Session 4 - Diuretics

Question 1

What are the regulatory functions of the kidneys?

Answer 1

Fluid balance
Acid-base balance
Electrolyte balance

Question 2

What are the excretory functions of the kidneys?

Answer 2

Waste product removal
Drug elimination
Through either glomerular filtration of tubular secretion

Question 3

What are the endocrine functions of the kidneys?

Answer 3

Produce the following hormones:
Renin
Erythropoietin 
Prostaglandins 
1-alpha calcidol

Question 4

What are the metabolic functions of the kidneys?

Answer 4

Metabolise:
Vitamins D
Polypeptides (e.g. insulin)
Drugs (e.g. morphine, paracetamol)

Question 5

What is the difference between diuresis and natriuresis?

Answer 5

Diuresis - loss of water

Natriuresis - loss of sodium

Question 6

Give examples of classes of drugs that act on the renal tubules.

Answer 6

Carbonic anhydrase inhibitors 
Osmotic diuretics
Loop diuretics
Thiazides 
Potassium sparing diuretics
Aldosterone antagonists
ADH antagonists

Question 7

What is the effect of aldosterone on the nephron?

Answer 7

Aldosterone increases the expression of ENaC and Na/K/ATPase in principle cells of the collecting duct. This allows more sodium uptake from the collecting duct and therefore more water uptake.

Question 8

Give an example of an aldosterone antagonists.

Answer 8

Spironolactone

Question 9

How do loop diuretics act on the nephron?

Answer 9

Loop diuretics inhibit the Na+/K+/2Cl- symporter in the thick ascending limb of the loop of Henle. Less sodium is reabsorbed so therefore less water is reabsorbed.

Question 10

Gives two examples of loop diuretics.

Answer 10

Furosemide

Bumetanide

Question 11

How do thiazides act on the nephron?

Answer 11

Thiazides inhibit the Na+/Cl- symporter in the distal tubule.

Question 12

Give two examples of thiazides.

Answer 12

Bendroflumethiazide

Metolazone

Question 13

What are the two types of potassium sparing diuretics?

Answer 13

Inhibitors of Epithelial Na Channels (ENaC) - Amiloride, Triamterene
Aldosterone antagonists - Spironolactone, Eplerenone

Both act on the late distal tubule and collecting duct

Question 14

Give an example of a carbonic anhydride inhibitor. Where in the nephrons does it act?

Answer 14

Acetazolamide

Acts in the proximal tubule.

Question 15

Give an example of an osmotic diuretic.

Answer 15

Mannitol

Acts in the proximal tubule and other sites of water absorption

Question 16

Give two examples of other substances which have diuretic action.

Answer 16

Alcohol - inhibits ADH release

Caffeine - increases GFR and decreases tubular Na+ reabsorption

Question 17

Give two examples of ADH antagonists.

Answer 17

Lithium - diuretic but not natriuretic. Inhibits action of ADH

Tolvaptan - diuretic but not natriuretic. Inhibits action of ADH.

Question 18

What is Tolvaptan used to treat?

Answer 18

Hyponatraemia

Prevents cyst enlargement in Adult Polycystic Kidney Disease (APCKD)

Question 19

What are the generic adverse drug reactions caused by diuretics?

Answer 19

Anaphylaxis/photosensitivity rash
Hypovolaemia and hypotension (activates RAS - can lead to acute kidney injury)
Electrolyte disturbances (Na+, K+, Mg2+, Ca2+)
Metabolic abnormalities (depends on individual drug)

Question 20

What common adverse drug reactions are specific to thiazides?

Answer 20

Gout 
Hyperglycaemia 
Erectile dysfunction 
Increased LDL and triglycerides 
Hypercalcaemia

Question 21

What common adverse drug reactions are specific to spironolactone?

Answer 21

Hyperkalaemia
Impotence
Painful gynaecomastia

Question 22

What common adverse drug reactions are specific to furosemide?

Answer 22

Ototoxicity
Alkalosis
Increased LDL and triglycerides
Gout

Question 23

What common adverse drug reaction is specific to bumetanide?

Answer 23

Myalgia

Question 24

Drug interactions between ACE inhibitors and K+ sparing diuretics could lead to what problems?

Answer 24

Increased hyperkalaemia —> cardiac problems

Question 25

Drug interactions between aminoglycosides and loop diuretics leads to what problems?

Answer 25

Ototoxicity | Nephrotoxicity

Question 26

Drug interactions between digoxin and thiazides or loop diuretics can cause what problems?

Answer 26

Hypokalaemia —> increases digoxin binding and toxicity

Question 27

Drug interactions between beta blockers and thiazides diuretics can lead to what problems?

