Does midodrine (alpha-adrenergic agonist) cause tachycardia (increased heart rate)?

Midodrine and Heart Rate Effects

Midodrine typically causes a slight slowing of the heart rate (bradycardia) rather than increasing heart rate, primarily due to vagal reflex mechanisms. 1

Mechanism of Action and Cardiovascular Effects

• Midodrine is a prodrug that is converted to its active metabolite, desglymidodrine, which acts as an alpha-1 adrenergic receptor agonist 1
• Desglymidodrine causes vasoconstriction of arteriolar and venous vasculature, increasing vascular tone and elevating blood pressure 1
• Unlike some other vasopressors, desglymidodrine does not stimulate cardiac beta-adrenergic receptors, which would typically increase heart rate 1
• A slight slowing of heart rate (bradycardia) may occur after administration of midodrine, primarily due to vagal reflex in response to the increased blood pressure 1

Clinical Evidence

• The FDA drug label specifically notes that midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure 1
• The American Journal of Kidney Diseases recommends monitoring for bradycardia as midodrine is associated with reflex parasympathetic stimulation 2
• In overdose cases, midodrine has been associated with severe hypertension and reflex bradycardia 3
• One older study from 1986 did report heart rate increases after 5-10 mg doses of midodrine that were statistically significant at 120 minutes 4, but this finding is inconsistent with more recent evidence and FDA labeling

Precautions and Monitoring

• Caution should be exercised when midodrine is used concomitantly with cardiac glycosides (such as digitalis), psychopharmacologic agents, beta blockers, or other agents that directly or indirectly reduce heart rate 1
• The American Journal of Kidney Diseases advises avoiding concomitant use with other negative chronotropic agents (beta-blockers, digoxin, non-dihydropyridine calcium channel blockers) due to increased risk of bradycardia 2
• Patients who experience signs or symptoms suggesting bradycardia (pulse slowing, increased dizziness, syncope, cardiac awareness) should be advised to discontinue midodrine and be re-evaluated 1

Clinical Implications

• When prescribing midodrine, clinicians should be aware that the expected cardiovascular effect is increased blood pressure with potential bradycardia, not tachycardia 2, 1
• In a study of healthy volunteers, midodrine was found to decrease heart rate from 57.2 to 54.9 bpm (P = 0.022) at maximum concentration 5
• The same study found a significant correlation between desglymidodrine concentration and heart rate reduction 5

Common Pitfalls

• Assuming midodrine increases heart rate like other vasopressors that have beta-adrenergic effects can lead to inappropriate prescribing 1
• Failing to monitor for bradycardia, especially when midodrine is combined with other medications that slow heart rate 2, 1
• Not recognizing that the parasympathetic reflex bradycardia is a normal physiologic response to the increased blood pressure caused by midodrine 1