Atenolol

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]

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. Due to lack of membrane stabilizing or intrinsic sympathomimetic activity, atenolol has low lipid solubility, and reduced brain penetrance is thereby 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 for the treatment of supraventricular tachycardia and the prevention of 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.

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. 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 or a maximum dose of 50 mg a day if the creatinine clearance is 15 to 35 ml/min. Careful monitoring of their blood pressure before administering a new dose is necessary.

Angina Pectoris: 

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.

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. 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. 

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. 

Atenolol should not be stopped abruptly - doing so may result in exacerbation of angina, acute myocardial infarction, or ventricular arrhythmias. Administering atenolol concurrently with amiodarone, digoxin, or verapamil may cause heart block, bradycardia, and left ventricular dysfunction.

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.[5][6]

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. Use during breastfeeding is recommended against by the American Academy of Pediatrics due to a risk of neonatal hypoglycemia and bradycardia.[7]