Ascites

Question 1

Aldosterone antagonist (Spironolactone/eplerenone)

Common indications

Answer 1

• Ascites + oedema due to liver cirrhosis- spironolactone is the first-line diuretic
• Chronic heart failure- of at least moderate severity or arising within 1 month of myocardial infarction, usually as an addition to a BB and an ACEI/ARB
• Primary hyperaldosteronism-For patients awaiting surgery or for whom surgery is not an option

Question 2

Aldosterone antagonist (Spironolactone/eplerenone)

MOA

Answer 2

• Aldosterone is a mineralocorticoid that is produced in the adrenal cortex
• It acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium channels (ENaC)
• This increases the reabsorption of sodium and water (which elevates BP) with the by-product of increased potassium excretion
• Aldosterone antagonists inhibit the effect of aldosterone by competitively binding to the aldosterone receptor
• This increases sodium and water excretion and potassium retention
• Their effect is greatest in primary hyperaldosteronism or when aldosterone is increased e.g. Liver cirrhosis

Question 3

Aldosterone antagonist (Spironolactone/eplerenone)

Adverse effect

Answer 3

• Hyperkalaemia- leading to muscle weakness, arrhythmias and cardiac arrest
• Spironolactone causes gynecomastia, which can have a significant impact on patient adherence
• Aldosterone antagonists can cause liver impairment and jaundice and a cause of stevens-johnson syndrome (T-cell mediated hypersensitivity reaction) that causes a bullous skin eruption

Question 4

Aldosterone antagonist (Spironolactone/eplerenone)

Warnings

Answer 4

• Aldosterone antagonists are contraindicated in patients
  
  • severe renal impairment
  • Hyperkalaemia
  • Addison’s disease
• Can cross placenta and breast milk therefore not in pregnancy or lactating women

Question 5

Aldosterone antagonist (Spironolactone/eplerenone)

Interactions

Answer 5

• Combination with
  
  • Potassium-elevating drugs- ACEI/ARB- increase risk of hyperkalaemia
  • Should not be combined with potassium supplements

Question 6

Aldosterone antagonist (Spironolactone/eplerenone)

Commiunication

Answer 6

• For growth and tenderness of tissue under the nipples and impotence
• Monitor renal function and U&E (K) due to risk of renal impairment and hyperkalaemia

Question 7

Loop diuretics (Furosemide)

Common indications

Answer 7

• Acute pulmonary oedema
• Chronic HF
• Other oedematous states- e.g. due to renal disease or liver failure, where they may be given combination with other diuretics

Question 8

Loop diuretics (Furosemide)

MOA

Answer 8

• As their name suggests, loop diuretics act principally on the ascending limb of the loop of Henle, where they inhibit the Na+/K+/2Cl−co- transporter
• This protein is responsible for transporting sodium, potassium and chloride ions from the tubular lumen into the epithelial cell
• Water then follows by osmosis. Inhibiting this process has a potent diuretic effect. Also, loop diuretics have a direct effect on blood vessels, causing dilatation of capacitance veins
• . In acute heart failure, this reduces preload and improves contractile function of the ‘overstretched’ heart muscle. Indeed, this is probably the main benefit of loop diuretics in acute heart failure, as illustrated by the fact that the clinical response is usually evident before a diuresis is established

Question 9

Loop diuretics (furosemide)

Adverse effects

Answer 9

• Dehydration and hypotension
• Inhibiting the Na/K.2Cl co-transporter increases urinary losses of sodium, potassium and chloride ions
• Indirectly, this also increases excretion of Mg, Ca and H ions
• You can therefore associate loop diuretics with almost any low electrolyte state
• A similar Na/K/2Cl co-transporter is responsible for regulating endolymph composition in the inner ear
• At high doses, loop diuretics can affect this too, leading to hearing loss and tinnitus

Question 10

Loop diuretic (furosemide)

Warnings

Answer 10

• Contraindicated in patient: Hypovolaemia or dehydration
• Use with caution in hepatic encephalopathy (Where hypokalaemia can cause or worsen coma)
• Hypokalaemia and or hyponatraemia
• Taken chronically they can inhibit uric acid excretion and this can worsen gout

Question 11

Loop diuretic (Furosemide)

Interactions

Answer 11

• Drugs that are excreted by the kidneys
• Li levels are increased due to reduced excretion
• Digoxin toxicity may also be increased, due to the effects of diuretic-associated hypokalaemia
• Loop diuretics can increase the ototoxicity and nephrotoxicity of aminoglycosides

Question 12

Loop diuretics

Warnings

Answer 12

• We are trying to increase urine flow, which will hopefully improve this
• The medicine will inevitably cause them to need to pass water more often. Provided they do not take doses late in the day it should not affect them at night

Question 13

Loop diuretics

Monitoring

Answer 13

• For efficacy in the acute management of pulmonary oedema, evidence for a good response will include improvements in the patient’s symptoms, tachycardia, HTN and oxygen requirement
• Increased UO typically occurs later and indicates the onset of the diuretic effect
• In long-term therapy, you should monitor your patient’s symptoms, signs and BW
• Periodic U&E and renal function is also advisable, particularly in the first few weeks of therapy