Pharmacolgy of drugs acting on the kidney

Question 1

How do diuretics fundamentally increase urine output?

Answer 1

By interfering with salt reabsorption in the nephron

Question 2

What is the fundamental indication for diuresis?

Answer 2

Diseases associated with increase in the ICF volume (oedema)

Question 3

What is the main driving force behind formation of interstitial fluid?

Answer 3

Capillary pressure

Question 4

Why does protein (e.g. albumin) filtered at the glomerulus always appear in the urine?

Answer 4

Cannot be reabsorbed

Question 5

Why does decreased blood volume cause decreased cardiac output?

Answer 5

Starling laws- lower preload

Question 6

How does the nephrotic syndrome cause oedema?

Answer 6

Loss of protein causes decreased oncotic pressure ????????

Question 7

For what two reasons does hepatic cirrhosis cause odoema?

Answer 7

Increased portal pressure; combined with decreased albumin

(also made worse by activation of RAAS)

Question 8

Why are carbonic anhydrase inhibitors now obsolete?

Answer 8

Tachyphylaxis

Question 9

Why are potassium-sparing diuretics used?

Answer 9

To try and modulate the amount of potassium being excreted (for example with use of loop and thiazide diuretics- correct the hypokalaemia)

Question 10

Where must the diuretics be in order to have their effects?

Answer 10

Within the filtrate (because they act at the apical membrane)

Question 11

Why do diuretics rarely gain access to the filtrate by filtration at the glomerulus? How do they gain access?

Answer 11

Most are protein-bound (not filtered)

Organic anion transporters (acidic drugs e.g. thiazides and loops)

Organic cation transporters (basic drugs)

Question 12

What is the basic mechanism of action of loop diuretics?

Answer 12

Inhibits the triple co-transporter in the thick ascending loop of Henle

Question 13

What drives the movement of calcium and magnesium across the tight junctions?

Answer 13

Transepithelial potential caused by potassium

Question 14

What are two adverse effects of loop diuretics other than hypokalaemia? Why is this?

Answer 14

Hypocalcaemia and hypomagnesia. Ablation of the trans-epithelial potential driving Mg and Ca reabsorption

Question 15

Where do furoesemide and bumetanide bind to the triple transporter?

Answer 15

The chloride site

Question 16

What other action of loop agents is beneficial in pulmonary oedema?

Answer 16

Indirect venodilation

Question 17

Why does diuretic efficacy decrease in nephrotic syndrome?

Answer 17

Becomes bound to protein in the filtrate

Question 18

The toxicity of which drugs can be enhanced by loop diuretics? What is the cause?

Answer 18

Cardiac glycosides (e.g. digoxin) and Class III antidysrythmics

Hypokalaemia

Question 19

How is acid-base balance shifted in loop diuretics?

Answer 19

Towards alkalosis (metabolic)- increased secretion of hydrogen

Question 20

What is the mechanism of action of the thiazide diuretics?

Answer 20

Blocks the NaCl co-transporter in the distal tubule

Question 21

What are the adverse effects of thiazide diuretics?

Answer 21

Hypokalaemia

Hypercalcaemia

Hyperuricaemia (gout)

Metabolic alkalosis

Hypovolaemia/hypotension

Male sexual dysfunction

Impaired glucose tolerance

Question 22

What other action of thiazide diuretics makes them useful in the treatment of hypertension?

Answer 22

Indirect vasodilatory effect

Question 23

Considering the effect of thiazide diuretics in calcium reabsorption, what other indication is there for their use?

Answer 23

Increased re-absorption of calcium- nephrolithiasis

Question 24

What are the effects of aldosterone?

Answer 24

Increases synthesis of the Na/K ATPase and increases the synthesis of a protein which activates ENaC (epithelial sodium channel)

Question 25

How do spironolactone and eplerenone work?

Answer 25

Competitive aldosterone antagonists

Question 26

Given alone, what do potassium-sparing diuretics cause?

Answer 26

Hyperkalaemia