2.06 - Modulation Of Renal Excretion By Diuretics

Question 1

What are the seven classes of diuretics?

Answer 1

Osmotic diuretics Carbonic Anhydrase Inhibitors Loop diuretics Thiazide derivatives and analogues Inihibotrs of ENaC Antagonists of Mineralocorticoid Receptors Methylxanthines

Question 2

Provide an example of an osmotic diuretic

Answer 2

Mannitol Sorbitol Urea

Question 3

Describe the mechanism of action of osmotic diuretics

Answer 3

PT and TAL (TAL most important target) Substances ‘bind’ water in tubule and will not let it be reabsorbed. Recruit H20 from ICF –> increase in ECF –> increased RBF

Question 4

What are some indications for the use of osmotic diuretics?

Answer 4

Brain oedema Impending anuria (crush syndrome) Forced diuresis (intoxications)

Question 5

What are some contraindications for the use of osmotic diuretics?

Answer 5

Heart failure and its complications: because it is drawing water in to the ECF, the heart will have to work harder Persisting oliguria and anuria: have to have excretory side of the kidney open as this is the only way to excrete the osmotic agent

Question 6

Provide an example of a Carbonic Anhydrase (CAH) Inhibitor

Answer 6

Acetazolamide

Question 7

Describe the mechanism of action of CAH inhibitors

Answer 7

CAH inhibitors block CAH on the luminal side of tubular cells. This prevents the breakdown of H2CO3 to CO2 and H2O. This then means there is no proton to be exchanged with Na on the luminal side. This result in prevention of Na reabsorption and therefore water loss

Question 8

List some clinical uses of CAH inhibitors

Answer 8

Open angle glaucoma Oedema (cardiac or toxic)

Question 9

Provide an example of a Loop Diuretic

Answer 9

Furosemide

Question 10

Describe the mechanism of action of loop diuretics

Answer 10

TAL Block of Na/2Cl/K (NACK; furosemide has a nack) Reabsorption of 25% of Na+ is blocked Paracellular diffusion is blocked as voltage difference decreases

Question 11

What are some indications for the use of loop diuretics?

Answer 11

Oedemas Forced diuresis Impending anuria

Question 12

What are some adverse effects of loop diuretics?

Answer 12

Loss of electrolytes (as they block paracellular diffusion)

Question 13

Provide an example of a thiazide diuretic

Answer 13

Hydrochlorothiazide

Question 14

Describe the mechanism of action of Thiazide diuretics

Answer 14

DT Antagonist at Na/Cl symporter Prevent reabsorption of Na and therefore water

Question 15

What are some indications for the use of thiazide diuretics?

Answer 15

Oedemas with good GFR Hypertension

Question 16

What are some side effects, and contraindications for the use of thiazide diuretics?

Answer 16

Side effects: Loss of K+ (key), retention of uric acid Contraindications: anuria, hypokalemia

Question 17

Provide some examples of the Inhibitors of ENaC

Answer 17

Amiloride

Question 18

Describe the mechanism of action of the inhibitors of ENaC

Answer 18

DT/CD Filtered and secreted in PT Block action of endothelial sodium channel, preventing its reabsorption –> water loss Potassium sparing

Question 19

List some indications for the use of ENaC inhibitors

Answer 19

Hypertension (in combination with other diuretics)

Question 20

List some contraindications for the use of ENaC inhibitors

Answer 20

Hyperkalemia Anuria

Question 21

Provide an example of a mineralocorticoid receptor antagonist

Answer 21

Spironolactone

Question 22

Describe the effect of mineralocorticoid receptor antagonists

Answer 22

DT/CD Bind to MC-receptor and prevent the action of aldosterone. E.g. block the up regulation of basolateral Na/K pumps and epithelial sodium channels (ENaC). This prevents the reuptake of sodium and thus water diuresis. Potassium sparing Only small sodium load

Question 23

List some indications for the use of mineralocorticoid receptor antagonists

Answer 23

Hypertension (in combination with other agents) Hyperaldosteronism Diuretic of choice in hepatic cirrhosis

Question 24

What are some contraindications for the use of mineralocorticoid receptor antagonists?

Answer 24

Hyperkalaemia Hyponatraemia Anuria

Question 25

Provide an example of a methylxanthine

Answer 25

Caffeine

Question 26

Describe the mechanism of action of methylxanthines

Answer 26

Increase GFR via a pre-renal mechanism (increase in blood pressure) and slightly decreased Na+ resorption. Not clinically important

Question 27

Selma Radic, a 35yo female, has been involved in an accident with serious head injuries. To reduce and limit brain oedema, Mannitol is used as a diuretic.

After 12h of therapy, which of the following answers best describes the findings in this patient as compared to “normal” pre-treatment values?

Answer 27

D