Studies on debrisoquine sulphate.

Abstract

Chloramphenicol and Renal Function-Lindberg et al. MEDIIMiRNAL caused by bacterial strains whose patterns of resistance exclude the usual primary agents-sulphanilamide, nitrofurantoin, and penicillins. SummaryThe excretion of biologically active chloramphenicol in urine diminishes linearly with decreasing renal function. When the renal function is reduced to an endogenous creatine clearance under 20 ml./min., less than 1% of the dose administered is excreted as the active compound, compared with 5-10% for normal renal function. The maximum excretion of chloramphenicol found at this degree of renal insufficiency was 10-20 fug./ml. of urine, compared with 150-200 ttg./ml. for normal renal function.The low concentrations of urine might explain the poor correlation between chloramphenicol sensitivity tests in vitro and the results when treating infections of the urinary tract in patients with renal insufficiency. In elderly patients with a physiologically decreased renal filtration the urinary concentrations of chloramphenicol might be too low, increasing the risk for development of drug-resistant micro-organisms.The level of biologically active chloramphenicol in blood was only slightly influenced by the renal function, while metabolites of the drug accumulated in patients with decreased renal function. REFERENCES Barber, M., and Garrod, L. P. (1963 Control of the blood-pressure in hypertensive patients is now easier with drugs in current use. In the majority of patients blood-pressure can be reduced considerably, and usually, but not always, maintained at the desired level without undue sideeffects or intermittent hypotension. Consequently, with adequate drugs already available it is becoming more difficult to assess the relative merits of new preparations.It takes at least 12 months to form a preliminary assessment of a promising new drug, and the first patients have usually been under treatment for two to three years before a confident opinion can be given on an adequate number of cases, particularly as regards tolerance.In this country ganglion-blocking agents have been largely superseded by preparations which have no effect on the parasympathetic nervous system. At the present time most patients with severe hypertensive disease are probably being treated with the sympathetic-blocking drugs guanethidine or methyldopa, but clinical trials on new preparations are going on in many hospitals.Patients vary in their preferences for different drugs largely owing to the varying side-effects.Rather than carry out comparative trials or double-blind trials with different preparations in the same group, it is now sufficient to try different preparations only in those who cannot tolerate the drug with which most experience has been gained. (Lowther and Turner, 1963).Methyldopa proved to be equally effective as regards reduction of blood-pressure. On the whole, side-effects were fewer and less unpleasant, but some patients were completely intolerant of side-effects ; others felt generally unwell, and most experienced unplea...

The metabolism of [14C]‐debrisoquine in man.

“…Debrisoquine was first introduced into the U.K. as an orally active antihypertensive agent in 1966 (see Athanassiadis, Cranston, Juel-Jensen & Oliver, 1966;Kitchin & Turner, 1966;Editorial, 1966). Chemically, debrisoquine is described as 3,4-dihydro-2-(1H)-isoquinoline-carboxamidine and is related structurally and pharmacologically to other guanidine based antihypertensives such as bethanidine and guanethidine.…”

Drug resistance, inappropriate dosing and non‐compliance in hypertensive patients.

“…Only four patients were resistant to debrisoquine and this could be overcome by using very large doses. The reasons for their resistance are unclear but fluid retention and tolerance (Kitchen & Turner, 1966;Jackson, 1972) are possibilities. Retrospective analyses (Silas, 1978) lend no support to this explanation and we agree with the view (Jackson, 1972;Turner, White & Benton, 1976) that tolerance is not a cause of resistance to debrisoquine.…”

The Scientific Basis for the Use of Drugs in Cardiovascular Disease

“…(d) Other sympathetic blocking drugs: More recently introduced sympathetic blocking drugs, debrisoquine (Pocelinko & Abrams 1964, Kitchin & Turner 1966) and guanoclor (Sinniah & Gatenby 1965), also have the disadvantages inherent in this mode of action. Cardiovascular effects of sympathetic nieurone blockade: The various physiological events that stress the sympathetic and therefore potentiate the hypotensive effect of sympathetic blocking drugs, whether acting at ganglia or sympathetic nerve endings, are included in Table 1.…”