Loop diuretics are the strongest type of diuretic – they cause an increase in the excretion of sodium and water from the kidney. They are very effective, and prevent the reabsoprtion of about 25% of filtered sodium.
Loop diuretics find their way into the tubule in the proximal region, via anion exchange (probably mainly for sodium). They bind to the sodium / potassium / chloride channel, in the thick ascending loop of Henle and inhibit chloride reabsoprtion. Thus this prevents this channel from functioning properly, and sodium is not reabsorbed. This prevents the formation of a very concentrated fluid in this region – as less sodium is reabsorbed, so less water is reabsorbed via osmosis.
- There is also a secondary effect – loop diuretics cause the concentration of sodium and chloride to be higher in the DCT than they are normally. This means when the tubular fluid passes the juxtamedually apparatus, the apparatus thinks that BP is high, and thus renin is not secreted. This means that there is NOT much vasoconstriction of the efferent arteriole, and there is vasoconstriction of the afferent arteriole. (this is a bit counter intuitive for the drug, but doesn’t seem to have too much effect).
Loop diuretics have a short half-life, and when they are stopped, there is rebound sodium retention, and thus short-term they aren’t much use.
They remain effective even in advanced renal failure, however you may need a pretty large dose!
When given intravenously, these drugs have a venodilating effect that cause pooling of blood and can be particularly useful in left ventricular failure.
They also cause vasodilation, but because of their short duration of action they are rarely used to treat hypertension.
They are absorbed from the gut but there is wide individual variation (10-90% depending on the individual). With normal kidney function, their half-life is short. They are excreted by the kidney.
The kidney is complicated, if you haven’t already, you might want to read about renal physiology to help understand how diuretics work.
Loop diuretics e.g. furosemide (aka frusemide), bumetanide
- Can cause excessive salt and water loss, and thus lead to renal impairment and hypotension.
- Can cause hyponatremia as a result of excessive sodium loss. This effect is exaggerated because the body will produce ADH in response to loop diuretics, resulting in water retention, despite the sodium loss, and thus the blood becomes ‘diluted’ with too little sodium.
- Can cause hypokalaemia
- Hypomagnesia – which may lead to arrhythmia
- Can cause ototoxicity resulting in damage to the cochlear fluid. This is rare, and tends to occur in renal failure, where the drug is not excreted quickly enough.
- Can cause incontinence due to rapid loss of large amounts of fluid. In some older men with BPH, this can cause retention.
- Hypomagnesaemia and hypocalcaemia
- Can precipitate gout – due to induction of hyperuraemia – particularly in patients with a past history of gout. Urate levels should be monitored in these patients and allopurinol may need to be titrated up accordingly. Gout is unusual with loop diuretics and much more common with thiazide diuretics.
- Tolerance may sometimes occur to due hypertrophy of the tubular epithelium at the site of action of the drug
Indications and Uses
- Heart failure
- Liver failure / cirrhosis
- Renal impairment
- A typical dose of frusemide is 40mg daily
- Up to 120mg daily (often in divided doses) is not unusual
- IV dose is the same as the oral dose (although IV is probably more effective, due to additional venodilation effects, and variable oral absorption)
- 40mg frusemide is equivalent to 1mg budesonide
- Australian Medicines Handbook – Frusemide
- Waller, DG., Renwick AG., Hillier K. (2005). Medical Pharmacology and Therapeutics. 2nd ed. Elsevier Saunders