Beta-blockers, also known as beta-blockers or beta-sympatholytics, are antagonists of the β1 and β2 receptors, thus inhibiting the sympathetic nervous system. Through their action, beta-blockers affect the functioning of almost the entire body. For many years, beta-blockers have been the basic drugs in cardiology, but they are also used in many other diseases.
Beta-blockersare drugs used primarily in cardiology (mainly in patients with arterial hypertension and in patients with ischemic heart disease), but also used in the treatment of other diseases. Beta-blockers work on the body by suppressing the sympathetic nervous system.
The sympathetic nervous system belongs to the autonomic nervous system, which regulates the work of many systems in our body. The sympathetic nervous system can also be called excitatory because it helps a person cope with stressful situations. It has become known that the sympathetic nervous system is a "fight-and-flight" system because its actions, such as increasing the heart rate, contracting blood vessels, and increasing the respiration rate, help the body withstand various threats.
Beta-adrenergic receptors are located in various organs. Β1 receptors are found mainly in the heart, and thanks to them, the heart rate increases, its contractility increases and conduction in the stimulus-conducting system increases. In addition, β1 receptors also affect the increase in renin secretion in the kidneys and the activation of amylase in the digestive glands.
In turn, β2 receptors play a major role in the relaxation of the coronary vessels and have a relaxing effect on the smooth muscle of the bronchi, bladder, uterus, and the gastrointestinal tract (as a result, the intestinal passage decreases). The stimulation of β2 receptors also affects our metabolism by increasing glycogenolysis and gluconeogenesis in the liver, increasing lipolysis in adipose tissue and increasing glycogenolysis in skeletal muscles. This action is aimed at releasing energy reserves from tissues, which can then be used by the body in a more or less stressful situation.
Therefore, the blockade of beta-adrenergic receptors will lead to the abolition of all the above-described actions. So beta blockers work as followsway:
- in the heart: negative chronotropic effect (decrease in heart rate), negative inotropic effect (decrease in myocardial contractility), negative dromotropic effect (decrease in atrioventricular conductivity), and also decrease in cardiac output by reducing stroke volume as well , increased flow through the coronary vessels and lower oxygen consumption by the heart muscle;
- in blood vessels: decrease in peripheral resistance and vasodilation;
- smooth muscle contraction;
- inhibition of renin secretion, which leads to lower blood pressure;
- decrease in the production of aqueous humor in the eye and, consequently, decrease in intraocular pressure.
In addition, beta-blockers will inhibit the above-described metabolic effects on tissues.
Beta-blockers: division and classification
Beta-blockers can be divided according to the following distinguishing features:
- selectivity for β1 receptors (so-called "cardioselectivity")
Beta-blockers may be selective or non-selective for certain receptors. This means that some of them only act by inhibiting the β1 receptors, and some by acting on the β1 and β2 receptors simultaneously. It should be remembered, however, that this selectivity is only relative, that is, even selective beta-blockers may have even a slight effect on both types of receptors, and selectivity may be completely lost in an overdose of a given beta-blocker. The following drugs are non-selective beta-blockers: propranolol, bupranolol, metipranolol, penbutolol, timolol and sotalol. In turn, selective beta-blockers in relation to the β1 receptor are acebutolol, atenolol, betaxolol, metoprolol, bisoprolol, talinolol.
- partial agonistic activity (with so-called intrinsic sympathomimetic activity - ISA)
These beta-blockers, apart from inhibiting beta receptors, show a small, trace activity stimulating these receptors, which can be called "weaker" or "incomplete" blocking.
- non-specific effect on the cell membrane
- partial vasodilator effect
These beta-blockers, apart from their basic action, are also characterized by the ability to expand blood vessels. This group includes: nebivolol, carvedilol, celiprolol. Each of these drugs dilates the vessels by a different mechanism. Nebivolol indirectly releases nitric oxide, which has a vasodilating effect. Carvedilol causes simultaneous inhibition of the α1 receptor (similarly tolabetalol), and celiprolol shows simultaneous stimulating activity on β2 receptors.
Beta-blockers: indications
Beta-blockers are used for a wide variety of conditions. Taking into account all indications for beta-blocker therapy, the most commonly used are those selective for β1 receptors. Due to the fact that beta-blockers are known mainly as cardiological drugs, non-selective preparations are used much less frequently. Due to the blocking of both types of receptors, non-selective beta-blockers are used in therapy, for example:
- essential tremor,
- anxiety disorders,
- migraine attack prophylaxis.
This effect is demonstrated, inter alia, by propranolol, which, by blocking β2 receptors, shows some activity in the central nervous system. Propranolol can also be used in the treatment of hyperthyroidism, as it to some extent inhibits the conversion of thyroxine to triiodothyronine, which in turn reduces the concentration of active thyroid hormones in the blood.
Another non-selective beta-blocker, sotalol, is an anti-arrhythmic drug used to moderate the heartbeat. Due to their "cardioselectivity" beta-selective beta-blockers have almost completely displaced their nonselective "colleagues" in cardiology.
