Atenolol

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Atenolol
Atenolol.svg
Atenolol 3d structure.png
Systematic (IUPAC) name
(RS)-2-{4-[2-Hydroxy-3-(propan-2-ylamino)propoxy]phenyl}acetamide
Clinical data
Trade names Tenormin
AHFS/Drugs.com monograph
MedlinePlus a684031
Licence data US FDA:link
Pregnancy cat. C (AU) D (US)
Legal status Prescription only
Routes Oral or IV
Pharmacokinetic data
Bioavailability 40-50%
Protein binding 6-16%
Metabolism Hepatic <10%
Half-life 6-7 hours
Excretion Renal
Lactic (In lactiferous females)
Identifiers
CAS number 29122-68-7 YesY
ATC code C07AB03
PubChem CID 2249
IUPHAR ligand 548
DrugBank DB00335
ChemSpider 2162 YesY
UNII 50VV3VW0TI YesY
KEGG D00235 YesY
ChEBI CHEBI:2904 YesY
ChEMBL CHEMBL24 YesY
Chemical data
Formula C14H22N2O3 
Mol. mass 266.336 g/mol
 YesY (what is this?)  (verify)

Atenolol is a selective β1 receptor antagonist, a drug belonging to the group of beta blockers (sometimes written β-blockers), a class of drugs used primarily in cardiovascular diseases. Introduced in 1976, atenolol was developed as a replacement for propranolol in the treatment of hypertension. It works by slowing down the heart and reducing its workload. Unlike propranolol, atenolol does not pass through the blood–brain barrier thus avoiding various central nervous system side effects.[1]

Atenolol is one of the most widely used β-blockers in the United Kingdom and was once the first-line treatment for hypertension. The role for β-blockers in hypertension was downgraded in June 2006 in the United Kingdom to fourth-line, as they perform less appropriately or effectively than newer drugs, particularly in the elderly.

Medical uses[edit]

Atenolol is used for a number of conditions including: hypertension, angina, Long cough, acute myocardial infarction, supraventricular tachycardia, ventricular tachycardia, and the symptoms of alcohol withdrawal.[2]

It is also used to treat the symptoms of Graves' disease until antithyroid medication can take effect.

Due to its hydrophilic properties, the drug is less suitable in migraine prophylaxis compared to propranolol, because, for this indication, atenolol would have to reach the brain in high concentrations, which is not the case.[citation needed]

Hypertension[edit]

Atenolol is currently recommended only in special circumstances as complementary medication in hypertension. More frequently one or more of ACE Inhibitors, calcium antagonists and or diuretics are used as first line therapy.

Contraindications[edit]

  • bradycardia (pulse less than 60 bpm)
  • cardiogenic shock
  • asthma (may cause broncho-constriction).
  • symptomatic hypotension (blood pressure of less than 90/60 mm Hg with dizziness, vertigo etc.)
  • angina of the Prinzmetal type (vasospastic angina)
  • metabolic acidosis (a severe condition with a more acidic blood than normal)
  • severe disorders in peripheral arterial circulation
  • Atrioventricular blockage of second and third degree (a particular form of arrhythmia)
  • acutely decompensated congestive heart failure (symptoms may be fluid retention with peripheral edema and/or abdominal fluid retention (ascites), and/or lung edema)
  • sick sinus syndrome (a particular form of arrhythmia)
  • hypersensitivity and/or allergy to atenolol
  • pheochromocytoma (a rare type of tumor of the adrenal glands)
  • Atenolol should not be taken by patients with preexisting bronchial asthma.[citation needed]
  • Atenolol may retard fetal growth and possibly cause other abnormalities, and is classified by FDA in pregnancy category D. It should be used during pregnancy only if absolutely necessary.

Side effects[edit]

Atenolol causes significantly fewer central nervous system side effects (depression, nightmares).

It was the main β-blocker identified as carrying a higher risk of provoking type 2 diabetes, leading to its downgrading in the United Kingdom in June 2006 to fourth-line agent in the management of hypertension.[3]

In addition, β-blockers blunt the usual sympathetic nervous system response to hypoglycemia (i.e. sweating, agitation, tachycardia). These drugs therefore have an ability to mask a dangerously low blood sugar, which further decreases their safety and utility in diabetic patients.

