From the Guidelines
Midodrine works as an alpha-1 adrenergic receptor agonist to increase blood pressure in patients with orthostatic hypotension, and its mechanism of action involves the stimulation of alpha-1 receptors in blood vessels, causing vasoconstriction of both arteries and veins. The typical dosing regimen is 2.5-10 mg taken three times daily, with the last dose at least 4 hours before bedtime to avoid supine hypertension, as recommended by the 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope 1. When taken orally, midodrine is rapidly converted to its active metabolite, desglymidodrine, which stimulates alpha-1 receptors in blood vessels, causing vasoconstriction of both arteries and veins. This vasoconstriction increases peripheral vascular resistance and reduces venous pooling, thereby raising blood pressure, particularly when standing. Some key points to consider when using midodrine include:
- Doses should be taken during daytime hours when the patient is upright to maximize benefit and minimize risks.
- Patients should be monitored for potential side effects including supine hypertension, piloerection (goosebumps), scalp tingling, urinary retention, and bradycardia.
- The medication typically begins working within an hour of administration and effects last for 2-3 hours, making the timing of doses important for symptom management throughout the day, as noted in the study on guidelines for the diagnosis and management of syncope 1. It's also important to note that midodrine is the only medication approved by the Food and Drug Administration for the treatment of symptomatic orthostatic hypotension, as mentioned in the study on cardiovascular autonomic neuropathy in diabetes 1. Overall, midodrine is a useful medication for the treatment of orthostatic hypotension, but its use should be carefully monitored and adjusted to minimize risks and maximize benefits.
From the FDA Drug Label
Midodrine forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. The mechanism of action of Midodrine for blood pressure support in patients with orthostatic hypotension is through its active metabolite, desglymidodrine, which is an alpha1-agonist. It works by activating the alpha-adrenergic receptors of the arteriolar and venous vasculature, resulting in an increase in vascular tone and elevation of blood pressure 2.
- The effect of midodrine on blood pressure is characterized by an increase in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension.
- Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10 mg dose of midodrine, with some effect persisting for 2 to 3 hours.
From the Research
Mechanism of Action of Midodrine
The mechanism of action of midodrine for blood pressure support in patients with orthostatic hypotension involves its role as a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration 3. This active metabolite increases vasomotor and venomotor tone, thereby improving orthostatic blood pressure 4.
Key Effects of Midodrine
- Increases standing systolic blood pressure 4, 3, 5, 6
- Improves symptoms of orthostatic hypotension, including dizziness, lightheadedness, and syncope 4, 3, 5, 6
- Enhances standing time and energy level 3
- Well-tolerated, with common adverse effects being piloerection, pruritus, paraesthesias, urinary retention, and chills 3, 7
Therapeutic Use
Midodrine is an effective therapeutic option for the management of various forms of orthostatic hypotension 3, 7. It is at least as effective as other sympathomimetic agents and dihydroergotamine in improving standing blood pressure and symptoms of orthostatism 3, 7. The recommended dosage is typically 10 mg, prescribed two to three times daily 6.