Anticoagulant drugs: What are they? What are they for? I.Randi's Action Mechanism and Side Effects

Introduction

Anticoagulant drugs are drugs that can hinder blood clotting .

Given their therapeutic action, these drugs are used to prevent thrombus formation and to hinder the growth of those that have already formed. The formation of thrombi in the blood vessels, in fact, is an event that can lead to very serious and sometimes fatal consequences, especially if the thrombus detaches from the wall of the vessel in which it is formed and enters the bloodstream.

Currently there are different types of anticoagulant drugs - administered through different routes - that exercise their therapeutic activity through specific mechanisms of action.

Unlike platelet antiaggregating agents that act on platelet aggregation, anticoagulant drugs interfere with the coagulation process by acting on co-factors and coagulation factors whose activation leads to the formation of a fibrin network that traps blood cells giving origin to the clot.

Curiosity

In common parlance, anticoagulant drugs are commonly known as " blood thinners ".

What are

What are Anticoagulant Drugs and what are they for?

As mentioned, anticoagulant drugs are drugs used to prevent the formation of new thrombus and / or to hinder the growth of those already formed. Thanks to their activity, therefore, anticoagulants are useful in the treatment and prevention of cardiovascular diseases and events caused by the presence of thrombi.

The anticoagulant drugs currently used in therapy are different, are administered through different routes and can be divided, depending on the mechanism of action and according to their chemical structure, in the following way:

  • Oral coumarin-type anticoagulants : these are cumarinic derivatives administered orally which act as antagonists of vitamin K (vitamin implicated in the coagulation cascade).
  • Heparin anticoagulants : include heparin and its derivatives and are administered parenterally . They perform their action by activating antithrombin III, a physiological inhibitor of coagulation.
  • Factor Xa-inhibiting anticoagulants : they act directly on the coagulation factor Xa, consequently hindering the transformation of prothrombin I into thrombin (factor IIa).
  • Factor IIa-inhibiting anticoagulants : they act directly on factor IIa, or thrombin, preventing the formation of the fibrin network that traps erythrocytes and gives rise to a blood clot.

Therapeutic indications

Possible therapeutic indications of anticoagulant drugs

Depending on the active substance under consideration, the therapeutic indications of each anticoagulant may vary. However, the use of anticoagulant drugs is useful in the presence of:

  • Deep venous thrombosis;
  • Venous and arterial thromboembolytic disease;
  • Pulmonary embolism;
  • Atrial fibrillation with risk of embolization;
  • Mechanical heart valve prostheses (to prevent thrombus formation on the valves);
  • Heart attack;
  • Recent heart attack in order to prevent the onset of new cardiovascular events (another heart attack, stroke, etc.);
  • Unstable angina;
  • Acute peripheral arterial occlusion;
  • Unstable coronary syndromes.

For more information about the therapeutic indications of the anticoagulant drug that you must use, it is a good idea to ask your doctor for advice and read the package insert for the prescribed medicinal product.

Did you know that ...

The anticoagulant drugs seem to be particularly effective in preventing the formation of thrombus in the venous level, where the blood flow is slower and where the thrombi that are formed are more rich in erythrocytes and fibrin . In arterial vessels where blood flow is faster, thrombi are composed to a greater extent of platelets and have lower amounts of fibrin; for this reason, in these cases, the administration of antiplatelet agents - when possible - is the first choice treatment.

Cumarinic anticoagulants

Cumarinic Oral Anticoagulant Drugs

Cumarinic anticoagulant drugs are so defined because, from the chemical point of view, they are derivatives of coumarin (a natural organic compound).

They are also known as vitamin K antagonists, because they hinder the role played by this vitamin in the process of coagulation; but in common language, they are often called " oral anticoagulants ".

Among the anticoagulant drugs of this type present in therapy, we recall:

  • Warfarin (Coumadin®);
  • Acenocoumarol (Sintrom®).

Did you know that ...

In some cases, oral anticoagulants - at the appropriate dosages - can be administered in combination with antiplatelet drugs .

