Beta-adrenoreceptor Blocking Drugs

• Duration of action: Some beta-blockers have a longer duration of action and need only be taken once daily e.g. atenolol. Others have a shorter duration e.g. propranolol, although they may be available as a modified release preparation.
• Cardioselective beta-blockers: These have less effect on the beta-2 bronchial receptors and are less likely to cause bronchospasm in susceptible individuals; they may be used with extreme caution in these individuals under specialist supervision. They include atenolol, bisoprolol,metoprolol, nebivolol and, to a lesser degree, acebutolol.
• Intrinsic Sympathomimetic Activity: This is seen in oxprenolol, pindolol, acebutolol and celiprolol. They stimulate, as well as block, adrenergic receptors. They generally cause less bradycardia and impairment of peripheral circulation.
• Water or lipid soluble: Those which are lipid soluble are able to cross the blood-brain barrier and cause sleep disturbance and nightmares. Water soluble beta-blockers (atenolol, celiprolol, nadolol and sotalol) may accumulate if there is renal impairment, and dose reduction may be necessary.

Hypertension

See Management of Hypertension.¹

• Reducing systolic blood pressure by 10mmHg results in a 20% reduction in the risk of coronary heart disease.² Beta-blockers have been recommended first-line drugs in the management of hypertension for several years.³
• The exact mode of action is not completely understood but is thought to be effected by a reduction in cardiac output, altered baroreceptor reflex sensitivity and blocking peripheral adrenoreceptors. It may also be linked to a central effect and a depression of plasma renin secretion, found in some beta-blockers. The dose of atenolol given to hypertensive patients is 50 mg, which is not high. Blood pressure is usually controlled with few side-effects.
• However, recent evidence from the Anglo-Scandinavian Cardiac Outcomes Trial- Blood Pressure Lowering Arm (ASCOT-BPLA⁴) has altered guidance about the use of beta-blockers in hypertension. This study was stopped prematurely, after 5.5 median years of follow-up, as patients on the beta-blocker arm of the trial were experiencing more cardiovascular events and stroke than those on the amlodipine arm. A subsequent meta-analysis revealed that relative risk of stroke was 16% higher for beta-blockers, with less effective treatment of hypertension when compared to other drugs readily available.⁵
• Atenolol has been shown in clinical trials to be inferior to other antihypertensive agents in reducing cardiovascular outcomes (especially strokes).

Angina

See Angina Pectoris and Acute Coronary Insufficiency.

• Exercise tolerance is improved and symptoms relieved by reducing cardiac output and work.
• There is no evidence to suggest that any one beta-blocker gives superior efficacy in angina, but patients may tolerate some better than others.
• Twice-daily treatment may be required, even if longer acting preparations are used.
• There should be gradual reduction of dose rather than a sudden stop, as this may exacerbate symptoms.
• Care should be taken if verapamil and beta-blockers are used together in established ischaemic heart disease, as there is a risk of precipitating heart failure.

Myocardial Infarction

See Management of MI

• Acebutolol, metoprolol, propranolol, and timolol reduce mortality after myocardial infarction.⁶
• There is no evidence that other beta-blockers have similar effects,⁷ and no evidence from clinical trials supporting atenolol use after a myocardial infarction.⁸ There is also no evidence relating to a persisting protective effect after 2-3 years of use, and suddenly stopping the medication can lead to rebound worsening of the ischaemia.
• They are not suitable for all patients; see contraindications below.

Arrhythmias

Beta-blockers lessen the effects of the sympathetic system on the automaticity and conductivity of the heart. They may be used in atrial fibrillation, in conjunction with digoxin. This works well in thyrotoxicosis. They also work well in supraventricular tachycardias (SVT).

• Esmolol is relatively cardioselective (see below) beta-blocker with a very short duration of action. It is used intravenously for the short term, particularly peri-operative management of SVT, sinus tachycardia or hypertension.
• Sotalol is a non-cardioselective beta-blocker which also has class 3 anti-arrhythmic activity. It is used for prophylaxis in paroxysmal SVT, suppression of ventricular ectopics and non-sustained ventricular tachycardia. It is more effective than lignocaine in suppressing sustained VT due to cardiomyopathy or coronary disease. It may induce torsades de pointes in susceptible patients.

Heart Failure

• Beta-blockers produce the positive effect by blocking sympathetic activity.
• Strong evidence from clinical trials shows that bisoprolol, carvedilol, and metoprolol improve prognosis in heart failure.^9,10
• Treatment should be started under guidance of specialist.¹¹

Cardioprotection

• Beta-blockers may have a favourable effect on atherosclerosis development.¹²
• Perioperative blockade of beta-adrenergic receptors with bisoprolol has been shown to reduce the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.

Thyrotoxicosis

See Hyperthyroidism.

• Beta-blockers are used in the pre-operative preparation for thyroidectomy.
• Propranolol reverses clinical symptoms of thyrotoxicosis in 4 days.
• The vascularity of the gland is also reduced, making surgery easier.
• Thyroid biochemistry will be unaltered.

Other Uses

• Beta-blockers can be useful in managing panic attacks. Treatment is most successful where patients complain of tremor, palpitations and tachycardia.
• Migraines may be prevented by their use.
• Patients with a phaeochromocytoma may have their pulse rate controlled with beta-blockers. However they should never be used without simultaneous alpha blockade (phenoxybenzamine)or an hypertensive crisis may be precipitated.

• Second or third degree heart block.
• Worsening, or unstable heart failure.
• Asthma or episodes of bronchospasm - if there is no alternative, use a cardioselective beta-blocker. They are NOT cardio-specific. They still have some effect on airway resistance.

Although diabetes is NOT a contraindication, beta-blockers are associated with a deterioration in glucose tolerance and interfere with the normal autonomic response to hypoglycaemia (and hence patients' hypoglycaemic awareness). They should be avoided in patients having frequent hypoglycaemic episodes. Cardioselective beta-blockers may be preferable.

• Sleep disturbance and nightmares. Water soluble beta-blockers are less likely to cause this problem.
• Sotalol may prolong the QT interval and can occasionally cause life-threatening ventricular arrhythmias; or may precipitate hypokalaemia.
• Beta-blockers are associated with fatigue and cold extremities. Those beta-blockers with intrinsic sympathomimetic activity tend to cause less bradycardia and less coldness of the extremities.

• Are non-atenolol beta-blockers (especially metoprolol and bisoprolol) superior to atenolol in preventing adverse cardiovascular outcomes in hypertensive patients?
• Are beta-blockers equivalent to other classes of antihypertensive agents in reducing clinical events in younger patients?
• Can beta-blockers reduce clinical events and improve prognosis in patients with coronary disease?
• Will perioperative use of beta-blockers reduce postoperative cardiovascular morbidity and mortality?