Etamsylate

Last updated
Etamsylate
Ethamsylate.png
Etamsylate ball-and-stick animation.gif
Clinical data
Trade names Cyclonamine, Dicynene, Dicynone, Haemostop, Menostat
Other namesDiethylammonium 2,5-dihydroxybenzenesulfonate; diethylammonium dobesilate
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • 2,5-Dihydroxybenzenesulfonic acid; N-ethylethanamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.018.265 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H17NO5S
Molar mass 263.31 g·mol−1
3D model (JSmol)
  • CCNCC.c1cc(c(cc1O)S(=O)(=O)O)O
  • InChI=1S/C6H6O5S.C4H11N/c7-4-1-2-5(8)6(3-4)12(9,10)11;1-3-5-4-2/h1-3,7-8H,(H,9,10,11);5H,3-4H2,1-2H3 X mark.svgN
  • Key:HBGOLJKPSFNJSD-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Etamsylate (sometimes spelled ethamsylate) is an antihemorrhagic agent which is believed to work by increasing resistance in the endothelium of capillaries and promoting platelet adhesion. [1] [2] It also inhibits biosynthesis and action of those prostaglandins which cause platelet disaggregation, vasodilation and increased capillary permeability. [3]

Contents

Etamsylate is the salt of dobesilic acid and diethylamine.

Indications

Prophylaxis and control of haemorrhages from small blood vessels, neonatal intraventricular haemorrhage, [4] :1065 capillary bleeding of different etiology, including: menorrhagia and metrorrhagia without organic pathology, after trans-urethral resection of the prostate, hematemesis, melena, hematuria, epistaxis; secondary bleeding due to thrombocytopenia or thrombocytopathia, hypocoagulation, prevention of periventricular hemorrhages in prematurely born children. [5]

Mechanism of action

Etamsylate is a haemostatic agent; also promotes angioprotective and proaggregant action. It stimulates thrombopoiesis and their release from bone marrow. Haemostatic action is due to activation of thromboplastin formation on damaged sites of small blood vessels and decrease of PgI2 (Prostacyclin) synthesis; it also facilitates platelet aggregation and adhesion, that at last induce decrease and stop of hemorrhage. [6]

The precise mechanism of action of etamsylate is unknown. It has been shown to reduce bleeding time and blood loss from wounds. This appears to relate to increased platelet aggregation mediated by a thromboxane A2 or prostaglandin F2a dependent mechanism. It has also been associated with decreased concentrations of 6-oxoprostaglandin F1a, a stable metabolite of prostacyclin. Prostacyclin is a potent vasodilator, and may be implicated in reperfusion; it is also a disaggregator of platelets. Whereas prostaglandins themselves may have a role in regulating cerebral blood flow, etamsylate appears to have no effect on cerebral blood flow. Etamsylate was also thought to stabilize capillaries, reinforcing capillary membranes by polymerizing hyaluronic acid. [7]

Etamsylate limits capillary bleeding through its action on hyaluronic acid and initial studies showed a reduction in intraventricular haemorrhage. [4] :1050

Etamsylate may also have an effect on the microcirculation, encouraging platelet aggregation and vasoconstriction and therefore haemostasis. It also inhibits the effects of the prostaglandin mediated vasodilatation and increased capillary permeability, thereby reducing oedema secondary to capillary leakage. It is also possible that etamsylate would reduce reperfusion haemorrhage in ischaemic areas of the brain, preventing secondary damage. [1]

By inhibiting the effects of prostaglandins, etamsylate may exert an effect by closing the patent ductus and thereby increasing cerebral blood flow. [8] Further, etamsylate has demonstrated interference with heparin, antagonizing its pro-hemorrhagic and anti-coagulant effects, without inhibiting its vasodilatory properties. [9]

Related Research Articles

<span class="mw-page-title-main">Prostaglandin</span> Group of physiologically active lipid compounds

Prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derived enzymatically from the fatty acid arachidonic acid. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are a subclass of eicosanoids and of the prostanoid class of fatty acid derivatives.

<span class="mw-page-title-main">Bleeding</span> Loss of blood escaping from the circulatory system

Bleeding, hemorrhage, haemorrhage or blood loss is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagina or anus, or through a puncture in the skin. Hypovolemia is a massive decrease in blood volume, and death by excessive loss of blood is referred to as exsanguination. Typically, a healthy person can endure a loss of 10–15% of the total blood volume without serious medical difficulties. The stopping or controlling of bleeding is called hemostasis and is an important part of both first aid and surgery.

