RT Journal
A1 Chemtob S, Doray J, Laudignon N, Papageorgiou A, Varma DR, Aranda JV
T1 ALternating sequential dosing with furosemide and ethacrynic acid in drug tolerance in the newborn
JF American Journal of Diseases of Children
JO American Journal of Diseases of Children
YR 1989
FD July 1
VO 143
IS 7
SP 850
OP 854
DO 10.1001/archpedi.1989.02150190100032
UL http://dx.doi.org/10.1001/archpedi.1989.02150190100032
AB • Drug tolerance seems to develop rapidly after the administration of sequential doses of the same loop diuretic. We evaluated whether alternating different loop diuretics could achieve the same initial diuretic response in the newborn. In a randomized double crossover study, we examined the diuretic and saliuretic effects of alternating doses of furosemide and ethacrynic acid (1 mg/kg administered intravenously every 24 hours) in 10 newborns, who received the drugs in the following sequential order: (1) furosemide, (2) ethacrynic acid, and (3) furosemide (group 1, n = 5); and (1) ethacrynic acid (2) furosemide, and (3) ethacrynic acid (group 2, n = 5). Hourly urine specimens were collected for the determination of rates of urinary and fractional excretion of sodium, chloride, and potassium and of urinary flow, before and 6 hours after dosing. There were no differences between the groups at each dose for all parameters measured. A significant decrease in prediuretic and postdiuretic rates of urinary flow, in sodium and chloride excretion, and in the fractional excretion of these electrolytes was observed before and after dosing. The associated reduction in patients' weights suggested a depletion in plasma volume. In conclusion, consecutive alternation of furosemide and ethacrynic acid in the same newborn does not prevent the development of pharmacologic tolerance to loop diuretics, since diuresis, natriuresis, and chloriuresis decrease after successive sequential administration of these drugs.(AJDC. 1989;143:850-854)