Side effects of a beta-receptor blocker can occur at the beginning, but also at a later stage of treatment. Learn more about side effects and fine-tuning treatment with a beta-blocker here.
Beta-receptor blockers are part of the standard therapy for the treatment of cardiovascular diseases, for example, high blood pressure, cardiac arrhythmias, heart failure and coronary heart disease. The efficacy on symptoms of the individual diseases and a positive influence on long-term survival are in part very well proven scientifically.
However, beta-receptor blockers also have symptomatic side effects that are often not recognized as a result of beta-receptor blocker treatment, which in turn usually results in the unnecessary additional use of other medications.
Treatment with a beta-blocker requires special sensitivity to achieve a balanced circuit without side effects.
Beta-receptor blockers - mechanism of action via cell receptors
Beta-receptor blockers block receptors on the cell surface that mediate the action of norepinephrine and epinephrine. Norepinephrine and epinephrine are essential mediators of the "fight-or-flight" mechanism and consequently activate your body; in simple terms, they belong to the "stress hormones".
We know different beta receptors that are distributed differently in body tissues:
- Beta-1 receptors (heart)
- Beta-2 receptors (bronchial, uterine, vascular, muscular).
- Beta-3 receptors (brown, beige and white adipose tissue)
Beta-receptor blockers in cardiovascular medicine.
In cardiovascular medicine, so-called selective beta-1 receptor blockers are predominantly used, for example metoprolol, bisoprolol, nebivolol. They act on the heart primarily via the following mechanisms:
- electrical excitation and conduction
- Pumping force
- Suction power
The effect on excitation formation and conduction primarily means that your heart beats more slowly during beta-blocker therapy at rest and under stress, which is associated with reduced oxygen consumption by the heart. In addition, cardiac arrhythmias mediated by norepinephrine and epinephrine are partially suppressed.
Beta-blockers reduce the pumping force of the heart by reducing the ability of the heart muscle cells to contract. This mechanism significantly reduces blood pressure, especially the upper systolic value.
Closely related to the pumping force is the suction force of the heart. The heart is a pressure-suction pump. The suction is created by the cardiac apex moving forward during the ejection phase of the main chambers. As the main chambers pump blood into the downstream circuit, blood from the upstream circuit is simultaneously drawn into the atria. Beta-receptor blockers cause less blood to be drawn in, so that fluid accumulation, known as edema, can occur in the upstream tissue, in front of the right part of the heart in the legs and in front of the left heart in the lungs.
Beta-1 receptor blockers are considered selective, meaning that they should only act on beta-1 receptors of the heart. In reality, however, this is not exclusively so because a) there is a cross-reaction with beta-2 and beta-3 receptors, which means that these receptors can also be blocked, albeit more weakly, and b) beta-1 receptors are also present in other tissues, for example in the pineal gland in the brain (melatonin release).
Side effects due to beta-receptor blockers
Symptoms are an initial and important indication of beta-receptor blocker side effects, which then need to be further clarified using instrumental methods.
Symptoms due to beta-receptor blockers
Some symptomatic side effects of treatment with beta-receptor blockers can be summarized as follows:
- langsame Herzfrequenz in Ruhe (<50 bpm)
- Heart rate during load not >100
- Low blood pressure
- high systolic blood pressure (paradoxical, with low heart rate)
- Water in the legs (leg edema)
- Facial pallor at rest with disappearance when speaking or laughing
- cold feet and hands
- Power limitation under load
- Shortness of breath due to bronchial constriction
- Shortness of breath due to accumulation of water in the lungs
- Muscle weakness
- Cold feeling
- Weight gain
- Lack of drive
- Sleep disorders
Timing of onset of side effects of beta-receptor blocker therapy.
The side effects of beta-receptor blockers can occur at any time during therapy, even years later.
At the beginning of treatment, it is often an overdose that causes the symptoms. Over time, the balance may shift in favor of the parasympathetic nervous system, the calming part of the autonomic nervous system, for example through less stress at work, remediation of sleep disorders, or exercise. Beta-blockers can then be relatively overdosed and the side effects only then become apparent.
The older we get, the less need we have for beta blockers, and the dose almost always has to be adjusted downward as the years go by.
Special case - beta-blocker therapy after heart surgery
A special case is the condition after heart surgery, for example, aorto-coronary bypass surgery or heart valve surgery.
In most heart surgeries, cardiac surgeons open the surrounding pericardium over the right heart to access the heart. Upon completion of the surgery, the pericardium is usually not resealed so that if the heart muscle swells in the immediate post-operative period, the pericardium does not constrict the heart. Actually, this procedure is no longer necessary nowadays due to new methods (modern cardiology solution), but it is still practiced, not least because the long-term consequences are not known.
In the immediate post-operative phase, the heart and the overall organism are inflammatory activated as part of the healing process and thus the risk of cardiac arrhythmias is also increased, which justifies the use of even higher doses of beta-blockers for several weeks.
