What Are the Different Types of Anticoagulant Drugs?

Anticoagulants can be used to prevent intravascular embolism or thrombosis, and prevent stroke or other thrombotic diseases. Is a drug that blocks the coagulation process by affecting certain coagulation factors in the coagulation process

Introduction to anticoagulants

Anticoagulant

anticoagulant drugs

It can be used to prevent and treat intravascular embolism or thrombosis, and prevent stroke or other thrombotic diseases. Is pass

Anticoagulant Drugs that block the coagulation process by affecting certain coagulation factors during the coagulation process. Normal people have a complete blood coagulation system and anticoagulation and fibrinolytic system, so blood neither coagulates nor bleeds in the blood vessels, and always freely flows to complete its function, but when the body is in a hypercoagulable state or the anticoagulation and fibrinolysis are weakened At that time, thromboembolic disease occurs.

The most frequently used anticoagulants in clinical practice include: parenteral anticoagulants (such as heparin), coumarin anticoagulants (such as warfarin), antiplatelet agglutination drugs (such as aspirin), and so on.

Classification of anticoagulants

Classification of commonly used anticoagulants:

1. Heparin. It has a strong anticoagulant effect in vivo and in vitro. This is achieved by antithrombin III, which has an inhibitory effect on many aspects of the coagulation process, and its effect is rapid. This preparation can only be administered intravenously, because it is convenient to use (subcutaneous injection), it is often used for those who need rapid anticoagulant therapy or as a pre-oral medication for oral anticoagulants. When the excessive amount causes bleeding, it can be used in the same amount of protamine with. Long-term use of heparin has the risk of causing bleeding and side effects.

2. Coumarins. Commonly used are dicoumarin, warfarin, and new anticoagulation. By antagonizing vitamin K, the liver can reduce prothrombin and factors , , and X to reduce anticoagulation, because there are still sufficient coagulation factors in the body at the beginning of medication, so Only when these factors are depleted can they exert anticoagulant effect, so its effect starts slowly, but the effect lasts longer. It is suitable for those who need a longer period of anticoagulation such as deep vein thrombosis and pulmonary embolism. When bleeding, in addition to vitamin K, the most important thing is to transfuse fresh blood to supplement coagulation factors.

3. Antiplatelet drugs such as aspirin and persantin are effective in preventing thrombosis.

Because aspirin inhibits platelet cyclooxygenase and prevents platelet cyclooxygenase from converting arachidonic acid into prostaglandin intermediates. The lack of prostaglandin intermediates in the blood makes it impossible (or difficult) to form a thrombus. Countries around the world have widely adopted oral low-dose aspirin to prevent thrombotic diseases caused by vascular fibrosis. The results of a large-scale adjustment of aspirin users confirm that this medicine can indeed reduce the incidence of stroke, myocardial infarction or other thrombotic diseases by 40-50%. More importantly, low-dose aspirin preparations are very inexpensive, and even if taken regularly, they will not increase the financial burden on patients.

4. In addition, snake venom thrombolytic agents such as defibrase, antithrombotic enzyme and thrombolytic enzyme can dissolve the formed thrombus and reopen the blood vessels.

5. New oral anticoagulants

At present, new oral anticoagulants specifically refer to newly developed and marketed oral factor Xa and direct inhibitors of factor IIa. The former includes apixaban, rivaroxaban, edoxaban, and dabigatran. These two types of drugs are for a single active coagulation factor, and the anticoagulant effect does not depend on antithrombin. It takes a fast oral effect, has a short half-life relative to warfarin, and has a good dose-effect relationship with food and drugs. There is very little interaction between them. Oral use does not require monitoring of conventional coagulation indicators. It can reduce or minimize adverse drug effects or adverse bleeding events caused by improper medication, and small differences in individual doses require only fixed doses. Convenient ^[1] .

Heparin

Anticoagulant Sources and Chemistry

Heparin contains acid mucopolysaccharides of varying lengths. It is mainly composed of two disaccharide units in sulfuric acid-D-glucosamine, sulfuric acid-L-iduronic acid, sulfuric acid-D-glucosamine, and D-glucuronic acid. It has a molecular weight of 5000 to 30,000. mixture. Contains a large number of sulfate groups and carboxyl groups, with a large number of negative charges is strongly acidic. Medicinal heparin is obtained from the small intestine of pigs and bovine lungs.

Anticoagulant pharmacological effects

Heparin has a strong anticoagulant effect in vivo and in vitro. After intravenous injection, anticoagulation occurs immediately, which is related to its large negative charge, which can inactivate a variety of coagulation factors. This effect is dependent on antithrombin III (AT III). At III is an inhibitor of thrombin and serine-containing proteases such as factors , , , X. It binds to thrombin via an arginine-serine peptide bond. The formation of At thrombin complex and inactivation of the enzyme, heparin can accelerate this reaction by more than a thousand times. Heparin binds to the lysine contained in At and causes the conformational change of AT , which makes the arginine residue contained in At easier to bind to the serine residue of thrombin. Once the heparin-At thrombin complex is formed, heparin is dissociated from the complex, and is bound to another molecule of At and reused. At III-thrombin complex is eliminated by the reticuloendothelial system. The effect of inhibiting thrombin activity is related to the length of the heparin molecule. The longer the molecule, the greater the enzyme inhibition.

Heparin also has a lipid-lowering effect because it can release lipoprotein lipase from vascular endothelium, hydrolyze chylomicrons and VLDL. But after stopping the drug, it will cause a "rebound" and make blood lipids rise.

