What are the guidelines for using Propanolol (a beta-blocker) in treating hypertension and angina?

Propranolol for Hypertension and Angina

Dosing for Angina Pectoris

For angina, start propranolol at 20-80 mg twice daily and titrate upward to achieve a resting heart rate of 50-60 beats per minute, with typical effective doses ranging from 160-320 mg daily in divided doses. 1

• Propranolol lacks beta-1 selectivity, meaning it blocks both cardiac (beta-1) and bronchial/vascular (beta-2) receptors 1
• The drug has no intrinsic sympathomimetic activity, which is preferred for acute coronary syndromes 1
• Studies in acute settings have validated propranolol alongside metoprolol and atenolol for unstable angina/NSTEMI 1

Intravenous Administration for Acute Angina

• Give 0.5-1.0 mg IV as initial dose, followed in 1-2 hours by 40-80 mg orally every 6-8 hours 1
• IV administration may be warranted for ongoing rest pain with tachycardia or hypertension 1
• Monitor heart rate, blood pressure, and ECG continuously during IV therapy 1

Oral Dosing Strategy

• Extended-release formulation: start 80 mg once daily, increase to 120-160 mg once daily for maintenance 2
• Average optimal dose for angina appears to be 160 mg once daily with extended-release formulation 2
• Maximum studied dose is 320 mg daily; safety beyond this has not been established 2
• Dose-response studies show progressive reduction in angina attacks up to 417 mg daily average dose 3

Dosing for Hypertension

For hypertension, initiate propranolol extended-release at 80 mg once daily and titrate to 120-160 mg once daily for maintenance, with maximum doses up to 640 mg daily if needed. 2

• Usual maintenance dose is 120-160 mg once daily 2
• Full hypertensive response may take several days to weeks 2
• Extended-release formulation provides sustained beta-blockade over 24 hours with once-daily dosing 4

Important Conversion Considerations

• Propranolol extended-release is NOT a simple mg-for-mg substitute for immediate-release formulation 2
• Extended-release produces lower blood levels than equivalent doses of immediate-release 2
• When switching from immediate-release to extended-release, retitration upward may be necessary 2
• Metoprolol 50 mg twice daily is approximately equivalent to propranolol 80-100 mg twice daily 5

Absolute Contraindications

Do not administer propranolol in patients with marked AV block (PR >0.24s), second- or third-degree heart block without pacemaker, history of asthma, severe LV dysfunction/heart failure, or high risk for cardiogenic shock. 1

• Patients with systolic BP <90 mmHg should not receive acute beta-blocker therapy 1
• Heart rate <50 bpm is a contraindication to acute administration 1
• Evidence of low-output state (oliguria) requires resolution before initiating therapy 1
• Risk factors for cardiogenic shock include older age, female sex, higher Killip class, lower BP, and higher heart rate 1

Special Populations and Precautions

Chronic Obstructive Pulmonary Disease

• Use propranolol very cautiously in COPD patients with reactive airway component 1
• If beta-blocker is needed in patients with mild wheezing or COPD, choose a beta-1 selective agent like metoprolol at reduced dose (12.5 mg) rather than propranolol 1
• Propranolol's non-selective blockade causes bronchoconstriction via beta-2 receptor inhibition 1

Heart Failure Considerations

• Beta-blockers are strongly recommended before discharge in patients with compensated HF or LV systolic dysfunction for secondary prevention 1
• Avoid in acute decompensated heart failure (rales, S3 gallop) 1
• Early aggressive beta-blockade poses substantial hazard in hemodynamically unstable patients 1

Mechanism of Action and Clinical Effects

• Propranolol reduces myocardial oxygen demand by decreasing heart rate, systolic blood pressure, and myocardial contractility 1
• Slowing heart rate increases diastolic duration, improving coronary perfusion and collateral flow 1
• In angina, propranolol delays onset of pain and increases work capacity during exercise 2
• Antihypertensive effects may involve decreased cardiac output, renin inhibition, and reduced sympathetic outflow 2

Pharmacokinetics

• Propranolol is highly lipophilic with nearly complete oral absorption but undergoes extensive first-pass metabolism 2
• Only 25% reaches systemic circulation on average 2
• Extended-release formulation peaks at approximately 6 hours 2
• Terminal half-life of extended-release is 8-11 hours vs. shorter for immediate-release 4
• 90% protein bound (albumin and alpha-1-acid glycoprotein) 2

Critical Warnings

Abrupt Discontinuation

• Never abruptly discontinue propranolol—taper gradually over several weeks to prevent rebound hypertension, worsening angina, myocardial infarction, and ventricular arrhythmias 2, 6
• Sudden withdrawal eliminates therapeutic benefit and may precipitate acute myocardial ischemia 6

Drug Interactions

• Propranolol increases nifedipine concentrations by 64% (Cmax) and 79% (AUC) 2
• Cimetidine increases propranolol AUC by 46% and Cmax by 35% 2
• Cholestyramine or colestipol decrease propranolol concentrations up to 50% 2
• Propranolol increases warfarin bioavailability and prothrombin time 2
• Zolmitriptan AUC increases 56% and rizatriptan AUC increases 67% when combined with propranolol 2

Monitoring Parameters

• Target resting heart rate: 50-60 beats per minute unless limiting side effects occur 1
• Check blood pressure approximately 5 minutes after local anesthesia in dental procedures to detect hypertensive response 6
• Monitor for signs of heart failure, bronchospasm, and hypotension during initiation 1
• In hypertensive emergency from propranolol-epinephrine interaction, use phentolamine 5 mg IV or sublingual nitroglycerin 0.4 mg 6