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Atenolol | A Second-Generation beta-1-selective adrenergic antagonist

 

IntroductionAtenolol, available under brand names of Tenormin, Blokium, Zafnol is Synthetic beta-1 selective blocker. Atenolol is used to treat hypertension, chronic angina, and to lower mortality in individuals with known or suspected myocardial infarction who are hemodynamically stable.
Class of MedicineAtenolol is a second-generation beta-1-selective adrenergic antagonist lowers myocardial contractility, blood pressure, and heart rate.
Mode of ActionBecause it selectively binds to the 1-adrenergic receptor as an antagonist up to a reported 26 fold more than 2 receptors, atenolol is a cardioselective beta-blocker. 15 Due to the greater population of this receptor in cardiac tissue, selective action at the 1 receptor results in cardioselectivity. Therapeutic doses can still cause some binding to 2 and potentially 3 receptors, but the effects caused by antagonising these receptors are greatly diminished compared to those caused by non-selective drugs. Due to the Gs coupling between the 1 and 2 receptors, inhibiting their activation decreases the activity of adenylyl cyclase and the downstream signalling that it produces via cyclic adenosine monophosphate and protein kinase A.
PKA is hypothesised to mediate the activation of ryanodine receptors and L-type calcium channels in cardiomyocytes by phosphorylating these proteins. The release of calcium from the sarcoplasmic reticulum (SR) and an increase in contractility can then be caused by the 16 L-type calcium channels, which can first cause an increase in intracellular calcium. By phosphorylating phospholamban, which in turn enhances the SR Ca2+ ATPase’s affinity to promote calcium reuptake into the SR, PKA also contributes to the termination of contraction. Additionally, it phophorylates troponin I to lessen the protein’s affinity for calcium. Both of these occurrences result in a contraction reduction, which when combined with the initial contraction increase, enables faster cycling and, as a result, a higher heart rate with increased contractility.
PKA is hypothesised to mediate the activation of L-type calcium channels and ryanodine receptors in cardiomyocytes by the phosphorylation of these proteins. The ryanodine receptors are then triggered to release calcium that has been held in the sarcoplasmic reticulum (SR), leading to enhanced contractility, after an initial spike in intracellular calcium is provided by 16 L-type calcium channels. The phosphorylation of phospholamban by PKA, which enhances the SR Ca2+ ATPase’s affinity to promote calcium absorption into the SR, contributes to the termination of contraction as well. In order to lessen troponin I’s affinity for calcium, it also phophorylates the protein. When combined with the initial rise in contraction, both of these occurrences result in a contraction reduction, enabling faster cycling and, as a result, a greater heart rate with increased contractility.
IndicationsA second-generation beta-1-selective adrenergic antagonist called atenolol is used to treat acute myocardial infarction, angina pectoris, and hypertension. Treatment of arrhythmias, migraine prevention, paroxysmal supraventricular tachycardia, alcohol withdrawal, thyrotoxicosis prevention, and prophylaxis against subsequent myocardial infarction are only a few of the non-FDA authorised uses. In cases of infantile hemangiomas, atenolol may also be used instead of propranolol, though further study is necessary before use.
Avaiability & UsageFor oral treatment, atenolol comes in 25 mg, 50 mg, and 100 mg tablets; 0.5 mg/mL is also available for intravenous injection. Depending on the indication, a different dosage and administration method is used.

Hypertension
Atenolol’s starting dose for adults is 50 mg per day, either either as a single tablet or along with diuretic medication. After a few weeks, if there hasn’t been a significant therapeutic response, the dosage may be increased to one 100 mg tablet taken once daily. Higher daily doses are unlikely to result in additional advantages.  If the patient has a creatinine clearance of less than 15 ml/min, a lower dose of 25 mg per day may be utilised for elderly or renally impaired patients. Before giving them a new dose, careful blood pressure monitoring is required.

