[Digoxin-quinidine interactions].
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Biomedical subjects
Publications and source records attributed to E Steiness.
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A kinetic and dynamic study of digoxin was performed in 6 healthy subjects, and repeated in the same subjects after administration of quinidine for 1 wk. Myocardial performance evaluated by systolic time intervals increased in parallel with plasma digoxin concentration, whereas left ventricular end-diastolic diameter on echocardiography and arterial blood pressure remained constant. The positive inotropic effect of digoxin was abolished during concomitant treatment with quinidine. Quinidine has been reported to increase the risk of digitoxicity, and therefore the treatment with digoxin and quinidine in combination should be reconsidered.
In order to measure the effect of a decrease in preload on systolic time intervals and left ventricular end-diastolic diameter (LVEDD) measured by echocardiography, eight healthy young subjects were given 40 mg frusemide intravenously. The pre-ejection period index (PEPI) increased and the left ventricular end-diastolic diameter decreased. A correlation between delta PEPI and delta LVEDD was shown. Using changes in systolic time intervals in the evaluation of changes in contractility it is important to correct for changes in preload. For normal subjects it is suggested that the relation between delta PEPI and delta LVEDD as a percentage of the mean values should be used for this correction. A method is suggested for estimating the changes in pre-ejection period index induced by changes in left ventricular end-diastolic diameter.
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1. In hypertension, the beta-adrenoreceptor-blocker-withdrawal syndrome comprises tachycardia, sweating, tremor and general malaise, symptoms resembling thyrotoxicosis. 2. The effect of abrupt cessation of propranolol on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was therefore investigated in five patients with uncomplicated essential hypertension, treated with propranolol in doses from 160 to 480 mg/day. 3. Four of the five patients developed one or more of the above-mentioned symptoms within 2-6 days after withdrawal of propranolol. 4. A mean relative increase in serum free T3 of 51% (range 22-74%) was found in these four patients on the day of onset of symptoms. 5. The increase in free T3 in the five patients correlated positively with total serum propranolol on the last day the drug was given (r = 0.91, 2P = 0.03). 6. As an increase in T3 was found only in patients suffering the withdrawal syndrome, and was maximal the day the symptoms appeared, despite a variation in time of onset from 2 to 6 days, it is suggested that the beta-adrenoreceptor-blocker-withdrawal syndrome, at least partially, is caused by rebound increased production of T3, induced by the well-known inhibition of the monodeiodination of T4 to T3 during beta-adrenoreceptor blockade. 7. This assumption may explain the clinical symptoms and the reported transient increased beta-adrenoreceptor sensitivity with unchanged serum concentrations of catecholamines.
The CK activity was measured in muscle tissue taken from the injected area (dorsal longissimus muscle) and the contralateral side of the injection site 72 hours after intramuscular injection into rabbits of 1 ml of different dilutions of propylene glycol or glycerol formal in distilled water or 0.9% saline. The total loss of CK activity from the injection site was calculated as the difference between the CK concentration in the normal muscle tissue and that of the injection site from the same animal. From the results the arbitrary amount of muscle tissue depleted of CK activity was further calculated and compared with the severity of the gross pathological findings. A large necrotic area at the injection site was present in all samples with more than 1 g of muscle tissue depleted of CK activity. Minor and probably acceptable pathological changes were found in samples with less than 1 g of muscle tissue depleted of CK activity. The local damaging effect of drug preparations for intramuscular use can thus be evaluated from the calculated amount of muscle tissue depleted of CK activity.
In a prospective study comprising 43 patients with atrial fibrillation after mitral valve surgery, an evaluation was made of the prognostic significance of clinical, radiological, haemodynamic and operative factors for the maintenance of sinus rhythm after DC-conversion. Atrial fibrillation with a duration of less than 12 months proved to be the only single factor of significance for sustained sinus rhythm after 12 months and it is suggested as a simple clinical criterion for selection of patients for DC-conversion after mitral valve operation.
Inulin and digoxin clearances were simultaneously measured in 19 normokalemic and 4 hypokalemic patients. In normokalemia the renal digoxin clearance exceeded the inulin clearance, indicating both glomerular filtration and active tubular secretion of digoxin. The tubular secretion increased with increasing plasma digoxin concentration. In hypokalemia, however, the tubular secretion of digoxin was significantly reduced but increased after the plasma potassium level was raised to normal.
