Catecholamines (adrenaline and noradrenaline) are stimulants and cause an increase in the force of contraction of the heart increasing heart rate, blood pressure, and blood sugar. An outpouring of catecholamines is neces¬sary to prepare the body for a fight-or-flight response. Therefore, we need this surge of adrenaline if we have to flee from a charging bull. Although adrenaline and noradrenaline have positive effects, in excess they can cause overcharging of the cardiovascular system, which can pre¬cipitate ventricular fibrillation.
It is well documented that during a heart attack large quantities of noradrenaline are released into the heart muscle, which can precipitate abnormal heart rhythms, particularly, ventricular fibrillation. Adrenaline causes an increase in heart rate and an increase in blood pressure, thus causing the heart to work harder. Because a coronary artery is blocked during a heart attack, the increased work with less available oxygen causes further damage to the heart muscle and increases the size of the muscle damage, causing a larger heart attack.
Beta-blocking drugs were originally discovered by Sir James Black of Imperial Chemical Industries. Since the introduction of the prototype, propranolol, for the management of hypertension in 1964, more than 12 beta-blocking drugs have become available. Beta-adrenergic blocking drugs have become the cornerstone of cardiac drug therapy.

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• I. BETA-RECEPTORS
  By definition, beta-blockers block beta-receptors. Structur¬ally they resemble the catecholamines (adrenaline and noradrenaline) and block the action of these catechol-amines at their receptor sites. The beta-receptors are situated on the cell membrane and are believed to be a part of the adenyl cyclase system. An agonist acting on its receptor site activates adenyl cyclase to produce cyclic adenosine-5-monophosphate, which is believed to be the intracellular messenger of beta stimulation. There are two types of beta-receptors, beta-1 and beta-2.
• II. MECHANISM OF ACTION
  Blockade of cardiac beta-1 receptors causes a decrease in heart rate, myocardial contractility, and velocity of cardiac contraction. Beta-blockers cause the heart muscle to work less, thus requiring less oxygen; in time of oxygen lack, such as during a heart attack or severe angina, this action can be life-saving. Because of the reduction in the oxygen requirement of the heart muscle, the beta-blocking drugs are effective in preventing the chest pain of angina pectoris. Because patients with angina have a high risk of devel¬oping a heart attack over ensuing years, beta-blockers are important for both pain and prevention.
• III. SALUTARY EFFECTS
  Beta-blockers have been shown to prevent fatal and non-fatal heart attacks and sudden cardiac death. (The salutary effects of beta-adrenergic blockade are depicted in Fig. 1. A decrease in heart rate increases the diastolic interval during which the coronary arteries are filled with blood.
• IV. INDICATIONS A. Angina
  Beta-blockers are first-line therapy for the management of stable angina. They have been shown to be more effective than oral nitrates and calcium antagonists. They reduce the recurrence of chest pain in more than 66% of patients. Many patients with angina manifest little pain, but they may have several episodes of ischemia during the day or night.These episodes can be adequately suppressed by the use of beta-blocking drugs (see the chapter Angina). In patients with unstable angina these drugs are used immediately with aspirin when the patient arrives in the emergency room.
• V. CLINICAL TRIALS
  Clinical trials have documented that beta-blockers signifi¬cantly prevent death in patients who are given the drug from the first week of the heart attack and for an additional two years.
• VI. ADVERSE EFFECTS AND CAUTIONS
  Beta-blockers are safe cardioactive agents if the warnings and contraindications are followed. They are not advisable in patients with severe class IV heart failure. They are indi¬cated, however, in class I–III heart failure. Class IV patients who have been stabilized and are no longer decompensated can be started on very small doses of carvedilol (3.5 mg).
• VII. CLASSIFICATION
  A classification of beta-blockers is given in Fig. 3. Cardio-selectivity indicates that the drug chiefly blocks beta-1 Propranolol Nadolol Sotalol Timolol Teratolol (E) *Carvedilol Bucindolol
• VIII. SUBTLE DIFFERENCES AND RESEARCH IMPLICATIONS
  The subtle differences that exist among the available beta-blocking drugs are often overlooked. Figure 3 gives a working classification. Cardioselective agents are safer than nonselective beta-blockers in diabetic patients and in those with mild-to-moderate chronic obstructive pulmo¬nary disease. This information appears to be well known worldwide. Agents with beta-agonist activity (intrinsic sympathomimetic activity, ISA) are not cardioprotective, e.g., pindolol, and should become obsolete. Of the cardio-selective agents only metoprolol has been shown in randomized clinical trials to significantly reduce coronary heart disease mortality and events. Bisoprolol has not been tried in trials of infarction patients but was beneficial in heart failure trials. Atenolol, a popular cardioselective agent, is used worldwide but has never been tested in a randomized trial of post myocardial infarction patients or in patients with left ventricular dysfunction or heart failure. It should not be assumed that this agent has similar cardioprotective properties as metoprolol, carvedilol, propranolol, bisoprolol, and timolol (see earlier discussion of clinical trials in Section IV).
• IX. INDIVIDUAL BETA-BLOCKERS A. Acebutolol
  This relatively cardioselective, partially hydrophilic and lipophilic agent possesses mild beta-agonist activity. A dosage of 200–300 mg twice daily is given for hyper¬tension. Because of the presence of beta-agonist activity, this drug is not indicated for the management of angina or myocardial infarction.
• BIBLIOGRAPHY
  Abald, B., Bjorkman, J. A., Edstrom, T. et al. The role of central nervous system beta-adrenoreceptors in the prevention of ventricular fibrilla¬tion through augmentation of cardiac vagal tone (abstract). J. Am. Coll. Cardiol., 17:165A, 1991.