What is the duration of action of midodrine?

Duration of Action of Midodrine

Midodrine has a duration of action of 2-3 hours, with some effect persisting for up to 4 hours after administration. 1

Pharmacokinetics and Mechanism

Midodrine is a prodrug that is rapidly absorbed after oral administration and converted to its active metabolite, desglymidodrine, which is responsible for its therapeutic effects:

• Absorption and Conversion:

  • Plasma levels of midodrine peak after approximately 30 minutes 1
  • Midodrine has a half-life of about 25 minutes 1
  • Desglymidodrine (active metabolite) reaches peak blood concentrations 1-2 hours after administration 1
  • Desglymidodrine has a half-life of 3-4 hours 1

• Mechanism of Action:

  • Desglymidodrine is an alpha-1 adrenergic agonist that activates alpha-adrenergic receptors in arteriolar and venous vasculature 1
  • This increases vascular tone and elevates blood pressure 1
  • It does not stimulate cardiac beta-adrenergic receptors or cross the blood-brain barrier significantly 1

Clinical Effects Timeline

The time course of midodrine's effects has been well-documented:

• Blood Pressure Effects:

  • Standing systolic blood pressure increases by approximately 15-30 mmHg at 1 hour after a 10 mg dose 1
  • Effects persist for 2-3 hours after administration 1
  • Blood pressure effects peak at 1 hour post-dose 2

• Symptom Relief:

  • Improvement in orthostatic symptoms (dizziness, lightheadedness, weakness) corresponds to the blood pressure effects 2, 3
  • The half-life of desglymidodrine (approximately 4 hours) correlates with the duration of clinical effect 2

Clinical Application

Based on the pharmacokinetic profile and duration of action:

• Dosing Schedule:

  • Midodrine is typically administered three times daily 4
  • The American Heart Association, American College of Cardiology, and Heart Rhythm Society recommend dosing ranges of 5-20 mg three times daily 4
  • The last dose should be taken at least 4 hours before bedtime to minimize the risk of supine hypertension 5

• Important Considerations:

  • The relatively short duration of action (2-3 hours) necessitates multiple daily doses for sustained effect 1, 2
  • Timing of doses should be planned around daily activities requiring upright posture 3
  • The final daily dose should not be taken later than 6 PM to avoid supine hypertension during sleep 1

Common Pitfalls and Caveats

• Supine Hypertension:

  • Occurs in up to 25% of patients taking midodrine 5
  • Risk can be reduced by timing the last dose at least 4 hours before bedtime 5

• Other Adverse Effects:

  • Piloerection, pruritus, paresthesias, and urinary retention are common side effects 5, 3
  • These side effects correlate with the duration of action of the medication

• Monitoring:

  • Regular blood pressure monitoring in both supine and standing positions is essential 4
  • The relatively short duration of action may leave patients vulnerable to orthostatic symptoms between doses