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Coumarin
Coumarin anticoagulants 27. Katzir Z, Shvil Y, Landau EH, Popovtzer MM. Thiazide therapy for ACTH-induced hypercalciuria and nephrolithiasis. Acta Paediatr 1992;81(3):277–9. 28. Riikonen R, Simell O, Dunkel L, Santavuori P, Perheentupa J. Hormonal background of the hypertension and fluid derangements associated with adrenocorticotrophic hormone treatment of infants. Eur J Pediatr 1989;148(8):737–41. 29. Glass D, Nuki G, Daly JR. Development of antibodies during long-term therapy with corticotrophin in rheumatoid arthritis. II. Zinc tetracosactrin (Depot Synacthen). Ann Rheum Dis 1971;30(6):593–6. 30. Dunagan DP, Rubin BK, Fasano MB. Pneumocystis carinii pneumonia in a child receiving ACTH for infantile spasms. Pediatr Pulmonol 1999;27(4):286–9. 31. Hellem AJ, Solem JH. The influence of ACTH on prothrombin–proconvertin values in blood during treatment with dicumarol and phenylindanedione. Acta Med Scand 1954;150(5):389–93. 32. Van Cauwenberge H, Jaques LB. Haemorrhagic effect of ACTH with anticoagulants. Can Med Assoc J 1958; 79(7):536–40. 33. Chatterjea JB, Salomon L. Antagonistic effect of A.C.T.H. and cortisone on the anticoagulant activity of ethyl biscoumacetate. BMJ 1954;4891:790–2.
Corynebacterium parvum General Information Inactivated Corynebacterium parvum has been tried as an adjuvant in patients with cancer and in the treatment of malignant pleural effusions. Fever and chills were frequent, with sustained fever and chest or abdominal pain in several patients (1,2).
References 1. Ludwig Lung Cancer Study Group. Adverse effect of intrapleural Corynebacterium parvum as adjuvant therapy in resected stage I and II non-small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1985;89(6):842–7. 2. Foresti V. Intrapleural Corynebacterium parvum for recurrent malignant pleural effusions. Respiration 1995;62(1):21–6.
Coumarin General Information The plant lactone coumarin (not to be confused with coumarin anticoagulants) is a constituent of some plants, including:
Alyxia lucida Dalea tuberculata Dipteryx odorata Dipteryx oppositofolia Levisticum officinale Melilotus officinalis Scabiosa comosa.
ª 2006 Elsevier B.V. All rights reserved.
983
Organs and Systems Hematologic Coumarin is devoid of anticoagulant activity, but the molding of sweet clover can give it hemorrhagic potential by transforming coumarin to the anticoagulant dicoumarol. This transformation could explain a case of abnormal clotting function and mild bleeding after the drinking of an herbal tea prepared from tonka beans, sweet clover, and several other ingredients. Unfortunately, this possibility was not investigated, as the reporting physician was not aware of the exact phytochemistry and pharmacology of coumarin-yielding plants. Liver Coumarin has hepatotoxic potential in man, when taken in daily doses of 25–100 mg (1). Bile-duct carcinomas have been reported to occur in rats fed coumarin, but the correctness of this diagnosis has been seriously criticized.
Reference 1. Cox D, O’Kennedy R, Thornes RD. The rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone). Hum Toxicol 1989;8(6):501–6.
