Anticoagulant drug

An anticoagulant is a substance that prevents coagulation (clotting) of blood. Such

substances occur naturally in leeches and blood-sucking insects. A group of pharmaceuticals
called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some
anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and
renal dialysis equipment.

Mechanisms of action
Rivaroxaban and dabigatran etexilate have low molecular weights. They have specific and
restricted anticoagulant activities.Although their mechanisms of action are

different, the specificity of activity has no known clinical relevance and both drugs are effective
anticoagulants.

Rivaroxaban is a competitive reversible antagonist of activated factor X (Xa). Factor Xa is the

active component of the prothrombinase complex that catalyses conversion of prothrombin
(factor II)

Dabigatran etexilate is a competitive reversible non-peptide antagonist of thrombin. Thrombin is

a multifunctional enzyme which converts fibrinogen to fibrin, cross-linking fibrin monomers via

activation of factor XIII and augmenting further thrombin production via the activation of factors
V and VIII. It also activates platelets, generates anticoagulant activity via activation of protein

C and initiates numerous cellular processes including wound healing. Most of the actions of
thrombin are inhibited in vitro by dabigatran etexilate.

Mechanism of clotting
       A blood clot forms as a result of concerted action of some 20 different substances, most of
which are plasma glycoproteins.

Coagulation Factors
Factor Name Plasma half-life (h)
     
I Fibrinogen 72 - 96
II Prothrombin 60

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 III Tissue Factor or thromboplastin --
IV Ca++ --
V Proaccelerin 15
VII Proconvertin 5
VIII Antihemophilic A factor 10
Antihemophilic B factor or
IX 25
Christmas factor
X Stuart or Stuart-Prower factor 40
XI Plasma thomboplastin antecedent 45-65
XII Hageman factor, contact factor 60
XIII Fibrin stabilizing factor 150
  Prekallikrein factor --
High-molecular-weight
  156
kininogen

Marketed anticoagulent drug

Antithrombotic drugs, which include anticoagulants, antiplatelet drugs and thrombolytic
drugs, are used in a wide range of indications for the prevention and treatment of ischaemic
events. These include acute coronary syndromes (ACS), myocardial infarction (MI), stroke,
venous thromboembolism (VTE) and peripheral arterial occlusion (PAO).

Oral antiplatelet drugs account for most long-term prevention prescriptions, as the most widely
used oral anticoagulant, warfarin, is plagued with drug–drug and food–drug interactions, and
requires extensive monitoring. So, even preventative use of anticoagulants is largely confined to
the hospital setting; for example, for VTE prophylaxis in surgical patients. Thrombolytic drugs,
the most powerful class of agents, are solely indicated for acute MI and stroke. Moreover, their
use has declined over recent years owing to the superior efficacy of coronary angioplasty for
reperfusion. However, they remain widely used in markets such as the UK, where angioplasty
facilities are limited.

Despite the wide range of therapeutic options available for the whole spectrum of ischaemic
events, there remains a need for more efficacious and safer compounds. Given the downward
pressure on the use of thrombolytic drugs, the thrombolytic drug pipeline is sparse. Therefore,
this article focuses on future developments in the anticoagulant and antiplatelet drug markets.

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Mechanism of action of anticoagulant drug: They are given in
below-

 Warfarin

Warfant is an anticoagulant normally used in the prevention of thrombosis and

thromboembolism, the formation of blood clots in the blood vessels and their migration
elsewhere in the body respectively. It was initially introduced in 1948 as a pesticide against rats
and mice and is still used for this purpose, although more potent poisons such as brodifacoum
have since been developed. In the early 1950s warfarin was found to be effective and relatively
safe for preventing thrombosis and embolism (abnormal formation and migration of blood clots)
in many disorders. It was approved for use as a medication in 1954 and has remained popular
ever since; warfarin is the most widely prescribed oral anticoagulant drug in North America.[1]

Despite its effectiveness, treatment with warfarin has several shortcomings. Many commonly
used medications interact with warfarin, as do some foods (particularly leaf vegetable foods or
"greens," since these typically contain large amounts of vitamin K) and its activity has to be
monitored by blood testing for the international normalized ratio (INR) to ensure an adequate yet
safe dose is taken.[2] A high INR predisposes to a high risk of bleeding, while an INR below the
therapeutic target indicates that the dose of warfarin is insufficient to protect against
thromboembolic events.

Warfarin and related 4-hydroxycoumarin-containing molecules decrease blood coagulation by

inhibiting vitamin K epoxide reductase, an enzyme that recycles oxidized vitamin K to its
reduced form after it has participated in the carboxylation of several blood coagulation proteins,
mainly prothrombin and factor VII. Despite being labeled a vitamin K antagonist, warfarin does
not antagonize the action of vitamin K, but rather antagonizes vitamin K recycling, depleting
active vitamin K. Thus, the pharmacologic action may always be reversed by fresh vitamin K.
When administered, these drugs do not anticoagulate blood immediately. Instead, onset of their
effect requires about a day before remaining active clotting factors have had time to naturally
disappear in metabolism, and the duration of action of a single dose of warfarin is 2 to 5 days.
Reversal of warfarin's effect when it is discontinued or vitamin K is administered, requires a
similar time.

Apixaban
It is INN, trade name Eliquis. It is an anticoagulant for the prevention of venous
thromboembolism and venous thromboembolic events. It is a direct factor Xa inhibitor.
Apixaban has been available in Europe since May 2011 and was approved for preventing venous
thromboembolism after elective hip or knee replacement.[1] The FDA approved apixaban in

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December 2012 with an indication of reducing the risk of stroke and dangerous blood clots
(systemic embolism) in patients with atrial fibrillation that is not caused by a heart valve
problem. The drug was developed in a joint venture by Pfizer and Bristol-Myers Squibb.

Ticlopidine
These medications make it more difficult for your blood to clot and because of this, you may
have trouble with bleeding after certain dental procedures.  It may take longer than you would
expect for any bleeding to stop.  In light of this, you might consider reducing your dosage or stop
taking the medications entirely before receiving dental care.  However, it is generally agreed that
anticoagulant drug regimens should not be altered prior to dental treatment.  If you stop taking,
or take less of, the anticoagulant medication, you increase your chance for blood clot
development, which could result in thromboembolism, stroke or heart attack.  The risks of
stopping or reducing this medication routine outweigh the consequences of prolonged bleeding,
which can be controlled with local measures.  For example, you may be asked to bite down on
sponges treated with a liquid that helps control bleeding.

Rivaroxaban is an oral anticoagulant invented and manufactured by Bayer; in a number of

countries it is marketed as Xarelto.[1] In the United States, it is marketed by Janssen
Pharmaceutica.[2] It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is
well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose.
The effects lasts 8–12 hours, but factor Xa activity does not return to normal within 24 hours so
once-daily dosing is possible. There is no specific way to reverse the anticoagulant effect of
rivaroxaban in the event of a major bleeding event, unlike warfarin.