Continuing Education Activity

Atenolol is a second-generation beta-1-selective adrenergic antagonist indicated in treating hypertension, angina pectoris, and acute myocardial infarction. Non-FDA-approved indications include treatment of arrhythmias, migraine prophylaxis, paroxysmal supraventricular tachycardia, alcohol withdrawal, thyrotoxicosis, and prophylaxis against secondary myocardial infarction. This activity outlines the indications, mechanism of action, safe administration, adverse effects, contraindications, monitoring, and toxicity of atenolol.

Objectives:

• Outline the accepted indications for atenolol use.
• Identify the mechanism of action of atenolol and other selective beta-blocking agents.
• Summarize the adverse event profile of atenolol.
• Review interprofessional team strategies for improving care coordination and communication to enhance patient outcomes and minimize adverse events with atenolol.

Indications

Atenolol is a second-generation beta-1-selective adrenergic antagonist indicated in the treatment of hypertension, angina pectoris, and acute myocardial infarction. Non-FDA-approved indications include treatment of arrhythmias, migraine prophylaxis, paroxysmal supraventricular tachycardia, alcohol withdrawal, thyrotoxicosis, and prophylaxis against secondary myocardial infarction.[1]

Mechanism of Action

Cardioselective beta-1-adrenergic antagonists such as atenolol work by selectively binding to the beta-1 adrenergic receptors found in vascular smooth muscle and the heart, blocking the positive inotropic and chronotropic actions of endogenous catecholamines such as isoproterenol, norepinephrine, and epinephrine, thereby inhibiting sympathetic stimulation.[2] This activity results in a reduction in heart rate, blood pressure and decreases myocardial contractility. However, in heart failure patients, atenolol can increase the end-diastolic pressure and left ventricular fiber lengths - conversely resulting in increased oxygen demand.

In higher doses, it also exerts its effects by competitively blocking beta-2-adrenoreceptors, primarily located in the bronchial and vascular musculature. It has no membrane stabilizing or intrinsic sympathomimetic activity. Atenolol has low lipid solubility, resulting in reduced brain penetrance, resulting in fewer CNS side effects.[3] 

Beta-adrenergic receptor antagonists are also known to increase the AV node's refractory period. Therefore, it may also be used off-license to treat supraventricular tachycardia and prevent paroxysmal attacks of atrial fibrillation.[4] The duration of action is dose-related - following administration of a dose, the effects are apparent within an hour and are maximal at 2 to 4 hours, persisting for at least 24 hours.[5]

Administration

Atenolol is available in 25 mg, 50 mg, and 100 mg tablets for oral administration or 0.5 mg/mL for intravenous injection. The dosage and route of administration vary depending on the indication.

Hypertension

The initial adult dose of atenolol is 50 mg per day, given either as a single table or in conjunction with diuretic therapy. In the absence of an adequate therapeutic response after a few weeks, the dosage may be increased to a single 100 mg tablet once a day. Daily doses higher than this are unlikely to produce further benefits.[6]

For renal-impaired or elderly patients, a lower dose of 25 mg once a day may be used if they have a creatinine clearance of under 15 ml/min. Careful monitoring of their blood pressure before administering a new dose is necessary.[7]

Angina Pectoris 

For non-vasospastic angina, the initial adult dose is 50 mg tablet once a day. If, after a week, the patient has not reached the optimal response, the dose should be increased to one 100 mg tablet daily. Some patients may need 200 mg daily for an optimal therapeutic response. However, withdrawal should be achieved gradually with the patient monitored and advised to limit physical activity during this time.[8]

Acute Myocardial Infarction

Intravenous injection should occur as soon as possible after the patient arrives in the hospital within 12 hours of the myocardial infarction. For example, the FDA recommends for an adult the IV administration of 5 mg of atenolol over 5 minutes followed by another 5 mg IV injection after 10 minutes. A 50 mg oral dose should follow 12 hours later. After that, oral dosing can be either 50 mg twice a day or 100 mg once a day for 6 to 9 days or until discharged from the hospital.[9]

Migraine Prophylaxis

The initial adult daily dose is  25 mg once daily; titrated every 1-2 weeks to 100 mg once daily.[10]

Supraventricular Tachycardia

According to ACC and AHA guidelines, the initial adult dose of atenolol is 25- 50 mg per day which is titrate based on tolerability and response to 100 mg once daily.

Myocardial Infarction

beta-blocker should be started within the first 24 hours of myocardial infarction for most patients and continue for secondary prophylaxis titrating gradually up to 50 mg twice daily based on BP, heart rate, and adverse events.[9] 

Thyrotoxicosis

The initial daily dose is 25-50 mg once daily, which is titrated as needed to control tachycardia, palpitations, and tremulousness up to a maximum of 100mg twice-daily regimen.[11]

Special Population

Pregnancy category D[12]

Use with caution in breastfeeding women

Patients with impaired renal function should be monitored, and the dose needs to be adjusted based on creatinine clearance.[7]

• CrCl MT 30 mL/minute: no dose adjustment needed.
• CrCl 10-30 mL/minute: maximum dose up to 50mg per day.
• CrCl LT 10  mL/minute: maximum dose up to 25mg per day.

