Can metoprolol cause toe arthralgia or paresthesia?

Can Metoprolol Cause Toe Pain or Numbness?

Yes, metoprolol can cause toe pain and numbness through peripheral vasoconstriction, particularly in patients with underlying peripheral vascular disease, though this is not a direct toxic effect of the drug but rather a consequence of beta-blockade reducing peripheral blood flow.

Mechanism of Peripheral Symptoms with Beta-Blockers

Beta-blockers, including metoprolol, can induce Raynaud's phenomenon and peripheral circulatory symptoms through unopposed alpha-adrenergic vasoconstriction when beta-2 mediated vasodilation is blocked 1. This manifests as:

• Cold extremities (hands and feet) occurring in approximately 50% of patients on beta-blockers compared to only 5% on other antihypertensives like methyldopa 1
• Numbness and pain in the toes and fingers, particularly in patients with pre-existing peripheral arterial disease 1
• Worsening of claudication symptoms in some patients, though this effect appears less pronounced with beta-1 selective agents like metoprolol 2

Beta-1 Selectivity Provides Some Protection

Metoprolol's beta-1 selectivity offers theoretical advantages over non-selective beta-blockers:

• Lower incidence of peripheral symptoms compared to propranolol, with the frequency of cold extremities and absent pulses being highest with non-selective agents 1
• Maintained walking distance in patients with intermittent claudication, with one study showing pain-free walking distance actually increased from 225 to 348 meters during 8 weeks of metoprolol treatment 2
• No significant decrease in peripheral blood flow measured by Doppler pressure or venous occlusion plethysmography in patients with peripheral vascular disease 2

Critical Clinical Context: Rule Out Alternative Causes

Before attributing toe symptoms to metoprolol, you must systematically exclude more serious etiologies:

Diabetic Neuropathy

• Assess for diabetes as the primary cause of toe numbness, since diabetic peripheral neuropathy commonly presents with numbness, tingling, and burning in the feet 3
• Perform 10-g monofilament testing along with at least one other assessment (pinprick, temperature, or vibration) to evaluate for loss of protective sensation 3
• Obtain history of diabetes duration, glycemic control, and other microvascular complications 3

Peripheral Arterial Disease

• Check pedal pulses bilaterally, as absent pulses strongly correlate with cold extremities and increase likelihood of ischemic symptoms 1, 3
• Refer for ankle-brachial index if claudication symptoms are present or pedal pulses are decreased or absent 3
• Assess for vascular risk factors including smoking history, which significantly increases risk of peripheral arterial disease 3

Medication-Induced Neuropathy

• Review all medications for neurotoxic agents including chemotherapy, which can cause peripheral neuropathy independent of metoprolol 3
• Check vitamin B12 levels, as deficiency can mimic or exacerbate neuropathic symptoms 3

Management Algorithm

Step 1: Determine Temporal Relationship

• Document symptom onset relative to metoprolol initiation or dose increase
• If symptoms began within weeks of starting metoprolol and no other risk factors exist, drug-related etiology is more likely

Step 2: Assess Severity and Impact

• Mild symptoms (occasional cold toes without pain): Continue metoprolol with patient education and monitoring
• Moderate symptoms (persistent coldness with intermittent pain): Consider switching to a different antihypertensive class
• Severe symptoms (constant pain, color changes, or functional impairment): Discontinue metoprolol immediately and evaluate for critical limb ischemia

Step 3: Consider Alternative Beta-Blocker or Drug Class

• Switch to a different beta-1 selective agent like atenolol if metoprolol is strongly indicated for cardiac reasons 3
• Transition to alternative antihypertensive classes such as ACE inhibitors (enalapril) or calcium channel blockers if beta-blockade is not specifically required 3
• Avoid non-selective beta-blockers like propranolol, which have higher rates of peripheral symptoms 1

Common Pitfalls to Avoid

• Do not dismiss peripheral symptoms in diabetic patients as solely neuropathic without evaluating vascular status, as both conditions frequently coexist 3
• Do not continue metoprolol in patients with critical limb ischemia or severe peripheral arterial disease with rest pain 1, 2
• Do not assume all toe numbness is drug-related without performing comprehensive foot examination including neurological and vascular assessment 3
• Do not overlook orthostatic hypotension as a contributor to symptoms, particularly in diabetic patients where metoprolol may be used to treat supine hypertension associated with autonomic neuropathy 3

When Metoprolol Can Be Continued

Metoprolol is not contraindicated in patients with mild to moderate peripheral vascular disease (intermittent claudication, Fontaine stage II), as studies demonstrate it does not significantly worsen walking distance and may be well tolerated 2. However, this requires:

• Careful monitoring of symptoms and peripheral pulses
• Patient education about warning signs of worsening ischemia
• Regular reassessment of risk-benefit ratio, particularly if symptoms progress