18. Diuretics and Drugs in Kidney Failure

Question 1

What are the four roles of renal physiology?

Answer 1

Regulatory, excretory, endocrine, metabolism.

Question 2

What are the regulatory factors of renal physiology?

Answer 2

Fluid balance, acid-base balance, electrolyte balance.

Question 3

What are the excretory factors of renal physiology?

Answer 3

Waste products, drug eliminations - glomerular filtration and tubular secretion.

Question 4

What are the endocrine factors of renal physiology?

Answer 4

Renin-angiotensin-aldosterone, erythropoetin, prostaglandins.

Question 5

Where is angiotensinogen secreted?

Answer 5

The liver.

Question 6

Where is renin secreted?

Answer 6

Renin.

Question 7

What is the role of renin?

Answer 7

Converts angiotensinogen to angiotensin I.

Question 8

What are the metabolic factors of renal physiology?

Answer 8

Vitamin D, polypeptides - insulin and PTH.

Question 9

Where do carbonic anhydrase inhibitors act?

Answer 9

At the PCT.

Question 10

What is the mechanism of action of carbonic anhydrase inhibitors?

Answer 10

Acts at PCT to prevent carbonic anhydrase in tubule, reabsorption of Na+ ions is affected.

Question 11

What are carbonic anhydrase inhibitors used for?

Answer 11

Topical treatment for glaucoma.

Question 12

What are the risks of using carbonic anhydrase inhibitors as diuretics?

Answer 12

Metabolic acidosis and hypokalaemia.

Question 13

Name an osmotic diuretics.

Answer 13

Mannitol.

Question 14

What is the mechanism of action of osmotic diuretics?

Answer 14

Increase osmotic gradient systemically.

Question 15

What are the risks of osmotic diuretics?

Answer 15

Excessive water loss -> hypernatraemia.

Question 16

What are osmotic diuretics currently used for?

Answer 16

Severe cerebral or pulmonary oedema.

Question 17

What is the mechanism of action of ADH antagonists?

Answer 17

Reduce concentrating ability of urine in collecting ducts.

Question 18

Name an ADH antagonist.

Answer 18

Lithium or demeclocycline.

Question 19

Name a loop diuretic.

Answer 19

Furosemide.

Question 20

What is the mechanism of action of loop diuretics?

Answer 20

Act on NKCC2 transporters on thick ascending limb of loop of Henle so directly prevent Na_ and Cl- reabsorption. Concurrent excretion of Ca2+ and Mg2+ too.

Question 21

What are the risks of loop diuretics?

Answer 21

Hypokalaemia.

Question 22

What are indications of use of loop diuretics?

Answer 22

Heart failure and liver failure.

Question 23

What are the DDIs for loop diuretics?

Answer 23

Aminoglycosides - risk of ototoxicity and nephrotoxicity. Digoxin or steroids - risk of hypokalaemia.

Question 24

What is the mechanism of action of thiazides?

Answer 24

Act on Na+-Cl- symporter and promote Ca2+ reabsorption.

Question 25

What are the ADRs of thiazides?

Answer 25

Hypokalaemia, hypercalcaemia, hyperuricaemia, risk of erectile dysunction.

Question 26

What are the indications of use of thiazides?

Answer 26

Heart failure and hypertension, also kidney stones (calcium reabsorption from urine)

Question 27

What are the DDIs for thiazides?

Answer 27

Digoxin or steroids - risk of hypokalaemia. B-blockers - risk of hyperglycaemia, hyperlipidaemia, hyperuricaemia.

Question 28

Name a potassium sparing diuretic.

Answer 28

Amiloride.

Question 29

What is the mechanism of action of potassium-sparing diuretics?

Answer 29

Act on ENaC channel in late DCT and collecting duct.

Question 30

What is the important DDI with potassium-sparing diuretics?

Answer 30

ACE inhibitors - risk of hyperkalaemia.

Question 31

Name a aldosterone antagonist.

Answer 31

Spironolactone, eplerenone.

Question 32

What is the mechanism of action of aldosterone antagonist?

Answer 32

Inhibit action of aldosterone on mineralocorticoid receptors so affect Na+K+ATPase and ENaC protein synthesis.

Question 33

What is the half life of spironolactone?

Answer 33

18-24 hours so can be used long term.

Question 34

What are the ADRs of aldosterone antagonists?

Answer 34

Hyperkalaemia, androgenic cross-reactivity -> gynaecomastia.

Question 35

What are the indications of aldosterone antagonists?

Answer 35

Heart failure, hypertension, liver failure, hyperaldosteronism.

Question 36

What are the general ADRs of any diuretic use?

Answer 36

Anaphylaxis/rash, hypovolaemia, hypotension, electrolyte disturbance, and metabolic abnormalities.

Question 37

What is the mechanism of action of digoxin?

Answer 37

Inhibits tubular NaKATPase.

Question 38

What is the mechanism of action of amiloride?

Answer 38

Inhibits Na channels in DCT/CD, K+ sparing.

Question 39

What can cause apparent diuretic resistance?

Answer 39

Incomplete treatment of primary disorder, continuation of high Na+ intake, non-compliance, poor absorption, volume depletion decreases filtration and increases aldosterone, NSAIDs can reduce renal blood flow.

Question 40

What are some key considerations of prescribing in chronic renal failure?

Answer 40

Avoid nephrotoxins if possible, reduce dosages, monitor renal function and drug levels, watch out for hyperkalaemia, uraemia patients may bleed.

Question 41

How is hyperkalaemia managed?

Answer 41

Identify cause, ECG, treat with drugs.

Question 42

Which drugs can treat hyperkalaemia?

Answer 42

Calcium gluconate, insulin/dextrose, calcium resonium, sodium bicarbonate, salbutamol.

Question 43

What are the features of hyperkalaemia on ECGs?

Answer 43

Tall tented T waves, QRS elongation, fewer P waves.