Heart rate, beta-blocker effects

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

Effects on blood pressure and heart rate The hypertensive effects of adrenaline (epinephrine) can be markedly increased in patients taking non-selective beta blockers such as propranolol. A severe and potentially life-threatening hypertensive reaction and/or marked bradycardia can develop. Cardioselective beta blockers such as atenolol and metoprolol interact minimally. An isolated report describes a fatal hypertensive reaction in a patient given propranolol and phenylephrine, but concurrent use normally seems to be uneventful Paradoxically, marked hypotension occurred in one patient given low-dose carvedilol and dobutamine. Anaphylaxis Some evidence su ests that anaphylactic shock in... 

Some of the side effects due to beta blockers such as the slowing of heart rate can be counteracted by administration of drugs which antagonize the alpha adrenergic receptors. The... 

The beta blockers can cause a wide array of side effects including low blood pressure, slowed heart rate, dizziness, fatigue, and impotence. They may exacerbate asthma and depression, though this remains controversial, in vulnerable patients. Symptomatic bradycardia (slow pulse) and depression are probably less problematic when using pindolol, which in addition to blocking noradrenergic activity also increases serotonergic activity. 

Bnnch TJ, Mnhlestein JB, Bair TL, Renlnnd DG, Lappe DL, Jensen KR et al. Effect of beta-blocker therapy on mortality rates and future myocardial infarction rates in patients with coronary artery disease but no history of myocardial infarction or congestive heart failure. Am J Cardiol 2005 95(7) 827-31. 

Mechanism of Action A betaj-adrenergic blocker that competitively blocks beta,-adrenergic receptors in cardiac tissue. Reduces the rate of spontaneous firing of the sinus pacemaker and delays AV conduction. Therapeutic Effect Slows heart rate, decreases cardiac output, decreases BP, and exhibits antiarrhythmic activity. Pharmacokinetics ... 

Mecfianism of Action A nonselective beta-blocker that blocks beta - and betaj-ad-renergic receptors. Large doses increase airway resistance. Therapeutic Effect Slows sinus heart rate, decreases cardiac output and BP. Decreases myocardial ischemia severity by decreasing oxygen requirements. 

People with diabetes have a much worse outcome after acute myocardial infarction, with a mortality rate at least twice that in non-diabetics. However, tight control of blood glucose, with immediate intensive insulin treatment during the peri-infarct period followed by intensive subcutaneous insulin treatment, was associated with a 30% reduction in mortality at 1 year, as reported in the DIGAMI study. In addition, the use of beta-blockers in this group of patients had an independent secondary preventive effect (198). The use of beta-blockers in diabetics with ischemic heart disease should be encouraged (199). 

Beta antagonists are generally administered for their effect on the beta-1 receptors that are located on the heart.31 When stimulated, these receptors mediate an increase in cardiac contractility and rate of contraction. By blocking these receptors, beta antagonists reduce the rate and force of myocardial contractions. Consequently, beta antagonists are frequently used to decrease cardiac workload in conditions such as hypertension and certain types of angina pectoris. Beta blockers may also be used to normalize heart rate in certain forms of cardiac arrhythmias. Specific clinical applications of individual beta blockers are summarized in Table 20-2. 

Beta-adrenergic blockers have been used extensively to decrease blood pressure and are a mainstay of antihypertensive therapy in many patients.4,81 Beta blockers exert their primary effect on the heart, where they decrease heart rate and force myocardial contraction. In hypertensive patients, these drugs lower blood pressure by slowing down the heart and reducing cardiac output. This statement, however, is probably an oversimplification of how beta blockers produce an antihypertensive effect. In addition to their direct effect on the myocardium, beta blockers also produce a general decrease in sympathetic tone.19,39 Although their exact effects on sympathetic activity remain to be determined, beta blockers may decrease sympathetic activi-... 

Nonselective beta blockers (i.e., those with a fairly equal affinity for beta-1 and beta-2 receptors) may produce bronchoconstriction in patients with asthma and similar respiratory disorders. Cardiovascular side effects include excessive depression of heart rate and myocardial contractility as well as orthostatic hypotension. Some of the traditional beta blockers may impair glucose and lipid metabolism, but this effect can be reduced by using one of the newer vasodilating beta blockers such as carvedilol.97 Other side effects include depression, fatigue, gastrointestinal disturbances, and allergic reactions. Beta blockers are generally well tolerated by most patients, however, and the incidence of side effects is relatively low. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

In the past, beta blockers were considered detrimental in patients with heart failure.60 As indicated in Chapter 20, these drugs decrease heart rate and myocardial contraction force by blocking the effects of epinephrine and norepinephrine on the heart. Common sense dictated that a decrease in myocardial contractility would be counterproductive in heart failure, and beta blockers were therefore contraindicated in heart failure.60,69 It is now recognized that beta blockers are actually beneficial in people with heart failure because these drugs attenuate the excessive sympathetic activity associated with this disease.56,64 As indicated earlier,... 

The side effects and problems associated with beta blockers were addressed in Chapter 20. The primary problem associated with these drugs is that they may cause excessive inhibition of the heart, resulting in an abnormally slow heart rate and reduced contraction force. This effect is especially problematic in heart failure because the heart is already losing its ability to pump blood. Nonetheless, the risk of this and other side effects is acceptable in most people with heart failure, and this risk is minimized by adjusting the dosage... 

Systemic Effects. Because levobunolol is a potent and effective Pi and P2 blocker, it shares with timolol the same potential for systemic beta-blockade. Mean resting heart rate may decrease 3 to 10 bpm during use of levobunolol, and some reduction in blood pressure may occur.Topical ocular dosing with levobunolol results in plasma levels of approximately 1 ng/ml. As with timolol, 0.5% levobunolol reduces maximal exercise-induced heart rate by approximately 9 bpm. 

Some pharmacodynamic effects, e.g. heart rate with beta-adrenoceptor blocker, provide a physiological marker as an indication of the presence of drug in the body. 

The adverse effects of beta-blockers are usually mild, with occurrence rates of 10-20% for the most common in most studies. Most are predictable from the pharmacological and physicochemical properties of these drugs. Examples include fatigue, cold peripheries, bradycardia, heart failure, sleep disturbances, bronchospasm, and altered glucose tolerance. Gastrointestinal upsets are also relatively common. Serious adverse cardiac effects and even sudden death can follow abrupt withdrawal of therapy in patients with ischemic heart disease. Most severe adverse reactions can be avoided by careful selection of patients and consideration of individual beta-blockers. Hjrpersensitivity reactions have been relatively rare since the withdrawal of practolol. Tumor-inducing effects have not been estabhshed in man. 

The safety and efficacy of mibefradil in association with beta-blockers was assessed in 205 patients with chronic stable angina, randomized to placebo or mibefradil 25 or 50 mg/day for 2 weeks (6). Besides an improvement in angina with mibefradil, it dose-dependently reduced heart rate and increased the PR interval. One patient taking mibefradil had an escape junctional rhythm 26 hours after the last dose of 50 mg. The nodal rhythm disappeared on withdrawal of mibefradil, but based on the overall results it was concluded that mibefradil was safe and effective when given for a short time with beta-blockers. 

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