Mechanism of action and concept of cardioselectivity
The key difference of this drug group lies in their ability to act selectively on $\beta_1$-adrenergic receptors, which are located predominantly in the heart. Effects on $\beta_2$-receptors (located in the bronchi and blood vessels) are minimal.
To assess this selectivity, the cardioselectivity index is used. It shows the ratio of the potency of $\beta_1$ to $\beta_2$ receptor blockade. For example, for metoprolol and betaxolol, this index is 25/1 (moderate selectivity), while for nebivolol it reaches 290/1 (high selectivity). For comparison: for non-selective propranolol, this ratio is 1/1.8.
Main representatives
In clinical practice, the following cardioselective beta-blockers are most commonly used (trade names in parentheses):
- Metoprolol (Betaloc, Eгилок, Vasocardin);
- Bisoprolol (Concor);
- Nebivolol (Nebilet);
- Atenolol (Tenormin);
- Betaxolol (Lokren);
- Talinolol (Cordanum);
- Esmolol (Brevibloc).
Benefits and clinical use
Due to their low affinity for $\beta_2$-receptors, these drugs have several advantages over non-selective analogues:
- They cause less increase in bronchial tone.
- They have a weaker effect on peripheral vascular tone.
- They interfere less with carbohydrate metabolism (do not increase insulin resistance as much and have less impact on the efficacy of hypoglycemic agents).
Main indications include arterial hypertension, stable angina, myocardial infarction, and tachyarrhythmias. In coronary artery disease, it is important that these drugs reduce cardiac output while practically not increasing afterload and total peripheral vascular resistance.
Features of chronic heart failure (CHF) therapy
In CHF, the body attempts to compensate for reduced cardiac pump function by activating the sympathoadrenal and renin-angiotensin systems. Excess noradrenaline and angiotensin II lead to an increased heart rate, myocardial overload, and ultimately to cardiomyocyte death (apoptosis), fibrosis, and arrhythmias.
Cardioselective $\beta$-blockers eliminate the toxic effects of noradrenaline. They slow the heart rate, prolong diastole (which improves myocardial perfusion), and reduce renin secretion. Therapy is always started at minimum doses and gradually increased (titration). The drugs are combined with ACE inhibitors, and a sustained positive effect develops within 2–3 months.
Briefly: answers to topical questions
What side effects do cardioselective beta-blockers cause?
Cardioselective $\beta_1$-blockers can cause the following side effects:
- Cardiac effects: suppression of AV conduction with a risk of heart block, excessive bradycardia, reduced myocardial contractility, arterial hypotension.
- Respiratory system: may slightly increase bronchial tone; if selectivity decreases, effects typical of non-selective $\beta$-blockers, including bronchospasm, are possible.
- Blood vessels: increase peripheral vascular tone to a lesser extent than non-selective $\beta$-blockers.
- Metabolism: have less effect on the action of hypoglycemic agents and induce less tissue insulin resistance.
- Withdrawal syndrome: abrupt discontinuation of $\beta$-blockers may cause increased frequency and severity of anginal attacks.
Cardioselectivity is relative and significantly decreases when drugs are used in high doses.
Which drug combinations are used with beta-blockers in the treatment of chronic heart failure?
In the treatment of chronic heart failure, beta-blockers are combined with several drug classes as part of standard and quadruple therapy. The baseline treatment regimen (quad-therapy) together with beta-blockers includes:
- ACE inhibitors, angiotensin II receptor blockers (ARBs), or ARNI (valsartan/sacubitril).
- Aldosterone antagonists (potassium-sparing diuretics).
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), such as dapagliflozin or empagliflozin.
Other diuretics may also be included in standard medical therapy to improve symptoms and prognosis.
What are the absolute contraindications for prescribing cardioselective beta-blockers?
Contraindications for prescribing cardioselective $\beta_1$-blockers include:
- Bronchial asthma — the drugs may slightly increase bronchial tone.
- Cardiogenic shock.
- Second- or third-degree atrioventricular block in patients without a functioning pacemaker.
- Severe chronic obstructive pulmonary disease in the acute stage.
- Allergy or intolerance to drug components.
Contraindications for $\beta$-blockers also include signs of heart failure decompensation, severe bradycardia, marked fluid retention, and bronchospasm.
Class and exam questions
Can cardioselective beta-blockers be prescribed in bronchial asthma?
No, they cannot. Despite their selectivity, they can still increase bronchial tone to a small extent; therefore, they are contraindicated in bronchial asthma.
Does cardioselectivity remain when the drug dosage is increased?
No. One of the main pharmacological rules for these agents is that cardioselectivity is relative and decreases significantly when high doses are used.
How quickly does the therapeutic effect of beta-blockers occur in heart failure?
The positive effect in CHF develops with a delay — a noticeable improvement occurs after 2–3 months of regular intake of properly selected (titrated) doses.
What else to study on this topic
- Chemical structure of atenolol and metoprolol
- Principles of dose titration in CHF
- Hemodynamic features of use in coronary artery disease
- Mechanisms of cardioprotection (prevention of fibrosis and apoptosis)
- Interaction with ACE inhibitors in heart failure
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