Atenolol

Last updated

Atenolol
Atenolol.svg
Atenolol 3d structure.png
Clinical data
Trade names Tenormin, others
AHFS/Drugs.com Monograph
MedlinePlus a684031
License data
Pregnancy
category
  • AU:C
Routes of
administration 		oral, Intravenous (IV)
Drug class Selective β1 receptor antagonist
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 40–50%
Protein binding 6–16% [1]
Metabolism Minimal [1]
Onset of action IV: <5 minutes [1]
Oral: <1 hour [1]
Elimination half-life 6–7 hours [1]
Duration of action >24 hours [1]
Excretion Urine (>85% IV, 50% oral) [1]
Identifiers
  • (RS)-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.044.941 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C14H22N2O3
Molar mass 266.341 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • O=C(N)Cc1ccc(cc1)OCC(O)CNC(C)C
  • InChI=1S/C14H22N2O3/c1-10(2)16-8-12(17)9-19-13-5-3-11(4-6-13)7-14(15)18/h3-6,10,12,16-17H,7-9H2,1-2H3,(H2,15,18) Yes check.svgY
  • Key:METKIMKYRPQLGS-UHFFFAOYSA-N Yes check.svgY
   (verify)

Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. [2] Atenolol, however, does not seem to improve mortality in those with high blood pressure. [3] [4] Other uses include the prevention of migraines and treatment of certain irregular heart beats. [2] [5] It is taken orally (by mouth) or by intravenous injection (injection into a vein). [2] [5] It can also be used with other blood pressure medications. [5]

Contents

Common side effects include feeling tired, heart failure, dizziness, depression, and shortness of breath. [2] Other serious side effects include bronchial spasm. [2] Use is not recommended during pregnancy [2] and alternative drugs are preferred when breastfeeding. [6] It works by blocking β1-adrenergic receptors in the heart, thus decreasing the heart rate and workload. [2]

Atenolol was patented in 1969 and approved for medical use in 1975. [7] It is on the World Health Organization's List of Essential Medicines. [8] It is available as a generic medication. [2] In 2020, it was the 53rd most commonly prescribed medication in the United States, with more than 12 million prescriptions. [9] [10]

Medical uses

Atenolol is used for a number of conditions including hyperthyroidism, [11] hypertension, angina, long QT syndrome, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, and the symptoms of alcohol withdrawal. [12]

The role for β-blockers in general in hypertension was downgraded in June 2006 in the United Kingdom, and later in the United States, as they are less appropriate than other agents such as ACE inhibitors, calcium channel blockers, thiazide diuretics and angiotensin receptor blockers, particularly in the elderly. [13] [14] [15]

Side effects

Hypertension treated with a β-blocker such as atenolol, alone or in conjunction with a thiazide diuretic, is associated with a higher incidence of new onset type 2 diabetes mellitus compared to those treated with an ACE inhibitor or angiotensin receptor blocker. [16] [17]

β-blockers, of which atenolol is mainly studied, provides weaker protection against stroke and mortality in patients over 60 years old compared to other antihypertensive medications. [18] [19] [20] [13] Diuretics may be associated with better cardiovascular and cerebrovascular outcomes than β-blockers in the elderly. [21]

Overdose

Symptoms of overdose are due to excessive pharmacodynamic actions on β1 and also β2-receptors. These include bradycardia (slow heartbeat), severe hypotension with shock, acute heart failure, hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic. Hospitalization and intensive monitoring is indicated. Activated charcoal is useful to absorb the drug. Atropine will counteract bradycardia, glucagon helps with hypoglycemia, dobutamine can be given against hypotension and the inhalation of a β2-mimetic such as hexoprenalin or salbutamol will terminate bronchospasms. Blood or plasma atenolol concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 3 mg/L during therapeutic administration, but can range from 3–30 mg/L in overdose victims. [22] [23]