Selective beta-blockers do not show metabolic activity as non-selective beta blockers do, so they are especially desirable in patients who have diabetes or have impaired glucose tolerance, because they do not affect carbohydrate metabolism, so they are easier to maintain constant blood glucose levels. The selectivity of beta-blockers also plays an important role in the pharmacotherapy of pregnant women. Non-selective beta-blockers can reduce blood flow in the uterus and placenta, while selective beta-blockers are much safer in this respect.
Beta-blockers: main therapeutic indications
As mentioned before, beta-blockers are drugs associated mainly with cardiological diseases. However, their use is much wider and nowadays almost every specialist can find an indication for prescribing them, and the main ones will be described below.
- Cardiology - the "kingdom" of beta-blockers
Among the cardiological indications for the use of beta-blockers, we can distinguish several main ones:
- ischemic heart disease
- hypertension
- heart failure
- heart rhythm disturbance.
Beta-blockers, by blocking β1 receptors, protect the heart from excessive stimulation by the sympathetic nervous systemnervous, especially in stressful situations or during physical exertion. By reducing the heart rate and weakening its contractility, beta-blockers cause the heart to work slower and less intensively, and thus, use less blood and oxygen, which is why it is less prone to their deficiency, which manifests itself in ischemic heart disease. coronary pains.
The exception is vasospastic angina. In this case, beta-blocker monotherapy may worsen the symptoms of the disease, so when diagnosed, beta-blockers must only be used in conjunction with vasodilators, such as nitrates or calcium channel blockers.
Beta-blockers in the treatment of ischemic heart disease are especially recommended in patients who have had a heart attack or are diagnosed with arterial hypertension. Beta-blockers are considered "cardioprotective" drugs because they are one of the key components of the secondary prophylaxis of myocardial infarction. It is believed that if there are no contraindications for their use, beta-blockers should be used by all patients suffering from ischemic heart disease.
Beta-blockers, together with angiotensin converting enzyme inhibitors, AT1 receptor antagonists, diuretics and calcium antagonists, belong to the first-line drugs in the treatment of arterial hypertension. It has been proven that they have a positive effect on the life expectancy and quality of life in these patients. The effectiveness of beta-blockers in the treatment of hypertension largely depends on the age of the patient. Hypertension in elderly patients will result primarily from increased peripheral vascular resistance, therefore beta-blockers in this situation will not necessarily lower blood pressure to the same extent as in patients 50-60. years of age, in whom the pathophysiology of hypertension is based primarily on the greater activity of the sympathetic nervous system.
How exactly beta-blockers lower blood pressure has not yet been established. This can be by lowering cardiac output, reducing the activity of the renin-angiotensin-aldosterone system or the sympathetic nervous system, and also by reducing the release of norepinephrine from nerve synapses.
In the treatment of arterial hypertension, beta-blockers can be used as monotherapy, and if necessary, they can be successfully combined with diuretics or calcium channel blockers. Beta blockers can also be used to treat high blood pressure in women who are breastfeeding, but be careful about their dose as high blood levels in the mother's blood may cause a decrease in the baby's blood pressure.pressure or bradycardia.
Until some time ago, beta-blockers were considered contraindicated in patients with heart failure, but now, after many clinical trials, analyzes have shown that beta-blockers have a huge impact on extending life and increasing its quality in patients suffering from this disease. Beta-blockers in heart failure should be used in all patients with left ventricular dysfunction (considered to be a left ventricular ejection fraction below 40%) and symptoms of heart failure NYHA class II to IV, as well as in patients with asymptomatic left ventricular dysfunction. ventricles who have had a heart attack. The beta-blockers used in heart failure include mainly bisoprolol, metoprolol succinate, nebivolol and carvedilol.
Beta-blockers are class II antiarrhythmic drugs according to the Vaughan Williams classification. Only sotalol is classified in class III. Beta-blockers are used to treat sinus tachycardias, paroxysmal supraventricular tachycardias, and ventricular extrasystoles. As long as there are no contraindications, beta-blockers should be included in the treatment of arrhythmias as they are considered basic antiarrhythmic drugs for which a reduction in mortality has been additionally demonstrated.
Beta-blockers have also found their application in ophthalmology. They are the first-line medications for the treatment of open angle glaucoma. Beta-blockers lower intraocular pressure by reducing the production of aqueous humor. Beta-blockers are readily used in the treatment of glaucoma because, in addition to being very effective, they do not affect pupil width or accommodation. In addition, they have a long duration of action, so you can use them only twice a day.
Timolol remains the most floppy beta-blocker in the treatment of glaucoma. If the therapeutic effect is unsatisfactory, other drugs, such as carbonic anhydrase inhibitors or prostaglandin analogues, can be added to the beta-blocker. Topical beta-blockers can also cause systemic side effects, such as arrhythmias, bradycardia and asthmatic symptoms. Therefore, beta-blockers cannot be used in the treatment of glaucoma in asthmatics, with atrioventricular conduction disorders and in severe allergic rhinitis.