Coumarin anticoagulants General Information The coumarins were first discovered in Wisconsin, when bleeding in cattle was found to be due to the consumption of bruised sweet clover in the 1920s (1). The causative agent, dicoumarol, was isolated in 1940, and a range of related compounds was then synthesized, the most popular of which proved to be warfarin (named after the Wisconsin Alumni Research Foundation). Other coumarins that have been used are acenocoumarol (nicoumalone), bishydroxycoumarin, dicoumarol, ethyl biscoumacetate, and phenprocoumon. The coumarins act as competitive inhibitors of vitamin K epoxide reductase, which is responsible for regenerating reduced vitamin K from vitamin K epoxide after it has been consumed as a co-factor in the synthesis of coagulation factors II, VII, IX, and X. Uses The main use of the coumarins is in the treatment and prevention of thromboembolic disease, including deep vein thrombosis, pulmonary embolism, and cerebral embolism from cardiac and other sources. Protein C, another vitamin K-dependent serine protease zymogen in plasma, is a regulatory protein that, when activated, limits the activity of two activated procoagulant co-factors, factors Va and VIIIa. Heterozygotes for hereditary isolated protein C deficiency tend to develop a thrombotic disease which has been successfully treated with long-term coumarins (2,3). Apparently, the
Corynebacterium parvum General Information Inactivated Corynebacterium parvum has been tried as an adjuvant in patients with cancer and in the treatment of malignant pleural effusions. Fever and chills were frequent, with sustained fever and chest or abdominal pain in several patients (1,2).
References 1. Ludwig Lung Cancer Study Group. Adverse effect of intrapleural Corynebacterium parvum as adjuvant therapy in resected stage I and II non-small cell carcinoma of the lung. J Thorac Cardiovasc Surg 1985;89(6):842–7. 2. Foresti V. Intrapleural Corynebacterium parvum for recurrent malignant pleural effusions. Respiration 1995;62(1):21–6.
Coumarin General Information The plant lactone coumarin (not to be confused with coumarin anticoagulants) is a constituent of some plants, including:
Alyxia lucida Dalea tuberculata Dipteryx odorata Dipteryx oppositofolia Levisticum officinale Melilotus officinalis Scabiosa comosa.
ª 2006 Elsevier B.V. All rights reserved.
983
Organs and Systems Hematologic Coumarin is devoid of anticoagulant activity, but the molding of sweet clover can give it hemorrhagic potential by transforming coumarin to the anticoagulant dicoumarol. This transformation could explain a case of abnormal clotting function and mild bleeding after the drinking of an herbal tea prepared from tonka beans, sweet clover, and several other ingredients. Unfortunately, this possibility was not investigated, as the reporting physician was not aware of the exact phytochemistry and pharmacology of coumarin-yielding plants. Liver Coumarin has hepatotoxic potential in man, when taken in daily doses of 25–100 mg (1). Bile-duct carcinomas have been reported to occur in rats fed coumarin, but the correctness of this diagnosis has been seriously criticized.
Reference 1. Cox D, O’Kennedy R, Thornes RD. The rarity of liver toxicity in patients treated with coumarin (1,2-benzopyrone). Hum Toxicol 1989;8(6):501–6.
Coumarin anticoagulants General Information The coumarins were first discovered in Wisconsin, when bleeding in cattle was found to be due to the consumption of bruised sweet clover in the 1920s (1). The causative agent, dicoumarol, was isolated in 1940, and a range of related compounds was then synthesized, the most popular of which proved to be warfarin (named after the Wisconsin Alumni Research Foundation). Other coumarins that have been used are acenocoumarol (nicoumalone), bishydroxycoumarin, dicoumarol, ethyl biscoumacetate, and phenprocoumon. The coumarins act as competitive inhibitors of vitamin K epoxide reductase, which is responsible for regenerating reduced vitamin K from vitamin K epoxide after it has been consumed as a co-factor in the synthesis of coagulation factors II, VII, IX, and X. Uses The main use of the coumarins is in the treatment and prevention of thromboembolic disease, including deep vein thrombosis, pulmonary embolism, and cerebral embolism from cardiac and other sources. Protein C, another vitamin K-dependent serine protease zymogen in plasma, is a regulatory protein that, when activated, limits the activity of two activated procoagulant co-factors, factors Va and VIIIa. Heterozygotes for hereditary isolated protein C deficiency tend to develop a thrombotic disease which has been successfully treated with long-term coumarins (2,3). Apparently, the