Adverse Effects

According to product labeling following are the adverse effects of atenolol.

• Black Box Warning: Atenolol should not be stopped abruptly - doing so may result in exacerbation of angina, acute myocardial infarction, or ventricular arrhythmias.
• Common side effects include bronchospasm, bradycardia, diarrhea, dizziness, constipation, confusion, dyspnea, headache, heart failure, erectile dysfunction, nausea, fatigue, paraesthesia, peripheral coldness, rash, sleep disorders, syncope, visual impairment, and vomiting.
• Rare side effects include alopecia, dry mouth, hepatic disorders, depression, postural hypotension, psychosis, skin reactions, and thrombocytopenia. 
• Administering atenolol concurrently with amiodarone, digoxin, or verapamil may cause heart block, bradycardia, and left ventricular dysfunction.

Contraindications

• Contraindications to atenolol include sinus bradycardia, second or third-degree heart block, cardiogenic shock, heart failure, severe peripheral arterial disease, metabolic acidosis, and pheochromocytoma. It should also be avoided in patients with a history of asthma, bronchospasm, or other obstructive airway diseases unless there is no alternative, in which case it may be given alongside a bronchodilator.[13][14]
• Caution is necessary when prescribing to diabetic or thyroid patients as its effects may mask the symptoms of hypoglycemia and thyrotoxicosis - rapid withdrawal may also precipitate a thyroid storm.
• Prescribers should exercise caution during pregnancy - atenolol has been shown to cross the placental barrier and is associated with intrauterine growth restriction.[12]
• American Academy of Pediatrics advises against the use of atenolol during breastfeeding due to the risk of neonatal hypoglycemia and bradycardia.[15]

Monitoring

The elimination half-life of atenolol is approximately 6 to 7 hours. The beta-blocking effects manifest within an hour of ingesting a single oral dose and last for 24 hours. With an intravenous dose, effects are evident within 5 minutes but dissipate after 12 hours.

Unlike its other beta-1-blocking counterparts, there is little hepatic metabolism of atenolol - it is primarily renally excreted. Therefore, while no hepatic dosage adjustment is needed, it is imperative to assess renal function before starting treatment, with regular monitoring throughout the duration of treatment. In addition, impaired glomerular function results in a significant accumulation of the drug in the body; therefore, patients with creatinine clearance under 35 mL/min should receive much lower doses.[7]

Blood pressure and heart rate should also undergo periodic monitoring.[6]

Patients with a history of obstructive airway disease should have regular lung function tests, and patients with diabetes should monitor blood glucose levels[16]

Toxicity

Symptoms of atenolol toxicity may include bradycardia, lethargy, hypotension, respiratory drive disorders, hypothermia, hypoglycemia, and/or seizures. Treatment of beta-blocker toxicity is primarily supportive. Any unabsorbed drug (if administered orally) is removable by gastric lavage or activated charcoal (within 1 to 2 hours), while hemodialysis can remove atenolol from general systemic circulation.[17]

The use of inotropes and chronotropes such as intravenous epinephrine and atropine is a recommended measure for treating severe bradycardia. Usually, atropine is administered as a 0.5 mg IV or IO bolus and repeated every 3 to 5 minutes to a total dose of 3 mg. A transvenous cardiac pacemaker may be used in refractory cases or for the treatment of second or third-degree heart block. 

A titrated bolus of glucagon at a dose of 50 mcg/kg can improve myocardial contractility, atrioventricular conduction and increase heart rate in patients. Blood pressure must undergo continuous monitoring, and in cases of hypotension, vasopressors such as levarterenol are an option. For patients with bronchospasm, a beta-2 agonist such as aminophylline or isoproterenol may be used to alleviate symptoms. In cases that are refractory to the usual treatment, high dose insulin at 1 unit/kg bolus followed by 1 unit/kg per hour drip may be used to treat overdose in consultation with a toxicologist.[18]

In cases of asymptomatic, beta-1-blocker overdoses, the recommendation is to monitor the patient for at least 6 hours.[19] The use of atenolol is not recommended in children, as even small amounts can result in an overdose.

Enhancing Healthcare Team Outcomes

Beta-1-selective adrenergic antagonists such as atenolol are widely used worldwide to treat hypertension, angina, and myocardial infarction. Therefore, an interprofessional team including all physicians, pharmacists, and PAs/nurse practitioners must be aware of atenolol's side effects and contraindications. Nurses who administer the atenolol need to monitor for signs of adverse drug reactions actively and be mindful that the effects of the drug could mask the symptoms of hypoglycemia and thyrotoxicosis. Pharmacists should verify dosing based on the individual patient parameters and check for potential interactions that could alter therapeutic results. Nursing staff can counsel on medicine administration, verify patient adherence, assess regimen effectiveness on follow-up visits, and report concerns to the clinical team leader. The healthcare team involved in the patient's care must also ensure that they regularly monitor renal function, heart rate, and blood pressure. This interprofessional team approach will lead to therapeutic success and ensure an optimal outcome for the patients using atenolol. [Level V]