Usage
Midodrine is primarily prescribed for the treatment of symptomatic orthostatic hypotension, a condition characterized by a drop in blood pressure upon standing, leading to dizziness, lightheadedness, and even syncope. It can also be used off-label to treat certain types of urinary incontinence (stress incontinence) and for weaning patients off intravenous vasopressors in intensive care unit settings. It is classified as a vasopressor and an α1-adrenergic agonist.
Midodrine’s mechanism of action involves its conversion to the active metabolite, desglymidodrine, which stimulates alpha-1 adrenergic receptors in arterioles and veins. This stimulation causes vasoconstriction, increasing peripheral vascular resistance and venous return, thereby raising blood pressure.
Alternate Names
Midodrine hydrochloride is the chemical name. Brand names include ProAmatine and Orvaten.
How It Works
Pharmacodynamics: Midodrine itself is inactive but is rapidly converted to desglymidodrine, its active metabolite. Desglymidodrine acts as an agonist at α1-adrenergic receptors, causing vasoconstriction in both arteries and veins. This leads to an increase in peripheral vascular resistance and venous return, elevating blood pressure. It has minimal effect on beta-adrenergic or dopaminergic receptors.
Pharmacokinetics: Midodrine is rapidly absorbed after oral administration. It undergoes rapid hepatic conversion to desglymidodrine. Peak plasma concentrations of desglymidodrine are reached in approximately 1-2 hours. The elimination half-life is about 3-4 hours. It’s primarily excreted by the kidneys.
Mode of Action: Desglymidodrine binds to α1-adrenergic receptors on vascular smooth muscle cells, activating intracellular signaling pathways that result in vasoconstriction. This increased vascular tone leads to the observed pressor effect.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Desglymidodrine is an α1-adrenergic receptor agonist and does not directly inhibit enzymes or modulate neurotransmitters.
Elimination Pathways: Primarily renal excretion of desglymidodrine.
Dosage
Standard Dosage
Adults:
- Orthostatic Hypotension: Initial dose: 2.5 mg orally two to three times daily. The dose can be increased weekly by 2.5 mg increments until an optimal response is achieved, usually up to 10 mg three times a day. Maximum dose is 30mg/day.
- Intravenous Vasopressor Weaning: 5-40 mg orally every 8 hours.
Children:
Limited data available. Use with caution and initiate at lower doses.
Special Cases:
- Elderly Patients: Initiate with a lower dose (2.5 mg twice or thrice daily) and titrate cautiously.
- Patients with Renal Impairment: Start with 2.5 mg every 8 hours and adjust based on response.
- Patients with Hepatic Dysfunction: Exercise caution and monitor closely. Data limited.
- Patients with Comorbid Conditions: Close monitoring is necessary for patients with diabetes, cardiovascular disease, and other relevant conditions.
Clinical Use Cases
The use of Midodrine in clinical settings like Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, and Emergency Situations (e.g., status epilepticus, cardiac arrest) is off-label and requires careful monitoring. The common dosage range for weaning off intravenous vasopressors is 5–40 mg every 8 hours
Dosage Adjustments
Dose adjustments should be made based on patient-specific factors, including renal or hepatic dysfunction and other comorbid conditions.
Side Effects
Common Side Effects
- Piloerection (goosebumps)
- Pruritus (itching)
- Paresthesias (tingling or numbness)
- Urinary urgency/retention
- Chills/shivering
Rare but Serious Side Effects
- Supine hypertension (high blood pressure while lying down)
- Reflex bradycardia (slow heart rate)
- Allergic reactions
Long-Term Effects
Chronic complications are rare but may include persistent hypertension.
Adverse Drug Reactions (ADR)
Supine hypertension is a clinically significant ADR requiring immediate intervention.
Contraindications
- Severe organic heart disease
- Acute renal disease
- Urinary retention
- Pheochromocytoma
- Thyrotoxicosis
- Supine hypertension
Drug Interactions
Midodrine can interact with other alpha-adrenergic agonists, beta-blockers, and certain medications that prolong the QT interval. Monitor closely.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Use only if potential benefit justifies the risk to the fetus.
- Midodrine may cause fetal harm.
- It’s unknown whether midodrine is excreted in breast milk. Avoid breastfeeding while taking midodrine.
Drug Profile Summary
- Mechanism of Action: α1-adrenergic receptor agonist, leading to vasoconstriction.
- Side Effects: Piloerection, pruritus, paresthesias, urinary urgency, chills, supine hypertension, reflex bradycardia.
- Contraindications: Severe heart disease, renal disease, urinary retention, pheochromocytoma, thyrotoxicosis, supine hypertension.
- Drug Interactions: Alpha agonists, beta blockers, QT-prolonging drugs.
- Pregnancy & Breastfeeding: Category C; avoid during breastfeeding.
- Dosage: Orthostatic hypotension: Start 2.5 mg BID-TID, increase to 10 mg TID; ICU: 5-40mg q8h.
- Monitoring Parameters: Blood pressure (supine and standing), heart rate.
Popular Combinations
Often used in combination with fludrocortisone for orthostatic hypotension.
Precautions
- General Precautions: Monitor blood pressure regularly. Caution in patients with renal or hepatic impairment.
- Specific Populations: Careful monitoring in pregnant women, breastfeeding mothers, children, and elderly individuals.
- Lifestyle Considerations: Limit alcohol intake.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Midodrine?
A: For orthostatic hypotension, start at 2.5 mg two or three times daily, increasing as needed up to 10 mg three times a day. For weaning off IV vasopressors, doses range from 5-40 mg every 8 hours.
Q2: What is the mechanism of action of Midodrine?
A: Midodrine is converted to desglymidodrine, an active metabolite that stimulates α1-adrenergic receptors, causing vasoconstriction.
Q3: What are the most common side effects of Midodrine?
A: Common side effects include piloerection, pruritus, paresthesias, urinary urgency, and chills.
Q4: What are the serious side effects of Midodrine?
A: Serious side effects include supine hypertension and reflex bradycardia.
Q5: When should Midodrine be avoided?
A: Midodrine is contraindicated in patients with severe heart disease, renal disease, urinary retention, pheochromocytoma, thyrotoxicosis, and supine hypertension.
Q6: How should Midodrine be administered?
A: Midodrine is administered orally. For orthostatic hypotension, it should be taken during daytime hours when the patient is upright. The last dose should be taken at least 4 hours before bedtime to avoid supine hypertension.
Q7: What should I monitor in patients taking Midodrine?
A: Closely monitor blood pressure (both supine and standing) and heart rate in patients taking midodrine.
Q8: Can Midodrine be used in pregnant or breastfeeding women?
A: Midodrine is Pregnancy Category C. Use only if the benefit outweighs the risk. It’s not known if it is excreted in breast milk; it’s best to avoid breastfeeding while on Midodrine.
Q9: How is Midodrine used in the ICU?
A: In the ICU, midodrine is used off-label to wean patients from intravenous vasopressors.
Q10: Are there any drug interactions I should be aware of with Midodrine?
A: Yes, midodrine can interact with other alpha-adrenergic agonists, beta-blockers, and certain medications that can prolong the QT interval. Consult a drug interaction database for further information.