The effect of abrupt withdrawal of propranolol on serum concentrations of triiodothyronine (T3) and thyroxine (T4) was investigated in 5 patients with uncomplicated essential hypertension. The patients had been treated from 2 to 18 mo before the study was begun. Doses varied from 160 to 480 mg propranolol daily. Four of the patients studied developed tachycardia, sweating, or tremor within 2 to 6 days after withdrawal of propranolol. In 1 patient reversible ischemic ECG changes were recorded. The serum concentrations of free T3 increased in the 4 patients suffering from withdrawal symptoms. The mean increase on the day the symptoms started was 51% (range, 22 to 74, 2 p = 0.01). This increase in serum-free T3 correlated positively with the serum propranolol concentration on the last day propranolol was given (r = 0.91, 2 p = 0.03). In the one patient, who did not develop withdrawal symptoms, the serum concentration of propranolol was very low, and the free T3 level remained unchanged. No significant changes in serum concentrations of free T4 or total thyroid hormones were found in any of the patients. We suggest that the propranolol withdrawal symptoms are, at least partially, caused by an increase in the thyroid hormone, T3.
Plasma clearance, volumes of distribution, and renal and extrarenal clearances of digoxin were calculated from plasma digoxin concentrations and urinary excretion of digoxin after intravenous injection of digoxin in 8 subjects. The investigation was repeated in the same subjects during long-term treatment with spironolactone. Increased plasma concentration of digoxin was detected during spironolactone treatment. Calculated plasma and renal clearances of digoxin and the volumes of distribution decreased statistically significant. Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used. It is suggested that unless spironolactone decreases the myocardial sensitivity for digoxin, the loading dose as well as the maintenance dose of digoxin should be reduced during treatment with spironolactone.
Thirteen aged persons receiving digoxin until the time of death were examined by autopsy, and digoxin concentrations were determined in samples from various tissues (the choroid plexus, grey and white brain matter, left and right ventricular and left and atrial myocardium, diaphragm, and musculus psoas major). These concentrations were related to the digoxin dose and duration of treatment. No significant difference was found between the concentration of digoxin in the choroid plexus and left ventricular myocardium, whereas there were significantly lower concentrations in the right ventricular myocardium and still lower concentrations in the other tissues analyzed. Independent of the digoxin dose, the digoxin concentrations in the choroid plexus tended to be lower in persons treated for a short time before death than in those treated for longer periods of time. Similar differences were not observed in the other tissues, suggesting a slower rate of digoxin uptake in the chroid plexus compared with the myocardium and other tissues. The implications of these findings for the effects of digoxin treatment on the production of cerebrospinal fluid are discussed.
The changes in plasma renin activity (PRA) during short-term salt depletion (and peroral furosemide on the first day) and after bolus injection of propranolol were compared to the change during long-term treatment with diuretic and with propranolol in 19 patients with benign primary hypertension. A highly significant correlation was found between PRA on short-term and long-term salt depletion (r=0.02). A highly significant correlation was likewise found between initial PRA and decrement of PRA after bolus injection of or long-term treatment with propranolol. Only a weak inverse correlation was found between PRA reached during short-term salt depletion or long-term diuretic treatment and the fall in diastolic BP during long-term treatment (r=0.60). No significant correlation was found between decrease in PRA on propranolol (bolus/long-term) and diastolic BP reduction. It is concluded that the short-term PRA response to salt depletion and propranolol in the individual patient gives a good prediction of the PRA level on long-term diuretic or propranolol treatment, but is of no value in predicting the BP reduction during treatment.
1 Twenty-nine dogs were given digoxin (0.25 mg) by mouth twice daily for eight days. Some of them (group 1) also received diuretics and others (group 2) a mineralocorticoid. The dogs were then given an intravenous bolus injection of digoxin and plasma and cardiac muscle were analysed for digoxin and potassium. 2 In the digitalized dogs, myocardial potassium concentration decreased following the intravenous injection of either 0.05 or 0.15 mg/kg digoxin; in contrast, in those dogs given diuretics or mineralocorticoid the potassium concentration increased. 3 Ventricular arrhythmias occurred after digoxin injection (0.05 mg/kg) in the hypokalemic dogs, in those given a mineralocortocoid and in those dogs which received a toxic digoxin dose (0.15 mg/kg). No arrhythmias where seen in the control (digitalized) group. 4 Myocardial digoxin concentrations were similar in the control digitalized group and in the mineralocorticoid-treated dogs after the intravenous administration of the lower digoxin dose (0.05 mg/kg). The myocardial digoxin concentration was significantly higher in the hypokalemic group and in the group receiving the higher digoxin dose (0.15 mg/kg). 5 There was no obvious relationship between the occurrence of arrhythmias and the myocardial concentration of digoxin or potassium.