Atenolol

Atenolol is a water soluble, beta 1 selective blocker given once daily for hypertension, angina and rate control. It has low lipid solubility, so it causes fewer central effects but accumulates in kidney failure. Outcome evidence in hypertension is weaker than for other classes, so it is no longer a preferred first line antihypertensive.

Classification. Cardioselective (beta 1) blocker; no intrinsic sympathomimetic activity; hydrophilic.

Mechanism. Blocks beta 1 receptors in the heart, lowering heart rate, contractility and renin release. Selectivity is dose dependent and is lost at high doses.

Pharmacodynamics. Effect begins within 1 hour of an oral dose, peaks at 2 to 4 hours and lasts 24 hours. Little effect on bronchi at usual doses; masks tachycardia of hypoglycaemia.

Pharmacokinetics. Oral bioavailability about 50%. Half life 6 to 7 hours (prolonged in kidney impairment). Minimal liver metabolism; about 85% of an IV dose is excreted unchanged in urine. Crosses the placenta and accumulates in breast milk.

Hypertension, adult (not first line).

• Start 25 to 50 mg orally once daily.

• Increase after 1 to 2 weeks to 50 to 100 mg once daily.

• Maximum 100 mg daily; higher doses add little.

Angina, adult. 50 to 100 mg once daily; some markets allow 200 mg daily in divided doses.

Arrhythmia (rate control), adult. Oral 50 to 100 mg daily. IV 2.5 mg over 2.5 minutes, repeated every 5 minutes to a maximum of 10 mg.

Acute myocardial infarction, adult. 5 to 10 mg IV slowly (1 mg/minute) in selected haemodynamically stable patients, followed by 50 mg orally after 15 minutes and 12 hours, then 100 mg once daily; use is declining and early IV doses are not routinely advised.

Children, hypertension. 0.5 to 1 mg/kg once daily, increased as needed to a maximum 2 mg/kg daily or 100 mg daily.

Kidney dose adjustment. Creatinine clearance 15 to 35 mL/min: maximum 50 mg daily; under 15 mL/min: maximum 25 mg daily (or 50 mg every other day); haemodialysis: 25 to 50 mg after each session.

Contraindications. Second or third degree atrioventricular block; sick sinus syndrome; severe bradycardia; cardiogenic shock; decompensated heart failure; untreated phaeochromocytoma; severe peripheral arterial disease; metabolic acidosis; hypotension.

Warnings. Abrupt withdrawal can precipitate angina, myocardial infarction and arrhythmia; taper over 1 to 2 weeks. Masks signs of hypoglycaemia and thyrotoxicosis. Caution in asthma and chronic obstructive pulmonary disease (use only if essential and at the lowest dose). Worsens peripheral arterial disease. Fatigue and depression.

Adverse effects. Bradycardia, fatigue, cold extremities, dizziness, sleep disturbance, erectile dysfunction, bronchospasm at higher doses, heart failure in susceptible patients.

Interactions. Verapamil and diltiazem: bradycardia and heart block; never give IV verapamil to a patient on a beta blocker. Digoxin and amiodarone: bradycardia. Clonidine: rebound hypertension on withdrawal. Insulin and sulphonylureas: masking of hypoglycaemia. Non steroidal anti-inflammatory drugs reduce the antihypertensive effect. Adrenaline: unopposed alpha effect in anaphylaxis.

Special groups.

• Pregnancy: associated with foetal growth restriction, neonatal bradycardia and hypoglycaemia, especially if started in the first or second trimester; avoid and use labetalol or nifedipine.

• Breastfeeding: accumulates in milk; neonatal bradycardia and cyanosis reported; avoid or monitor the infant.

• Older adults: reduce dose with age related decline in kidney function.

• Kidney impairment: reduce the dose to the limits for each creatinine clearance band given in the dosing section.

• Liver impairment: no adjustment.

Overdose. Bradycardia, hypotension, bronchospasm and hypoglycaemia. Atropine 0.5 to 1 mg IV, glucagon 5 mg IV then infusion 1 to 5 mg/hour, high dose insulin with glucose, calcium, and haemodialysis (atenolol is dialysable).

Formulations. Tablets 25, 50 and 100 mg; injection 0.5 mg/mL; oral solution in some markets.

Administration. Oral once daily, with or without food. IV slow injection at a maximum rate of 1 mg/minute with continuous ECG and blood pressure monitoring.

Baseline. Heart rate, blood pressure, ECG, creatinine and eGFR, lung history.

Monitoring. Resting heart rate (hold or reduce for rate under 50 to 55/min), blood pressure, eGFR at least annually, symptoms of heart failure, glucose in diabetes.

Stopping. Taper over 1 to 2 weeks, especially with ischaemic heart disease.

Common prescribing errors. Not reducing the dose in kidney impairment; stopping abruptly; using it as first line hypertension therapy in patients of African ancestry; using it in pregnancy; combining with IV verapamil.