Frusemide

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Frusemide (or furosemide in the UK and the USA) is a loop diuretic that is used commonly in heart failure, and also as a second line diuretic in cirrhosis causing ascites. An unusual route of administration that is sometimes used in palliative medicine is via a continuous subcutaneous infusion.

Indications

Oedema associated with

  • Heart failure
  • Cirrhosis (second line after spironolactone)
  • Renal failure and nephrotic syndrome

Often used also in patients with peripheral oedema in advanced cancer, often without good effect.

Pharmacokinetics

Onset of action and half life

Frusemide is well absorbed orally and has a rapid onset of action with peak onset within 1 hour orally, 30 minutes subcutaneously and 5 minutes intravenously.

The half life is 1-2 hours and the average duration of action is 6 hours when taken orally and 2 hours when given intravenously.

Bioavailability

It has an oral bioavailability somewhere around 50%, although absorption can be reduced when there is significant intestinal mucosal oedema.

Pharmacodynamics

Mechanism of action

Frusemide acts from within the loop of Henle in the renal tubules to inhibit reabsorption of sodium and thus water, causing a very effective diuresis.

Adverse effects

The rapid diuresis that frusemide causes can lead to problems in frail patients who lack energy to get up to go to the toilet.

Biochemical side effects are common including

  • Hyponatraemia
  • Hypokalaemia
  • Hypomagnesaemia.

Blood pressure side effects are also common including:

  • Dizziness on standing and syncope
  • Hypotension

Other side effects include gout and, in IV injections, vertigo, tinnitus and deafness.

Dosing and routes of administration

A usual starting dose for oedema is 40mg each morning. The dose can be titrated up and given twice daily (morning and midday) if desired with a typical upper dose of 80mg twice daily. However, as frusemide works from within the renal tubules, to have an effect it must be filtered, and therefore higher doses are often needed in patients with renal failure (and a low GFR). Sometimes doses in the order of 250-500mg daily are required in patients with end-stage renal failure.

Intravenous frusemide

Frusemide can be given intravenously as a bolus or via a continuous infusion, the latter usually being reserved for treatment within coronary care units.

Subcutaneous infusion

Frusemide can be given via continuous subcutaneous infusion for severe oedema. This allows for treatment within both the inpatient and home setting.

Stat or bolus doses are not appropriate due to the the high volume required for injection (e.g. frusemide comes as 10mg per ml). A typical subcutaneous infusion dose might look something like this:

Frusemide 120mg via CSCI over 24 hours

Frusemide is incompatible with most drugs and therefore as a rule should be infused in its own syringe driver mixed with saline.

Nebulized frusemide

There are case reports of nebulized frusemide being helpful for dyspnoea and for bronchorrhoea secondary to alveolar cell cancer, however there are no controlled trials that have shown any benefit.

Comparative Dosing

1mg of bumetanide is equial to approximately 40mg of frusemide.

Authors

Graham Llewellyn Grove