Pharmacology

Pharmacodynamics

Atenolol is a beta blocker, that is, an antagonist of the β-adrenergic receptors. [24] [1] It is specifically a selective antagonist of the β1-adrenergic receptor with no intrinsic sympathomimetic activity (i.e., partial agonist activity) or membrane-stabilizing activity. [24] [1] However, the preferential action atenolol is not absolute, and at high doses it can also block β2-adrenergic receptors. [1]

Beta-blocking effects of atenolol include reduction in resting and exercise heart rate and cardiac output, reduction of systolic and diastolic blood pressure at rest and with exercise, inhibition tachycardia induced by isoproterenol (a non-selective β-adrenergic receptor agonist), and reduction of reflex orthostatic tachycardia. [1] The beta-blocking effects of atenolol, as measured by reduction of exercise-related tachycardia, are apparent within 1 hour and are maximal within 2 to 4 hours following a single oral dose. [1] The pharmacodynamic effects of atenolol, including beta-blocking and antihypertensive effects, last for at least 24 hours following oral doses of 50 or 100 mg. [1] With intravenous administration, maximal reduction in exercise-related tachycardia occurs within 5 minutes and following a single 10 mg dose has dissipated within 12 hours. [1] The duration of action of atenolol is dose-related and is correlated with circulating levels of atenolol. [1]

Pharmacokinetics

The absorption of atenolol with oral administration is rapid and consistent but is incomplete. [1] About 50% of an oral dose of atenolol is absorbed from the intestines, with the rest excreted in feces. [1] Maximal concentrations of atenolol occur 2 to 4 hours following an oral dose, whereas peak concentrations occur within 5 minutes with intravenous administration. [1] The pharmacokinetic profile of atenolol results in it having relatively consistent plasma drug levels with about 4-fold variation between individuals. [1]

The plasma protein binding of atenolol is 6 to 16%. [1] Atenolol is classified as a beta blocker with low lipophilicity and hence lower potential for crossing the blood–brain barrier and entering the brain. [24] This in turn may result in fewer effects in the central nervous system as well as a lower risk of neuropsychiatric side effects. [24]

Atenolol undergoes little to no metabolism by the liver. [1] This is in contrast to other beta blockers like propranolol and metoprolol, but is similar to nadolol. [1] Instead of hepatic metabolism, atenolol is eliminated mainly via renal excretion. [1] Atenolol is excreted 50% in urine with oral administration and more than 85% in urine with intravenous administration. [1]

The elimination half-life of atenolol is about 6 to 7 hours. [1] The half-life of atenolol does not change with continuous administration. [1] With intravenous administration, atenolol levels rapidly decline (5- to 10-fold) during the first 7 hours and thereafter decline at a rate similar to that with oral administration. [1] The elimination of atenolol is slowed in renal impairment, with the elimination rate being closely related to the glomerular filtration rate and with significant accumulation occurring when the creatinine clearance rate is under 35 mL/min/1.73 m2. [1]

Society and culture

Atenolol has been given as an example of how slow healthcare providers are to change their prescribing practices in the face of medical evidence that indicates that a drug is not as effective as others in treating some conditions. [25] In 2012, 33.8 million prescriptions were written to American patients for this drug. [25] In 2014, it was in the top (most common) 1% of drugs prescribed to Medicare patients. [25] Although the number of prescriptions has been declining steadily since limited evidence articles contesting its efficacy was published, it has been estimated that it would take 20 years for doctors to stop prescribing it for hypertension. [25] Despite its diminished efficacy when compared to newer antihypertensive drugs, atenolol and other beta blockers are still a relevant clinical choice for treating some conditions, since beta blockers are a diverse group of medicines with different properties that still requires further research. [13] As consequence, reasons for the popularity of beta blockers cannot be fully attributed to a slow healthcare system – patient compliance factor, such as treatment cost and duration, also affect adherence and popularity of therapy. [26]

Related Research Articles

<span class="mw-page-title-main">Beta blocker</span> Class of medications used to manage abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<span class="mw-page-title-main">Propranolol</span> Beta blocker drug