Anticoagulant in vivo processes

Heparin is a large molecule with a large negative charge and is not absorbed orally. Often administered intravenously, 60% is concentrated in the vascular endothelium, most of which are destroyed by the reticuloendothelial system, and rarely excreted in the original form. The heparin anticoagulant activity t1 / 2 is related to the administered dose. Intravenous injection of 100, 400, 800 U / kg, the anticoagulant activity t1 / 2 is 1, 2.5 and 5 hours, respectively. Patients with pulmonary embolism and cirrhosis had prolonged t1 / 2.

Clinical application of anticoagulants

1. Thromboembolic diseases prevent thrombosis and expansion, such as deep vein thrombosis, pulmonary embolism, cerebral embolism, and acute myocardial infarction.

2. Diffuse intravascular coagulation (DIC) should be applied early to prevent secondary bleeding due to depletion of fibrinogen and other coagulation factors.

3 Anticoagulation for cardiovascular surgery, cardiac catheterization, hemodialysis, etc.

Anticoagulant adverse reactions

Excessive application can easily cause spontaneous bleeding. Once this occurs, heparin is discontinued and protamine is injected with a positive charge. Each 1 mg of protamine can neutralize 100U heparin. In some patients, platelet deficiency may occur during 2 to 14 days of heparin application, which is related to the platelet aggregation effect caused by heparin.

Heparin does not easily pass through the placental barrier, but application in pregnant women can cause premature birth and fetal death.

Continuous application of heparin for 3 to 6 months can cause osteoporosis and spontaneous fracture. Heparin can also cause allergic reactions such as rash and drug fever. Liver and kidney insufficiency, bleeding quality, peptic ulcer, severe hypertension patients, pregnant women are prohibited.

Coumarins

Coumarins are a class of substances that contain the basic structure of 4-hydroxycoumarin. They take part in metabolism in the body to exert anticoagulant effect, so they are called oral anticoagulants. There are dicoumarol, warfarin (benzylacetone coumarin) and acenocoumarol (new anticoagulant). They have the same pharmacological effects.

Anticoagulant pharmacological effects

Coumarins are vitamin K antagonists that inhibit the conversion of vitamin K from epoxides to hydroquinones in the liver, thereby preventing the repeated use of vitamin K and affecting coagulation factors , , , containing glutamic acid residues The carboxylation of these factors causes these factors to stay in the precursor stage without coagulation activity, thereby affecting the coagulation process. There is no inhibitory effect on the above factors that have been formed, so the anticoagulant effect appears slowly. It usually takes 8 to 12 hours for it to take effect and reach its peak in 1 to 3 days. The anticoagulant effect can be maintained for several days after drug withdrawal. The anticoagulant effect of dicoumarin is slow and long lasting for 4-7 days. Warfarin appears quickly, lasting 2 to 5 days.

Anticoagulant in vivo processes

Warfarin is completely absorbed orally and can be detected in plasma after 1 hour, reaching a peak in 2-8 hours. The binding rate to plasma proteins is 90% to 99%. t1 / 2 is 10 to 60 hours. Metabolized mainly in the liver and kidneys. Dicoumarin is irregularly absorbed. The binding rate to plasma proteins is 90% to 99%. t1 / 2 is 10 to 30 hours. The acenocoumarol t1 / 2 is 8 hours, and the reduced metabolites still have anticoagulant effects, and t1 / 2 is 20 hours.

Clinical application of anticoagulants

The use is the same as heparin, which can prevent thrombosis and development. Can also be used as an adjuvant for myocardial infarction. It is effective when taken orally and has a longer duration of action. But the effect appears slow and the dose is not easy to control. It is also used to prevent venous thrombosis after rheumatic heart disease, hip fixation, and artificial heart valve replacement.

Anticoagulant adverse reactions

The dose should be adjusted according to the prothrombin time control within 25-30 seconds (normal value 12 seconds). Overdose is prone to bleeding, which can be counteracted with vitamin K, and fresh plasma or whole blood is transfused if necessary. Contraindications are the same as heparin. Other adverse reactions include gastrointestinal reactions and allergies.

Anticoagulant drug interactions

The lack of vitamin K in food or the use of broad-spectrum antibiotics to inhibit intestinal bacteria and reduce the vitamin K content in the body can enhance the effect of this class of drugs. Aspirin and other platelet inhibitors can work synergistically with this class of drugs. Chloraldehyde hydrate, hydroxybutazone, metsulfuronium, quinidine, etc. can replace plasma proteins, salicylates, imipramine, metronidazole, cimetidine, etc. can be used to inhibit liver drug enzymes. The role of this class of drugs is strengthened. Barbiturates and phenytoin sodium can induce liver drug enzymes, and oral contraceptives can reduce the effects of these drugs due to increased coagulation.

Anticoagulants Other Coumarins

Apixaban

Apixaban is an oral, direct inhibitor of the active site of factor Xa, which binds directly to the active site of factor Xa. It reduces anticoagulant and antithrombotic effects by reducing the conversion of prothrombin to thrombin, thereby reducing blood clotting. Enzymatic activation of the coagulation system and platelet activation. Regardless of whether factor Xa is bound to fibrin clot or prothrombin, apixaban can inhibit factor Xa free and bound to thrombus, and inhibit prothrombinase activity. Apixaban has no direct effect on platelet aggregation, but indirectly inhibits thrombin-induced platelet aggregation. By inhibiting factor Xa, apixaban inhibits thrombin production and inhibits thrombosis. The drug was jointly developed by Bristol-Myers Squibb and Pfizer ^[2] .