Drugs that have the effect of stimulating beta-adrenoreactive systems are a group of drugs called beta-blockers.
The adrenoblockers officially recognized and introduced into medical practice were in the middle of the twentieth century.
Since then, this class of antiadrenergic substances has been widely and successfully used as a vasodilator, antihypertensive, antianginal and other drugs.
However, the peculiarities of the pharmacological activity of beta-blockers cause some limitations in their appointment due to the presence of contraindications and the possibility of developing side effects.
The mechanism of action and properties
Adrenolytics block the process of nerve impulse transmission by binding to adrenoreceptors in place of catecholamines.
Beta-adrenoblockers specifically inhibit effects from the effects of sympathetic nerve impulses and sympathomimetic substances on beta-adrenergic receptors.
Thanks to the chemical structure, the bonding of beta-blockers to the receptors do not cause a stimulating but an overwhelming effect.
The set of physicochemical properties of different preparations from this group provides various characteristics of influence. Beta-adrenoblockers are antagonists, interacting with receptors produce an inhibitory effect.
A number of substances combine antagonistic action with agonistic, additionally having some stimulating effect. Antagonists reduce heart rate, weaken the force of heartbeats, inhibit automatism and slow conduction due to blockade of the nervous transmission.
The drug with a joint effect will not affect the heart rate or even slightly increase it. These drugs differ in the selectivity of the effect on beta 1- or beta 2-adrenergic receptors.
Cardioselective drugs are considered to accurately bind the beta 1-receptors of the heart muscle (Atenolol, Bisoprolol, ( Nebivolol ).
Others simultaneously act on both types of receptors – cardiac beta 1-adrenergic receptors and beta 2-adrenergic receptors of bronchial tubes, pancreas, small vessels (Propranolol), due to which the concomitant result of the action of non-selective blockers can be the development of bronchospasm.
There are drugs of combined effect on both types of adrenergic receptors – alpha and beta ( Carvedilol ).
Depending on the solubility in media, adrenolytics are lipophilic ( Nebivolol, Metoprolol ), hydrophilic (Atenolol) and with the combined solubility in water and lipids (bisoprolol).
Beta-blockers have a local anaesthetic and antiarrhythmic effect on the heart. Due to the antianginal effect of the heart muscle, oxygen needs less. The mechanism of antiarrhythmic influence is due to the elimination of arrhythmogenic sympathetic action on the conduction system of the heart.
The hypotensive effect is associated with a number of mechanisms: the volume of cardiac output decreases, the sensitivity of baroreceptors decreases, the work of the renin-angiotensin system is inhibited to some extent.
Beta-blockers also have a number of other influences:
- oppress the work of the central nervous system;
- stimulate uterine contractility;
- reduce intraocular pressure;
- interfere with the processes of formation of glucose in the body;
- cause vasoconstriction;
- promote the development of insulin resistance, etc.
A variety of effects explains the adverse reactions of taking beta-blockers and contraindications to their use, which must be taken into account when using them. In the treatment of cardiac diseases, highly selective drugs should be preferred.
It should be borne in mind that selectivity of exposure is not 100%, in high doses and cardioselective blockers can block beta 2-adrenergic receptors, causing serious undesirable effects.
Contraindications to the use of beta-blockers
In the following diseases and conditions, beta-blockers are contraindicated:
- sinus bradycardia ;
- intraventricular blockade incomplete or complete;
- severe heart failure;
- bronchial asthma and other lung diseases with obstructive syndrome;
- significant violations of peripheral arterial blood flow;
- pregnancy ;
- individual intolerance.
During treatment with beta-blockers, alcohol intake is contraindicated, since concomitant use is a dangerously abrupt development of hypotension.
Careful prescribing of this group of drugs is required for diabetes mellitus, moderate violations of peripheral arterial blood flow, COPD without bronchial obstruction and depressive states.
Side effects of beta-blockers
The development of undesirable reactions can accompany reception of medicines.
The main side effects when using beta-blockers are directly related to their adrenolytic action:
- increased fatigue, sleep disorders, depressive conditions are caused by the effect on the central nervous system;
- bradycardia, hypotonia, blockade of intracardiac conduction due to blockade of adrenoreceptors of the heart;
- bronchospasm due to blockage of bronchial adrenoreceptors;
- nausea, vomiting, diarrhoea, headaches and dizziness due to the intoxication of the body from the accumulation of the drug (with impaired liver function);
- hypoglycaemia due to suppression of glucose synthesis and formation of insulin resistance;
- erectile dysfunction, Raynaud’s syndrome, allergic reactions, etc.
Thus, it is possible to avoid undesirable effects on the central nervous system by preferring water-soluble beta-blockers instead of liposoluble, which are unable to penetrate the central nervous system.
To warn the development of bronchial obstruction is possible by prescribing a minimal initial dose of the drug with a slow build-up until the optimal amount of the drug is reached.
Application in pregnancy
When pregnant, do not take beta-blockers.
These drugs can adversely affect the fetus through indirect and direct effects.
Direct is associated with the ingestion of a drug into the fetal blood flow and the carrying out of a toxic effect on it: the probability of a decrease in heart rate, development of hypoglycemia, and depression of CNS functions is high.
Mediated beta-adrenoblockers act on the fetus through a decrease in uteroplacental blood flow, which can be manifested by delayed fetal development, especially when taking drugs in the 1st and 2nd trimester of pregnancy. Also, have the property of increasing the tone of the uterus and lead to the development of vasoconstriction.
Application for diabetes mellitus
The basis of therapy for chronic heart failure along with other drugs is the use of beta-blockers.
Restriction of the use of beta-blockers works in case the patient has diabetes mellitus because of the potential danger of developing a hypoglycemic state.
Especially this effect is characteristic of non-selective beta-blockers.
Drugs inhibit the formation of glucose in the body, contribute to a decrease in sensitivity to insulin and mask the clinic of hypoglycemia.
Beta-blockers and erectile dysfunction
When taking beta-blockers, an adverse effect on potency is observed – sexual function is inhibited, up to impotence in 1% of cases.
The exact mechanism of this effect is not clear. A presumptive cause is considered the depressing effect of beta-adrenoblockers on the central nervous system, on the hormonal background and on the cavernous bodies.
However, taking not every drug from this group is accompanied by the appearance of this undesirable effect, which makes it possible to choose beta-blockers instead of refusing to use them.