Recommended Oral Vasopressor for Orthostatic Hypotension
Midodrine is the recommended first-line oral vasopressor for symptomatic orthostatic hypotension, initiated at 2.5-5 mg three times daily, with the last dose taken at least 3-4 hours before bedtime to prevent supine hypertension. 1, 2
Mechanism and Efficacy
Midodrine is a prodrug that converts to desglymidodrine, a selective alpha-1 adrenergic agonist that increases vascular tone through arteriolar and venous vasoconstriction without cardiac beta-receptor stimulation 2
Standing systolic blood pressure increases by approximately 15-30 mmHg at 1 hour after a 10 mg dose, with effects persisting for 2-3 hours 1, 2
Midodrine has the strongest evidence base among pressor agents, supported by three randomized placebo-controlled trials demonstrating significant improvements in standing blood pressure, symptoms of lightheadedness, dizziness, and global symptom relief 1, 3
Dosing Algorithm
Titration: Increase individually up to 10 mg three times daily based on symptom response and blood pressure monitoring 1
Timing: Administer doses during daytime hours when the patient needs to be upright; the last dose must be taken at least 3-4 hours before bedtime (not later than 6 PM) 1, 2
Special populations: In patients with renal impairment, start at 2.5 mg due to renal elimination of the active metabolite 2
Critical Monitoring Requirements
Measure blood pressure after 5 minutes of lying/sitting, then at 1 and 3 minutes after standing to document orthostatic changes 1
Monitor for supine hypertension: This occurs in up to 22-25% of patients on 10 mg doses and is the most important limiting factor 1, 2
Patients should report symptoms of supine hypertension immediately (cardiac awareness, pounding in ears, headache, blurred vision) and discontinue medication if it persists 2
Monitor for bradycardia, particularly when used with cardiac glycosides, beta-blockers, or other agents that reduce heart rate 2
Alternative and Adjunctive Agents
Fludrocortisone (0.05-0.1 mg daily) can be added if midodrine alone provides insufficient symptom control, acting through sodium retention and vessel wall effects 1
Droxidopa is FDA-approved and particularly effective for neurogenic orthostatic hypotension in Parkinson's disease, pure autonomic failure, and multiple system atrophy 1
Pyridostigmine may be beneficial in patients refractory to other treatments, with a favorable side effect profile and no risk of supine hypertension or fluid retention 4, 1
Common Pitfalls to Avoid
Do not administer midodrine after 6 PM as this significantly increases the risk of nocturnal supine hypertension 1
Do not use in patients with severe supine hypertension (>180/110 mmHg), as midodrine can cause marked elevation of supine blood pressure (>200 mmHg systolic) 2
Use caution when combining with other vasoconstrictors (phenylephrine, pseudoephedrine, ephedrine) or MAO inhibitors, as this increases hypertension risk 2
Avoid in patients with urinary retention problems, as desglymidodrine acts on alpha-adrenergic receptors of the bladder neck 2
Non-Pharmacological Adjuncts
Increase fluid intake to 2-3 liters daily and salt intake to 6-9 grams daily unless contraindicated by heart failure 1
Use waist-high compression stockings (30-40 mmHg) and abdominal binders to reduce venous pooling 1
Elevate the head of the bed by 10 degrees during sleep to prevent nocturnal polyuria and ameliorate supine hypertension 1
Teach physical counter-maneuvers (leg crossing, squatting, muscle tensing) during symptomatic episodes, particularly effective in patients under 60 years 1
Treatment Goals
The therapeutic objective is minimizing postural symptoms and improving functional capacity, not restoring normotension 1
Continue midodrine only in patients who report significant symptomatic improvement after initiation 2
Reassess within 1-2 weeks after medication changes to evaluate efficacy and monitor for adverse effects 1