Fillers

ANY QUESTIONS

BMJ 1995; 310 doi: https://doi.org/10.1136/bmj.310.6971.30 (Published 07 January 1995) Cite this as: BMJ 1995;310:30
  1. D Craig Brater

    Are there any objective measurements of the potency of diuretics? If so, how much does adding 5 mg amiloride to 40 mg frusemide increase the potency?

    Potency of diuretics is determined in several ways. Formal assessment requires studies in which the dose or concentration of the diuretic is related to response. From the studies you can construct a curve from which the dose or concentration causing half the maximal response can be derived. Relative potency among diuretics then compares the difference in this value. As an example, 1 mg bumetanide has essentially the same potency as 40 mg frusemide. It is important to emphasise that potency determined in this fashion differs from efficacy. Efficacy is essentially the maximal response that can be elicited. Again using bumetanide and frusemide as an example, maximal response is the same for both of these loop diuretics, though the milligram amount needed to cause this response differs by a factor of 40—that is, potency. Analyses have been performed only with loop diuretics and to a lesser extent thiazides.

    The most pertinent question concerning a combination of amiloride and frusemide is not really potency but rather efficacy. How much is the response to frusemide increased if amiloride is added? There is no easy answer because it partly depends on the patient. Some patients have a poor response to a loop diuretic because of increased proximal tubular reabsorption of sodium. Activity at more distal nephron sites, where amiloride has its effect, is irrelevant. Amiloride would add nothing to the effects of frusemide in terms of sodium excretion. Conversely, if a patient is receiving a loop diuretic and considerable reabsorption of sodium is occurring at more distal sites then addition of amiloride could cause a substantial increase in sodium excretion and at the same time have potassium sparing properties. Thus the expectation of the effect of amiloride on response to frusemide will be greatly influenced by the individual patient. Incremental natriuresis would be expected if active distal reabsorption of solute was occurring. One could predict this in an individual patient by assessing urinary sodium and potassium excretion; low urinary sodium and high urinary potassium would suggest that addition of amiloride would result in an incremental increase in sodium excretion. On the other hand, low sodium and low potassium in the urine would suggest little, if any, effect of adding amiloride.—D CRAIG BRATER, professor of pharmacology and toxicology, Indianapolis

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