Influence of atenolol and nifedipine on digoxin‐induced inotropism in humans.

Abstract

1 Short term effect of digoxin on left ventricular performance was studied in six healthy volunteers before and during atenolol or nifedipine administration. Left ventricular function was evaluated by systolic time intervals and echocardiography. 2 No changes in left ventricular end diastolic or systolic dimensions occurred throughout the study, indicating unchanged ventricular pre-and afterload. Thus, changes in the systolic time intervals must be attributed to changes in cardiac contractility. Changes in the pre-ejection period index (PEPI) obtained from the systolic time intervals were used as a measure of digoxin-induced inotropism. 3 A concentration-response relationship between plasma digoxin level and changes in PEPI was revealed when digoxin was given alone. Atenolol did not influence the digoxin-induced inotropism at a given serum digoxin level. During nifedipine administration no inotropic effect of digoxin could be demonstrated. 4 Thus, it is concluded that nifedipine attenuates digoxin-induced inotropism, while atenolol seems without this effect. 5 These results are in accordance with previous experiments and reflect the different pharmacological sites of action of P-adrenoceptor antagonists and calcium channel blocking agents. 6 Plasma digoxin concentration, renal digoxin clearance and creatinine clearance did not change during atenolol or nifedipine.

Investigation of possible pharmacokinetic and pharmacodynamic interactions between epanolol and digoxin

“…As the reduction in PEPI is a measure of digoxin-induced inotropism, the lowering during treatment with epanolol indicates that this substance certainly does not interfere with 507 the positive inotropic action of digoxin. Both in patients with angina pectoris (Crawford et al 1975) and in healthy volunteers (Hansen et al 1984), digoxin alone reduced PEPI, but no further fall was seen on concomitant administration of propranolol or atenolol. In contrast, the reduction in PEPI caused by epanolol can be explained by its partial agonism.…”

Effects of Oral Prazosin on Total Plasma Digoxin Levels

“…In this respect, quinidine, verapamil, nifedipine, spironolactone, amiodarone, and diltiazem have beem reported to increase plasma digoxin levels by various mechanisms (Bussey, 1982;Bussey, 1984;Hansen et al, 1984;Schwartz et al, 1984;Fenster et ul., 1984;Waldorff et ul., 1983 ;Waldorff et al, 1978 ;Lichey et al, 1977 ;Elkayam et al, 1985 ;Oetgen et al, 1984). The low therapeutic concentration range of digoxin has emphasized the clinical importance of these interactions in terms of both enhanced efficacy and toxicity (Bussey, 1982;Bussey, 1984).…”

Positive Inotropic Drugs–digitalis

“…The inompic $Qct in man can be followed by measuring the systolic time intemls, and seved drugs have been found to inhibit digitalis-iiduced in* spironolamne, and d o & different both chemically and pharmaadogically (8,11,12).…”