The binding or noradrenaline (or adrenaline) to the beta₁ receptor on the cardiac myocyte under normal conditions activates adenylyl cyclase which promotes the conversion of ATP to cAMP. Increased levels of cAMP activates cAMP-dependent protein kinase (PK-A). PK-A opens L-type calcium channels increasing the amount of calcium (Ca²⁺) in the cardiac monocyte as well as encouraging the release of calcium from the sarcoplasmic reticulum. The increased intracellular calcium binds to cardiac troponin-C component of the troponin complex on the actin thin filaments on the cardiac muscle.

This moves tropomyosin out of the way allowing the myosin head to interact with the actin facilitating contraction. In short, increased intracellular calcium allows more myosin heads to interact with the actin filament on the cardiac muscle – this allows an increased contraction of the muscle tissue (see video explanation below).

Beta-antagonists block the action of the catecholamines at the beta-receptor thereby decreasing the amount of intracellular calcium that is available and this in turn reduces contraction of the heart.

The effect of the beta-receptor on heart rate is also linked to intracellular calcium stores. Stimulation of the beta-receptors in the SA node, AV node and atrial tissue increase the intracellular concentration of calcium in a similar fashion to that described previously – it facilitates the opening of L-type calcium channels allowing the movement of calcium into the cell and encourages the release of calcium from the sarcoplasmic reticulum. The increase in intracellular calcium levels alters the electrical potential of the cell bringing it closer to threshold (about -40 to -30 mV) where phase 0 of the action potential (depolarization) can occur (see figure below).

There are three main groups of the beta-adrenoreceptor antagonists:

1. B_1-selective blockers or cardioselective blockers because they block Beta1-adrenoceptors mainly located in the heart.
2. Non-selective B-adrenoreceptor antagonists which block both types of adrenoreceptors B1 and B2, and
3. Non-selective B-adrenoreceptor antagonists with intrinsic sympathomimetic activity (ISA) which causes partial stimulation of the B-adrenoreceptor with the effect being less than that of a pure agonist.

The blockade of B₁ receptors in myocardial tissues produces the following effects:

• In the Sinoatrial node blockade reduces heart rate (negative chronotropic effect)
• In the Myocardial tissue blockade reduces contractility (negative ionotropic effect)
• In the Juxtaglomerular cells in the kidney blockade reduces the release of renin (important in the reabsorption of sodium in the distal tubule and collecting ducts)
• In the Central nervous system blockade reduce outflow of the sympathetic nervous system from the medulla oblongata.

The reduction in heart rate and contractility combined with a reduction in the release of renin and a reduced outflow of the sympathetic nervous system reduces blood pressure – a very common use of beta-blockers.

The effect of beta-blockers on a resting heart is modest, it exerts a more significant reduction in heart rate and contractility during exercise, so beta-blockers also reduce exercise tolerance. The benefit of a reduction in heart rate and contractility aside from a reduction in blood pressure is it also reduces myocardial tissue oxygen demand, which makes it useful in people with conditions with reduced coronary artery blood flow (for example angina).

Listed below are the B-adrenoreceptor antagonist (Beta Blocker) drugs in their classifications:

Beta-blockers can also be classed according to their lipid solubility. The lipid soluble beta-blockers tend to have greater central nervous system adverse effects (they penetrate the CNS more readily) and are typically metabolized by the liver. Most beta-blockers are lipid soluble. Where unwanted central nervous system side effects occur with the use of beta-blockers, for example, nightmares, a beta-blocker with low lipid solubility such as atenolol or sotalol may be more appropriate.

Common adverse effects of beta blockers

There are some clinical conditions where beta blockers are contraindicated because of their adverse effects such as in asthma and chronic obstructive pulmonary disease (COPD). This is because Beta blockers can precipitate bronchospasm leading to airway compromise. Remember that the B₂ receptor was found on the smooth muscle of the airways?

Other adverse effects include bradycardia, orthostatic hypotension, cold extremities, fatigue, changes in glucose and lipid metabolism and they can have a transient negative effect on symptoms of heart failure.