What is the recommended protocol for propranolol (beta-blocker) titration?

Propranolol Titration Protocol

For adult hypertension and angina, start propranolol immediate-release at 80 mg daily in 2 divided doses (or 80 mg once daily for extended-release), then titrate upward every 3-7 days based on clinical response, with typical maintenance doses of 120-160 mg daily for hypertension and 160-240 mg daily for angina, up to a maximum of 640 mg daily if needed. 1, 2

Pre-Treatment Assessment

Before initiating propranolol, perform the following mandatory screening:

• Cardiovascular examination including heart rate, blood pressure measurement, and cardiac auscultation 1
• ECG and echocardiogram only in patients with suspected cardiac abnormalities or segmental head/neck conditions (not routinely required in healthy adults) 3, 1
• Screen for absolute contraindications: second or third-degree heart block, decompensated heart failure, asthma/obstructive airway disease, cardiogenic shock, sinus node dysfunction without pacemaker 3, 1
• Assess for relative contraindications: history of bronchospasm, diabetes (propranolol masks hypoglycemia symptoms), hypotension, concurrent medications affecting cardiac conduction 3, 1

Standard Adult Titration Protocol

Hypertension

• Starting dose: 80 mg daily in 2 divided doses (immediate-release) OR 80 mg once daily (extended-release) 1, 2
• Titration schedule: Increase gradually at intervals of several days to weeks based on blood pressure response 2
• Maintenance dose: 120-160 mg once daily 1, 2
• Maximum dose: 640 mg daily if needed 1, 2
• Time to full response: Variable, ranging from days to several weeks at any given dose 2

Angina Pectoris

• Starting dose: 80 mg once daily (extended-release) 2
• Titration schedule: Increase gradually at 3-7 day intervals until optimal response 2
• Maintenance dose: Average optimal dose is 160 mg once daily 2
• Maximum dose: 320 mg daily (safety and efficacy beyond this not established for angina) 2
• Higher doses for severe angina: In patients with more than mild angina, average optimal dosage may be 500-800 mg daily 4

Migraine Prophylaxis

• Starting dose: 80 mg once daily (extended-release) 2
• Maintenance dose: 160-240 mg once daily 2
• Trial duration: If no satisfactory response within 4-6 weeks at maximal dose, discontinue therapy 2

Hypertrophic Subaortic Stenosis

• Usual dosage: 80-160 mg once daily (extended-release) 2

Special Population Considerations

Elderly Patients

• Lower doses required due to altered pharmacokinetics 1
• Start at the lower end of dosing ranges and titrate more cautiously 1

Patients with Comorbidities

• Reduce doses in patients experiencing adverse effects or those with conditions increasing risk 1
• Consider starting at lower doses and slower titration schedules 1

Monitoring During Titration

Routine Monitoring

• No routine vital sign monitoring required between appointments if patient is stable and asymptomatic 1
• Monitor for hypotension and bradycardia, especially during dose escalation 1
• Blood glucose monitoring only needed in patients at risk for hypoglycemia 5

Signs of Adequate Beta-Blockade

• Target heart rate: Some protocols aim for supine heart rate of 55-60 beats/minute, though this is not universally required 4
• Therapeutic plasma levels: Maximum therapeutic benefit typically occurs at 30 ng/mL plasma propranolol, though plasma levels are not a practical guide to therapy 6
• Degree of beta-blockade: Maximum therapeutic response in angina occurs between 64-98% of total beta-blockade 6

Critical Safety Considerations

Adverse Effects to Monitor

• Common: Fatigue, bradycardia, hypotension, dizziness, cold extremities 1
• Serious: Worsening heart failure, bronchospasm, severe bradycardia 3, 1
• Metabolic: Masking of hypoglycemia symptoms in diabetic patients 3

Discontinuation Protocol

• Never abruptly discontinue propranolol, especially after chronic use 1, 2, 7
• Taper gradually over several weeks to prevent rebound hypertension, tachycardia, or angina 1, 2
• Prolonged small-dose tapering: Reduce to 30 mg daily for 2 weeks before complete withdrawal to prevent withdrawal syndrome and enhanced beta-adrenergic sensitivity 7
• Serial dose reduction alone (over 6-9 days) decreases but does not fully prevent cardiac hypersensitivity 7

Temporary Discontinuation

• Hold doses during significantly reduced oral intake or vomiting 3
• Temporarily discontinue if patient has wheezing requiring treatment 3

Common Pitfalls and Caveats

Formulation Considerations

• Extended-release is NOT mg-for-mg equivalent to immediate-release formulations 2
• Extended-release produces lower blood levels and different kinetics; retitration may be necessary when switching 2
• Once-daily dosing: Studies show regular-release propranolol can be given once daily for hypertension, though some loss of control may occur at end of dosing interval 8

Drug Interactions

• Avoid routine combination with non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to increased risk of bradycardia and heart block 3, 1
• Both drug classes slow AV node conduction and have negative inotropic effects 3

Dose-Response Relationship

• Variable individual response: The dose producing optimal therapeutic effect varies widely among patients 4, 6
• Plasma levels not predictive: Wide variation in both dose and plasma concentration at maximum therapeutic response makes plasma levels impractical for guiding therapy 6
• No dose-dependent effect at higher ranges: In some conditions (e.g., portal hypertension), increasing from 80 to 120 mg daily shows no additional hemodynamic benefit but increases intolerance 9

Titration Speed

• Greatest risk at initiation: Most dramatic change in sympathetic environment occurs when starting treatment, making this the highest risk period for precipitating heart failure even with small doses 4
• Safer to increase gradually: Once treatment begun, even 25% dose increases represent small pharmacological increments with lower risk 4
• Minimum interval: Allow at least 24 hours between dose increases in pediatric populations 5