Propranolol, sold under the brand name Inderal among others, is a medication of the beta blocker class. It is used to treat high blood pressure, a number of types of irregular heart rate, thyrotoxicosis, capillary hemangiomas, performance anxiety, and essential tremors, as well to prevent migraine headaches, and to prevent further heart problems in those with angina or previous heart attacks. It can be taken orally or by intravenous injection. The formulation that is taken orally comes in short-acting and long-acting versions. Propranolol appears in the blood after 30 minutes and has a maximum effect between 60 and 90 minutes when taken orally.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Metoprolol</span> Medication of the selective β1 receptor blocker type

Metoprolol, sold under the brand name Lopressor among others, is a medication used to treat high blood pressure, chest pain due to poor blood flow to the heart, and a number of conditions involving an abnormally fast heart rate. It is also used to prevent further heart problems after myocardial infarction and to prevent headaches in those with migraines. It is a selective β1 receptor blocker medication. It is taken by mouth or is given intravenously.

<span class="mw-page-title-main">Sotalol</span> Medication

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.

<span class="mw-page-title-main">Nadolol</span> Non-selective beta blocker used in the treatment of high blood pressure and chest pain

Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, atrial fibrillation, and some inherited arrhythmic syndromes. It has also been used to prevent migraine headaches and complications of cirrhosis. It is taken orally.

<span class="mw-page-title-main">Doxazosin</span> Group of stereoisomers

Doxazosin, sold under the brand names Cardura among others, is a medication used to treat symptoms of benign prostatic hyperplasia and hypertension. For high blood pressure, it is a less preferred option. It is taken by mouth.

<span class="mw-page-title-main">Isoprenaline</span> Medication for slow heart rate

Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).

Alpha-1 blockers constitute a variety of drugs that block the effect of catecholamines on alpha-1-adrenergic receptors. They are mainly used to treat benign prostatic hyperplasia (BPH), hypertension and post-traumatic stress disorder. Alpha-1 adrenergic receptors are present in vascular smooth muscle, the central nervous system, and other tissues. When alpha blockers bind to these receptors in vascular smooth muscle, they cause vasodilation.

<span class="mw-page-title-main">Moxonidine</span> Antihypertensive medication

Moxonidine (INN) is a new-generation alpha-2/imidazoline receptor agonist antihypertensive drug licensed for the treatment of mild to moderate essential hypertension. It may have a role when thiazides, beta-blockers, ACE inhibitors, and calcium channel blockers are not appropriate or have failed to control blood pressure. In addition, it demonstrates favourable effects on parameters of the insulin resistance syndrome, apparently independent of blood pressure reduction. It is also a growth hormone releaser. It is manufactured by Solvay Pharmaceuticals under the brand name Physiotens and Moxon.

<span class="mw-page-title-main">Labetalol</span> Medication used to treat high blood pressure

Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.

<span class="mw-page-title-main">Bisoprolol</span> Beta-1 selective adrenenergic blocker medication used to treat cardiovascular diseases

Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

<span class="mw-page-title-main">Carvedilol</span> Oral blood-pressure medication

Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is generally a second-line treatment. It is taken by mouth.

<span class="mw-page-title-main">Fenoldopam</span> Antihypertensive agent, also used in hypertensive crisis

Fenoldopam mesylate (Corlopam) is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. Fenoldopam is used as an antihypertensive agent. It was approved by the Food and Drug Administration (FDA) in September 1997.

<span class="mw-page-title-main">Nebivolol</span> Chemical compound

Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.

