Beta-Blockers
I. Beta-Receptors
II. Mechanism of Action
III. Salutary Effects
IV. Indications
V. Clinical Trials
VI. Adverse Effects and Cautions
VII. Classification
VIII. Subtle Differences and Research Implications
IX. Individual Beta-Blockers
pulmonary edema a condition in which heart failure causes marked congestion of blood in the lungs, and fluid escapes into the air sacs and alveoli preventing the oxygenation of blood, this is associated with severe shortness of breath at rest.
systole period of contraction of the heart muscle especially of the ventricles; blood is ejected from the ventricles.
ventricular fibrillation the heart muscle does not contract but quivers; therefore there is no heartbeat (cardiac arrest) and no blood is pumped out of the heart; death occurs within minutes if the abnormal heart rhythm is not corrected.
GLOSSARY
afterload arterial impedance, restriction to blood flow delivered from the left ventricle; force against which the myocardium contracts in systole; a major determinant of wall stress.
angina short duration, recurrent chest pain or pressure often accompanied by feelings of suffocation and impending doom; most frequently associated with lack of blood and oxygen to the heart muscle.
- 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.