Why is a patient with thyrotoxicosis (condition of having too much thyroid hormone) and tachycardia (rapid heart rate) experiencing tiredness while on diltiazem (calcium channel blocker) 30 mg twice daily (BD)?

Diltiazem-Induced Fatigue in a Patient with Thyrotoxicosis and Tachycardia

The tiredness experienced by the patient with thyrotoxicosis on diltiazem 30 mg BD is likely due to excessive heart rate reduction and negative inotropic effects of the calcium channel blocker, which may be exacerbated in the setting of thyroid hormone excess. 1

Mechanisms of Fatigue in This Patient

• Excessive heart rate reduction: Diltiazem effectively lowers heart rate in thyrotoxicosis, with studies showing approximately 17% reduction in heart rate, which may cause fatigue if the reduction is too pronounced 2
• Negative inotropic effects: Calcium channel blockers like diltiazem have negative inotropic properties that can reduce cardiac output, particularly problematic in thyrotoxicosis where cardiac demands are increased 1
• Reflex sympathetic activation: Diltiazem may induce reflex sympathetic activation secondary to blood pressure reduction, which can paradoxically worsen symptoms in thyrotoxicosis 1
• Vasodilatory effects: The vasodilatory properties of diltiazem can cause hypotension, contributing to fatigue and tiredness 1

Appropriate Management of Tachycardia in Thyrotoxicosis

First-line Therapy

• Beta-blockers are first-line therapy for controlling ventricular rate in thyrotoxicosis-associated tachycardia and should be used unless contraindicated 1
• Beta-blockers are more effective for rate control in thyrotoxicosis, achieving heart rate endpoints in approximately 70% of patients compared to 54% with calcium channel blockers 1
• Beta-blockers also address the peripheral manifestations of thyrotoxicosis (tremor, anxiety) that calcium channel blockers do not 3

Second-line Therapy

• Non-dihydropyridine calcium channel antagonists (diltiazem or verapamil) should only be used when beta-blockers are contraindicated 1
• When using calcium channel blockers in thyrotoxicosis:
  • Start with lower doses and titrate carefully to avoid excessive rate reduction 1, 2
  • Monitor for symptoms of fatigue which may indicate excessive rate control 2, 4
  • Consider dose adjustment rather than discontinuation if the medication is otherwise effective 4

Clinical Considerations for This Patient

• Dose adjustment: The current dose of diltiazem (30 mg BD) may be excessive for this patient, causing undue fatigue through excessive rate control 2
• Alternative therapy: Consider switching to a beta-blocker if not contraindicated, as this is the preferred first-line therapy for thyrotoxicosis with tachycardia 1
• Underlying thyroid management: Ensure appropriate treatment of the underlying thyrotoxicosis, as definitive management will ultimately resolve the tachycardia 1, 3
• Monitoring: Regular assessment of heart rate, blood pressure, and symptoms is essential to optimize therapy 2, 4

Important Caveats

• Avoid abrupt discontinuation: If changing therapy, taper diltiazem to prevent rebound tachycardia 1
• Contraindications to beta-blockers: If the patient has contraindications to beta-blockers (e.g., asthma, COPD), diltiazem remains an appropriate choice but may require dose adjustment 1
• Atrial fibrillation risk: Patients with thyrotoxicosis have a 10-25% risk of developing atrial fibrillation, which requires appropriate anticoagulation assessment 1
• Avoid certain medications: In patients with thyrotoxicosis and Wolff-Parkinson-White syndrome with pre-excited AF, calcium channel blockers are contraindicated 1

By addressing the medication regimen appropriately, the patient's symptoms of fatigue should improve while maintaining adequate control of the thyrotoxicosis-related tachycardia.