<span class="mw-page-title-main">Adrenergic antagonist</span>

An adrenergic antagonist is a drug that inhibits the function of adrenergic receptors. There are five adrenergic receptors, which are divided into two groups. The first group of receptors are the beta (β) adrenergic receptors. There are β1, β2, and β3 receptors. The second group contains the alpha (α) adrenoreceptors. There are only α1 and α2 receptors. Adrenergic receptors are located near the heart, kidneys, lungs, and gastrointestinal tract. There are also α-adreno receptors that are located on vascular smooth muscle.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<span class="mw-page-title-main">Landiolol</span> Chemical compound

Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparison to other beta blockers, landiolol has the shortest elimination half-life, ultra-rapid onset of effect, and predictable effectiveness with inactive metabolites. The pure S-enantiomer structure of landiolol is believed to develop less hypotensive side effects in comparison to other β-blockers. This has a positive impact on the treatment of patients when reduction of heart rate without decrease in arterial blood pressure is desired. Landiolol was developed by modifying the chemical structure of esmolol to produce a compound with a higher rate of cardioselectivity and a greater potency without increasing its duration of action. It is sold as landiolol hydrochloride. Based on its positive benefit risk profile, landiolol has been granted the marketing authorization and introduced to the European markets under the brand names Rapibloc, Raploc, Runrapiq, Landibloc mid 2016. Landiolol is available in Japan under the brand names Onoact (50 mg) and Corbeta.

<span class="mw-page-title-main">Discovery and development of beta-blockers</span>

β adrenergic receptor antagonists were initially developed in the 1960s, for the treatment of angina pectoris but are now also used for hypertension, congestive heart failure and certain arrhythmias. In the 1950s, dichloroisoproterenol (DCI) was discovered to be a β-antagonist that blocked the effects of sympathomimetic amines on bronchodilation, uterine relaxation and heart stimulation. Although DCI had no clinical utility, a change in the compound did provide a clinical candidate, pronethalol, which was introduced in 1962.

