[Interactions of quinidine and digoxin].
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Biomedical subjects
Publications and source records attributed to B Grabensee.
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After full digitalisation, 11 healthy subjects received 0.375 mg digoxin daily as maintenance dose. Under steady-state conditions and determination of serum concentration and renal clearance of digoxin, they were then given 500 or 1000 mg quinidine daily in addition to the digoxin. While serum concentration of digoxin rose significantly from 0.75 +/- 0.2 ng/ml after one week on 500 mg quinidine, and to 1.8 +/- 0.6 ng/ml after 1000 mg of quinidine, renal digoxin clearance fell from 186.2 +/- 67.4 to 125.4 +/- 61.8 ml/min after 500 mg of quinidine. Raising quinidine dosage to 1000 mg daily caused no further digoxin clearance reduction. During the total experimental period endogenous creatinine clearance remained unchanged. The results indicate that the rise in serum digoxin concentration on simultaneous quinidine administration is largely due to reduction in renal digoxin clearance. A clinical observation confirms the considerable practical importance of this interaction.
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Digitalis therapy is frequently accompanied by adverse drug reactions. Severe digitalis intoxications are still a problem. Therapeutical methods, which could be used in the case of a life threatening digoxin intoxication, are known, but not yet generally available. Hemodialysis has only a minor effect on digoxin excretion. This study was planned to test the hypothesis that hemoperfusion across dextran-cocoated charcoal or the resin Amberlite XAD 4 could be more effective in the therapy of digoxin intoxications. The ability of hemoperfusion to eliminate digoxin was tested in a patient who had to undergo treatment beacuse of a severe bromcarbamide intoxication. Additionally we compared the effect of several modifications on this method in 12 dogs, which had received 0.05 mg/kg body weight per day for three days prior to the experiment. Although hemoperfusion across Amberlite XAD 4 may eliminate as much digoxin as normal human kidneys during the few hours of treatment, the amount of digoxin removed after all is only a small percentage of the total body pool. Thus compared to the risks of hemoperfusion as an invasive treatment its effect is small. According to our results, hemoperfusion cannot be recommended as a standard therapy of severe digoxin intoxications.
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EEGs were recorded and initial CSF and blood lactate measurements (135) made in 104 patients who were in coma of differing severity from a variety of medical conditions. There were two patterns: in one, the CSF lactate alone was due to cerebral tissue hypoxia; and in the other factors, such as cerebral haemorrhage, meningitis or lactacidosis were predominantly present. In those with cerebral hypoxia there was a connection between the severity of the disease picture and the level of CSF lactate. In extreme cases with dissociated cerebral death, there was a mean CSF lactate concentration of 11.78 +/- 1.66 mmol/1. The prognosis of coma with concentrations above 9 mmol/l is, therefore, poor if not hopeless. To some extent one may draw prognostic conclusions from lower concentrations but this is not possible in individual cases. There was no definite correlation between the severity of EEG changes and the level of CSF lactate in coma, although there was some relationship to the degree of cerebral hypoxia. In case of meningitis, CSF lactate allowed differentiation between bacterial and viral cause, the average concentration in the former being four times normal.
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Renal transplantation was performed 3 to 64 months after the onset of dialysis in 6 patients with histologically ascertained malignant nephrosclersosis and malignant hypertension, as well as terminal renal failure. Three patients were nephrectomized on both sides before and one after the transplantation. 24 to 105 months after the transplantation all patients were normotensive. Only one patient required low-dosage antihypertensive medication. There was evidence for marked improvement of cardiovascular complications, and no evidence for recurrence of malignant nephrosclerosis in the transplanted kidney.
Long-term dialysis treatment of diabetics with terminal renal failure is beset with severe complications. In 19 unselected diabetics in terminal renal failure (13 juvenile diabetics and 6 maturity-onset diabetics) the clinical course during long-term dialysis was observed. A total of 1377 dialyses during 167 months of treatment were performed. Diabetic angiopathy, hypertension, and hyperhydration were the most prominent complications. The interval between the onset of diabetes and the beginning of dialysis treatment was 21,5 years in the juvenile diabetics and 5,2 years in maturity-onset diabetes. The survival time during dialysis was on average 13,2 months for the juvenile diabetics and 0,6 months for maturity-onset diabetics. The patients died chiefly from cardiovascular complications.
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