Diuretics

Question 1

Give the 3 common clinical indications for use of loop diuretics.

Answer 1

1) For relief of breathlessness in acute pulmonary oedema (with Oxygen and Nitrates.
2) Symptomatic treatment of fluid overload in chronic heart failure.
3) Symptomatic treatment of fluid overload in other oedematous states (in renal disease or liver disease, where they may be used in conjunction with other diuretics).

Question 2

1) Give the site and mechanism of action of loop diuretics.
2) Give the 2 loop diuretic P-drugs.
3) What is another direct effect of loop diuretics?
4) Why is this action beneficial in patients with heart failure?

Answer 2

1) Ascending loop of Henle; inhibit NaKCl co-transporter.
2) Furosemide (IV and oral); Bumetanide (Oral)
3) Cause dilatation of capacitance vessels
4) Reduces preload and improves contractile function of the over stretched heart muscle.

Question 3

1) What are 2 important adverse effects of loop diuretics?
2) Inhibition of the NaKCl co-transporter causes losses of which 3 electrolytes?
3) Indirectly, the excretion of which 3 other electrolytes is increased?
4) Use of diuretics can be associated with almost any low state of what?

Answer 3

1) Dehydration and hypotension.
2) Sodium, Potassium and Chloride.
3) Magnesium, Calcium and Hydrogen.
4) Loop diuretic use can cause almost any low electrolyte state.

Question 4

Why might use of loop diuretics cause tinnitus and hearing loss?

Answer 4

Because a similar NaKCl co-transporter in the inner ear is responsible for regulating endolymph composition, and at high doses, loop diuretics can affect this too.

Question 5

1) Name 2 conditions that loop diuretics are contraindicated in.
2) Name 4 conditions that loop diuretics should be used with caution in.
3) What does diuretic use do in hepatic encephalopathy?
4) Why should loop diuretics not be used in people with gout?

Answer 5

1) Patients with severe hypovolaemia or dehydration.
2) Hepatic encephalopathy, severe hypokalaemia, severe hyponatraemia, gout.
3) Causes nypokalamia > causes or worsens coma.
4) When taken chronically, they inhibit Uris acid excretion and this can worsen gout.

Question 6

1) What types of drugs do loop diuretics have the potential to affect?
2) If loop diuretics are given to a patient taken digoxin, Why might the risk of digoxin be increased?
3) Why is it a problem that diuretics might reduce the excretion of aminoglycosides?

Answer 6

1) Drugs that are excreted by the kidney.
2) The risk of digoxin may be increased due to diuretic-associated hypokalaemia.
3) Loop diuretics can increase the ototoxicity and/ or nephrotoxicity of aminoglycosides.

Question 7

1) Why might Bumetanide be preferable to furosemide?
2) In cases of essential hypertension, why are loop diuretics usually less effective than Thiazides?
3) What combination of conditions responds best to loop diuretics?

Answer 7

1) It is 40 times more potent and has a better bioavailability.
2) Because even though they have a more powerful action, their duration of action is too short.
3) HTN with advanced chronic kidney disease/ HTN resistant to multiple drug treatment.

Question 8

1) What condition is Spironolcatone (Aldosterone antagonist) particularly effective for?
2) What drug might be a useful alternative to spironolactone for treatment of Conn’s syndrome.

Answer 8

1) HTN caused by Conn’s syndrome (Primary hyperaldosteronism).

Question 9

1) Give the common clinical indication for the use of Aldosterone antagonists.
2) Name the 2 Aldosterone antagonist P-drugs.
3) Name another Potassium sparing diuretic.

Answer 9

1) As part fo combination therapy for the treatment of hypokalaemia resulting from loop or thiazide diuretic therapy.
2) Spironolactone and Eplerenone.
3) Amiloride.

Question 10

1) Give the site and mechanism of action of Amiloride.

2) Give the site and mechanism of action of Aldosterone antagonists.

Answer 10

1) Amiloride acts in the DCT and inhibits ENaC, leading to Sodium wand water excretion and retention of Potassium.
2) Act in the DCT and competitively inhibit the aldosterone dependant NAK exchanger, leading to increased Sodium and water excretion and Potassium retention.

