Midodrine

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Midodrine
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Systematic (IUPAC) name
(RS)- N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]glycinamide
Clinical data
Trade names Proamatine
AHFS/Drugs.com monograph
MedlinePlus a602023
Legal status ?
Identifiers
CAS number 133163-28-7 7pxY
ATC code C01CA17
PubChem CID 4195
DrugBank DB00211
ChemSpider 4050 7pxY
UNII 6YE7PBM15H 7pxY
KEGG D08220 7pxY
ChEBI CHEBI:6933 7pxY
ChEMBL CHEMBL1076 7pxN
Synonyms 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide
Chemical data
Formula C12H18N2O4 
Mol. mass 254.282 g/mol
 14pxN (what is this?)  (verify)

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]

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 α1-receptor 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 blood–brain barrier, and is therefore not associated with effects on the central nervous system.

File:Desglymidodrine.svg
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. In a critical care setting, it is widely used as an adjunctive therapy to weaning patients off of intravenous vasopressive medications. It has been suggested also as a treatment for chronic fatigue syndrome[5] as well as for hepato-pulmonary syndrome. It is also used with octreotide for hepatorenal syndrome; the proposed mechanism is constriction of splanchnic vessels and dilation of renal vasculature.

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]

See also

References

  1. U.S. proposes withdrawal of Shire hypotension drug, Aug 16, 2010.
  2. O'Riordan, Michael. "FDA recommends withdrawal of midodrine". Food and Drug Administration. FDA proposes withdrawal of low blood pressure drug [press release]. August 16, 2010. TheHeart.org. Retrieved 1 April 2011. .
  3. Midodrine (ProAmatine, generic) Proposed Market Withdrawal – Update September 10, 2010.
  4. Shire Announces Update on ProAmatime September 27, 2011.
  5. Naschitz J, Dreyfuss D, Yeshurun D, Rosner I (April 2004). "Midodrine treatment for chronic fatigue syndrome". Postgrad Med J 80 (942): 230–2. PMC 1742969. PMID 15082846. doi:10.1136/pgmj.2003.011429. 

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