From the Guidelines
Midodrine is an alpha-1 adrenergic receptor agonist that works primarily by causing constriction of blood vessels, which increases blood pressure. When taken orally, midodrine is rapidly converted to its active metabolite, desglymidodrine, which then binds to alpha-1 receptors on vascular smooth muscle cells. This binding activates a signaling cascade that leads to increased intracellular calcium, causing smooth muscle contraction in arterioles and veins. The resulting vasoconstriction increases peripheral vascular resistance and reduces venous pooling, effectively raising blood pressure. According to the most recent study 1, midodrine improves symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Some key points to consider when prescribing midodrine include:
- Typical dosing is 2.5-10 mg taken three times daily for conditions like orthostatic hypotension
- The medication should be taken during waking hours to avoid supine hypertension while sleeping
- Patients should be aware of common side effects such as piloerection, scalp tingling, urinary urgency, and headache
- Blood pressure should be monitored regularly while using this medication, especially when initiating therapy or adjusting doses, to ensure appropriate response and avoid excessive hypertension As noted in 1, midodrine is a first-line drug that exerts a pressor effect through both arteriolar constriction and venoconstriction of the capacitance vessels, and its dosing should be individually tailored. Additionally, 1 highlights the importance of monitoring for bradycardia and supine systolic hypertension with long-term use of midodrine. Overall, midodrine is a effective treatment option for orthostatic hypotension, but its use requires careful consideration of potential side effects and individual patient factors.
From the FDA Drug Label
Mechanism of Action: 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 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 active metabolite desglymidodrine does not stimulate cardiac beta-adrenergic receptors.
- Desglymidodrine has a limited ability to cross the blood-brain barrier, and therefore does not have significant effects on the central nervous system.
From the Research
Mechanism of Action of Midodrine
The mechanism of action of midodrine involves its role as a peripheral alpha-adrenergic agonist, which is used in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies 3.
Pharmacological Properties
Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, desglymidodrine 3, 4. This active metabolite acts as a selective alpha 1-adrenoceptor agonist, which increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision, and fatigue, without any associated cardiac stimulation 3.
Therapeutic Effects
The therapeutic effects of midodrine include:
- Increasing 1-minute standing systolic blood pressure compared with placebo 4
- Improving standing time and energy level and clinical symptoms of orthostatic hypotension, including dizziness, light-headedness, and syncope 4
- Improving orthostatic blood pressure drop at 1 and 3 months after treatment 5
- Ameliorating orthostatic symptoms, with midodrine being better than pyridostigmine at improving OH-related symptoms 5
Comparison with Other Agents
Midodrine has been compared with other agents, including:
- Norfenefrine, etilefrine, dimetofrine, and ephedrine, with midodrine being at least as effective as these agents in the management of orthostatic hypotension 3, 4
- Dihydroergotamine, with midodrine having similar efficacy to dihydroergotamine mesylate in patients with orthostatic hypotension 4
- Pyridostigmine, with single or combination treatment with midodrine and pyridostigmine being effective and safe in patients with neurogenic orthostatic hypotension 5