What is the effect of Midodrine on orthostatic hypotension?

Midodrine Effect on Orthostatic Hypotension

Midodrine effectively elevates standing systolic blood pressure by approximately 15-30 mmHg at 1 hour after a 10 mg dose in patients with orthostatic hypotension, with effects persisting for 2-3 hours, significantly improving symptoms such as dizziness and lightheadedness. 1

Mechanism of Action

Midodrine is a prodrug that is converted to its active metabolite, desglymidodrine, which:

• Acts as an alpha-1 adrenergic receptor agonist 1
• Increases vascular tone in arteriolar and venous vasculature 1
• Elevates blood pressure without stimulating cardiac beta-adrenergic receptors 1
• Does not cross the blood-brain barrier significantly, minimizing central nervous system effects 1

Clinical Efficacy

Midodrine demonstrates significant clinical benefits for orthostatic hypotension:

• Increases standing systolic blood pressure by 15-30 mmHg at 1 hour after a 10 mg dose 1
• Improves symptoms including dizziness, lightheadedness, and syncope 1
• Effects typically persist for 2-3 hours after dosing 1
• Recommended dosage is 5-20 mg three times daily for symptomatic orthostatic hypotension refractory to non-pharmacological measures 2
• In controlled trials, midodrine significantly improved standing time and reduced orthostatic symptoms compared to placebo 3

Pharmacokinetics

• Rapidly absorbed after oral administration with 93% bioavailability 1
• Prodrug peaks at 30 minutes with a half-life of 25 minutes 1
• Active metabolite (desglymidodrine) peaks at 1-2 hours with a half-life of 3-4 hours 1
• Food does not affect bioavailability 1
• Primarily eliminated by renal clearance (80% by active secretion) 1

Monitoring and Precautions

Key Monitoring Parameters

• Blood pressure in both supine and standing positions 2
• Symptom improvement (dizziness, lightheadedness, syncope) 2
• Signs of supine hypertension 1

Important Precautions

• Supine hypertension risk: The last daily dose should be taken at least 3-4 hours before bedtime to minimize nighttime supine hypertension 1
• Caution with concomitant use of other vasoconstrictors (phenylephrine, ephedrine, etc.) 1
• Monitor for bradycardia when used with cardiac glycosides or beta-blockers 1
• Use cautiously in patients with urinary retention problems 1
• Adjust dosing in renal impairment (starting with 2.5 mg) 1

Common Pitfalls to Avoid

• Administering vasopressors too close to bedtime, increasing supine hypertension risk 2
• Focusing solely on blood pressure numbers rather than symptom improvement 2
• Inadequate monitoring for supine hypertension 2
• Overlooking non-pharmacological measures before starting pharmacological treatment 2

Algorithm for Management of Orthostatic Hypotension

1. First-line: Non-pharmacological measures

   • Increased fluid intake (2-3 liters daily)
   • Compression garments (30-40 mmHg pressure)
   • Small, frequent meals with reduced carbohydrates
   • Physical counterpressure maneuvers
   • Increased salt intake (6-9g daily)

2. Second-line: Pharmacological treatment with midodrine

   • Initial dose: 5 mg three times daily
   • Titrate up to 10-20 mg three times daily as needed
   • Last dose no later than 6 PM or at least 3-4 hours before bedtime
   • Monitor for supine hypertension

3. Alternative pharmacological options if midodrine inadequate:

   • Fludrocortisone (0.1 mg daily) for suspected hypovolemia
   • Droxidopa (100-600 mg three times daily) for neurogenic orthostatic hypotension
   • Pyridostigmine (30 mg 2-3 times daily) for refractory cases