Key drugs used in treating orthostatic hypotension
| Drug | Class | Advantages | Disadvantages | Comments |
|---|---|---|---|---|
| Fludrocortisone | Synthetic mineralocorticoid | Increases extracellular volume and blood pressure Increases sensitivity to catecholamines | Supine hypertension Edema Long-acting (half-life 18–36 hours) | Start at 0.1 mg daily; increase to 0.2 mg after 2 weeks Onset of action is not immediate; full effect takes several days to 1 week |
| Midodrine | Prodrug of desglymidodrine (a direct alpha-1 agonist) | Increases arterial and venous tone and blood pressure Short-acting (half-life 3–4 hours) | Supine hypertension Urinary retention | Start with 2.5 mg three times a day (TID) (early morning, lunchtime, late afternoon); avoid doses within 4–6 hours before bedtime Increase dose by 2.5 mg TID every 3–7 days until symptoms controlled or maximum dose of 10 mg TID reached Higher doses are approved for other indications, but there is a flat dose-response curve at doses above 10 mg |
| Droxidopa | Precursor of norepinephrine (after conversion by dopa decarboxylase) | Increases arterial and venous tone Short-acting (half-life 2.5 hours) | Supine hypertension | Start with 100 mg TID (early morning, lunch-time, late afternoon) Avoid doses within 4–6 hours before bedtime Increase dose by 100 mg TID every 3–7 days until symptoms controlled or maximum dose of 600 mg TID reached |
| Pyridostigmine | Anticholinesterase | Improves standing blood pressure without change in supine blood pressure Short-acting (half-life 3–4 hours) | Wheezing Abdominal pain Diarrhea Hyperhidrosis | Useful in patients with constipation with or without urinary hesitancy Start with a 30-mg test dose; if well tolerated, give 60 mg twice a day, increasing to TID after 1–2 weeks if tolerated Seldom used at doses > 90–120 mg TID Titrations made every 1–2 weeks |
| Atomoxetine | Selective norepinephrine reuptake inhibitor | Increases standing blood pressure | Supine hypertension Irritability Insomnia Aggressive behavior Suicidal ideation | Used in lower doses than for attention deficit hyperactivity disorder Start at 10 mg once daily in morning, increasing to 18 mg, then 25 mg once daily Higher doses avoided, though safe to use up to 50 mg daily Titrations made every 1–2 weeks Half-life 5 hours, active metabolites 6–8 hours |