Heart, beta-blockers affecting

Nonselective beta blockers affect beta-2 receptors on the lungs as well as beta-1 receptors on the heart, and these nonselective agents can increase bronchocon-striction in patients with asthma and chronic obstructive pulmonary disease. Hence, a drug that is more specific for beta-1 receptors is preferred in these patients. Beta blockers can also produce excessive slowing of cardiac conduction in some patients, resulting in an increase in arrhythmias. Severe adverse reactions are rare, however, and beta blockers are well-tolerated by most patients when used appropriately to treat arrhythmias. 

In a systematic review, the beneficial interaction has been confirmed (249). Four groups of patients who had been studied in EMIAT and CAMIAT (SEDA-21, 198) were defined patients who had taken amiodarone plus beta-blockers, patients who had taken beta-blockers or amiodarone alone, and patients who had taken neither. The relative risks for all-cause mortality and all forms of cardiac death or resuscitated cardiac arrest were lower in the patients who had taken amiodarone plus beta-block-ers than in the other three groups. The results of this post hoc analysis should be regarded with caution, but in view of previous similar reports they are suggestive of a beneficial interaction of amiodarone with beta-blockers in patients who have had a previous myocardial infarction. The interaction was statistically significant for cardiac deaths and for dysrhythmic deaths or resuscitated cardiac arrest. In all other cases the relative risk was reduced, although not significantly. The risk was not affected by heart rate. This interaction has been reviewed (250). 

Nonselective blockers affect multiple beta-adrenergic receptor sites. Propranolol NCL (Inderal) is a nonselective beta-adrenergic blocker that blocks both beta and beta2 receptors, resulting in a slower heart rate, decreased cardiac output, and lower blood pressure. 

All calcium-channel blockers cause vasodilatation, but the cardiac response to the decrease in peripheral resistance is variable. An initial reflex increase in heart rate usually occurs with the dihydropyridines (nifedipine, nicardipine, isradipine, and felodipine) verapamil and diltiazem cause little or no change in heart rate. Verapamil and diltiazem can, however, slow atrioventricular (AV) conduction and should be used with caution in patients also taking a beta-blocker dihydropyridines generally do not affect AV conduction and can be used with a beta-blocker, which decreases reflex tachycardia. All calcium-channel blockers should be used with caution in patients with heart failure. 

A single 20-mg dose of nisoldipine increased the steady-state AUC and peak plasma level of propranolol 160 mg daily by 35% and 55%, respectively. After combined treatment for 7 days, the AUC of propranolol was increased by 60% and the peak plasma level was increased by 55%. The combination enhanced blood pressure reduction to a small extent, but nisoldipine did not significantly reduce the effect of propranolol on heart rate. Similarly, another study found that a single 20-mg dose of nisoldipine increased the AUC and peak plasma level of a single 40-mg dose of propranolol by 43% and 68%, respectively, and that the AUC and peak plasma level of nisoldipine increased 30% and 57%, respectively. In this study, nisoldipine was reported to enhance beta-blockade. However, the same research group later found that the steady-state pharmacokinetics of propranolol 80 mg twice daily and nisoldipine 10 mg twice daily were not affected by concurrent use for 7 days, but nisoldipine attenuated the decrease in forearm blood flow seen with propranolol. The manufacturer of nisoldipine notes that severe hypotension can occur when it is given at the same time as beta blockers, and that, in isolated cases, signs of heart failure can also occur. ... 

A report briefly mentions a patient taking a beta blocker for angina who developed profound sinus bradycardia (36 bpm) and hypotension when cimetidine was also given. The beta blocker was not specified, but it was identified as atenolol elsewhere. Three well controlled studies in healthy subjects and patients found that cimetidine did not significantly alter blood levels of atenolol, nor did it alter the affect of atenolol on heart rate. Atenolol did not affect cimetidine pharmacokinetics. ... 

Beta-adrenoceptor blockers. The realisation that the coiuse of chronic heart failure can be adversely affected by activation of the renin-angiotensin-aldosterone and sympathetic nervous systems led to exploration of possible benefit from P-adrenoceptors in a condition where, paradoxically, such drugs can have an adverse effect. Clinical trials have, indeed, shown that bisoprolol, carvedilol or metoprolol lower mortality and decrease hospitalisation when added to diuretics, digoxin and an ACE inhibitor (see below). 

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