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Trade names | Amatine, Proamatine, Gutron, others |
Other names | 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide |
AHFS/Drugs.com | Monograph |
MedlinePlus | a602023 |
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Routes of administration | By mouth |
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ECHA InfoCard | 100.151.349 100.050.842, 100.151.349 |
Chemical and physical data | |
Formula | C12H18N2O4 |
Molar mass | 254.286 g·mol−1 |
3D model (JSmol) | |
Chirality | Racemic mixture |
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Midodrine is a vasopressor/antihypotensive agent (it raises the blood pressure). 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, failed to complete required studies after the medicine reached the market. [2] [3] In September 2010, the FDA reversed its decision to remove midodrine from the market and allowed it to remain available to patients while Shire plc collected further data regarding the efficacy and safety of the drug. [4] Shire announced on September 22, 2011, that it was withdrawing completely from supplying midodrine. Several Indian generic drug manufacturers now produce the world's supply of midodrine tablets. [5]
Midodrine is 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, skin itch, gastrointestinal discomfort, chills, elevated blood pressure while lying down, and urinary retention. [6] A meta-analysis of clinical trials of midodrine or droxidopa in patients with low blood pressure when standing found that midodrine increased standing blood pressure more than droxidopa but that midodrine but not droxidopa increased the risk of high blood pressure when lying down. [7] Small studies have also shown that midodrine can be used to prevent excessive drops in blood pressure in people requiring dialysis. [8]
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. [9]
Midodrine is contraindicated in patients with severe organic heart disease, acute kidney disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be used in patients with persistent and excessive supine hypertension. [10]
Headache, feeling of pressure/fullness in the head, vasodilation/flushing face, scalp tingling, confusion/thinking abnormality, dry mouth, nervousness/anxiety and rash. [11]
Midodrine is a prodrug which forms the 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.
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%. [12]
Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble in methanol. [13]
Midodrine contains a stereocenter and consists of two enantiomers, making it a racemate; i.e., a 1:1 mixture of (R)- and (S)-forms: [14]
Enantiomers of midodrine | |
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(R)-midodrine CAS number: 133163-25-4 | (S)-midodrine CAS number: 133267-39-7 |
Acylation of 1,4-dimethoxybenzene with chloroacetyl 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). [15] Acylation of the amino group in this last intermediate with chloroacetyl chloride affords the amide 5. The halogen is then displaced with azide and the resulting product 6 reduced catalytically to the glycinamide, midodrine (7). [16]
Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypotension is also often referred to as neurogenic orthostatic hypotension. The drop in blood pressure may be sudden, within 3 minutes or gradual. It is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg after 3 minutes of standing. It occurs predominantly by delayed constriction of the lower body blood vessels, which is normally required to maintain adequate blood pressure when changing the position to standing. As a result, blood pools in the blood vessels of the legs for a longer period, and less is returned to the heart, thereby leading to a reduced cardiac output and inadequate blood flow to the brain.
Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is indicated by two numbers, the systolic blood pressure and the diastolic blood pressure, which are the maximum and minimum blood pressures within the cardiac cycle, respectively. A systolic blood pressure of less than 90 millimeters of mercury (mmHg) or diastolic of less than 60 mmHg is generally considered to be hypotension. Different numbers apply to children. However, in practice, blood pressure is considered too low only if noticeable symptoms are present.
Clonidine, sold under the brand name Catapres among others, is an α2A-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal, menopausal flushing, diarrhea, spasticity, and certain pain conditions. The drug is often prescribed off-label for tics. It is used orally, by injection, or as a transdermal skin patch. Onset of action is typically within an hour with the effects on blood pressure lasting for up to eight hours.
Atenolol is a beta blocker medication primarily used to treat high blood pressure and heart-associated chest pain. Atenolol, however, does not seem to improve mortality in those with high blood pressure. Other uses include the prevention of migraines and treatment of certain irregular heart beats. It is taken orally or by intravenous injection. It can also be used with other blood pressure medications.
Pyridostigmine is a medication used to treat myasthenia gravis and underactive bladder. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.
Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.
Isosorbide mononitrate, sold under many brand names, is a medication used for heart-related chest pain (angina), heart failure and esophageal spasms. It can be used both to treat and to prevent heart-related chest pain; however, it is generally less preferred than beta blockers or calcium channel blockers. It is taken by mouth.
Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage. It was originally developed within the calcium channel blocker class as it was used for the treatment of high blood pressure, but is not used for this indication.
Octreotide, sold under the brand name Sandostatin among others, is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. It was first synthesized in 1979 by the chemist Wilfried Bauer, and binds predominantly to the somatostatin receptors SSTR2 and SSTR5.
Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth.
Alpha-1 blockers constitute a variety of drugs that block the effect of catecholamines on alpha-1-adrenergic receptors. They are mainly used to treat benign prostatic hyperplasia (BPH), hypertension and post-traumatic stress disorder. Alpha-1 adrenergic receptors are present in vascular smooth muscle, the central nervous system, and other tissues. When alpha blockers bind to these receptors in vascular smooth muscle, they cause vasodilation.
Lercanidipine is an antihypertensive drug. It belongs to the dihydropyridine class of calcium channel blockers, which work by relaxing and opening the blood vessels allowing the blood to circulate more freely around the body. This lowers the blood pressure and allows the heart to work more efficiently.
Levobunolol is a non-selective beta blocker. It is used topically in the form of eye drops to manage ocular hypertension and open-angle glaucoma.
Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure; today, it is more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist. It was approved for use by the Food and Drug Administration in the United States in 2018.
Nitrendipine is a dihydropyridine calcium channel blocker. It is used in the treatment of primary (essential) hypertension to decrease blood pressure and can reduce the cardiotoxicity of cocaine.
Tolvaptan, sold under the brand name Samsca among others, is an aquaretic drug that functions as a selective, competitive vasopressin receptor 2 (V2) antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca. Tolvaptan, as Jynarque, was granted approval for medical use in the United States in April 2018.
Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine (noradrenaline). Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier (BBB).
Dopamine beta (β)-hydroxylase deficiency is a human medical condition involving inadequate dopamine beta-hydroxylase. It is characterized by increased amounts of serum dopamine and the absence of norepinephrine (NE) and epinephrine.
Orthostatic syncope refers to syncope resulting from a postural decrease in blood pressure, termed orthostatic hypotension.
Supine hypertension is a paradoxical elevation in blood pressure upon assuming a supine position from a standing or sitting position. It is assumed to be a manifestation of disorders of the autonomic nervous system or due to side effects of medications such as midodrine and droxidopa.
Media related to Midodrine at Wikimedia Commons