Diuretics

Question 1

What are the regulatory functions of the kidney?

Answer 1

Fluid balance Acid-base balance Electrolyte balance

Question 2

What are the excretory functions of the kidneys?

Answer 2

Waste products Drug elimination

Question 3

What are the endocrine functions of the kidneys?

Answer 3

RAAS Erythropoietin Prostaglandins

Question 4

What are the metabolic functions of the kidney?

Answer 4

Vitamin D Polypeptides - insulin and PTH

Question 5

What do carbonic anhydrase inhibitors do?

Answer 5

Prevent action of carbonic anhydrase in the PCT, which affects reabsorption rate of Na due to Na-H antiport

Question 6

General functions of kidneys?

Answer 6

REEM Regulatory Excretory Endocrine Metabolic

Question 7

Why are carbonic anhydrase inhibitors rarely used as a diuretic?

Answer 7

Risk of metabolic acidosis and hypokalaemia

Question 8

What are carbonic anhydrase inhibitors used for?

Answer 8

Glaucoma

Question 9

Name an osmotic diuretic

Answer 9

Mannitol

Question 10

How do osmotic diuretics work?

Answer 10

Increase the osmotic gradient systemically and in the renal tubules.

Question 11

When are osmotic diuretics used?

Answer 11

Severe cerebral or pulmonary oedema

Question 12

Why are osmotic diuretics not commonly used?

Answer 12

Can cause excessive water loss and hypernatraemia

Question 13

Name some ADH antagonists

Answer 13

Lithium

Demeclocycline

Question 14

How do ADH antagonists work?

Answer 14

Reduce the concentrating ability of collecting ducts by decreasing expression of aquaporin

Question 15

Which transporters do loop diuretics work on and where? Effect of this?

Answer 15

Na-K-2Cl in the thick ascending limb of the loop of Henle

Prevent reabsorption of Na and Cl and prevent concurrent excretion of Ca and Mg due to a more positive lumen potential from K

Question 16

Name a loop diuretic

Answer 16

Furosemide

Question 17

Adverse effects of loop diuretics?

Answer 17

Hypokalaemia due to no reabsorption by Na-K-2Cl

Bumetanide can cause myalgia

Furosemide can cause reversible ototoxicity

Question 18

Indications for loop diuretics?

Answer 18

Heart failure - also have a slight venodilatory effect

Liver failure causing fluid overload

Question 19

DDIs of loop diuretics

Answer 19

Cannot be used with aminoglycosides due to risk of ototoxicity and nephrotoxicity

Rarely with digoxin or steroids due to risk of hypokalaemia

Question 20

Which transporters do thiazide diuretics affect and where? Effect of this?

Answer 20

The Na-Cl symporter in the DCT

Have a diuretic affect whilst promoting Ca reabsorption

Question 21

ADRs of thiazide diuretics?

Answer 21

Hypokalaemia

Hypercalcaemia

Hyperuricaemia (leading to gout)

Erectile dysfunction

Question 22

Indications for thiazide diuretics?

Answer 22

Heart failure

Hypertension

Kidney stones due to calcium reabsorption

Question 23

DDIs of thiazide diuretics?

Answer 23

Digoxin or steroids due to risk of hypokalaemia

Beta-blockers due to risk of hyperglycaemia, hyperlipidaemia and hyperuricaemia

Carbamazepine due to risk of hyponatraemia

Question 24

Name some potassium sparing diuretics

Answer 24

Amiloride

Spironolactone

Question 25

How do potassium-sparing diuretics work?

Answer 25

Act on ENaC channels in the late DCT and CD - so have no effect on potassium reaborption

Question 26

DDIs of potassium-sparing diuretics?

Answer 26

ACE-inhibitors - risk of hyperkalemia Amiloride often given alongside furosemide to balance potassium

Question 27

Why can any diuretic that decreases sodium absorption before the DCT cause hypokalaemia?

Answer 27

Less sodium is reabsorbed, so there is a decrease in circulating volume and activation of RAAS Causes aldosterone to be expressed, increasing expression of Na-K-ATPase in basolateral membrane of principal cells, and increasing K+ channels for excretion

Question 28

Name some aldosterone antagonists

Answer 28

Spironolactone Eplerenone

Question 29

How do aldosterone-antagonists work?

Answer 29

Inhibit action of aldosterone on mineralocorticoid recepors Less Na-K-ATPase and ENaC synthesis

Question 30

Half-life of spironolactone?

Answer 30

Metabolised to canrenone, which has a half-life of 18-24 hours, allowing longer-term use.

Question 31

ADRs of spironolactone?

Answer 31

Hyperkalemia Some androgenic cross-reactivity causing gynaecomastia

Question 32

Indications for spironolactone?

Answer 32

Heart failure Hypertension Liver failure Hyperaldosteronism e.g. Conn's syndrome

Question 33

How does digoxin have a diuretic effect?

Answer 33

Inhibits tubular Na-K-ATPase

Question 34

What are general ADRs of any diuretic?

Answer 34

Anaphylaxis or rash Hypovolaemia Hypotension (which can cause acute renal failure) Electrolyte disturbances Metabolic abnormalities

Question 35

What is digoxin used for?

Answer 35

AF

Question 36

What must be monitored with diuretics?

Answer 36

U&Es

Question 37

Which diuretics would you prescribe in HF? Alongside what?

Answer 37

Loop or thiazide diuretics Alongside ACEi or beta-blockers

Question 38

What diuretics are used for hypertension?

Answer 38

Thiazide diuretics or aldosterone antagonists

Question 39

What diuretics are used for liver failure?

Answer 39

Aldosterone antagonists and loop diuretics

Question 40

What are the two main issues with prescribing drugs in renal disease?

Answer 40

Drugs may reduce kidney function by direct or indirect toxicity Drugs at normal doses may accumulate to toxic levels of they are excreted via kidneys and renal function is impaired

Question 41

Name some potentially nephrotoxic drugs

Answer 41

ACE inhibitors Aminoglycosides Penicillins Cyclosporin A Metformin NSAIDs

Question 42

Why is renal function in the elderly over-estimated?

Answer 42

Creatinine is dependent on body mass Therefore start with a low dose and titrate cautiously

Question 43

What can cause diuretic resistance?

Answer 43

Incomplete treatment of primary disorder Continuation of high Na intake Patient non-compliance Poor absorption Volume depletion decreasing filtration of diuretics Volume depletion increasing aldosterone NSAIDs reducing renal bloodflow

Question 44

What are the effects of angiotensin and prostaglandins on renal blood flow?

Answer 44

Angiotensin constricts the efferent, increasing filtration pressure and GFR Prostaglandin dilates the afferent, increasing GFR

Question 45

ECG changes in hyperkalaemia?

Answer 45

No P-waves Prolonged QRS complex Tented T waves

Question 46

Treatment of hyperkalaemia?

Answer 46

Calcium gluconate Insulin/dextrose Calcium resonium Sodium bicarbonate (Salbutamol)