Midodrine (brand names Amatine, ProAmatine, Gutron) is a vasopressor/antihypotensive

agent. Midodrine was approved in the United States by the Food and Drug Administration
(FDA) in 1996 for the treatment of dysautonomia and orthostatic hypotension. In August
2010, the FDA proposed withdrawing this approval because the manufacturer, Shire plc, has
failed to complete required studies after the medicine reached the market.[1][2]
In September 2010, the FDA reversed its decision to remove Midodrine from the market and
has allowed it to remain available to patients while Shire plc collects further data regarding
the efficacy and safety of the drug.[3] Shire plc announced on September 27, 2011 that it was
continuing the process to work with the FDA towards a final approval of the drug.[4]

Contents

1 Chemical properties
2 Mechanism of action

3 Metabolism

4 Indications

5 Contraindications

6 Side effects

7 See also

8 References

9 External links

Chemical properties
Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble in
methanol.

Mechanism of action
Midodrine is a prodrug which forms an active metabolite, desglymidodrine, which is an 1receptor 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.
Desglymidodrine diffuses poorly across the bloodbrain barrier, and is therefore not
associated with effects on the central nervous system.

Metabolite desglymidodrine

Metabolism
After oral administration, midodrine is rapidly absorbed. 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. The absolute bioavailability of midodrine (measured
as desglymidodrine) is 93%.

Indications
Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic
hypotension. It can reduce dizziness and faints by about a third, but can be limited by
troublesome goose bumps.[5] Small studies have also shown that midodrine can be used to
prevent excessive drops in blood pressure in people requiring dialysis.[6]
Midodrine has been used in the complications of cirrhosis. It is also used with octreotide for
hepatorenal syndrome; the proposed mechanism is constriction of splanchnic vessels and
dilation of renal vasculature. Studies have not been sufficiently well conducted to show a
clear place for midodrine.[7]

Contraindications
Midodrine is contraindicated in patients with severe organic heart disease, acute renal
disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be
used in patients with persistent and excessive supine hypertension.

Side effects
Headache; feeling of pressure/fullness in the head, vasodilation/flushing face,
confusion/thinking abnormality, dry mouth; nervousness/anxiety and rash.[citation needed]