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CAS No: 9046-56-4
Synonyms: A 38414 (Enzyme), Abbott 38414, Agkistrododon rhodostoma venom proteinase, Ancrod, Ancrodo, Ancrodo [INN-Spanish], Ancrodum, Ancrodum [INN-Latin], Arvin, Arwin, Brevinase, E.C. 184.108.40.206, EINECS 232-933-6, IRC-50 arvin, Proteinase obtained from the venom of the Malayan pit-viper Agkistrodon rhodostoma, acting specifically on fibrinogen, UNII-EL55307L15, Venacil, Viprinex
ATC Code: B01AD09
Assay/Purity: Typically NLT 98%
IUPAC: Proteinase obtained from the venom of the Malayan pit-viper Agkistrodon rhodostoma, acting specifically on fibrinogen Proteinase, agkistrodon rhodostoma venom Proteinase, Agkistrodon serine
For the treatment of established deep vein thrombosis; central retinal and branch vein thrombosis; priapism; pulmonary hypertension of embolic origin; embolism after insertion of prosthetic cardiac valves; rethrombosis after thrombolytic therapy and rethrombosis after vascular surgery. It is also indicated for the prevention of deep venous thrombosis after repair of the fractured neck of a femur.
The decreased viscosity is directly attributable to lowered fibrinogen levels and leads to important improvements in blood flow and perfusion of the microcirculation.Ancrod decreases the blood viscosity in affected arteries, leads to less intense pain, improves physical limb mobility, and facilitates physical and ergo therapy. Finally, ancrod decreases the likelihood of local thrombotic events.
Mode of Action:
Ancrod's anticoagulant effects are through the rapid removal of fibrinogen from the blood within hours following ancrod administration. Ancrod specifically cleaves only the alpha chain of fibrinogen, producing the characteristic fibrinopeptides A, AP and AY, not the B-fibrinopeptide. The resulting fibrin polymers are imperfectly formed and much smaller in size (1 to 2 µm long) than the fibrin polymers produced by the action of thrombin. These ancrod-induced microthrombi are friable, unstable, urea-soluble and have significantly degraded a-chains. They do not cross-link to form thrombi. They are markedly susceptible to digestion by plasmin and are rapidly removed from circulation by either reticuloendothelial phagocytosis or normal fibrinolysis, or both. The blood viscosity in patients receiving ancrod is progressively reduced by 30 to 40%. Ancrod does not activate plagminogen and does not degrade preformed, fully cross-linked thrombin fibrin. Consequently, unlike fibrinolytic agents, ancrod can be used postoperatively. Unlike thrombin, ancrod does not directly activate Factor XIII, nor does it produce platelet aggregation nor cause the release of ADP, ATP, potassium, nor serotonin from platelets.
Currently, a new dosing strategy is being investigated in two international phase III trials as part of the 'Ancrod Stroke Program (ASP).' Each of these studies will enroll 650 patients and assess whether a brief, relatively rapid ancrod infusion with no maintenance dosing will be both effective and safe. Contraindications and precautions Known bleeding disorders of any origin or any unexplained excessive bleedings in the past. Platelet counts of less than 100,000 (even if asymptomatic), exemption : HIT (Heparin- induced thrombocytopenia). Planned surgery or short before delivery. Active ulcerations of the GIT. Any kind of malignant disease. Renal stones (increased likelihood of significant urological bleeding). Severe and uncontrolled arterial hypertension. Active pulmonary tuberculosis. Impaired fibrinolysis. Severe liver disease. Manifest or impending shock. I.M.-Injection : Ancrod should not be injected i.m., because of rapid induction of neutralizing antibodies and therefore drug resistance. Pregnancy Category X : Ancrod was not found to be teratogenic in animal studies, but some fetal deaths occurred as a result of placental hemorrhages in animals given high doses; therefore, it should not be used during pregnancy as the defibrinogenation mechanism of ancrod might be expected to interfere with the normal implantation of the fertilized egg. Side effects Hypersensitivity reactions : Local or generalized skin reactions (rash and urticaria); appearance of neutralizing antibodies to ancrod with partial or total loss of ancrod activity (drug resistance). Sometimes pain at injection site (normally mild)
Hennerici MG, Kay R, Bogousslavsky J, Lenzi GL, Verstraete M, Orgogozo JM: Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. Lancet. 2006 Nov 25;368(9550):1871-8. PubmedKelton JG, Smith JW, Moffatt D, Santos A, Horsewood P: The interaction of ancrod with human platelets. Platelets. 1999;10(1):24-9. Pubmed
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