<span class="mw-page-title-main">Intracranial hemorrhage</span> Hemorrhage, or bleeding, within the skull

Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds, subarachnoid bleeds, epidural bleeds, and subdural bleeds.

<span class="mw-page-title-main">Prostacyclin</span> Chemical compound

Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator.

<span class="mw-page-title-main">Thromboxane</span> Group of lipids

Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring.

<span class="mw-page-title-main">Indometacin</span> Anti-inflammatory drug

Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms. It does this by inhibiting cyclooxygenase, an enzyme that catalyzes the production of prostaglandins.

<span class="mw-page-title-main">Intracerebral hemorrhage</span> Type of intracranial bleeding that occurs within the brain tissue itself

Intracerebral hemorrhage (ICH), also known as hemorrhagic stroke, is a sudden bleeding into the tissues of the brain, into its ventricles, or into both. An ICH is a type of bleeding within the skull and one kind of stroke. Symptoms can vary dramatically depending on the severity, acuity, and location (anatomically) but can include headache, one-sided weakness, numbness, tingling, or paralysis, speech problems, vision or hearing problems, memory loss, attention problems, coordination problems, balance problems, dizziness or lightheadedness or vertigo, nausea/vomiting, seizures, decreased level of consciousness or total loss of consciousness, neck stiffness, and fever.

<span class="mw-page-title-main">Fetal circulation</span> Circulatory system of fetuses

In humans, the circulatory system is different before and after birth. The fetal circulation is composed of the placenta, umbilical blood vessels encapsulated by the umbilical cord, heart and systemic blood vessels. A major difference between the fetal circulation and postnatal circulation is that the lungs are not used during the fetal stage resulting in the presence of shunts to move oxygenated blood and nutrients from the placenta to the fetal tissue. At birth, the start of breathing and the severance of the umbilical cord prompt various changes that quickly transform fetal circulation into postnatal circulation.

<span class="mw-page-title-main">Periventricular leukomalacia</span> Degeneration of white matter near the lateral ventricles of the brain

Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis of white matter near the lateral ventricles. It can affect newborns and fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.

Prostaglandin E<sub>2</sub> Chemical compound

Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.

<span class="mw-page-title-main">Uterine atony</span> Loss of tone in the uterine musculature

Uterine atony is the failure of the uterus to contract adequately following delivery. Contraction of the uterine muscles during labor compresses the blood vessels and slows flow, which helps prevent hemorrhage and facilitates coagulation. Therefore, a lack of uterine muscle contraction can lead to an acute hemorrhage, as the vasculature is not being sufficiently compressed. Uterine atony is the most common cause of postpartum hemorrhage, which is an emergency and potential cause of fatality. Across the globe, postpartum hemorrhage is among the top five causes of maternal death. Recognition of the warning signs of uterine atony in the setting of extensive postpartum bleeding should initiate interventions aimed at regaining stable uterine contraction.

Germinal matrix hemorrhage is a bleeding into the subependymal germinal matrix with or without subsequent rupture into the lateral ventricle. Such intraventricular hemorrhage can occur due to perinatal asphyxia in preterm neonates.

<span class="mw-page-title-main">Treprostinil</span> Chemical compound

Treprostinil, sold under the brand names Remodulin for infusion, Orenitram for oral, and Tyvaso for inhalation, is a vasodilator that is used for the treatment of pulmonary arterial hypertension.

Neonatal alloimmune thrombocytopenia is a disease that affects babies in which the platelet count is decreased because the mother's immune system attacks her fetus' or newborn's platelets. A low platelet count increases the risk of bleeding in the fetus and newborn. If the bleeding occurs in the brain, there may be long-term effects.

<span class="mw-page-title-main">Prostacyclin synthase</span> Enzyme found in humans

Prostaglandin-I synthase also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene. This enzyme belongs to the family of cytochrome P450 isomerases.

<span class="mw-page-title-main">Intraventricular hemorrhage</span> Medical condition

Intraventricular hemorrhage (IVH), also known as intraventricular bleeding, is a bleeding into the brain's ventricular system, where the cerebrospinal fluid is produced and circulates through towards the subarachnoid space. It can result from physical trauma or from hemorrhagic stroke.

<span class="mw-page-title-main">Prostacyclin receptor</span> Mammalian protein found in Homo sapiens

The Prostacyclin receptor, also termed the prostaglandin I2 receptor or just IP, is a receptor belonging to the prostaglandin (PG) group of receptors. IP binds to and mediates the biological actions of prostacyclin (also termed Prostaglandin I2, PGI2, or when used as a drug, epoprostenol). IP is encoded in humans by the PTGIR gene. While possessing many functions as defined in animal model studies, the major clinical relevancy of IP is as a powerful vasodilator: stimulators of IP are used to treat severe and even life-threatening diseases involving pathological vasoconstriction.

