Vascular endothelial damage, collagen exposure, platelet aggregation

Vasoconstriction, slow blood flow, activation of coagulation factors

Surface activation → 12 → 11 → 9 (deficiency: hemophilia B) → 8 (deficiency: hemophilia A)

3 (tissue thromboplastin)→7

10→5→2 (prothrombin)→1 (fibrinogen)→fibrin

Heparin is a mucopolysaccharide sulfate. A mixture with a molecular weight of 5,000 to 30,000. It has a large negative charge and is strongly acidic.

Medicinal heparin is extracted from pig intestinal mucosa and cow and pig lungs

Heparin is a macromolecule with a large negative charge

60% is concentrated in the vascular endothelium, most of which are destroyed by the monocyte-macrophage system, and very little is excreted in the urine in its original form.

The anticoagulant activity t1/2 of heparin is related to the dosage. For intravenous injection of 100U/kg, 40OU/kg, and 80OU/kg, the anticoagulant activity t1/2 is 1h, 2.5h, and 5h respectively. Patients with pulmonary embolism and liver cirrhosis have prolonged t1/2

Heparin combines with AT-Ⅲ lysine residues to form a reversible complex, which changes the configuration of AT-Ⅲ, fully exposes the active part of arginine, and quickly binds to factors (2, 9, 10, 11, 12) a, etc. Combined with the serine active center to accelerate the inactivation of coagulation factors

Ineffective when taken orally

IV has a quick onset of action (10min) and short action time (3~4h)

It has powerful anticoagulant effects both in vivo and in vitro

Make vascular endothelium release lipoprotein lipase and regulate blood lipids

anti-inflammatory effect

Inhibit vascular smooth muscle proliferation and intimal hyperplasia

Inhibit platelet aggregation

Thromboembolic disease

Disseminated intravascular coagulation (DIC)

Prevent and treat myocardial infarction, cerebral infarction, and thrombosis after cardiovascular surgery

Cardiovascular surgery, cardiac catheterization, hemodialysis and other extracorporeal anticoagulation

Overuse may cause spontaneous bleeding

Thrombocytopenia

Heparin can also cause allergic reactions such as rashes and drug fever.

Continuous application of heparin for 3 to 6 months can cause osteoporosis and spontaneous fractures

Use in pregnant women can cause premature birth and fetal death

bleeding tendency blood disease

Tissue ulceration, intracranial hemorrhage, active tuberculosis, postpartum, miscarriage, trauma and surgery, etc.

Heparin allergy, liver and kidney dysfunction

Low molecular weight-6.5kDa

The effect only needs to be combined with AT-Ⅲ

Selective inactivation of Xa

Different half-lives—extended

Separation of antithrombotic and hemorrhagic effects

Less likely to cause thrombocytopenia

Intravenous injection, difficult to pass through the blood-brain barrier

Potent and specific thrombin inhibitor

Inhibits thrombin activity and reduces fibrin production; inhibits platelet aggregation and secretion caused by thrombin, thereby producing anti-thrombotic effects

Synthetic arginine derivatives

Binds to the catalytic site of thrombin to inhibit its proteolysis

Inhibit thrombin-induced platelet aggregation and secretion

Can also be used topically on grafts to prevent blood clots

Inhibits the conversion of vitamin K from epoxide (inactive) to hydroquinone form (active) in the liver

Prevent the repeated utilization of vitamin K and affect the carboxylation of coagulation factors II, VII, IX and X containing glutamic acid residues

These factors remain in the precursor stage without coagulation activity, thus affecting the coagulation process.

Ineffective in vitro, slow onset of action, long-lasting effect

Warfarin (benzylpropanocoumarin)

dicoumarol

Acenocoumarol (new anticoagulant)

Prevention and treatment of thromboembolic diseases

It can be used as an auxiliary drug for myocardial infarction. It is effective when taken orally and has a long duration of action. However, the effects appear slowly and the dosage is difficult to control.

It is also used to prevent venous thrombosis after operations such as rheumatic heart disease, hip arthrodesis, and artificial heart valve replacement.

The dose should be adjusted according to the prothrombin time control of 18 to 24 seconds (normal value 12 seconds). Excessive bleeding is prone to occur, and vitamin K can be used to combat it. If necessary, fresh plasma or whole blood can be transfused.

Other adverse reactions include gastrointestinal reactions, allergies, etc.

Contraindications are the same as for heparin

Lack of vitamin K in food or the use of broad-spectrum antibiotics to inhibit intestinal bacteria will reduce the content of vitamin K in the body, which can enhance the effect of this type of drug.

Platelet inhibitors such as aspirin can have synergistic effects with this class of drugs

Chloral hydrate, hydroxyphenbutazone, tolbutamide, quinidine, etc. may displace plasma proteins; salicylates, imipramine, metronidazole, cimetidine, etc. may inhibit liver enzymes. Drug-like effects are enhanced

Barbiturates and phenytoin induce liver enzymes, and oral contraceptives can weaken the effect of these drugs by increasing coagulation.

effect

Features

Inhibit phosphodiesterase → increase cAMP

Activate adenosine activity

Enhance the activity of PGI2

Mild inhibition of cyclooxygenase → TXA2 reduction

Irreversibly inhibits the binding of ADP to receptors

Inhibits ADP-induced exposure of GPIIa and GPIIIa receptor complexes to fibrin binding sites

Intravenous or intracoronary injection can reduce the area of ​​infarcted vessels and reestablish blood flow.

All are effective, but they must be taken early and the thrombosis does not exceed 6 hours for the best effect.

A few people experienced fever, chills, and headache after use. sudden drop in blood pressure

Treat with antifibrinolytic drugs and transfuse whole blood or fibrinogen if necessary

VitK1—exists in the plant alfalfa and can now be synthesized artificially

VitK2—present in putrefactive fish meal, human intestinal Bacteria can synthesize

VitK3

VitK4

synthetic

Such as abnormal bleeding during surgery of the lungs, liver, spleen, prostate, thyroid, adrenal glands, etc.

Hemoglobin synthesis disorder substances: folic acid, VITB12, iron deficiency or reduced intake

Abnormal red bone marrow hematopoiesis

Excessive cell destruction, chronic blood loss, etc.

physiological state

Factors affecting iron absorption

iron transport

store

excretion

Participate in the synthesis of heme

Participate in the synthesis of cytochromes, peroxidase, catalase, etc.

Only for iron deficiency anemia

Gastrointestinal reactions: nausea, upper gastrointestinal discomfort, abdominal cramps, constipation (Fe combines with hydrogen sulfide), etc.

Side effects of parenteral iron therapy

Acute poisoning - deferoxamine

Folic acid and folic acid preparations in food enter the body and are reduced and methylated into active 5-methyltetrahydrofolate.

After entering the cell, one carbon unit is transferred to participate

megaloblastic anemia

pernicious anemia

For megaloblastic anemia caused by folic acid antagonists such as methotrexate, pyrimethamine, and trimethoprim, the application of folic acid is ineffective due to the inhibition of dihydrofolate reductase.

Vitamin B12 combines with intrinsic factor to be absorbed in the jejunum

Promote tetrahydrofolate recycling

Maintain the integrity of the myelin sheath of nervous tissue