Adrenergic blocking agents are a class of drugs that exhibit its pharmacological action through inhibiting the action of the sympathetic nervous system in the body. The sympathetic nervous system(SNS) is an autonomic nervous system that we cannot control by will. It triggers a series of responses after the body releases chemicals named noradrenaline and epinephrine. These chemicals will act on adrenergic receptors, with subtypes Alpha-1, Alpha-2, Beta-1, Beta-2, Beta-3, which ultimately allow the body to trigger a "fight-or-flight" response to handle external stress. These responses include vessel constriction in general vessels whereas there is vasodilation in vessels that supply skeletal muscles or in coronary vessels. Additionally, the heart rate and contractile force increase when SNS is activated, which may be harmful to cardiac function as it increases metabolic demand.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 "DailyMed - TENORMIN- atenolol tablet". DailyMed. 30 June 2021. Archived from the original on 27 January 2022. Retrieved 20 November 2023.
  2. 1 2 3 4 5 6 7 8 "Atenolol Monograph for Professionals". Drugs.com. AHFS. Archived from the original on 18 April 2019. Retrieved 23 December 2018.
  3. ↑ Tomiyama H, Yamashina A (2014). "Beta-Blockers in the Management of Hypertension and/or Chronic Kidney Disease". International Journal of Hypertension. 2014: 919256. doi: 10.1155/2014/919256 . PMC   3941231 . PMID   24672712.
  4. ↑ DiNicolantonio JJ, Fares H, Niazi AK, Chatterjee S, D'Ascenzo F, Cerrato E, et al. (2015). "β-Blockers in hypertension, diabetes, heart failure and acute myocardial infarction: a review of the literature". Open Heart. 2 (1): e000230. doi:10.1136/openhrt-2014-000230. PMC   4371808 . PMID   25821584.
  5. 1 2 3 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 151–153. ISBN   9780857113382.
  6. ↑ "Atenolol use while Breastfeeding". Drugs.com. Archived from the original on 23 December 2018. Retrieved 23 December 2018.
  7. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 461. ISBN   9783527607495.
  8. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  9. ↑ "The Top 300 of 2020". ClinCalc. Archived from the original on 16 March 2017. Retrieved 7 October 2022.
  10. ↑ "Atenolol - Drug Usage Statistics". ClinCalc. Archived from the original on 11 April 2020. Retrieved 7 October 2022.
  11. ↑ Rehman B, Sanchez DP, Shah S (2021). "Atenolol". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   30969666. Archived from the original on 10 October 2022. Retrieved 5 September 2021.
  12. ↑ "Atenolol". The American Society of Health-System Pharmacists. Archived from the original on 18 April 2019. Retrieved 8 May 2018.
  13. 1 2 3 Wiysonge CS, Bradley HA, Volmink J, Mayosi BM, Opie LH (January 2017). "Beta-blockers for hypertension". The Cochrane Database of Systematic Reviews. 1 (1): CD002003. doi:10.1002/14651858.CD002003.pub5. PMC   5369873 . PMID   28107561. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people [...] Beta-blockers were not as good at preventing the number of deaths, strokes, and heart attacks as other classes of medicines such as diuretics, calcium-channel blockers, and renin-angiotensin system inhibitors. Most of these findings come from one type of beta-blocker called atenolol. However, beta-blockers are a diverse group of medicines with different properties, and we need more well-conducted research in this area." (p. 2-3)
  14. ↑ Sheetal Ladva (28 June 2006). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. Archived from the original on 11 May 2008. Retrieved 19 August 2012.
  15. ↑ Cruickshank JM (August 2007). "Are we misunderstanding beta-blockers". International Journal of Cardiology. 120 (1): 10–27. doi:10.1016/j.ijcard.2007.01.069. PMID   17433471.
  16. ↑ Lindholm LH, Ibsen H, Borch-Johnsen K, Olsen MH, Wachtell K, Dahlöf B, et al. (September 2002). "Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study". Journal of Hypertension. 20 (9): 1879–86. doi:10.1097/00004872-200209000-00035. PMID   12195132. S2CID   23613019.
  17. ↑ Elliott WJ, Meyer PM (January 2007). "Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis". Lancet. 369 (9557): 201–7. doi:10.1016/s0140-6736(07)60108-1. PMID   17240286. S2CID   37044384.
  18. ↑ Lindholm LH, Carlberg B, Samuelsson O (October 2005). "Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis". The Lancet. 366 (9496): 1545–1553. doi:10.1016/S0140-6736(05)67573-3. PMID   16257341. S2CID   34364430.
  19. ↑ Khan N, McAlister FA (June 2006). "Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis". CMAJ. 174 (12): 1737–42. doi:10.1503/cmaj.060110. PMC   1471831 . PMID   16754904.
  20. ↑ Kuyper LM, Khan NA (May 2014). "Atenolol vs nonatenolol β-blockers for the treatment of hypertension: a meta-analysis". The Canadian Journal of Cardiology. 30 (5 Suppl): S47-53. doi: 10.1016/j.cjca.2014.01.006 . PMID   24750981.
  21. ↑ Messerli FH, Grossman E, Goldbourt U (June 1998). "Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review". JAMA. 279 (23): 1903–7. doi:10.1001/jama.279.23.1903. PMID   9634263.
  22. ↑ DeLima LG, Kharasch ED, Butler S (July 1995). "Successful pharmacologic treatment of massive atenolol overdose: sequential hemodynamics and plasma atenolol concentrations". Anesthesiology. 83 (1): 204–7. doi:10.1097/00000542-199507000-00025. PMID   7605000.
  23. ↑ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, Calif.: Biomedical Publications. pp. 116–117.
  24. 1 2 3 4 Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin MM (February 2021). "Neuropsychiatric Consequences of Lipophilic Beta-Blockers". Medicina (Kaunas). 57 (2): 155. doi: 10.3390/medicina57020155 . PMC   7914867 . PMID   33572109.
  25. 1 2 3 4 Epstein D (22 July 2017). "When Evidence Says No, But Doctors Say Yes". The Atlantic . Archived from the original on 9 May 2018. Retrieved 8 May 2018.
  26. ↑ Choi HY, Oh IJ, Lee JA, Lim J, Kim YS, Jeon TH, et al. (November 2018). "Factors Affecting Adherence to Antihypertensive Medication". Korean Journal of Family Medicine. 39 (6): 325–332. doi:10.4082/kjfm.17.0041. PMC   6250947 . PMID   30384549.
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