Have you ever pondered the remarkable influence a tiny pill can exert on the intricate dance of physiological processes within the human body? Enter beta blockers – a class of pharmaceutical marvels that have revolutionised the landscape of medical therapeutics.
Beta-blockers (β-blockers) are a type of medication primarily used to prevent secondary heart attacks after the first one and manage abnormal heart rates and rhythms.1 They work by blocking the release of stress hormones such as adrenaline and noradrenaline, which bind to the beta receptors present in the sympathetic nervous system of our body. This ultimately results in a decrease in blood pressure and a reduced more regular heart rate.2,3
The first β-blockers - Propranolol, was synthesised in 1964 by Sir James Black and revolutionised the treatment of angina pectoris. Nowadays, Propranolol is one of the most commonly used medications for the management of high blood pressure, heart attacks and migraines for millions of people around the world. In this article, we will delve into the types of beta blockers, as well as their benefits, side effects, and profound impact on the ever-evolving landscape of modern medicine.
Pharmacology of beta blockers
Before exploring the mechanism of action of beta blockers, it is important to understand our body’s signalling system. The body employs a chemical signalling system to regulate various processes and functions. Specific sites on the surface of cells, called receptors, play a crucial role in this system. These receptors act like locks, where neurotransmitters (chemical signalling molecules) with the right structure bind, therefore functioning like keys to their respective receptor to activate the cells.
The response of the cell depends on its location and function. If the body requires specific cells to take action, it can produce an increased amount of the neurotransmitter needed to activate the receptors on those cells. There are three types of beta receptors, often with one kind more predominant in certain organs than the other two. The different types of beta receptors, their location in our body and the effect they have upon their activation are shown in the chart below.2,4,5
| Types | Location | Function |
| Beta-1 receptors | a) Heart b) Kidneys | - Increase heart rate and cardiac output - Aid in the secretion of an enzyme called renin |
| Beta-2 receptors | a) Smooth muscles of: - Trachea and bronchial tubes - Blood vessels - Gastrointestinal tract - Uterus b) Skeletal muscles c) Heart d) Liver | - Relaxation of the smooth muscles of the respiratory tract aids in breathing - Helps lower blood pressure - Helps in peristalsis ( movement of broken-down food particles in the digestive system) and aids in nutrient absorption - Relaxes uterine muscles and aids in childbirth - Activation in the skeletal muscles may lead to tremors - Increases cardiac output - Aid in glycogenolysis ( conversion of glycogen into glucose) |
| Beta-3 receptors | a) Fat cells b) Urinary bladder | - Break down fat and induce lipolysis - convert lipid triglycerides into glycerol and free fatty acids.4,5 - Relax muscles in the bladder and increase bladder capacity |
Beta-blockers act on beta-adrenergic receptors found throughout the body and block its activity. They are, therefore, described as beta-adrenergic receptor antagonists. These receptors are the site of adrenaline binding, hence the name - adrenergic receptors.
Types of beta-blockers
Beta-blockers are generally classified into two categories based on the receptor they act upon. This feature is characterised as “selectivity”. Cardioselective beta-blockers are drugs that act specifically on β-1 receptors - mainly found in the heart - and inhibit their processes and functions. On the other hand, non-cardioselective beta-blockers can inhibit the properties of all beta receptors in the body.
Aside from these two categories, there are some beta blockers which may show additional features known as Intrinsic Sympathomimetic Activity (ISA). Agents from both cardioselective and non-cardioselective may fall into this category. Beta-blockers with ISA act as both blockers and inducers at the beta receptors, depending on the dosage of the drugs and the concentration of neurotransmitters present at any given point in the body.
The chart below lists different beta blockers based on their cardioselective and non-cardioselective properties, including those with Intrinsic Sympathomimetic Activity.6,7
| Cardioselective beta blockers | Non-cardioselective beta blockers |
| Acebutolol (has intrinsic sympathomimetic activity, ISA) | Propranolol |
| Metoprolol | Carvedilol* |
| Celiprolol (has intrinsic sympathomimetic activity, ISA) | Labetalol*(has intrinsic sympathomimetic activity, ISA) |
| Bisoprolol* | Pindolol(has intrinsic sympathomimetic activity, ISA) |
| Atenolol | Sotalol* |
| Esmolol* | Timolol |
| Nebivolol* | Nadolol |
| Betaxolol | Bucindolol* |
| Landiolol* | Oxprenolol(has intrinsic sympathomimetic activity, ISA)8 |
| Penbutolol(has intrinsic sympathomimetic activity, ISA) | |
| Carteolol |
* These agents possess additional unique characteristics. Some examples are as follows:
- Bisoprolol and Nebivolol work as the most cardioselective beta-blockers.9
- Labetalol, carvedilol, and bucindolol also block the activities of alpha receptors in addition to beta-1 and beta-2 receptors. Hence, they are more effective in reducing the heart rate and blood pressure.10
- Esmolol can only be administered intravenously. Hence, it is only used in the hospital setting.