Answer 27

Hyperglycaemia, hyperlipidaemia, hyperuricaemia

Question 28

Drug interactions between steroids and thiazide or loop diuretics can lead to what problems?

Answer 28

Increased risk of hypokalaemia

Question 29

Drug interactions between lithium and thiazide or loop diuretics can lead to what problems?

Answer 29

``` Lithium toxicity (thiazides) Reduced lithium levels (loop diuretics) ```

Question 30

Drug interactions between carbamazepine and thiazides can lead to what problem?

Answer 30

Increased risk of hyponatraemia.

Question 31

What drugs are used to treat hypertension?

Answer 31

First line treatment: ACE inhibitors/Angiotensin II antagonists Beta-blockers If not responding to first line treatment, add diuretic: Thiazide (vasodilation as well as diuresis) Spironolactone Loop diuretics (best for hypertension in renal failure, less effective when kidney function is normal)

Question 32

What drugs are used to treat heart failure?

Answer 32

Loop diuretics Spironolactone (for its non-diuretic effects - remodelling of the heart) ACE inhibitors/Angiotensin II antagonists Beta-blockers

Question 33

What diuretics are used to treat decompensated liver disease?

Answer 33

Spironolactone | Loop diuretics

Question 34

What diuretics are used to treat nephrotic syndrome?

Answer 34

Loop diuretic (often big doses are needed) +/- thiazides +/- potassium-sparing diuretic / potassium supplements

Question 35

What diuretics are used to treat chronic kidney disease?

Answer 35

Loop diuretic (+/- thiazide) Generally avoid K+ sparing diuretics

Question 36

What dietary conditions must a patient on diuretics follow?

Answer 36

They must have a reduced salt diet. Too much salt intake negates the effects of the diuretic.

Question 37

Why is furosemide given IV if gut oedema is suspected?

Answer 37

Patients with gut oedema do not absorb well from the gut so less furosemide would be taken up if it was given orally.

Question 38

What is a carbonic anhydrase inhibitor used to treat?

Answer 38

Glaucoma | Altitude sickness

Question 39

What are osmotic diuretics used to treat?

Answer 39

High intracerebral pressure

Question 40

What are ADH antagonists used to treat?

Answer 40

Hyponatraemia

Question 41

What are aldosterone antagonists used to treat?

Answer 41

Heart failure Ascites Hypertension Hyperadrenalism

Question 42

Give examples of drugs which are potentially nephrotoxic.

Answer 42

``` Aminoglycosides e.g. gentamicin Vancomycin (intravenous only) Aciclovir NSAIDs + many more ```

Question 43

Give examples of drugs which cause problems with renal function.

Answer 43

ACE-inhibitors Diuretics NSAIDs Metformin

Question 44

How do ACE-inhibitors and NSAIDs affect renal perfusion?

Answer 44

They override the intrinsic autoregulatory mechanisms of the nephron. E.g. NSAIDs stop prostaglandins from vasodilating the afferent arteriole and ACE-inhibitors stop angiotensin II from vasoconstricting the efferent arteriole.

Question 45

What guidelines should be followed when prescribing to patients with chronic kidney disease?

Answer 45

Avoid nephrotoxins If gentamicin/vancomycin required, dose very carefully in consultation with pharmacist. Check with pharmacist whether any existing drugs need dose altering. The side effects of some common drugs are increased with renal disease due to the accumulation of metabolites (e.g. morphine, nitrofuratoin, statins)

Question 46

What are the possible causes of hyperkalaemia?

Answer 46

Excess intake (virtually never the only cause) Movement of potassium out of cells: - acidosis - hypertonicity - tissue (especially muscle) damage Reduced urine loss: - reduced GFR - reduced distal delivery of Na+ (oliguric AKD, obstruction) - reduced secretion in collecting duct Drugs: - RAAS inhibitors (ACE-inhibitors, spironolactone), NSAIDs, ENaC blockers (trimethoprim, amiloride)

Question 47

Hyperkalaemia can result in what?

Answer 47

Life threatening cardiac arrhythmias

Question 48

What progressive ECG changes are seen in hyperkalaemia?

Answer 48

Initial - tall T waves Progressive - small or absent P waves - increased P-R interval - wide QRS complex Severe - sine waves - asystole

Question 49

What is the management for hyperkalaemia?

Answer 49

Identify cause. Any ECG change calls for immediate action. Treatment: 1. Protect the heart - calcium gluconate 2. Lower serum K+ - insulin / dextrose 3. Remove K+ from the body - calcium resonium (binds potassium in the gut, stops it being absorbed)