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Coagulant & Anticoagulants (Med Chem:- 2) Notes Download

Description

Introduction
Blood coagulation is an important biochemical reaction which ensures the
cessation of blood loss from the damaged blood vessels. Coagulation is an
important part of the haemostatic mechanism. Disorders of blood coagulation
result to excessive haemorrhage and/or thrombosis and embolism.
Coagulants help in blood coagulation and are indicated in haemorrhagic
conditions. The elements or factors required for coagulation are found in the
fresh whole blood or pl asma and are therefore indicated in case of deficiency of
any clotting factor.
9.1.2. Classification
The coagulants are classified as follows:
1) Vitamin K
i) K1 (from plants, fat-soluble): Phytonadione (Phylloquinone).
ii) K3 (synthetic)
a) Fat-Soluble: Menadione and Acetomenaphthone.
b) Water-Soluble: Menadione sodium bisulfite and Menadione sodium
diphosphate.
2) Miscellaneous: Fibrinogen (human), Anti-haemophilic factor,
Desmopressin, Adrenochrome monosemicarbazone, Rutin, and Ethamsylate.
9.1.3. Mechanism of Action
The mechanism of action of coagulants is described as follows:
1) Vitamin K is required for the synthesis of clotting factors II, VII, IX, and X.
2) These factors are chemically glycoproteins with a number (10 or 11) or -
carboxyglutamic acid at the ─NH2 terminal of the peptide chains.
3) Synthesis of -carboxyglutamic acid residues is dependent of vitamin K and
the reaction occurs after peptide chain synthesis.
4) Vitamin K acts as a co-factor in the carboxylation reaction.

Uses
Coagulants has the following therapeutic uses:
1) Prolonged Antimicrobial Therapy: Antimicrobial therapy for a long period
causes destruction of GIT bacteria , thus formation of vitamin K is either
reduced or stopped. For the treatment of this condit ion, vitamin K
preparations are given through oral route.
2) Obstructive Jaundice: It is caused by malabsorption of dietary or intestinal
vitamin K. Vitamin K3 can be administered orally, or vitamin K1 or K2 can be
given through parenteral route.
3) Overdosage of Oral Anticoagulants: In this case, vitamin K is given as a
specific antidote. Vitamin K 1 is the preparation of choice due to its rapid
onset of action. Menadiol sodium diphosphate (K3) should not be used due to
its late onset of action (24 hours).
4) Malabsorption Syndrome: In this condition, parenteral vitamin K or oral
vitamin K3 may be used.
9.1.5. Study of Individual Drugs
The following coagulants are discussed below:
1) Menadione, and
2) Acetomenadione.
9.1.5.1. Menadione
Menadione is a synthetic naphtho quinone with no isoprenoid side chain and
biological activity. It can be converted to pharmacologically active vitamin K 2
(menaquinone) by undergoing in vivo alkylation. It can act as a precursor for
various forms of vitamin K, but it is not used as a nutritional supplement.
Mechanism of Action
Menadione (vitamin K 3) serves as a cofactor in the post -translational γ-
carboxylation of glutamic acid residues of certain body proteins. These proteins
are the vitamin K -dependent coagulation factors II (prothrombin), VII
(proconvertin), IX (Christmas factor), X (Stuart factor), p rotein C, protein S,
protein Zv, and a Growth-arrest-specific factor (Gas6).
Contrary to other vitamin K-dependent proteins in the blood coagulation cascade,
protein C and protein S have some anticoagulant roles to play. Two vitamin K-
dependent proteins are found in bones, i.e., osteocalcin, also known as bone G1a
(γ-carboxyglutamate) protein or BGP, and the matrix G Proteins containing γ-carboxyglutamate are called G 1a proteins. The vitamin K –
dependent γ-carboxylases catalyse the process of γ-carboxylation. The reduced
form of vitamin K is vitamin K hydroquinone, which is the actual cofactor for γ-
carboxylases.
Uses
1) It is used to support the normal clotting process of blood.
2) It also helps in normal bone calcification.
9.1.5.2. Acetomenadione
Acetomenadione (or menadiol diacetate) is a vitamin K analogue. It prevents
hypoprothrombinemia caused by vitamin K deficiency.
Mechanism of Action
Acetomenadione serves as a cofactor for the γ-carboxylase enzymes. These
enzymes catalyse the post-translational γ-carboxylation of glutamic acid residues
in inactive hepatic precursors of coagulation factors II (prothrombin), VII, IX and
X. In the process of γ-carboxylation, these inactive precursors are converted into
active coagulation factors. These factors a re secreted into the blood by
hepatocytes. Supplementing with acetomenadione relieves the symptoms of
vitamin K deficiency which include easy bruisability, epistaxis, gastrointestinal
bleeding, menorrhagia, and haematuria.
Uses
1) It is used for treating haemorrhagic conditions in infants.
2) It can be used as an antidote for coumarin anticoagulants in
hypoprothrombinaemia.
9.2. ANTICOAGULANTS
9.2.1. Introduction
Blood coagulation is a complex process in which blood forms solid clots. It is
essential part of haemostasis in w hich a damaged blood vessel wall is enclosed
by a fibrin clot to prevent haemorrhage and to repair the damage d vessel.
Disorders of blood coagulation increase the occurrence of haemorrhage and/or
thrombosis and embolism.

Subject:- Medicinal chemistry 2

Semester:- Sem 5

Course:- Bachelor of pharmacy

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