Question 11

1) Side effects of Amiloride are uncommon, but what type of adverse effect may occur?
2) When Amiloride is used in conjunction with other diuretics, name 4 adverse effects that may occur.

Answer 11

1) GIT disturbances.

2) Dizziness, hypotension, urinary symptoms, electrolyte disturbances.

Question 12

1) Give 2 contraindications to the use of Potassium sparing diuretics.
2) Give 2 cautions to the use of Potassium sparing diuretics.

Answer 12

1) Severe renal impairment and hyperkalaemia.
2) Hypokalaemia (do not start combinatino therapy if pt hypokalaemic) and avoid in states of hypovolaemia (as with all diuretics).

Question 13

1) What drugs should you not use in combination with Potassium sparing diuretics?
2) Renal clearance of what 2 drugs might be altered in a patient prescribed Potassium sparing diuretics?

Answer 13

1) Other potassium elevating drugs (Potassium supplements or other Potassium sparing drugs), due to risk of hyperkalaemia.
2) Digoxin and Lithium (drugs cleared renally).

Question 14

What adverse effect of spironolactone might mean that Amiloride is more acceptable?

Answer 14

Gynaecomastia.

Question 15

1) Name a directly acting Potassium sparing diuretic.

2) Name an indirectly acting Potassium sparing diuretic.

Answer 15

1) Amiloride - acts directly on ENaC to inhibit Sodium absorption.
2) Spironolactone/ Eplerenone - act indirectly by blocking aldosterone receptors.

Question 16

1) When do thiazide diuretics produce their maximum BP lowering effect?
2) Why is this an advantage?

Answer 16

1) At doses lower than those required for significant diuretic activity
2) Because most unwanted effects are dose related, and with this you can use a lower dos.

Question 17

1) State the 2 common clinical indications for the use of Thiazide diuretics.
2) State the thiazide and thiazide-like diuretic P-drugs.

Answer 17

1a) Alternative first line treatment for HTN where Calcium channel blockers are not suitable (due to oedema/ heart failure).
1b) Add on treatment for HTN in patients whose blood pressure is not adequately controlled by Ca chanel blocker + ACE inhibitor/ ARB.
2) Thiazide - Bendroflumethiazide. Thiazide like - Indapamide and Chlortalidone.

Question 18

1) State the site and mechanism of action of thiazide diuretics.
2) What is the long term anti-hypertensive effect of thiazides thought to be due to?

Answer 18

1) Act in DCT and inhibit NaCl co-transporter, preventing reabsorption of Sodium and osmotically associated water.
2) Thought to be mediated by vasodilation which is a mechanism that is not completely understood.

Question 19

1) Give 3 adverse effects of thiazide diuretics.

2) How can thiazides cause a protective CV effect?

Answer 19

1) Hyponatraemia and hypokalaemia, leading to possible cardiac arrhythmias. Impotence in men.
2) Increase plasma concentrations of glucose, LDL cholesterol and triglycerides which have a net protective effect.

Question 20

1) When should thiazide diuretics be avoided?
2) When should thiazide diuretics be used with caution?
3) Why should thiazide diuretics be used with caution in patients that suffer from gout?

Answer 20

1) In patients with hypokalaemia.
2) Patients with hyponatraemia and gout.
3) Because they reduce uric acid excretion, and this can precipitate acute attacks in patients with gout.

Question 21

1) Which class of drugs may reduce the effectiveness of thiazide diuretics?
2) What should be done if thiazide diuretics MUST be used in combination with another drug that lowers serum Potassium levels?

Answer 21

1) NSAIDs (aspirin at a low dose is no concern)

2) Intensive electrolyte monitoring.

Question 22

1) What combination of diuretic classes is very useful in clinical practice?
2) Why is this combination useful?

Answer 22

1) Combination of a thiazide and ACE inhibitor/ ARB.

2) Because together they improve BP control and maintain neutral potassium balance due to having opposing effects.