ANTICOAGULANT

An anticoagulant is a substance that prevents or reduces coagulation (clotting) of blood. This group of pharmaceuticals can be used in vivo as a medication for thrombotic disorders. Thrombosis is the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. If the clot becomes mobile and is carried away by the blood circulation, it is called an embolus.

Anticoagulants is required if one has been diagnosed with or treated for one or more of the following: Atrial fibrillation (AF)lack of an organized atrial contraction can result in some stagnant blood in the left atrium (LA) thrombus formation heparin, warfarin, dabigatran, rivaroxaban Arterial embolismsudden interruption of blood flow to an organ or body part due to an embolus adhering to the wall of an artery blocking the flow of blood warfarin, heparin

Deep vein thrombosis (DVT)formation of a blood clot (thrombus) in a deep vein, predominantly in the legs venous stasis, hypercoagulability, and changes in endothelial blood vessel lining (such as physical damage) LMWH, fondaparinux, unfractionated heparin, warfarin Pulmonary embolism (PE)blockage of the main artery of the lung or one of its branches due to an embolus most commonly results from deep vein thrombosis LMWH, fondaparinux, unfractionated heparin, warfarin Strokerapid loss of brain function due to disturbance in the blood supply to the brain thrombosis, arterial embolism Warfarin

Genetic clotting disorders like prothrombin thrombophilia, Factor V Leiden thrombophilia congenital thrombophilia -an inborn abnormality of blood coagulation that increases risk of thrombosis as a result of overactivity of coagulation factors prothrombin thrombophilia- a mutation in prothrombin factor V Leiden thrombophilia- a mutation in the F5 gene warfarin and during pregnancy LMWH

ANTICOAGULANT DRUGS

DIRECT THROMBIN INHIBITORS

Drug name Bivalent/ Univalent Route of administration Binding to active site and/or exosite Reversible Indications

Argatroban

Univalent

Parenteral (iv)

Dabigatran etexilate

Univalent

Oral

Reversible

Prevention and treatment of thrombosis Prevention of stroke and embolism in patients with AF Prevention of further thrombosis

Lepirudin

Bivalent

Parenteral (iv/sc)

Irreversible

Mechanism: Thrombin has three domains: one active site and two exosites. Exosite 1 acts as a dock for substrates such as fibrin in order to promote orientation for active site binding. Exosite 2 is the heparin-binding domain. Thus, DTIs are able to inactivate both fibrinbound and unbound thrombin, unlike UFH and LMWH.

Side-effects: Heart failure; bleeding in injection site, wounds and allergic skin reactions; nosebleed; gastrointestinal and rectal bleeding; abnormal kidney function, blood in urine

INDIRECT THROMBIN INHIBITORS

Mechanism of action of UFH and LMWH
A, To inactivate thrombin, unfractionated heparin forms a ternary complex with antithrombin and thrombin. B, Because of their lower molecular weight, LMWH species are unable to form the ternary complexes with antithrombin and thrombin. Thus, LMWHs produce their anticoagulant effect mainly by inhibiting factor Xa.

Fondaparinux: Mechanism of action

Overview:
Drug name
Fondaparinux

Route of Excretion Indications administration SC Renal (Eliminated Prophylaxis & treatment of unchanged in urine) acute deep vein thrombosis

Side effects of heparin:

1.Haemorrhage the risk is greatest in the elderly, and may be exacerbated by alcohol intake. This is by far the most common side effect. 2.Osteoporosis can occur if the drug is used for more than a few weeks. This does not occur with LMWHs. 3.Thrombocytopaenia can occur after 7-10 days of therapy. It is a result of heparin induced antiplatelet antibodies. 4.Hyperkalaemia due to inhibition of aldosterone secretion 5.Hypersensitivity
Side-effects of fondaparinux: Anemia; Hematoma; Hypokalemia; Hypotension; Thrombocytopenia; Urinary tract infection; edema; fever;; local irritation (injection site bleeding; rash); nausea

VITAMIN K ANTAGONISTS

Side-effects: Haemorrhage this is especially common to the bowel and brain; hematuria; epistaxis; teratogenicity; necrosis of soft tissues; leukopenia, agranulocytosis

DIRECT Xa INHIBITORS
Rivaroxaban and Apixaban oral, reversible, specific inhibitors of both free and fibrin-bound factor Xa do not involve antithrombin III (ATIII) to exert their anticoagulant effects decrease thrombin generation and thrombus development side-effects: upper GI, lower GI, and rectal bleeding (0.1% to 1%); skin rash (less than 1%); anaphylactic reactions (such as allergic edema) (less than 1%); intracranial bleeding (0.33%); syncope (less than 1%); intraocular bleed (0.21%)