PubMed · 5837345
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L Hillestad. 1965-04-01. [Brinaldix--a new diuretic].. https://pubmed.ncbi.nlm.nih.gov/5837345/
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A case of erythromycin-induced acquired long QT syndrome and "torsades de pointes" ventricular tachycardia is reported. The peculiar ventricular tachyarrhythmia was evoked by orally administered erythromycin (1.5 g/die) in the presence of diuretic (clopamide)-induced hypokalaemia. The pause-dependent "torsades de pointes" was preceded by prolonged QTU interval (560 ms), "particular bigeminy" and "short-long-short" RR interval sequence. The recurrent ventricular tachycardia causing syncopal attacks was abolished by the discontinuation of erythromycin treatment, K+/Mg(2+)-supplementation and oral mexiletine therapy. It is emphasized that the macrolide antibiotic/prokinetic erythromycin, applied in therapeutic dosages, blocks the rapidly activating delayed rectifier potassium current (IKr), and as such, prolongs ventricular repolarization and may be "torsadogenic".
A first-derivative spectrophotometric method, using a 'zero-crossing' technique of measurement has been used for determining clopamide-pindolol mixture in tablets. In the first-derivative mode the zero-crossing points of clopamide and pindolol occur at 272.6 and 262.4 nm, respectively. The relative ease offered by this technique for the quantification of these drugs with closely overlapping bands was demonstrated. The linearity of the calibration curves was satisfactory (r = 0.9998) and the precision (RSD%) better than 1.89. Detection limits were 0.50 and 0.44 micrograms ml-1 for pindolol and clopamide, respectively. No spectral interferences from tablet excipients were found. Applications are given for the assay of commercial tablets and content uniformity test. The procedures proved to be suitable for rapid and reliable quality control.
From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively on the basis of the changes in 24-hour natriuresis, with respect to 24-hour natriuresis after placebo, caused by single oral doses administered to healthy adult subjects who are in habitual and steady-state external sodium balance. The potency of various formulations of loop (e.g., furosemide), of early distal tubular (e.g., the thiazides), and of potassium-retaining diuretics, as well as of several combinations of diuretics, has been evaluated in a series of studies. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are definitely nondiuretic. The majority of the other formulations of loop diuretics studied are, in general, comparatively less potent than most of the common formulations of early distal tubular diuretics studied. As a general rule, most common formulations of early distal tubular diuretics are at least not less potent than the majority of common formulations of loop diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. Loop diuretics increase mean renal sodium output strikingly within the first few (0-6) hours after dosing, but this forced excretion is followed by a rebound with respect to postplacebo mean urinary sodium flow; the rebound usually takes place between 6 and 24 hours after dosing. However, no rebound in mean urinary sodium flow occurs during the 24 hours following a single dose of a distal tubular diuretic; these substances increase urinary sodium excretion with lower maximal intensity but more protractedly than loop diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)