Side effects have been known to include the following:[citation needed]

The following more-serious side effects have also been observed and/or reported:[citation needed]

  • hallucinations
  • low blood pressure (hypotension)
  • skin reactions, e.g. rash, hives, flaking of skin, worsening of psoriasis
  • sensation of 'pins and needles' hands or feet
  • irritated eyes, visual disturbances
  • difficulty hearing
  • difficulty speaking
  • unsteadiness when walking

Atenolol is classified as a β1-selective (or 'cardioselective') drug, one that exerts greater blocking activity on myocardial β1-receptors than on β2 receptors in the lung. The β2 receptors are responsible for keeping the bronchial system open. If these receptors are blocked, bronchospasm with serious lack of oxygen in the body can result. However, due to its cardioselective properties, the risk of bronchospastic reactions if using atenolol is reduced compared to nonselective drugs as propranolol. Nonetheless, this reaction may also be encountered with atenolol at high doses. Although traditionally β-blockers have been contraindicated when a person carries a diagnosis of asthma, recent studies have revealed that at moderate doses selective β-blockers such as Atenolol are well tolerated.

Provisional data suggests that antihypertensive therapy with atenolol provides weaker protective action against cardiovascular complications (e.g. myocardial infarction and stroke) compared to other antihypertensive drugs. In some cases, diuretics are superior. However, controlled studies are lacking.[4]

Unlike most other commonly used β-blockers, atenolol is excreted almost exclusively by the kidneys. This makes it attractive for use in individuals with end-stage liver disease.

Overdose[edit]

Symptoms of overdose are due to excessive pharmacodynamic actions on β1 and also β2-receptors. These include bradycardia, severe hypotension with shock, acute heart failure, hypoglycemia and bronchospastic reactions. Treatment is largely symptomatic. Hospitalization and intensive monitoring is indicated. In early cases emesis can be induced. 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 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.[5][6]

Pharmacokinetic data[edit]

  • tcmax = 2 to 4 hours after oral dosing (time elapsed before maximal concentration in the blood plasma is reached)
  • The mean elimination halflife is 6 hours. However, the action of the usual oral dose of 25 to 100 mg lasts over a period of 24 hours.
  • Atenolol is a hydrophilic drug. The concentration found in brain tissue is approximately 15% of the plasma concentration only. The drug crosses the placenta barrier freely. In the milk of breastfeeding mothers, approximately 3 times the plasma concentrations are measured.
  • Atenolol is almost exclusively eliminated renally and is well removable by dialysis. A compromised liver function does not lead to higher peak-activity and/or a longer halflife with possible accumulation.

References[edit]

  1. ^ Agon P, Goethals P, Van Haver D, Kaufman JM (August 1991). "Permeability of the blood–brain barrier for atenolol studied by positron emission tomography". J. Pharm. Pharmacol. 43 (8): 597–600. doi:10.1111/j.2042-7158.1991.tb03545.x. PMID 1681079. 
  2. ^ "Atenolol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  3. ^ Sheetal Ladva (2006-06-28). "NICE and BHS launch updated hypertension guideline". National Institute for Health and Clinical Excellence. 
  4. ^ Carlberg B, Samuelsson O, Lindholm LH (2004). "Atenolol in hypertension: is it a wise choice?". Lancet 364 (9446): 1684–9. doi:10.1016/S0140-6736(04)17355-8. PMID 15530629. 
  5. ^ DeLima LG, Kharasch ED, Butler S (1995). "Successful pharmacologic treatment of massive atenolol overdose: sequential hemodynamics and plasma atenolol concentrations". Anesthesiology 83 (1): 204–207. doi:10.1097/00000542-199507000-00025. PMID 7605000. 
  6. ^ R. Baselt (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 116–117. 

7. .K.Viveksarathi et al.,Formulation Development and In-Vitro Evaluation of Gastroretentive Floating tablets of Atenolol. Journal of Pharmaceutical Sciences & Research;2011, Vol.3(12),p1632. http://www.jpsr.pharmainfo.in/Documents/Volumes/vol3Issue12/jpsr%2003111207.pdf

External links[edit]