Drugs and the Kidney

Question 1

In what parts of the kidney is NaCl and water reabsorbed?

Answer 1

The proximal tubule, the loop of henle, the distal tubule and the collecting ducts

Question 2

What proportion of NaCl and water is reabsorbed in the proximal tubule?

Answer 2

60-70%

Question 3

What proportion of NaCl and water is reabsorbed in the loop of Henle?

Answer 3

20-30%

Question 4

What proportion of NaCl and water is reabsorbed in the distal tubule and collecting ducts?

Answer 4

5-10%

Question 5

In what part of the kidney is potassium reabsorbed?

Answer 5

The loop of henle

Question 6

In what part of the kidney is potassium secreted?

Answer 6

In the distal tubule and collecting ducts

Question 7

What are diuretics?

Answer 7

Drugs which increase sodium and water excretion by decreasing sodium and chloride reabsorption

Question 8

What are the 4 classes of diuretics?

Answer 8

loop diuretics, thiazide diuretics, potassium sparing diuretics, osmotic diuretics

Question 9

What is frusemide?

Answer 9

A loop diuretic

Question 10

What is the mechanism of action of loop diuretics?

Answer 10

Inhibits sodium/potassium/2cholride carrier in the loop of henle to prevent sodium reabsorption and therefore water reabsorption and also by increasing the amount of sodium in the distal tubule which decreases water reabsorption

Question 11

What are the pharmacokinetics of loop diuretics?

Answer 11

Well absorbed, onset in less than an hour, binds strongly to plasma proteins so will undergo tubular secretion, duration of action is 3-6 hours

Question 12

What are the adverse effects of loop diuretics?

Answer 12

hypokalaemia, metabolic alkalosis, hypovolaemia and hypotension

Question 13

Why do loop diuretics cause hypokalaemia?

Answer 13

Because they cause an increase in sodium in the distal tubules which results in increased sodium reabsorption which means there is increased potassium secretion (due to sodium/potassium ATPase)

Question 14

What are the clinical uses of loop diuretics?

Answer 14

pulmonary oedema, heart failure, liver cirrhosis, renal failure, hypertension

Question 15

What is the mechanism of action of thiazide diuretics?

Answer 15

Inhibits sodium/chloride cotransporter in the distal tubule which prevents sodium reabsorption which prevents water reabsorption

Question 16

What are the pharmacokinetics of thiazide diuretics?

Answer 16

Orally active, maximum effect after 4-6 hours and have 8-12 hours of duration

Question 17

What are the adverse effects of thiazide diuretics?

Answer 17

hypokalaemia and gout

Question 18

Why do thiazide diuretics cause gout?

Answer 18

Because they inhibit the tubular secretion of uric acid

Question 19

What are the clinical uses of thiazide diuretics?

Answer 19

hypertension and severe resistant oedema

Question 20

When are potassium sparing diuretics used?

Answer 20

In combination with potassium losing diuretics to prevent potassium loss - this is particularly important in patients with heart failure

Question 21

What are the two types of potassium sparing diuretics?

Answer 21

Aldosterone receptor antagonists (spironolactone) and non aldosterone receptor antagonits (triameterene and amiloride)

Question 22

What is the mechanism of action of aldosterone receptor antagonist potassium sparing diuretics?

Answer 22

Potassium sparing diureitcs are aldosterone receptor antagonists which leads to inhibition of activation of sodium channels and prevents synthesis of sodium/potassium ATPase in the collecting ducts - overall this will lead to decreased sodium reabsorption but only at a relatively low level but will also prevent potassium secretion

Question 23

What is the mechanism of action of non aldosterone receptor antagonist potassium sparing diuretics?

Answer 23

Inhibits sodium channels which leads to reduced sodium reabsorption and reduced potassium secretion

Question 24

What are the pharmacokinetics of spironolactone?

Answer 24

orally active, slow onset, short half life but metabolite has long half life

Question 25

What are the adverse effects of spironolactone?

Answer 25

Hyperkalaemia, gastrointestinal upset

Question 26

What are the clinical uses for spironolactone?

Answer 26

in combination with loop or thiazide diuretics, heart failure, hyperaldosteronism

Question 27

What are osmotic diuretics?

Answer 27

Pharmacologically inert - they are filtered but not reabsorbed so the water will follow them and be prevented from being reabsorbed as well - does not affect sodium reabsorption

Question 28

What are the clinical uses of osmotic diuretics?

Answer 28

Raised intracranial pressure and raised intraoccular pressure and prevention of acute renal failure

Question 29

Why is the kidney susceptible to toxicity?

Answer 29

Because it receives a high blood supply, it concentrates things, metabolism may create reactive chemical species and is controlled by extra renal events (BP, nerves etc)

Question 30

What are the mechanisms of kidney toxicity?

Answer 30

ROS causing cell damage, interference with calcium metabolism, protein or enzyme binding (may inhibit enzyme function or cause an autoimmune response)