What are the potential interactions between metoprolol (beta-1 blocker) and propranolol (non-selective beta blocker)?

Metoprolol and Propranolol Interaction: Significant Risk of Additive Beta-Blockade

Concurrent use of metoprolol and propranolol should be avoided due to the significant risk of additive beta-blockade effects, which can lead to severe bradycardia, heart block, and hypotension. 1

Pharmacological Differences and Mechanism of Interaction

• Metoprolol is a beta-1 selective (cardioselective) adrenergic receptor blocker that primarily affects cardiac tissue, while propranolol is a non-selective beta blocker that affects both beta-1 and beta-2 receptors in cardiac tissue and bronchial/vascular smooth muscle 2, 3
• When used together, these medications can cause excessive beta-receptor blockade, resulting in profound bradycardia, hypotension, and heart block due to their overlapping mechanisms of action 1, 4
• At higher doses, metoprolol loses its cardioselectivity and also blocks beta-2 receptors, further increasing the risk of adverse effects when combined with propranolol 3

Clinical Risks and Adverse Effects

• The combination can lead to significant bradycardia, heart block, hypotension, and potential cardiovascular collapse 4
• Patients with pre-existing cardiac conduction disorders, sinus bradycardia, or heart failure are at particularly high risk for severe adverse effects 5
• The American College of Cardiology notes that both medications can cause marked first-degree AV block, second or third-degree heart block, and exacerbation of heart failure 5
• The risk of bronchospasm is increased, particularly in patients with asthma or COPD, as propranolol blocks beta-2 receptors in bronchial smooth muscle 6

Alternatives to Concurrent Use

• If beta blockade is needed, it is preferable to optimize the dose of a single beta blocker rather than combining two different agents 1
• For conditions requiring propranolol (such as essential tremor or migraine prophylaxis), consider alternative non-beta blocker treatments if the patient is already on metoprolol 1
• If additional antihypertensive effect is needed, consider adding agents from different classes such as calcium channel blockers, ACE inhibitors, or ARBs 1

Special Considerations

• Both medications undergo metabolism via CYP2D6, creating potential for drug interactions with other medications that inhibit this enzyme, such as certain antidepressants 7, 8
• Patients with impaired hepatic or renal function are at increased risk for adverse effects due to altered drug metabolism and clearance 4
• Abrupt discontinuation of either beta blocker can lead to rebound hypertension, worsening angina, or potential cardiac events, requiring gradual tapering 2

Monitoring Recommendations

• If concurrent use cannot be avoided in exceptional circumstances, close monitoring of heart rate, blood pressure, and cardiac rhythm is essential 1
• Patients should be educated about signs of excessive beta blockade: dizziness, fatigue, syncope, shortness of breath, or worsening heart failure symptoms 5
• Dose reduction of both medications may be necessary if used concurrently 1

Contraindications for Both Medications

• Both drugs are contraindicated in cardiogenic shock, marked sinus bradycardia, second or third-degree heart block without a pacemaker, and decompensated heart failure 5
• Caution is required in patients with bronchospastic disease, diabetes, and peripheral vascular disease 4, 3