Nonselective Beta-adrenergic Blocker Research Articles

The effects of a cardioselective (metoprolol) and a nonselective (propranolol) beta-adrenergic blocker on the response to dynamic exercise in normal men.

We compared the effects of a cardioselective beta-adrenergic blocking drug, metoprolol, with a nonselective beta-adrenergic blocker, propranolol, on the response of 10 normal men to dynamic treadmill exercise. The volunteers underwent a standard graded exercise test to exhaustion while receiving placebo; propranolol, 40 mg every 6 hours; propranolol, 80 mg every 6 hours; metoprolol, 50 mg every 6 hours; or metoprolol, 100 mg every 6 hours. The drugs were given in a double-blind fashion for 48 hours before exercise. Five days were allowed between successive drug administrations and the order of drug administration was randomized. Heart rate, arterial pressure, oxygen consumption, minute ventilation and CO2 production were monitored. Plasma drug concentrations were measured at the time of exercise. Judged by plasma levels, propranolol was about three times more potent than metoprolol in attenuating heart rate. Both drugs produced a wide variation in plasma levels after a given oral dose, and both drugs attenuated the systolic blood pressure response to exercise. Neither drug affected diastolic blood pressure or maximum oxygen consumption, maximum minute ventilation or the anaerobic threshold. We conclude that there is no evidence that the cardioselective drug metoprolol is superior to propranolol in terms of the ability to perform or respond to short-term maximal exercise. In addition, the fact that maximal oxygen consumption and the anaerobic threshold were unaffected implies that fatigue during exercise while on beta-adrenergic blocking drugs is not due to an effect of these drugs in limiting blood flow to the exercising extremities.

Pharmacodynamic studies in man of the beta-adrenoceptor antagonist DL 071 IT.

DL 071 IT, a new potent non-selective beta-adrenergic blocking drug with intrinsic sympathomimetic activity and weak membrane stabilizing activity, was evaluated alone and in comparison with oxprenolol, in six volunteers, at rest and during an exercise test. Heart rate and systolic pressure were monitored for up to 7 h after oral administration of the drugs. Exercise heart rate and systolic pressure were significantly reduced by both drugs, but only DL 071 IT caused a significant reduction in resting heart rate. As compared to oxprenolol, DL 071 IT has a longer duration of action and is from 5.0 to 13.5 times more potent.

Effect of propranolol on left ventricular function, segmental wall motion, and diastolic pressure-volume relation in man.

Precise quantitation of the effects of the non-selective beta adrenergic blocking drug propranolol (3.15 mg/kg body weight) on left ventricular function, segmental wall motion, and diastolic pressure-volume relation in man has been performed. High fidelity left ventricular pressure measurements and simultaneous single-plane angiocardiograms were recorded on a video disc and volumes calculated by a light-pen computer system. Systolic segmental wall motion was computer analysed using the long axis-quadrasection method. Patients were transvenously atrially paced to maintain a constant heart rate. The haemodynamic effects of propranolol may vary depending upon the extent of pre-existing myocardial disease. In some patients ventricular function, as measured by ejection fraction, may be reduced. This reduction in ejection fraction appears to result from overall reduction in segmental wall motion, but also from accentuation of segmental wall abnormalities. These results are consistent with the thesis that beta adrenergic blocking drugs may inhibit compensatory sympathetic mechanisms. The diastolic effects of propranolol may include quite substantial increases in ventricular volumes in those patients with impaired cardiac function. With respect to the intact human ventricle, propranolol may increase diastolic volume for a given level of ventricular pressure. Thus, in a static sense, the ventricle in these patients could be viewed as being more compliant after propranolol administration. However, the fact that the length-tension relation, as measured by the slope of the logarithmic pressure versus volume plot is unaltered by propranolol, suggests that the muscle comprising the ventricle itself exhibits no alteration in its passive elastic properties.