ProAmatine
ProAmatine - General Information
An ethanolamine derivative that is an adrenergic alpha agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. [PubChem]
Pharmacology of ProAmatine
ProAmatine 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. ProAmatine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure.
ProAmatine for patients
Patients should be told that certain agents in over-the-counter products, such as cold remedies and diet aids, can elevate blood pressure, and therefore, should be used cautiously with ProAmatine®, as they may enhance or potentiate the pressor effects of ProAmatine®. Patients should also be made aware of the possibility of supine hypertension. They should be told to avoid taking their dose if they are to be supine for any length of time, i.e., they should take their last daily dose of ProAmatine® 3 to 4 hours before bedtime to minimize nighttime supine hypertension.
ProAmatine Interactions
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 these drugs.
ProAmatine Contraindications
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.
Additional information about ProAmatine
ProAmatine Indication: For the treatment of symptomatic orthostatic hypotension (OH).
Mechanism Of Action: ProAmatine 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.
Drug Interactions: Betamethasone Increased arterial pressure
Cortisone acetate Increased arterial pressure
Dexamethasone Increased arterial pressure
Dobutamine Increased arterial pressure
Dopamine Increased arterial pressure
Ephedra Increased arterial pressure
Ephedrine Increased arterial pressure
Epinephrine Increased arterial pressure
Fenoterol Increased arterial pressure
Fludrocortisone Increased arterial pressure
Hydrocortisone Increased arterial pressure
Isoproterenol Increased arterial pressure
Mephentermine Increased arterial pressure
Methoxamine Increased arterial pressure
Metaraminol Increased arterial pressure
Methylprednisolone Increased arterial pressure
Prednisolone Increased arterial pressure
Prednisone Increased arterial pressure
Norepinephrine Increased arterial pressure
Orciprenaline Increased arterial pressure
Paramethasone Increased arterial pressure
Phenylephrine Increased arterial pressure
Pseudoephedrine Increased arterial pressure
Pirbuterol Increased arterial pressure
Phenylpropanolamine Increased arterial pressure
Procaterol Increased arterial pressure
Salbutamol Increased arterial pressure
Terbutaline Increased arterial pressure
Triamcinolone Increased arterial pressure
Tranylcypromine Possible hypertensive crisis with this combination
Rasagiline Possible hypertensive crisis with this combination
Phenelzine Possible hypertensive crisis with this combination
Isocarboxazid Possible hypertensive crisis with this combination
Food Interactions: Not Available
Generic Name: Midodrine
Synonyms: Midodrina [INN-Spanish]; Midodrine HCL; midodrine hydrochloride; Midodrinum [INN-Latin]; Midodrin
Drug Category: Adrenergic alpha-Agonists; Sympathomimetics; Vasoconstrictor Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Midodrine: ProAmatine;
Absorption: Rapidly absorbed following oral administration. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93% and is not affected by food.
Toxicity (Overdose): 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.
Protein Binding: Not Available
Biotransformation: 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 part by the liver.
Half Life: The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours.
Dosage Forms of ProAmatine: Tablet Oral
Chemical IUPAC Name: 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]acetamide
Chemical Formula: C12H18N2O4
Midodrine on Wikipedia: https://en.wikipedia.org/wiki/Midodrine
Organisms Affected: Humans and other mammals
