Generic Name

Midodrine

Mechanism

• Prodrug → hydrolyzed in the liver to clonidine (active metabolite).
• Selective α₁‑adrenergic stimulation on vascular smooth muscle → vasoconstriction.
• Increases afterload and systolic/diastolic BP, reducing orthostatic symptoms.
• No direct β‑blocking or central depressant effects; however, central α₁‑agonism contributes to the modest rise in heart rate.

Pharmacokinetics

• Absorption: Oral bioavailability ~70 % (first‑pass hepatic metabolism).
• Onset: Peak plasma ~4–5 h after dose; clinical effect starts 2–3 h.
• Half‑life: 1.5–3 h for active metabolite; total duration of action ~4–6 h.
• Metabolism: Primarily hepatic via aldehyde oxidase and xanthine oxidase.
• Excretion: Renally → ~40 % unchanged; remaining metabolites renal and fecal.
• Food interaction: High‑fat meals delay absorption; avoid food 2 h before dosing.

Indications

• Primary: Symptomatic orthostatic (postural) hypotension in adults.
• Secondary
• Neurogenic orthostatic hypotension secondary to Parkinson’s disease, multiple system atrophy, or autonomic failure.
• Hypotension associated with chronic hemodialysis (in select centers).
• Post‑operatively when invasive BP support is contraindicated.

Contraindications

• Contraindications
• Severe atherosclerotic peripheral arterial disease.
• Uncontrolled systemic hypertension (>200/110 mm Hg).
• Suspected or established intracranial hemorrhage (risk of worsening).
• Acute or chronic renal failure (eGFR <30 mL/min/1.73 m²) – use caution.
• Warnings
• Carotid bruits: elevate BP may precipitate transient ischemic attacks.
• Heart failure: raise afterload, worsening congestion; use with caution.
• Pregnancy: Category C; avoid if possible.
• Concomitant MAO inhibitors → potential hypertensive crisis.

Dosing

• Initiation: 2.5 mg PO QID × 2–3 days (≈20 mg/day).
• Titrate: Increase by 2.5 mg QID at 2–3 day intervals based on orthostatic BP response.
• Target: Max 20 mg QID (≈80 mg/day); never exceed 2.5 mg QID if adverse events present.
• Timing: Administer 1–2 h before standing activities.
• Dose‑reduction: Reduce frequency if supine hypertension develops.

Adverse Effects

• Common
• Piloerection (gooseflesh).
• Facial flushing, itching, pruritus.
• Supine hypertension (↑ systolic > 20 mm Hg).
• Headache, dizziness, nausea.
• Serious
• Severe hypertensive crisis (rare).
• Angioedema (rare).
• Persistent supine hypertension leading to end‑organ damage.
• Heart failure exacerbation in predisposed patients.
• Monitoring for
• Pulse rate changes; tachycardia >100 bpm warrants dose adjustment.
• Supine vs upright BP differences > 20 mm Hg.

Monitoring

• Blood Pressure
• Supine BP at 2 h intervals for first 10–12 h after initiation.
• Orthostatic BP (standing after 3 min) at each dose adjustment.
• Heart Rate
• Monitor for sinus tachycardia >100 bpm.
• Renal Function
• Serum creatinine eGFR; reevaluate if ≥30 % decline.
• Adherence & Symptoms
• Document orthostatic dizziness, edema, or palpitations.

Clinical Pearls

• “Double‑check the timing.” Midodrine peaks 4–5 h; if patients report symptoms just before standing, they may have missed the dose—reinforce adherence to the 1‑2 h pre‑standing schedule.
• Supine hypertension is predictable. Use a sliding scale: a rise of >20 mm Hg supine → reduce night‑time dosing or add a vasodilator (e.g., hydralazine) for nighttime BP control.
• Avoid meals high in fat. Fats delay absorption, so patients should take midodrine on an empty stomach or wait at least 2 h.
• Titrate cautiously in renal impairment. Because metabolism is hepatic but elimination is renal, in CKD (eGFR 30–60 mL/min/1.73 m²) start at lower doses (1.25 mg QID) and titrate slowly.
• Consider alternate routes if GI absorption is poor. Though no IV formulation exists, switching to norepinephrine infusion might be necessary if oral bioavailability is compromised (e.g., severe GI disease).

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