How can β-blockers cause bradycardia?

The negative chronotropic effect of β-blockers mean that a degree of sinus bradycardia can be expected with β-blockers.

When might this be harmful?

In conditions where the heart rate is already low (e.g. sick sinus syndrome) β-blockers are contraindicated as they could induce the development of dangerous bradyarrhythmias or sinus arrest.

Also, because β-blockers slow conduction through the AV node, they are also contraindicated in patient's with conduction disorders (e.g. 2nd-3rd degree heart block) and in patient's taking other drugs that slow AV nodal conduction (e.g. verapamil).

Chronic hyperglycaemia

β2-receptors are found in pancreatic β-cells. When activated they facilitate the release of insulin, helping to lower blood glucose. Studies have shown that β-blockers (particularly those which are non-selective) chronically increase blood glucose by up to 28% leading to poor diabetic control.

Reduced hypoglycaemic awareness

When patients with insulin-dependent diabetes develop hypoglycaemia, they often become aware of this because the physiological response to low blood glucose is to increase sympathetic drive and with this comes physical manifestations such as sweating and tachycardia.

β-blockers inhibit this sympathetic drive and mask the symptoms that present with hypoglycaemia causing patients to lose their hypoglycaemic awareness. This is extremely dangerous as it means patients can not acutely manage their hypoglycaemia by consuming carbohydrates ASAP.

β1 selective blockers are preferable in diabetes. This is because recovery from hypoglycaemia is determined partly by the rate of glucose production in the liver, which is mediated by β2 receptors.

It may seem counter-intuitive that β-blockers, which are a mainstay in the long-term management of chronic heart failure, can be contraindicated in heart failure...

How can β-blockers cause decompensation of heart failure?

In patients with compensated heart failure (i.e. where the heart is able to maintain sufficient cardiac output to prevent complications such as pulmonary oedema), β-blockers are therapeutic by reducing chronic sympathetic activation which worsens heart failure prognosis.

In patients with decompensated heart failure, sympathetic activation is key in maintaining some cardiac output. Therefore the cardiac depressing effect of β-blockers can worsen symptoms, and could push patients with borderline compensation into acute decompensated heart failure.

Many patients on β-blockers will complain of sleep-disturbance and unpleasant dreams. The exact mechanism behind this is unclear.

How can β-blockers cause insomnia?

Melatonin is a hormone that is essential in the regulation of sleep and wakefulness. At night, melatonin is produced in the pineal gland. In this process, noradrenaline binds to pineal β-receptors and this facilitates the conversion of serotonin into melatonin. β-blockers decrease nocturnal production of melatonin and this could increase the risk of insomnia.