Propranolol and metoprolol are recognized drugs in the prevention of migraine attacks. They are especially recommended for patients with cardiac burden, and for patients with asthma,diabetes or depression these drugs are contraindicated. For prophylaxis to be as effective as possible, beta-blockers should be used in an appropriate dose every day, for a minimum of three months, and ideally for six months.
Beta-blockers: other therapeutic indications
Beta-blockers in combination with alpha-blockers are used to treat pheochromocytoma. Contraindicated here are labetalol and carvedilol, which simultaneously inhibit the α and β receptors, because the sequence of "switching off" the corresponding elements of the sympathetic nervous system is important. Therefore, beta-blockers are only added to therapy after the optimal pressure has been reached by alpha-blockers in order to possibly slow down the heart rate.
As previously mentioned, beta-blockers may be helpful in treating hyperthyroidism and muscle tremors. In muscle tremors, non-selective beta-blockers are primarily used, because the pathogenesis of these symptoms is mainly based on the stimulation of β2 receptors. Beta-blockers can be used in the symptomatic treatment of Parkinson's disease in combination with other anti-Parkinsonian medications. An interesting fact is that beta-blockers are on the list of prohibited doping agents, because due to the fact that they reduce muscle tremors, they can be used in sports that require extreme precision and composure, for example in shooting. Beta-blockers are also used to treat anxiety. However, it should be remembered that they only affect the somatic symptoms of anxiety, such as tremors, palpitations, a feeling of shortness of breath, and do not eliminate the very feeling of anxiety present in our psyche.
Worth knowingBeta-blockers: what is "rebound"?
The term "rebound" refers to the so-called rebound effect. During beta-blocker therapy, when existing receptors are partially or completely blocked, the body tries to compensate for this by producing new ones. In addition, the production of norepinephrine is increased, because its current level, due to blockade of receptors, is not enough for the hormone to act on them. Therefore, if for any reason beta-blockers are suddenly discontinued, the body will be shocked because the activity of the sympathetic nervous system will be multiplied as a result of more β receptors and a higher concentration of norepinephrine. The dose of beta-blockers should therefore be reduced slowly and their complete withdrawal spread over time, so that the body gradually gets used to greater stimulation of the sympathetic nervous system, which will avoid rebound effects.
Beta-blockers: side effects
Like beta-blockers, they can be beneficial in therapymany diseases, so their use may result in side effects in many organs. The most common are:
- gastrointestinal complaints such as abdominal pain, nausea and vomiting, diarrhea or constipation;
- complaints related to excessive blockade of beta receptors in the cardiovascular system, for example bradycardia, hypotension, cold hands and feet, atrioventricular blocks;
- disorders related to the central action of some beta-blockers, for example depression, dizziness, concentration disorders, memory disorders, visual disturbances, hallucinations;
- side effects in the respiratory system may manifest as an exacerbation of the course of asthma or provoking its attacks;
- some patients may complain of impotence;
- disorders of carbohydrate metabolism, especially in diabetics. Beta-blockers are considered important diabetogenic factors, that is, those that significantly increase the risk of developing diabetes. It is very dangerous to mask the symptoms of hypoglycaemia. The decrease in blood glucose levels leads to the stimulation of the sympathetic system, which under physiological conditions is to warn the body of the danger. If beta-blockers block the sympathetic nervous system, the patient will not feel the increasing hypoglycaemia, which in extreme situations may even result in death.
Beta-blockers: contraindications
Beta-blockers are absolutely contraindicated in patients with second- and third-degree asthma or atrioventricular block. Relative contraindications, that is, those that are acceptable under certain conditions, also include: chronic obstructive pulmonary disease, peripheral arterial disease (for example, severe atherosclerosis), severe hypotension or bradycardia, vasospastic angina, metabolic syndrome, and impaired glucose tolerance. Beta-blockers should also not be used in athletes and physically active patients.
Interactions of beta-blockers with other drugs
The use of beta-blockers together with calcium blockers or other anti-arrhythmic drugs may increase their cardiodepressant effects, so patients must be closely monitored if necessary. Non-steroidal anti-inflammatory drugs may reduce the hypotensive effect of beta-blockers. In diabetic patients who use insulin, a beta-blocker may increase or prolong the hypoglycaemia, because when the two drugs are administered simultaneously, the beta-blocker will increase the effect of insulin. On the other hand, the action of antidiabetic sulfonylurea drugs may be counteracted by beta-blockers. Beta-blockers can increase and prolong the toxic effects of alcohol. These are just a few of the many beta-blocker interactions, the list is much longer, so always inform your doctor about all medications you take, as inadequately used beta-blockers can do more harm than good.
ImportantBeta-blocker poisoningSymptoms of beta-blocker poisoning may appear not only after overdosing, but also as an individual response of the body that we can never predict. Poisoning with beta-blockers will manifest itself as bradycardia, drop in blood pressure, arrhythmias, drowsiness, dizziness, and hypoglycemia. Treatment in this case includes possible administration of activated charcoal (if relatively little time has passed since the poisoning), as well as the administration of parasympatholytic drugs such as atropine or high doses of beta-mimetics, which will be reversed by the action of beta-blockers.