Etamsylate Explained

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]

Etamsylate is the salt of dobesilic acid and diethylamine.

Indications

Prophylaxis and control of haemorrhages from small blood vessels, neonatal intraventricular haemorrhage,[4] 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.

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]

Notes and References

  1. Schulte J, Osborne J, Benson JW, Cooke R, Drayton M, Murphy J, Rennie J, Speidel B . 6 . 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 . January 2005 . 15613570 . 1721806 . 10.1136/adc.2003.035790 .
  2. Elbourne D, Ayers S, Dellagrammaticas H, Johnson A, Leloup M, Lenoir-Piat S . 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 . May 2001 . 11320045 . 1721248 . 10.1136/fn.84.3.F183 .
  3. Kovács L, Falkay G . Etamsylate as inhibitor of prostaglandin biosynthesis in pregnant human myometrium in vitro . Experientia . 37 . 11 . 1182–1183 . November 1981 . 7319004 . 10.1007/BF01989908 . 36393605 .
  4. Book: Martindale: The complete drug reference . 2009 . Pharmaceuticale Press, PhP . London; Chicago . 978-0-85369-840-1 . 36th .
  5. Web site: Pharmacynon (Etamsylate) . Bulgarian Pharmaceutical Group Ltd. . 2013-08-10 . https://web.archive.org/web/20121010195023/http://www.sopharma.com/pharmacynon.phtml . 2012-10-10 . dead .
  6. Web site: 2008-03-27 . 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. ФГУ «Научный центр экспертизы средств медицинского применения» Росздравнадзора РФ . ru . 7 April 2008 . dead . https://web.archive.org/web/20110903144445/http://www.regmed.ru/search.asp . 3 September 2011.
  7. Hunt RW . Etamsylate for prevention of periventricular haemorrhage . Archives of Disease in Childhood. Fetal and Neonatal Edition . 90 . 1 . F3–F5 . January 2005 . 15613569 . 1721808 . 10.1136/adc.2003.045625 .
  8. Perlman JM, Hill A, Volpe JJ . 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 . November 1981 . 6795324 . 10.1016/S0022-3476(81)80408-8 .
  9. Cobo-Nuñez MY, El Assar M, Cuevas P, Sánchez-Ferrer A, Martínez-González J, Rodríguez-Mañas L, Angulo J . Haemostatic agent etamsylate in vitro and in vivo antagonizes anti-coagulant activity of heparin . European Journal of Pharmacology . 827 . 167–172 . May 2018 . 29555505 . 10.1016/j.ejphar.2018.03.028 . 207594182 .