Brands, Medical Use, Clinical Data
- Adrenergic alpha-Agonists
- Vasoconstrictor Agents
- 2.5-mg and 5-mg tablets for oral administration
Brands / Synonyms
Midodrin; Midodrina [INN-Spanish]; Midodrine HCL; midodrine hydrochloride
; Midodrine [INN:BAN]; Midodrinum [INN-Latin]; Proamatine
For the treatment of symptomatic orthostatic hypotension (OH).
Midodrine is a prodrug, i.e., the therapeutic effect of orally administered midodrine is due to the major metabolite desglymidodrine formed by deglycination of midodrine. Desglymidodrine diffuses poorly across the blood-brain barrier, and is therefore not associated with effects on the central nervous system. Administration of midodrine results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10-mg dose of midodrine, with some effect persisting for 2 to 3 hours. Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.
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. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors.
Rapidly absorbed following oral administration. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% and is not affected by food.
Symptoms of overdose could include hypertension, piloerection (goosebumps), a sensation of coldness and urinary retention. The single doses that would be associated with symptoms of overdosage or would be potentially life- threatening are unknown. The oral LD50 is approximately 30 to 50 mg/kg in rats, 675 mg/kg in mice, and 125 to 160 mg/kg in dogs. Desglymidodrine is dialyzable.
Biotrnasformation / Drug Metabolism
Thorough metabolic studies have not been conducted, but it appears that deglycination of midodrine to desglymidodrine takes place in many tissues, and both compounds are metabolized in party by the liver.
ProAmatine® is contraindicated in patients with severe organic heart disease, acute renal disease urinary
retention, pheochromocytoma or thyrotoxicosis. ProAmatine® should not be used in pat ients with persistent and
excessive supine hypertension.
When administered concomitantly with ProAmatine®, cardiac glycosides may enhance or precipitate bradycardia,
A.V. block or arrhythmia. The use of drugs that stimulate alpha-adrenergic receptors (e.g., phenylephrine,
pseudoephedrine, ephedrine, phenylpropanolamine or dihydroergotamine) may enhance or potentiate the pressor effects
of ProAmatine®. Therefore, caution should be used when ProAmatine® is administered concomitantly with agents
that cause vasoconstriction.
ProAmatine® has been used in patients concomitantly treated with salt-retaining steroid therapy (i.e.,
fludrocortisone acetate), with or without salt supplementation. The potential for supine hypertension should be
carefully monitored in these patients and may be minimized by either reducing the dose of fludrocortisone acetate or
decreasing the salt intake prior to initiation of treatment with. ProAmatine®. Alpha-adrenergic blocking agents,
such as prazosin, terazosin, and doxazosin, can antagonize the effects of ProAmatine®.
Potential for Drug Interactions: It appears possible, although there is no supporting experimental
evidence, that the high renal clearance of desglymidodrine (a base) is due to active tubular secretion by the
base-secreting system also responsible for the secretion of such drugs as metformin, cimetidine, ranitidine,
procainamide, triamterene, flecainide, and quinidine. Thus there may be a potential for drug-drug interactions with