Loop Diuretics
Examples
Indications
- Pulmonary oedema usually due to left-sided heart failure/chronic heart failure
- Peripheral oedema (but not where due to venous stasis, lymphoedema or calcium channel blockers)
- Resistant hypertension
Contraindications
Contraindications
- Hypovolaemia / severe electrolyte disturbance – hypokalaemia/hyponatraemia
- Anuria
- Renal failure due to nephrotoxic/hepatotoxic drugs
Caution
- Elderly
- Renal impairment
- Hepatic impairment
- Diabetes
- Pregnancy and breast feeding
- Impaired micturition / prostatic enlargement
- Gout
Mechanism
Loop diuretics work at the thick ascending limb of the loop of Henle in the renal tubule. They act by inhibiting the active Na+/K+2Cl- co transporter, preventing the reabsorption of sodium. This results in a diuresis by increasing sodium (and therefore water to balance the osmolarity) excretion. As this segment has a high capacity for sodium reabsorption, the drugs are particularly efficacious.
At high doses, loop diuretics can induce electrolyte changes in the endolymph (found in the semi circular canals of the inner ear) resulting in deafness.
Other properties of loop diuretics are pulmonary and systemic vasodilatation, this leads to a reduction in preload and is a further mechanism in the treatment of pulmonary oedema.
Administration
Intravenous therapy may be needed in acute pulmonary oedema or resistant heart failure.
Note: furosemide is more likely to be ototoxic if given quickly, a slow infusion should be used (not exceeding 4mg/minute).
Oral therapy is usually given for chronic heart failure.
Consider when diuresis will be most convenient. If two doses are required in a day, the second should be in the early afternoon so that the patient's sleep is not disturbed.
Bioavailability of oral furosemide is very variable between patients, and can be particularly low in severe fluid overload (possibly due to gut wall oedema). In this case, IV furosemide or oral bumetanide would be advisable.
Adverse Reactions
- Loop diuretics can cause severe hypokalaemia, hypocalcaemia, hyponatraemia and hypomagnesaemia
- Dehydration - fluid is reduced in the intravascular space, this reduces the circulating volume and can cause postural hypotension
- Hyperglycaemia - may precipitate type II diabetes or cause worsening of glycaemic control in established diabetes
- Deafness, high doses will affect the electrolyte balance in the endolymph (found in the semi circular canals of the inner ear)
- Precipitation of gout
- Urea and electrolytes should be monitored whilst loop diuretics are used
Interactions
- Do not prescribe with Aminoglycosides as this may precipitate acute renal failure or deafness
- Loop diuretics can cause hypokalaemia, which increases the risk of toxicity from anti-arrhythmic agents or Digoxin if used in combination
- Loop diuretics reduce the excretion of Lithium which can lead to Lithium toxicity
- Loop diuretics and Theophylline therapy will increase the risk of hypokalaemia
Education
Explain that the patient will need regular monitoring of urea and electrolytes.
Loop diuretics have a maximum effect at approximately 30 minutes and diuretic effect continues for 6 hours. Doses can therefore be taken at times to minimise disruption to the patient's lifestyle.
Patients may keep a diary of daily body weight which provides a measure of fluid loss. They can be trained to adjust the dose according to their clinical condition. This allows for the lowest dose possible to be administered.
Pharmacokinetics
Over time patients will become resistant to loop diuretics, the mechanism for this is complex and not fully known. To overcome the resistance higher doses may be required.
