the
filtrate.
They decrease the reabsorption of Na+ (and
usually Cl-) from the filtrate

Question 2

Where do the loop diuretics alter the filtrate?

Answer 2

Thick ascending limb

Question 3

Where do thiazides alter the filtrate?

Answer 3

DT

Question 4

Where does amiloride and spironolactone alter the filtrate?

Answer 4

CD

Question 5

How do carbonic anhydrase inhibitors work as diuretics? (not used anymore)

Answer 5

Stops the bicarb reaction outside the tubule cell so there is no pull for H+ ions and this stops the H+/Na transporter moving the Na into the cell

Question 6

What limits the use of carbonic anhydrase inhibitors?

Answer 6

As bicarbonate is eliminated, systemic acidosis results.

Diuretic effects in the proximal tubulus can be compensated in more distant part of the tubulus.

Question 7

How do loop diuretics work?

Answer 7

Na+, K+ and Cl- enter by a cotransport system. Loop diuretics act on the Na+-K+-2Cl- symporter (cotrans-porter) in the thick ascending limb of the loop of Henle to inhibit sodium and chloride reabsorption.

Question 8

How long do loop diuretics work for?

Answer 8

Peak 30min-2hours and action lasts for 6 hours

Question 9

What is the effect of loop diuretics on GFR?

Answer 9

Loop diuretics interfere with feedback control of glomerular filtration rate! No decrease of GFR!

Question 10

How do thiazides work as diuretics?

Answer 10

They bind to the Cl- site of the distal tubular Na+/Cl- co-transport system, inhibiting its action.
Inhibit sodium resorption and promote potassium excretion.

Question 11

How are thiazides excreted?

Answer 11

Excreted in the urine, mainly by tubular secretion

Question 12

What effect do thiazides have on calcium?

Answer 12

They stimulate Ca2+ reabsorption

Question 13

How do Triamterene and amiloride work as diuretics?

Answer 13

Amiloride and triamterene work by directly blocking the epithelial sodium channel thereby inhibiting sodium reabsorption in the distal convoluted tubules.

Question 14

Which acts faster Triamterene or amiloride?

Answer 14

Triamterene is well absorbed in the GI tract, amiloride is less well absorbed and has a slower onset

Question 15

What is the effect of Triamterene and amiloride on potassium?

Answer 15

They promote the loss of sodium and water from the body, but without depleting potassium.

Question 16

How do Aldosterone antagonists eg Spironolactone act as diuretics?

Answer 16

The cells are impermeable to Na+ in the absence of aldosterone. Aldosterone acts on a nuclear receptor within the tubule cell and on membrane receptors. Spironolactone competes with aldosterone at its receptor site.

Question 17

How is spirolactone metabolised?

Answer 17

It is highly protein bound (>90%) and extensively metabolized by the liver to the active metabolite, canrenone. It is primarily eliminated by the kidneys.

Question 18

How long does spirolactone last?

Answer 18

The onset of action for spironolactone is slow, and effects do not peak for 2-3 days.

Question 19

What salts does aldosterone move?

Answer 19

Aldosterone is responsible for increasing sodium and chloride reabsorption and potassium and calcium excretion from renal tubules.

Question 20

How do osmotic diuretics work?

Answer 20

Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.
eg IV mannitol

Question 21

Where do osmotic diuretics work?

Answer 21

Within the nephron, their main effect is exerted in those parts of the nephron that are freely permeable to water: proximal tubule, descending limb of the loop, and the collecting tubules.

Question 22

What is the effect of osmotic diuretics on Na?

Answer 22

The result is a decreased concentration of Na+ in lumen (more water!) and a decreased reabsorption of Na+.