Propranolol

Propranolol is a non selective beta adrenergic blocker with membrane stabilising activity and high lipid solubility. It is used in hypertension, angina, arrhythmia, migraine prophylaxis, essential tremor, thyrotoxic symptoms, portal hypertension and infantile haemangioma. It crosses the blood brain barrier and the placenta.

Classification. Non selective beta 1 and beta 2 blocker; no intrinsic sympathomimetic activity.

Mechanism. Competitively blocks beta 1 receptors in the heart, lowering heart rate, contractility and renin release, and beta 2 receptors in bronchi, vessels and metabolism. At high doses it blocks sodium channels (a toxic effect in overdose).

Pharmacodynamics. Heart rate falls within 1 hour of an oral dose; effect lasts 6 to 12 hours for immediate release and 24 hours for long acting forms. Raises airway resistance, blunts the response to hypoglycaemia and can worsen peripheral perfusion.

Pharmacokinetics. Oral absorption nearly complete but extensive first pass metabolism leaves bioavailability about 25%, with wide variation between patients. Half life 3 to 6 hours. Hepatic metabolism by CYP2D6 and CYP1A2; metabolites excreted in urine.

Hypertension, adult.

• Start 40 mg orally twice daily (or 80 mg long acting once daily).

• Increase at weekly intervals; usual maintenance 80 to 160 mg twice daily.

• Maximum 640 mg daily. Not first line, particularly in patients of African ancestry, who respond less to beta blocker monotherapy.

Angina, adult. 40 mg two or three times daily, increased to 120 to 240 mg daily in divided doses.

Arrhythmia, adult. Oral 10 to 40 mg three or four times daily. IV: 1 mg over 1 minute, repeated every 2 minutes if needed, to a maximum of 10 mg, with continuous ECG and blood pressure; keep atropine ready.

Secondary prevention after myocardial infarction. 40 mg three times daily, increased to 180 to 240 mg daily; selective agents are preferred.

Migraine prophylaxis, adult. 40 mg two or three times daily, usual 80 to 160 mg daily, maximum 240 mg; review at 8 to 12 weeks.

Essential tremor, adult. 40 mg twice daily, increased to 120 to 240 mg daily.

Thyrotoxicosis symptoms, adult. 10 to 40 mg three or four times daily until the patient is euthyroid. In thyroid storm: 60 to 80 mg orally every 4 hours under specialist direction, with monitoring.

Portal hypertension (variceal bleeding prevention), adult. Start 20 mg twice daily; titrate every 2 to 3 days to a resting heart rate of 55 to 60/min; maximum 160 mg daily without ascites and 80 mg daily with ascites; hold if systolic pressure is under 90 mmHg.

Infantile haemangioma, specialist. Start 0.5 to 1 mg/kg daily in 2 or 3 divided doses; increase weekly to 2 to 3 mg/kg daily (maximum 3 mg/kg daily). Give with feeds, hold during illness with poor feeding, and monitor glucose, heart rate and blood pressure after the first dose and each increase.

Situational anxiety (off label). 10 to 40 mg one hour before the event.

Contraindications. Asthma and bronchospasm; second or third degree atrioventricular block; sick sinus syndrome; severe bradycardia; cardiogenic shock; decompensated heart failure; severe peripheral arterial disease; untreated phaeochromocytoma; Prinzmetal angina; hypotension; metabolic acidosis.

Warnings. Abrupt withdrawal can precipitate angina, myocardial infarction and arrhythmia; taper over 1 to 2 weeks. Masks tachycardia and tremor of hypoglycaemia (sweating persists); caution in diabetes. Hypoglycaemia in neonates and children with poor feeding. Do not give IV verapamil to a patient taking a beta blocker (asystole). Worsens psoriasis and Raynaud phenomenon. Depression and fatigue.

Adverse effects. Bradycardia, fatigue, cold extremities, bronchospasm, sleep disturbance and vivid dreams, dizziness, impotence, hypoglycaemia masking, heart failure in susceptible patients.

Interactions. Verapamil and diltiazem: bradycardia and heart block. Digoxin and amiodarone: bradycardia. Clonidine: rebound hypertension on withdrawal. Insulin and sulphonylureas: masking of hypoglycaemia. Rifampicin lowers levels. Cimetidine and fluoxetine raise levels. Adrenaline: unopposed alpha effect with severe hypertension and bradycardia in anaphylaxis. Anaesthetics add myocardial depression.

Special groups.

• Pregnancy: may cause foetal growth restriction, neonatal bradycardia and hypoglycaemia; use only when benefit outweighs risk and monitor growth and the neonate.

• Breastfeeding: small amounts in milk; compatible with infant observation.

• Children: weight based doses; hypoglycaemia risk.

• Older adults: start at 10 to 20 mg; higher exposure and sensitivity.

• Kidney impairment: no adjustment; monitor in severe impairment.

• Liver impairment: reduce dose and monitor; bioavailability rises.

Overdose. Bradycardia, hypotension, hypoglycaemia, seizures and QRS widening. Give atropine 0.5 to 1 mg IV, glucagon 5 mg IV bolus (up to 10 mg) then 1 to 5 mg/hour infusion, high dose insulin with glucose, calcium, and sodium bicarbonate for QRS widening; seek toxicology advice.

Formulations. Tablets 10, 40, 80 mg; long acting capsules 80 and 160 mg; oral solution; injection 1 mg/mL.

Administration. Oral, consistently with or without food (food raises bioavailability). IV: slow injection over at least 1 minute; infusion in 5% glucose or 0.9% sodium chloride in monitored settings.

Baseline. Pulse, blood pressure, ECG, lung function or asthma history, glucose, liver function.

Monitoring. Resting heart rate (aim over 50 to 60/min), blood pressure, ECG at higher doses, wheeze, glucose in children and diabetes, signs of heart failure.

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

Common prescribing errors. Using it in asthma; stopping abruptly; combining with IV verapamil; omitting glucose checks in infants; using it as sole first line therapy for hypertension in patients of African ancestry.