Action mechanism

Cumarinic anticoagulant drugs interfere with the redox cycle of vitamin K, a very important cofactor in the synthesis and activation of some vitamin K-dependent coagulation factors, such as factor II - better known as prothrombin - and factors VII, IX and X.

The redox cycle of vitamin K involved in the blood coagulation process involves the use of different enzymes: vitamin K quinone reductase and vitamin K 2, 3-epoxide reductase. Cumarinic anticoagulant drugs act as inhibitors of vitamin K 2, 3-epoxide reductase .

Side effects

The side effects that can occur during therapy with coumarin anticoagulants are manifold; among these we remember:

  • Increased risk of bleeding and the appearance of bleeding complications in different organs and tissues;
  • Allergic reactions in sensitive individuals;
  • Nausea and vomit;
  • Abdominal pains;
  • Bruising;
  • Alopecia;
  • Liver damage;
  • Kidney damage.

Heparin anticoagulants

Heparin-type injectable anticoagulant drugs

When we talk about heparin anticoagulant drugs we want to indicate a set of drugs to which both the same heparin and its derivatives belong.

To be precise, heparin is not a single molecule, but is made up of a heterogeneous mixture of sulfated mucopolysaccharides ( sulphated glycosaminoglycans) located in the granules of mast cells, plasma and other tissues. It is therefore an endogenous compound, naturally present within the organism, but which has also been made available within medicinal products for use in therapy and from which lower molecular weight derivatives have been obtained. also employed in therapy.

Heparin preparations are administered exclusively parenterally by injection or infusion, as appropriate.

The heparin anticoagulant drugs currently used are basically of two types:

  • Standard or unfractionated heparin (high molecular weight), is characterized by a rapid onset of the anticoagulant effect but for a short duration of action. For this reason, it is also used in emergencies.
  • Low molecular weight heparins (or LMWH, from Low Molecular Weight Heparin ), have a longer duration of action than standard heparin. Active ingredients such as: belong to this group of anticoagulant drugs
    • Bemiparin (Ivor®);
    • Dalteparin (Daltepin®, Fragmin®);
    • Enoxaparin (Clexane®, Clexane T®);
    • Reviparin (Clivarina®);
    • Tinzaparin (Innohep®).

Did you know that ...

Since the heparinic preparations are heterogeneous mixtures of polysaccharides having different affinities for the various biological targets, the correlation between the dosage in milligrams and the anticoagulant effect produced by that same dosage is limited and not always true. In fact, the heparinic products are dosed in International Units (IU, or unit of measurement of the quantity of a drug based on its biological activity).

Action mechanism

The heparinic preparations carry out their anticoagulant action by binding to antithrombin III - a physiological inhibitor of the coagulation process - and by enhancing the inhibitory action against coagulation factors Xa and IIa (thrombin). More in detail, when the heparinic preparations bind to antithrombin III, they cause a conformational variation that causes an increase in the affinity and binding speed of antithrombin III itself with factors Xa and IIa.

The anticoagulant action physiologically exerted by antithrombin III, therefore, appears to be considerably increased by the administration of heparin anticoagulant drugs.

Please note

Low molecular weight heparins increase the activity of antithrombin III especially with respect to the coagulation factor Xa, but not with respect to factor IIa, or in any case increase its activity in a reduced manner and not meaningfully from a clinical point of view. Therefore, although the mechanism of action is similar to that of standard heparin, LMWHs are more selective for factor Xa.

Side effects

Among the side effects that may occur following the administration of heparin anticoagulant drugs, we find:

  • Increased risk of bleeding and the appearance of bleeding complications in different organs and tissues;
  • Allergic reactions in sensitive individuals;
  • Reactions at the injection site;
  • Skin reactions;
  • Thrombocytopenia.

Other Heparin Derivatives

Research in the pharmaceutical field has led to the creation of synthetic heparin derivatives in order to increase their bioavailability and reduce their side effects.

