β-blockers

Also known as

• Beta blockers

Key examples

• Bisoprolol
• Atenolol
• Propranolol
• Metoprolol

 

Common indications

• Ischaemic heart disease: as a first-line option to improve symptoms and prognosis associated with angina and acute coronary syndrome.
• Chronic heart failure: as a first-line option to improve prognosis.
• Atrial fibrillation: as a first-line option to reduce the ventricular rate and, in paroxysmal atrial fibrillation, to maintain sinus rhythm.
• Supraventricular tachycardia (SVT): as a first-line option in patients without circulatory compromise to restore sinus rhythm.
• Hypertension: although not generally indicated for initial therapy, they may be used when other medicines (e.g. calcium channel blockers, ACE inhibitors, thiazide diuretics) are insufficient or inappropriate.

 

Mechanisms of action

• Beta1-adrenoreceptors are located mainly in the heart, whereas β2-adrenoreceptors are found mostly in smooth muscle of blood vessels and the airways. Via the β1-receptor, β-blockers reduce force of contraction and speed of conduction in the heart. This relieves myocardial ischaemia by reducing cardiac work and oxygen demand, and increasing myocardial perfusion. They improve prognosis in heart failure by ‘protecting’ the heart from the effects of chronic sympathetic stimulation. They slow the ventricular rate in atrial fibrillation mainly by prolonging the refractory period of the atrioventricular (AV) node. SVT often involves a self-perpetuating (‘re-entry’) circuit that takes in the AV node; β-blockers may break this and restore sinus rhythm. In hypertension, β-blockers lower blood pressure through a variety of means, one of which is by reducing renin secretion from the kidney, since this is mediated by β1-receptors.

 

Important adverse effects

• Beta-blockers commonly cause fatigue, cold extremities, headache and gastrointestinal disturbance (e.g. nausea). 
• They can cause sleep disturbance and nightmares. 
• They may cause impotence in men.

 

Warnings

• In patients with asthma, β-blockers can cause life-threatening bronchospasm and should be avoided. This effect is mediated by blockade of β2-adrenoreceptors in the airways. Beta-blockers are usually safe in chronic obstructive pulmonary disease, although it is prudent to choose a β-blocker that is relatively β1-selective (e.g. atenolol, bisoprolol, metoprolol), rather than non-selective (e.g. propranolol). 
• When used in heart failure, β-blockers should be started at a low dose and increased slowly, as they may initially impair cardiac function. They should be avoided in patients with haemodynamic instability and are contraindicated in heart block. Beta-blockers generally require dosage reduction in significant hepatic failure.

 

Important interactions

• Beta-blockers must not be used with non-dihydropyridine calcium channel blockers (e.g. verapamil, diltiazem). 
• This combination can cause heart failure, bradycardia, and even asystole.