Loop diuretics e.g. furosemide, bumetanide

Introduction

These basically cause you to excrete more fluid. They are very effective, and prevent the reabsoprtion of about 25% of filtered sodium.
These 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 inhibits 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.
  • This also has a secondary effect – these drugs 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).
These drugs 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 useful in left ventricular failure.
They also cause vasodilation, but because of their short duration of action they are rarely used to treat hypertension.
The drugs are absorbed from the gut but there is wide individual variation. With normal kidney function, their half-life is short. They are excreted by the kidney.

Unwanted effects

  • 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 these drugs, resulting in water retention, but you still lose the sodium, and thus the blood becomes ‘diluted’ with too little sodium.
  • Can cause hypokalaemia.
  • 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.
  • Tolerance may sometimes occur to due hypertrophy of the tubular epithelium at the site of action of the drug.

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