However, the overall situation increasingly calms down and at the same time so-called right ventricular-pericardial adhesions occur, i.e. adhesion between the right heart muscle and the pericardium. As a result, the suction force of the right myocardium may be reduced by up to 50% measured against the cardiac output of the right main chamber. Non-adequate treatment with a beta-blocker can then be associated with significant side effects in the later phase after surgery, such as reduced physical performance, fatigue and leg edema.
Special case - beta-blocker therapy and leg edema
People often go to the doctor because of leg edema, the so-called "thick legs". Typically, the legs are slim in the morning and swollen in the evening. The causes for this can be manifold:
- too little physical activity
- Weak leg muscles
- Leg vein weakness
- Pelvic floor muscle weakness
- Heart failure
- Heart valve defect
- increased pulmonary artery pressure
- Pulmonary Hyperinflation
- Medications (especially calcium antagonists, beta-receptor blockers)
The majority of causes of leg edema are the result of impaired venous return against gravity, i.e. fluid remains "stuck" in the legs instead of being transferred to the arterial vascular system. This corresponds to a redistribution disorder.
Once a relevant heart and lung disease has been ruled out, irrespective of other causes, treatment is usually with diuretic drugs instead of eliminating the actual causes. As a result, the legs become slimmer, but the entire organism, especially the vascular system, is deprived of fluid, which in turn limits your performance.
Often enough, treatment with a beta-receptor blocker and the associated restriction of the heart's suction power is a major cause of leg edema. Consequently, if you have leg edema and are taking a beta-receptor blocker at the same time, then you should review the drug therapy together with your doctor and fine-tune the beta-blocker therapy if necessary.
Beta-receptor blocker clarification of side effects and medication fine-tuning
For a comprehensive clarification of possible side effects of a therapy with beta-receptor blockers, we evaluate the following points in Cardiopraxis®:
- Diameter of the inferior vena cava in supine and standing position (sonography)
- Cardiac apex forward motion of the right and left main ventricles (tissue Doppler on cardiac ultrasound).
- Widening of the airways (spirometry)
- Strength of the respiratory muscles (spiromanometry)
- Heart rate and blood pressure under stress (bicycle ergometry)
- Blood flow measurement in supine and standing position (photoplethysmography)
- Pressure increase by reflected pressure waves (arteriography)
- Body temperature and temperature sensation
Central to the evaluation of adverse effects of beta-blocker therapy are determination of inferior vena cava diameter, peak cardiac motion, and heart rate during exercise.
Diameter of inferior vena cava in side effect of beta-blocker therapy.
The diameter of the inferior vena cava is an indirect measure of the fluid content in the venous vascular system. From the supine position to standing, the diameter of the vena cava normally decreases or remains constant, because venous blood tends to remain in the deeper vessel sections, for example the pelvic veins, due to gravity, and at the same time blood is drawn into the chest cavity due to the suction force of the lungs and heart.
If the diameter of the vena cava is too wide in the supine position, for example >18 mm, taking into account body size, and the diameter increases in the standing position, for example to 20 mm, then this is a clear indication of a downstream venous outflow obstruction, a so-called right cardiac inflow congestion. Causes of right cardiac inflow congestion are essentially:
- limited respiratory muscle strength
- Valvular dysfunction (for example, tricuspid regurgitation of the right heart)
- Increased vascular resistance of the downstream arterial vascular systems (pulmonary arterial and systemic arterial circulation)
- Structural myocardial weakness (for example, after myocardial infarction)
- drug-induced heart failure (for example, beta blockers)
Suction force of the heart during side effect of beta-blocker therapy
Both the right and left parts of the heart are a pressure-suction pump. While the respective main chambers eject blood as stroke volume into the downstream circulation, when the connecting valves between the atrioventricular and main chambers (tricuspid and mitral valves, respectively) are closed, the atrioventricular chambers fill by suction caused by the movement of the heart toward the apex of the heart. This is similar to the principle of a milking motion when milking a cow.
The cardiac apex forward motion can be determined very reliably as "suction force" with the so-called tissue Doppler in cardiac ultrasound. A measurement volume is placed on the side wall of the respective main chamber and the velocity of the deflection of the ventricle towards the cardiac apex is determined in cm/sec. The normal velocities here are >10 cm/sec.
To determine the suction force, we use the integral, that is, the average value during an action. The reference values are at:
- right main chamber: 3.0-3.5 cm/sec
- left main chamber: 2.0-2.5 cm/sec
If the value falls below the lower limit, then this is a definite indication of restricted suction power. If there is simultaneous treatment with a beta-blocker, then we can assume at least a relevant partial causation of the beta-blocker. For the sake of completeness, it should be mentioned here that cardiotropic calcium antagonists, such as verapamil and diltiazem, which are rarely prescribed today, can also lead to this phenomenon.