- Landiolol is only available in an intravenous form and is an ultra-short-acting cardioselective beta blocker11, primarily used in the management of arrhythmia- a disorder of the heart and emergency cases of high blood pressure and rapid heart rate.
- Sotalol acts on both beta-1 and beta-2 receptors. In addition to this, it also acts on potassium channels and delays ventricular contraction.12
Medical uses
Beta-blockers have been typically used for the management of conditions related to heart and vascular abnormalities. However, they have also proven to be beneficial in the therapeutic management of conditions not related to the heart. Overall, beta-blockers possess a wide range of uses for different conditions in the human body.
Cardiovascular conditions
Beta-blockers used in the management of different cardiovascular conditions are listed below:2,13
- Essential and portal hypertension: Although beta blockers are not the primary choice of drug for the management of hypertension, they are still recommended in cases where other anti-hypertensive drugs cannot be used. Almost all beta-blockers can be used as anti-hypertensive depending upon the preexisting condition contributing to hypertension and beta-blocker indication. Atenolol is the most used beta-blocker in cases of essential hypertension. However, propranolol is indicated in cases of portal hypertension.
- Arrhythmias: Beta-blockers have significant roles in the management of arrhythmias. They are some of the first choices when it comes to the management of arrhythmias and have been proven effective in reducing mortality and maintaining good life quality in patients with arrhythmias. Some of the drugs proven effective in arrhythmias include- metoprolol, propranolol, and atenolol along with sotalol, esmolol, and landiolol being specifically prescribed for cardiac arrhythmias.
- Congestive heart failure: Beta-blockers used specifically for the management of congestive heart failure are bisoprolol, carvedilol and sustained-release metoprolol.
- Myocardial infarction: Atenolol, timolol, carvedilol, and immediate-release metoprolol and propranolol are indicated in cases of myocardial infarction (also known as a heart attack). Another beta-blocker, bisoprolol, is indicated in both preventive and post myocardial infarction.
Non-cardiovascular uses
Beta-blockers can be used for the following non-cardiovascular conditions:2,13
- Migraine prophylaxis: Propranolol and timolol are indicated as the prophylactic agents in cases of migraine and are effective in minimising future episodes.
- Glaucoma: Timolol is the beta-blocker of choice in the management of glaucoma. However, other agents such as carteolol, betaxolol, metipranolol, and levobunolol can also be used.
- Anxiety: Beta-blockers have been used extensively either as a prescription drug for the management of anxiety disorders or as an off-label drug to minimise stage fright and reduce anxiety, including misuse as a performance-enhancing drug. In the 2008 Summer Olympics, a North Korean double medalist was stripped of his medals and sent home after he tested positive for a beta-blocker, propranolol.
- Thyroid disorder: Beta-blockers, most commonly- propranolol, are used to manage symptoms such as palpitation and anxiety that occur in patients suffering from hyperthyroidism.
Note: Propranolol is the single most effective beta-blocker of choice used in the management of portal hypertension, oesophageal varices, and tremors, and it is also used in conjunction with an alpha-blocker medication for the management of pheochromocytoma.14
Adverse effects
Like many drugs, beta-blockers have their fair share of adverse effects. Some of the common side effects associated with beta-blocker use are as follows:2,15
- Nausea and dizziness
- Diarrhoea
- Bronchospasm
- Dyspnoea
- Bradycardia and hypotension
- Heart failure and heart block
- Alopecia (pattern baldness)
- Fatigue
- Exacerbation of Raynaud's syndrome
- Sexual disturbances including erectile dysfunction
- Alteration in glucose and lipid metabolism
- Insomnia
Contraindications and precautions
Beta-blockers can be dangerous and even fatal if used without consulting a healthcare professional. There are some underlying conditions where beta-blockers should be avoided whereas, in some conditions, it can be taken cautiously. These absolute contraindications and relative precautions are listed below.2,15
Absolute contraindications
- Bradycardia
- Hypotension
- Cardiogenic shock
- Allergic to beta-blockers
- Heart block
Precautions
- Diabetes
- Peripheral vascular disease
- Pregnancy and lactation
- Chronic obstructive lung disease and asthma
- Cerebrovascular disease
- Raynaud’s phenomenon
- Stroke
- Acute heart failure
- Renal (kidney) failure
- Abrupt discontinuation in patients with hyperthyroidism may cause thyroid storm
Drug interactions
Beta-blockers have extensive interactions with many other drugs. While some drug interactions may be nothing to worry about, others may prove dangerous and even fatal. Therefore, informing clinicians if you are taking any medications for underlying conditions is vital. Some common classes of medications that may interact with beta-blockers with or without causing adverse effects are as follows.16
- Antihypertensive and antianginal medications
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Sympathomimetic and inotropic agents
- Anti-ulcer medications
- Psychotropic drugs
- Antiarrhythmic drugs
- HMG-CoA reductase inhibitors, also known as statins
- Oral hypoglycemics
- Heparin and warfarin
- Rifampicin
Conclusion
Beta-blockers, pioneered by Sir James Black in 1964, play a pivotal role in medicine by regulating heart function and blood pressure. Acting on beta receptors, they offer therapeutic benefits in cardiovascular conditions like hypertension, arrhythmias, and heart failure. Beyond the heart, they aid in managing migraines, glaucoma, anxiety, and thyroid disorders.