Thromboregulation is the series of mechanisms in how a primary clot is regulated. These mechanisms include, competitive inhibition or negative feedback. It includes primary hemostasis, which is the process of how blood platelets adhere to the endothelium of an injured blood vessel. Platelet aggregation is fundamental to repair vascular damage and the initiation of the blood thrombus formation. The elimination of clots is also part of thromboregulation. Failure in platelet clot regulation may cause hemorrhage or thrombosis. Substances called thromboregulators control every part of these events.

Cranial ultrasound is a technique for scanning the brain using high-frequency sound waves. It is used almost exclusively in babies because their fontanelle provides an "acoustic window". A different form of ultrasound-based brain scanning, transcranial Doppler, can be used in any age group. This uses Doppler ultrasound to assess blood flow through the major arteries in the brain, and can scan through bone. It is not usual for this technique to be referred to simply as "cranial ultrasound". Additionally, cranial ultrasound can be used for intra-operative imaging in adults undergoing neurosurgery once the skull has been opened, for example to help identify the margins of a tumour.

Joseph J. Volpe is an American physician, the Bronson Crothers Professor of Neurology, Emeritus at Harvard Medical School and Neurologist-in-Chief Emeritus at Boston Children's Hospital. He was an early contributor to the field of neonatal neurology and has authored several editions of an influential textbook, Neurology of the Newborn.

References

  1. 1 2 Schulte J, Osborne J, Benson JW, Cooke R, Drayton M, Murphy J, et al. (January 2005). "Developmental outcome of the use of etamsylate for prevention of periventricular haemorrhage in a randomised controlled trial". Archives of Disease in Childhood. Fetal and Neonatal Edition. 90 (1): F31–F35. doi:10.1136/adc.2003.035790. PMC   1721806 . PMID   15613570.
  2. Elbourne D, Ayers S, Dellagrammaticas H, Johnson A, Leloup M, Lenoir-Piat S (May 2001). "Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of age". Archives of Disease in Childhood. Fetal and Neonatal Edition. 84 (3): F183–F187. doi:10.1136/fn.84.3.F183. PMC   1721248 . PMID   11320045.
  3. Kovács L, Falkay G (November 1981). "Etamsylate as inhibitor of prostaglandin biosynthesis in pregnant human myometrium in vitro". Experientia. 37 (11): 1182–1183. doi:10.1007/BF01989908. PMID   7319004. S2CID   36393605.
  4. 1 2 Martindale: The complete drug reference (36th ed.). London; Chicago: Pharmaceuticale Press, PhP. 2009. ISBN   978-0-85369-840-1.
  5. "Pharmacynon (Etamsylate)". Bulgarian Pharmaceutical Group Ltd. Archived from the original on 2012-10-10. Retrieved 2013-08-10.
  6. "Поиск по базе данных ЛС, опции поиска: МНН — Этамзилат, флаги "Искать в реестре зарегистрированных ЛС", "Искать ТКФС", "Показывать лекформы"" [Search in the drug database, search options: INN - Etamzilat, flags "Search in the register of registered drugs", "Search TKFS", "Show lekforms"]. Обращение лекарственных средств[Circulation of medicines, Federal State Institution "Scientific Center for Expertise of Medical Products" of Roszdravnadzor of the Russian Federation] (in Russian). ФГУ «Научный центр экспертизы средств медицинского применения» Росздравнадзора РФ. 2008-03-27. Archived from the original on 3 September 2011. Retrieved 7 April 2008.
  7. Hunt RW (January 2005). "Etamsylate for prevention of periventricular haemorrhage". Archives of Disease in Childhood. Fetal and Neonatal Edition. 90 (1): F3–F5. doi:10.1136/adc.2003.045625. PMC   1721808 . PMID   15613569.
  8. Perlman JM, Hill A, Volpe JJ (November 1981). "The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: ductal steal in the premature newborn infant". The Journal of Pediatrics. 99 (5): 767–771. doi:10.1016/S0022-3476(81)80408-8. PMID   6795324.
  9. Cobo-Nuñez MY, El Assar M, Cuevas P, Sánchez-Ferrer A, Martínez-González J, Rodríguez-Mañas L, Angulo J (May 2018). "Haemostatic agent etamsylate in vitro and in vivo antagonizes anti-coagulant activity of heparin". European Journal of Pharmacology. 827: 167–172. doi:10.1016/j.ejphar.2018.03.028. PMID   29555505. S2CID   207594182.