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MEDICINAL CHEMISTRY

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Warfarin and other coumarin derivatives are antagonists of vitamin K. Thus they act by<br />

depressing the vitamin K-dependent synthesis of coagulation factors 11 (prothrombin),<br />

VII, IX and X, and of the anticoagulant protein C and its protein cofactor protein S.<br />

Official Drugs<br />

Warfarin Sodium, B.P., I.P.: Warfarin sodium is the sodium salt of (RS)-4-hydroxy-3-<br />

(3-oxo-l-phenylbutyl)-coumarin. It is a white powder and hygroscopic. It is very soluble<br />

in water. It should be kept in an airtight container and protected from light. Warfarin<br />

sodium is readily absorbed from the gastrointestinal tract. It can also be absorbed through<br />

the skin. It is extensively bound to plasma proteins and its plasma half-life is about 37<br />

hours. Warfarin is transformed into inactive metabolites by the liver and kidneys. They<br />

are excreted in urine and stool. Warfarin is used in the prevention and treatment of deepvein<br />

thrombosis or pulmonary embolism. It is equally effective either orally or<br />

intravenously. Warfarin should not be given to patients who are haemorrhaging,<br />

Warfarin is used as a racemic mixture, and however the S-isomer is reported to be more<br />

potent. Usual dose of warfarin sodium is 10 mg daily by mouth for 2 days, but may be<br />

lower for patients with particular risk of haemorrhage. Subsequent maintenance doses<br />

usually range from 3 to 9 mg daily.<br />

Preparation: Warfarin Tablets, B.P. Proprietary Names: COUMADIN; PANWARFIN<br />

Warfarin Sodium tablets, I.P<br />

Warfarin Sodium Clathrate, B.P., I.P.: Warfarin sodium Clathrate is the Clathrate of<br />

the sodium salt of (RS)-4-hydroxy-3-(3-oxo-l-phenylbutyl)-coumarin with propan-2-ol. It<br />

consists of warfarin sodium and propan-2-ol in the molecular proportion of 2:1. It<br />

contains approximately 92% of warfarin sodium. It is a white powder and is very soluble<br />

in water. It should be kept in an airtight container and protected from light. It has actions<br />

and uses similar to those of warfarin sodium. Preparation: Warfarin Tablets, B.P.<br />

Acenocoumarin/Nicoumalone, B.P, I.P.: Nicoumalone is (RS)-4-hydroxy-3-[1-(4nitrophenyl)-3-oxobutyl]<br />

coumarin. It is a white to brownish white powder, practically<br />

insoluble in water. It is stored in light-resistant containers. Nicoumalone is readily<br />

absorbed when given by mouth. It is excreted chiefly in the urine mainly as metabolites.<br />

It is extensively bound to plasma proteins. Nicoumalone has actions and uses similar to<br />

those of warfarin sodium. It is administered orally. Though used as a racemic mixture,<br />

the R(+)-enantiomer of nicoumalone is reported to be pharmacologically active<br />

component of nicoumalone. The initial dose of nicoumalone is 12 to 20 mg; subsequent<br />

doses are given in accordance with the needs of the patient.<br />

Preparation: Nicoumalone Tablets, B.P., I.P. Proprietary Name: SINTHROME<br />

C. Indanedione<br />

Indanedione derivatives, such as phenindione and anisidione, were conceived as ring<br />

contracted analogues of coumarins. Like coumarins they also act as oral anticoagulants<br />

by inhibiting the synthesis of prothrombin and other factors VII, IX and X.

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