HIGH EFFICACY (LOOP) DIURETICS
Frusemide (furosemide, Lasix) acts on the thick portion of the ascending limb of the loop of Henle (site 2) to produce the effects described above. Because more sodium is delivered to site 4, exchange with potassium leads to urinary potassium loss and hypokalaemia. Magnesium and calcium loss are increased by frusemide to about the same extent as sodium; the effect on calcium is utilised in the emergency management of hypercalcaemia (see p. 740).
Pharmacokinetics. Frusemide is well absorbed from the gastrointestinal tract and is highly bound to plasma proteins. The tl/2 is 2h, but this rises to over 10 h in renal failure.
Uses. Frusemide is very successful for the relief of oedema. Progressively increasing the dose of frusemide increases urine production. Taken orally it acts within an hour and diuresis lasts up to 6 hours. Enormous urine volumes can result and overtreatment may lead to hypovolemia and circulatory collapse. Given i.v. it acts within 30 minutes and can relieve acute pulmonary oedema, partly by a vasodilator action which precedes the diuresis. An important feature of frusemide is its efficacy when the glomerular filtration rate is 10 ml/min or less.
The dose is 20-120 mg by mouth per day; i.m. or i.v. 20^40 mg is given initially. For use in renal failure, special high dose tablets (500 mg) are available, and a solution of 250 mg in 25 ml which should be infused i.v. at a rate not greater than 4 mg/min.
Adverse effects are uncommon, apart from excess of therapeutic effect (electrolyte disturbance and hypotension due to low plasma volume) and those mentioned in the general account for diuretics (below). They include nausea, pancreatitis and, rarely, deafness which is usually transient and associated with rapid i.v. injection in renal failure. NSAIDs, notably indomethacin, reduce frusemide-induced diuresis probably by inhibiting the formation of vasodilator prostaglandins in the kidney.
Bumetanide, piretanide and ethacrynic acid are similar to frusemide. Torasemide is also similar, but has also been demonstrated to be an effective antihypertensive agent at lower (non-natriuretic) doses (2.5-5 mg/d) than those used for oedema (5-40 mg). Ethacrynic acid is less widely used as it is more prone to cause adverse effects, especially nausea and deafness.
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