While they can be classified as both cardioselective and non-cardioselective, beta-blockers come with potential side effects, emphasising the importance of medical consultation. Contraindications, such as bradycardia, and precautions, like diabetes, need to be taken into consideration. Additionally, their interactions with various medications highlight the necessity of informing healthcare providers.
In essence, beta-blockers stand as indispensable agents, influencing a range of health conditions and contributing significantly to modern medical therapeutics.
References
- Freemantle N, Cleland J, Young P, Mason J, Harrison J. β Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ [Internet]. 1999 [cited 2024 Jan 11]; 318(7200):1730–7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31101/.
- Farzam K, Jan A. Beta Blockers. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK532906/.
- Baker JG. The selectivity of β ‐adrenoceptor antagonists at the human β 1, β 2 and β 3 adrenoceptors. British J Pharmacology [Internet]. 2005 [cited 2024 Jan 11]; 144(3):317–22. Available from: https://bpspubs.onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0706048.
- Katsarou M-S, Karathanasopoulou A, Andrianopoulou A, Desiniotis V, Tzinis E, Dimitrakis E, et al. Beta 1, Beta 2 and Beta 3 Adrenergic Receptor Gene Polymorphisms in a Southeastern European Population. Frontiers in Genetics [Internet]. 2018 [cited 2024 Jan 11]; 9. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2018.00560.
- Clément K, Vaisse C, Manning BStJ, Basdevant A, Guy-Grand B, Ruiz J, et al. Genetic Variation in the β 3 -Adrenergic Receptor and an Increased Capacity to Gain Weight in Patients with Morbid Obesity. N Engl J Med [Internet]. 1995 [cited 2024 Jan 11]; 333(6):352–4. Available from: http://www.nejm.org/doi/abs/10.1056/NEJM199508103330605.
- Tucker WD, Sankar P, Theetha Kariyanna P. Selective Beta-1 Blockers. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK499982/.
- Beta Adrenergic Blocking Agents. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548127/.
- PubChem. Oxprenolol [Internet]. [cited 2024 Jan 11]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/4631.
- Sinha SS, Gurm HS. The double jeopardy of chronic obstructive pulmonary disease and myocardial infarction. Open Heart [Internet]. 2014 [cited 2024 Jan 11]; 1(1):e000010. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189253/.
- Rosendorff C. Beta-blocking agents with vasodilator activity. Journal of Hypertension [Internet]. 1993 [cited 2024 Jan 11]; 11:S37. Available from: https://journals.lww.com/jhypertension/abstract/1993/06003/beta_blocking_agents_with_vasodilator_activity.9.aspx.
- Iguchi S, Iwamura H, Nishizaki M, Hayashi A, Senokuchi K, Kobayashi K, et al. Development of a Highly Cardioselective Ultra Short-Acting β-Blocker, ONO-1101. Chemical & Pharmaceutical Bulletin. 1992; 40(6):1462–9.
- Mubarik A, Kerndt CC, Cassagnol M. Sotalol. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2024 Jan 11]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK534832/.
- Comparison of Oral Beta-Blockers [Internet]. 2017 [cited 2024 Jan 11]. Available from: https://web.archive.org/web/20171018134059/https://pharmacist.therapeuticresearch.com/Content/Segments/PRL/2012/Dec/Comparison-of-Oral-Beta-Blockers-5052.
- Al-Majed AA, Bakheit AHH, Abdel Aziz HA, Alajmi FM, AlRabiah H. Propranolol. Profiles Drug Subst Excip Relat Methodol. 2017; 42:287–338.
- Frederix’ ’Ines, Mcintosh’ ’Michael. Cardio protective drugs: Beta-blockers [Internet]. [cited 2024 Jan 11]. Available from: https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Treatment-goals/Cardio-Protective-drugs/beta-blockers.
- Blaufarb I, Pfeifer TM, Frishman WH. beta-blockers. Drug interactions of clinical significance. Drug Saf. 1995; 13(6):359–70.
