midodrin

Midodrine is an oral prodrug of desglymidodrine, a selective alpha-1 adrenergic receptor agonist. By stimulating peripheral arteriolar and venous smooth muscle, midodrine increases systemic vascular resistance and venous return, raising standing blood pressure in patients with symptomatic orthostatic hypotension due to autonomic failure or dysautonomia. It helps reduce presyncope and improves upright tolerance, though it does not treat the underlying cause.

Indications and use: Midodrine is approved for symptomatic orthostatic hypotension in adults. It may be used off-label for some forms of neurogenic syncope or postural orthostatic tachycardia syndrome, but evidence varies. It is not indicated for acute hypotension due to volume depletion or shock.

Pharmacology: Midodrine is rapidly converted to desglymidodrine, the active metabolite. After oral administration, onset is about 30–60 minutes, with peak effect in 1–2 hours; the effect lasts several hours. It is given in divided daytime doses because of the risk of supine hypertension. Metabolism occurs in the liver; excretion is primarily renal.

Administration and dosing: Typical starting dose is 2.5 mg three times daily during waking hours, with gradual titration as needed. Doses are adjusted to a commonly used range up to 5–10 mg per dose, not taking doses within four hours of bedtime. Total daily dose is individualized and often kept below higher daily ceilings.

Adverse effects and safety: Common adverse effects include gooseflesh (piloerection), scalp pruritus, headache, and urinary retention. The principal safety concern is supine hypertension, so BP should be monitored and dosing timed to avoid lying down soon after dosing. Contraindications include severe organic heart disease, pheochromocytoma, and bladder outlet obstruction.

Interactions: May enhance effects of other vasopressors or monoamine oxidase inhibitors; caution with antihypertensives and other agents that raise blood pressure.