arrhythmia general term for an irregularity or rapidity of the heartbeat, an abnormal heart rhythm.
atherosclerosis same as atheroma, raised plaques filled with cholesterol, calcium, and other substances on the inner wall of arteries that obstruct the lumen and the flow blood; the plaque of atheroma hardens the artery, hence the term atherosclerosis (sclerosis ¼ hardening).
dyslipidemia the same as hyperlipidemia, elevated blood choles¬terol, LDL cholesterol, triglycerides, or low HDL cholesterol.
heart failure a failure of the heart to pump sufficient blood from the chambers into the aorta; inadequate supply of blood reaches organs and tissues.
ischemia temporary lack of blood and oxygen to an area of cells, for example, the heart muscle, usually due to severe obstruc¬tion of the artery supplying blood to this area of cells.
myocardial infarction death of an area of heart muscle due to blockage of a coronary artery by blood clot and atheroma; medical term for heart attack or coronary thrombosis.
preload the degree of ventricular muscle stretch present at the onset of myocardial contraction; often expressed as end diastolic volume or pressure.

THE SURFACES OF CELLS IN VARIOUS ORGANS and tissues have receptor sites. Hormones and other chemicals act at their respective receptor sites to bring about a particular action in the cell. Adrenaline and noradrenaline are called catecholamines and are released from sympathetic nerve endings and as hormones from the adrenal glands. They have their major actions on receptor sites called beta-receptors. Stimulation of the sympathetic– adrenal system during danger or severe stress, for example, causes an outpouring of adrenaline and noradrenaline into the blood circulation and at nerve endings.

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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.