Midodrine isindicated for the treatment of symptomatic orthostatic hypotension. It can reduce dizziness and faints by about a third, but can be limited by troublesomegoose bumps,skin itch, gastrointestinal discomfort, chills, elevated blood pressure while lying down, andurinary retention.[5] A meta-analysis of clinical trials of midodrine or droxidopa in patients withlow blood pressure when standing found that midodrine increased standing blood pressure more thandroxidopa but that midodrine but not droxidopa increased the risk of high blood pressure when lying down.[6] Small studies have also shown that midodrine can be used to prevent excessive drops in blood pressure in people requiringdialysis.[7]
Midodrine has been used in the complications ofcirrhosis. It is also used withoctreotide forhepatorenal 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.[8]
Headache, feeling of pressure or fullness in the head, vasodilation or flushing face, scalp tingling, confusion or thinking abnormality, dry mouth, anxiety, and rash, among others.[1]
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 25minutes, 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 to4 hours. The absolutebioavailability of midodrine (measured asdesglymidodrine) is 93%.[13][unreliable medical source?]
Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble inmethanol.[1]
Midodrine's experimentallog P is -0.5 and its predicted log P ranges from -0.49 to -0.95.[16] The predicted log P of itsactive metabolitedesglymidodrine ranges from -0.01 to 0.15.[17]
Acylation of1,4-dimethoxybenzene withchloroacetyl chloride gives the chloroketone 2. The halogen is then converted to the amine 3 by any set of standard schemes, and the ketone reduced to an alcohol with borohydride (4).[19] Acylation of the amino group in this last intermediate withchloroacetyl chloride affords the amide 5. The halogen is then displaced with azide and the resulting product 6 reduced catalytically to the glycinamide, midodrine (7).[20]
In August 2010, the FDA proposed withdrawing this approval because the manufacturer,Shire plc, failed to completerequired studies after the medicine reached the market.[24][25] In September 2010, the FDA reversed its decision to remove midodrine from the market and allowed it to remain available while Shire plc collected further data regarding the efficacy and safety of the drug.[26] Shire announced in September 2011, that it was withdrawing completely from supplying midodrine. Midodrine remains available as ageneric drug.[27]
^Izcovich A, González Malla C, Manzotti M, Catalano HN, Guyatt G (September 2014). "Midodrine for orthostatic hypotension and recurrent reflex syncope: A systematic review".Neurology.83 (13):1170–1177.doi:10.1212/WNL.0000000000000815.PMID25150287.S2CID5439767.
^Chen JJ, Han Y, Tang J, Portillo I, Hauser RA, Dashtipour K (December 2018). "Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials".The Annals of Pharmacotherapy.52 (12):1182–1194.doi:10.1177/1060028018786954.PMID29972032.S2CID49674644.
^Prakash S, Garg AX, Heidenheim AP, House AA (October 2004). "Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review".Nephrology, Dialysis, Transplantation.19 (10):2553–2558.doi:10.1093/ndt/gfh420.PMID15280522.
^Karwa R, Woodis CB (April 2009). "Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications".The Annals of Pharmacotherapy.43 (4):692–699.doi:10.1345/aph.1L373.PMID19299324.S2CID207263346.
^abcMcClellan KJ, Wiseman LR, Wilde MI (January 1998). "Midodrine. A review of its therapeutic use in the management of orthostatic hypotension".Drugs Aging.12 (1):76–86.doi:10.2165/00002512-199812010-00007.PMID9467688.
^Rote Liste Service GmbH (Hrsg.):Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57,ISBN978-3-946057-10-9, S. 196.
^Cao T, Martini ML, Park K, Kaniskan HÜ, Jin J (1 January 2022). "8.02 - Pyrimidines and Their Benzo Derivatives". In Black DS, Cossy J, Stevens CV (eds.).Comprehensive Heterocyclic Chemistry IV. Oxford: Elsevier. pp. 86–228.doi:10.1016/B978-0-12-818655-8.00041-X.ISBN978-0-12-818656-5.
^DE 2506110, Zoelss G, "Phenylethanolamine derivs prepn. - by reducing azides, useful as hypertensives", issued 21 April 1983, assigned to Lentia GmbH.
^O'Riordan M."FDA recommends withdrawal of midodrine".Food and Drug Administration. FDA proposes withdrawal of low blood pressure drug [press release]. August 16, 2010. TheHeart.org. Retrieved1 April 2011.
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