Heart rate under stress with side effect of beta-blocker therapy
When you exert yourself physically, the circulating blood volume must also be increased in order to supply the working muscles with nutrients and remove waste products. Your heart contributes to this via 2 mechanisms, it pumps more forcefully and faster. Up to a heart rate of about 100 bpm, both mechanisms are effective. However, since the main chambers of the heart can never empty completely during the ejection phase, from a heart rate of 100 bpm onwards it is only the heart rate that contributes to an increase in the so-called cardiac output.
The beta-blocker leads to a throttling, a so-called chronotropic incompetence. We can detect this very well in cycle ergometry and then adjust the medication accordingly.
Medicinal fine-tuning of beta-blocker therapy
Treatment with beta-blockers remains a valuable component of cardiovascular disease management. It is the fine-tuning of the dose that poses a challenge at the beginning but also during the course of treatment when side effects occur.
Measured values obtained using the above-mentioned methods are, in addition to the symptoms, the indispensable guideline for an optimal setting. The measured values must be checked after a change in medication, usually after two weeks.
Limitation of physical and mental performance due to beta-blockers - drug adaptation.
In principle, limitations in physical and mental performance should be considered as a side effect of beta-blocker therapy. In addition to the symptoms, the maximum heart rate under stress and the diameter of the inferior vena cava serve as orientation for fine-tuning.
If the maximum stress heart rate is ≤ 100 bpm, then we gradually reduce the beta blocker until a maximum heart rate of 120 bpm becomes possible, which roughly corresponds to the aerobic stress range and is perfectly adequate for completing everyday activities. At older ages, lower maximum heart rates are also possible on an individual basis.
Dilatation of the inferior vena cava signals increased stretching of the vein itself, but also indirectly of the cardiac ventricles. This, in turn, is associated with activation of the parasympathetic nervous system to protect against overstretching, which may explain fatigue and listlessness as a side effect. Here we pay attention during the reduction that the diameter of the vena cava decreases in supine position as well as in standing position.
Hypertension - fine-tuning beta-blocker therapy
Treten bei der Behandlung des Bluthochdrucks messbar verifizierte Nebenwirkungen des Beta-Blockers auf, dann reduzieren wir den Betablocker schrittweise. Gerade bei einer Ruheherzfrequenz von <64 bpm ist das erfolgversprechend, weil in bei niedrigen Herzfrequenzen der systolische Blutdruck durch reflektierte Druckwellen erhöht sein kann; Ziel ist eine Herzfrequenz von circa 72 bpm.
In addition, we use non-invasive blood flow measurement of the circulation in the Cardiopraxis , aiming for a resting value of 100-135% of the lower limit of 2.2 liters per minute perm2 of body surface at rest.
If blood pressure rises with reduction of the beta blocker, we use other medications that lower blood pressure, for example, increasing treatment with an AT1 blocker or ACE inhibitor.
Atrial fibrillation - optimal rate control with the most optimal dosage of a beta-blocker possible.
A beta-blocker is often used for rate control, i.e., to prevent excessive heart rates in permanent atrial fibrillation. If necessary, the beta-blocker can be replaced in whole or in part by a digitalis preparation, for example digoxin. In this case, control is carried out with a long-term ECG.
Heart failure - adjust dose to target values
Beta-blockers are used in heart failure to protect the heart from overstimulation by the sympathetic nervous system (norepinephrine, epinephrine).
The balance of the nervous system between sympathetic ("gas pedal") and parasympathetic ("brake pedal") can be fine-tuned by determining the diameter of the inferior vena cava and the "suction force" in cardiac ultrasound. Since normal values for the "suction force" cannot usually be achieved due to the underlying cardiac insufficiency, a reduction or disappearance of the symptoms is an important benchmark. Beta-blocker dosages of 6.25% of the maximum dosage may be sufficient.
Reduction of beta-blocker and other medications
If a beta-blocker is reduced, then the circulating blood volume is increased, which is also associated with increased blood flow to the kidney and thus also with increased urine excretion. There is a risk here that too much fluid is removed from the body, which can be associated with side effects such as inner restlessness, increased heart rate and even increased blood pressure.
When reducing a beta-blocker, we must therefore ensure that fluid balance is maintained. This means that diuretic drugs are reduced in the same way, if necessary, or the amount of fluid drunk is adjusted. This procedure also requires great medical care in which the determination of the diameter of the inferior vena cava is a valuable follow-up parameter.
Risks associated with reduction of beta-blocker therapy.
Since increased activity of the sympathetic nervous system is allowed with reduction of treatment with a beta-blocker, we must be alert to possible side effects. These include, for example:
- inner restlessness
- Increased heart rate
- Increased blood pressure
- Cardiac arrhythmias
The goal of reducing a beta-blocker is therefore to reduce the side effects of the beta-blocker without causing side effects of the reduction. This corresponds to a balance, which can only be achieved with special care and with the help of measurement methods. Therefore, you should never reduce the beta-blocker without consulting a doctor, otherwise you could also endanger your health.
- Porier L et al. Contemporary use of β-blockers: clinical relevance of subclassification. Can J Cardiol 2014;30:S9-S15.