Among these synthetic derivatives, fondaparinux (Arixtra®), a synthetic pentasaccharide sulphate whose structure is based on the active portion of heparin which, not surprisingly, is just a pentasaccharide portion, is currently used in therapy.

However, fondaparinux is able to indirectly and selectively inhibit coagulation factor Xa through binding to antithrombin III, similarly to what has been said for standard heparin and low molecular weight heparins. However, it has a fundamental advantage: being a synthetic active principle, its structure is reproducible and the composition of the medicines that contain it is always the same. all this has enabled the achievement of an improvement in the pharmacokinetic profile and the attainment of a more selective anticoagulant action than the heparin anticoagulant drugs proper.

Factor Xa inhibitors

Anticoagulant Drugs Direct Factor Xa Inhibitors

The direct factor Xa inhibitors are administered orally and exert their anticoagulant action by acting directly on this coagulation factor. Among the active ingredients with this anticoagulant action used in therapy, we find:

  • Rivaroxaban (Xarelto®);
  • The apixaban (Eliquis®).

Action mechanism

The anticoagulant drugs direct inhibitors of factor Xa carry out their action by acting directly on the latter. In the process of coagulation, factor Xa is involved in the formation of thrombin (or factor IIa, if you prefer). The anticoagulants, direct inhibitors of factor Xa, bind in a highly selective manner to its active site, interrupting its action in the coagulation process and consequently hindering the formation of thrombus.

Side effects

The side effects that can occur during therapy with anticoagulant drugs direct inhibitors of factor Xa are manifold, among these we recall:

  • Increased risk of bleeding and the appearance of bleeding complications in different organs and tissues;
  • Allergic reactions in sensitive individuals;
  • Hematoma;
  • Skin disorders;
  • Hepatic disorders.

Factor IIa inhibitors

Anticoagulant Drugs Direct Factor IIa Inhibitors

The anticoagulant drugs direct inhibitors of factor IIa - or thrombin, if you prefer - exercise their action by interfering with the latter's role in the process of coagulation. Among the anticoagulants of this type used in therapy we find the following active ingredients:

  • Bivalirudin (Angiox®), administered parenterally;
  • Argatroban (Novastan®), also administered parenterally;
  • The dabigatran (Pradaxa®), administered orally.

Action mechanism

The anticoagulant drugs direct inhibitors of factor IIa act directly on the latter, binding to it and hindering its action. In the coagulation process, thrombin splits fibrinogen into fibrin monomers and converts coagulation factor XIII to coagulation factor XIIIa which, in turn, favors the formation of the fibrin network that traps blood cells and gives rise to the clot . Thanks to their mechanism of action, the anticoagulant drugs direct inhibitors of factor IIa are, therefore, able to block the last phases of the coagulation process, preventing the formation of the thrombus.

Side effects

The side effects that can occur during therapy with anticoagulant drugs direct inhibitors of factor IIa are manifold and can vary depending on the active ingredient used and the way in which it is administered. However, among these we remember:

  • Increased risk of bleeding and the appearance of bleeding complications in different organs and tissues;
  • Allergic reactions in sensitive individuals;
  • Gastrointestinal disorders for oral administration;
  • Skin reactions;
  • Injection site reactions in case of parenteral administration.

Contraindications

When should anticoagulant drugs not be used?

Since the anticoagulants include a wide range of active ingredients, each with its own mechanism of action and with its own "target", the contraindications to their use can vary - even a lot - depending on the drug used. Nevertheless, it is possible to state that the use of most anticoagulant drugs is generally contraindicated:

  • In case of known hypersensitivity to the active ingredient or to any of the excipients contained in the medicinal product to be used;
  • In patients suffering from pathologies or who are in particular conditions capable of predisposing to the onset of bleeding and bleeding .

Furthermore, the use of most anticoagulant drugs is NOT recommended during pregnancy.

Please note

For more detailed information on therapeutic indications, warnings, drug interactions, dosage and use, use during pregnancy and lactation, side effects and contraindications of anticoagulant drugs, see the reading of the medicinal product prescribed by the doctor who must use.

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