Mechanism of action of Midodrine

Mechanism of Action of Midodrine

by

Introduction

Midodrine is a prodrug used in the treatment of symptomatic orthostatic hypotension. It works by increasing vascular tone through selective stimulation of alpha-1 adrenergic receptors after being metabolized into its active form, desglymidodrine.

Step-by-Step Mechanism of Action

  1. Prodrug Conversion
    After oral administration, midodrine is rapidly converted in the liver and systemic circulation into its active metabolite, desglymidodrine.
  2. Selective α1-Adrenergic Agonism
    Desglymidodrine selectively stimulates peripheral alpha-1 adrenergic receptors, primarily on arteriolar and venous smooth muscle.
  3. Vasoconstriction
    Activation of these receptors causes vasoconstriction, increasing peripheral vascular resistance.
  4. Elevation of Blood Pressure
    As a result of vasoconstriction, systolic and diastolic blood pressure increase, particularly beneficial in the upright posture.
  5. Minimal Central Effects
    Because midodrine and its active metabolite poorly cross the blood-brain barrier, central nervous system side effects are minimal.
Mechanism of action of Midodrine flowchart
Midodrine mechanism of action flowchart

Pharmacokinetic Parameters

ParameterValue
RouteOral
BioavailabilityApproximately 93%
Active FormDesglymidodrine
Tmax1–2 hours
Half-life3–4 hours (desglymidodrine)
MetabolismHepatic and systemic
ExcretionRenal (primarily as active metabolite)

Clinical Uses

  • Symptomatic orthostatic hypotension
  • Off-label: Intradialytic hypotension, hepatorenal syndrome (supportive)

Adverse Effects

  • Supine hypertension
  • Paresthesia
  • Piloerection
  • Urinary retention
  • Pruritus and scalp tingling

Comparative Analysis

DrugMechanismDurationComments
MidodrineAlpha-1 agonist (peripheral)3–4 hoursOral prodrug with minimal CNS penetration
DroxidopaNorepinephrine precursor~2–3 hoursCentral and peripheral effects
FludrocortisoneMineralocorticoidLong-actingActs via sodium and water retention

MCQs

  1. Midodrine is converted into which active metabolite?
    a) Noradrenaline b) Desglymidodrine c) Ephedrine d) Dopamine
    Answer: b) Desglymidodrine
  2. The main action of midodrine is:
    a) Beta-2 stimulation b) Alpha-1 receptor blockade c) Alpha-1 receptor agonism d) Inhibition of norepinephrine uptake
    Answer: c) Alpha-1 receptor agonism
  3. Which of the following is a contraindication to midodrine use?
    a) Asthma b) Supine hypertension c) Bradycardia d) Anemia
    Answer: b) Supine hypertension
  4. Midodrine is used primarily in the treatment of:
    a) Tachycardia b) Orthostatic hypotension c) Hypertension d) Heart failure
    Answer: b) Orthostatic hypotension
  5. Duration of action of midodrine is approximately:
    a) 1 hour b) 3–4 hours c) 8 hours d) 24 hours
    Answer: b) 3–4 hours
  6. Midodrine has minimal central nervous effects because:
    a) It is metabolized peripherally b) It cannot cross the blood-brain barrier c) It is rapidly degraded d) It acts on dopamine receptors
    Answer: b) It cannot cross the blood-brain barrier
  7. Supine hypertension occurs due to:
    a) Volume depletion b) Excessive vasodilation c) Unopposed vasoconstriction when lying down d) Beta-blockade
    Answer: c) Unopposed vasoconstriction when lying down
  8. Which is NOT a known side effect of midodrine?
    a) Goosebumps b) Urinary retention c) Bradycardia d) Tachypnea
    Answer: d) Tachypnea
  9. What is the bioavailability of midodrine?
    a) 20% b) 50% c) 93% d) 100%
    Answer: c) 93%
  10. Midodrine is metabolized mainly in:
    a) Kidney b) Lungs c) Liver and plasma d) Pancreas
    Answer: c) Liver and plasma

FAQs

1. What is the dosing frequency of midodrine?
Typically administered 2–3 times daily, avoiding late evening doses to prevent supine hypertension.

2. Can it be used in renal impairment?
Use with caution, as the drug is excreted renally and may accumulate.

3. Does midodrine cause tachycardia?
No, it generally has little effect on heart rate.

4. What precautions should be taken when using midodrine?
Blood pressure should be monitored in both supine and standing positions to avoid excessive hypertension.

5. Can it be used with beta-blockers?
Yes, but with caution due to additive effects on blood pressure and possible bradycardia.

References

Leave a Comment