Chronic chest pain
The initial adult dose for non-vasospastic angina is 50 mg once daily. One 100 mg pill should be used each day if, after a week, the patient has not had the best results. For the best therapeutic outcome, some patients could require 200 mg per day. The patient should be observed and told to reduce their physical activity during this period since withdrawal should be accomplished gradually. [

Myocardial Infarction Acute
Within 12 hours after the myocardial infarction, intravenous injection should take place as soon as the patient enters the hospital.

For instance, the FDA advises giving an adult a 5-minute IV atenolol injection followed by a 10-minute IV injection of another 5-mg dose. After 12 hours, an oral dose of 50 mg should be taken. Then, for the following 6 to 9 days or until the patient is discharged from the hospital, oral dose might be either 50 mg twice daily or 100 mg once daily.

Migraine Prevention
The initial adult dose is 25 mg once daily, which is increased to 100 mg once daily over the course of 1-2 weeks.

T-wave supraventricular rhythm
The first dose of atenolol for adults, as recommended by the ACC and AHA, is 25 to 50 mg per day, which is increased to 100 mg once daily based on tolerance and response.

Coronary infarction
Most patients should begin taking beta-blockers within 24 hours of their myocardial infarction, and they should continue taking them for secondary prophylaxis, gradually increasing their dose up to 50 mg twice day depending on their blood pressure, heart rate, and side effects.

Thyrotoxicosis
The initial dose is 25–50 mg once daily, which is increased as necessary to a maximum of 100 mg twice daily in order to treat tachycardia, palpitations, and trembling.

Employing in the Particular Patient Populations
Patients with hepatic impairment: The manufacturer’s labelling does not mention changing the dosage. Additionally, as was already mentioned, atenolol undergoes very little hepatic metabolism.
Patients with Impairment of Renal Function: Patients with impaired renal function should be watched closely, and the dose has to be changed in accordance with creatinine clearance.
No dose change is required if creatinine clearance is more than 30 mL/min.
Creatinine clearance 10–30 mL/min: 50 mg/day as the maximum dose.
Maximum dose up to 25 mg per day for creatinine clearance 10 mL/minute.
Those undergoing hemodialysis Hemodialysis effectively removes atenolol; provide atenolol after hemodialysis.

Considerations for Pregnancy:
Former FDA pregnancy category D drug is atenolol. [19] Atenolol is not advised during pregnancy, under the recommendations of The American College of Obstetricians and Gynecologists (ACOG), due to the possibility of growth restriction and low birth weight. Labetalol is the chosen beta blocker for pregnant women with persistent hypertension.

Considerations When Breastfeeding: Plasma protein binding is primarily responsible for the excretion of beta blockers in breast milk Drugs like atenolol (10% PPB), which have low plasma protein binding, are extensively excreted in breast milk.

Side EffectsThe following are atenolol’s side effects, per the product label.

Avoid stopping atenolol suddenly because doing so could make your angina, acute myocardial infarction, or ventricular arrhythmias worse. It is advised that the dose be reduced gradually.
It is advised that atenolol be swiftly reintroduced briefly if angina worsens or acute coronary insufficiency develops.
Bradycardia, dizziness, constipation, confusion, dyspnea, headaches, erectile dysfunction, nausea, lethargy, paraesthesia, peripheral numbness, rash, sleep disturbances, syncope, visual impairment, and bronchospasm are a few of the more typical adverse effects.
Alopecia, dry mouth, postural hypotension, psychosis, psoriasis, thrombocytopenia, depression, moderate transaminitis, and depression are uncommon adverse reactions.
Severe bradycardia, renal failure, atrioventricular blockage, shock, and hyperkalemia are the traits of the BRASH syndrome. If you suspect BRASH syndrome, stop taking atenolol.

Drug Interaction
CautionIn some cases, atenolol may result in cardiac failure. If you experience discomfort or pain in your chest, consult a doctor right once; Swelling of the face, fingers, feet, or lower legs; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; weight gain; or wheezing
Available BrandsTenormin
Blokium
Zafnol