From this article you will learn: how acts thrombolytics , to whom and for what purpose they are assigned. Varieties of drugs. Side effects, interaction with other medicines, contraindications.
The mechanism of action of thrombolytics
Thrombolytics( fibrinolytics) are drugs whose action is aimed at the destruction of blood clots. Unlike antiaggregants and anticoagulants, which lower the viscosity of the blood and prevent thrombosis, thrombolytics are able to dissolve already formed thrombi. Therefore, antiaggregants and anticoagulants are prevention of thrombosis, and thrombolytics are their treatment.
Introduces the drug of this group only an experienced resuscitator or cardiologist in a hospital.
Mechanism of action
For the "viscosity" of the blood is a special protein - fibrin. When there is not enough of it in his blood, a tendency to bleeding appears and the clotting process slows down with tissue damage. But when his level is elevated - blood clots are formed from him.
Cleaves an excessive amount of fibrin with a special enzyme called plasmin. The process of cleavage is called fibrinolysis. In the blood, this enzyme is present in large amounts in an inactive form - in the form of plasminogen. And only if necessary, it turns into plasmin.
Mechanism of physiological fibrinolysis In healthy people, the amount of fibrin and plasmin in the blood is balanced, but with a tendency to thrombogenesis, the level of plasmin is lowered.
Thrombolytic drugs( also known as fibrinolytics) activate blood clot resorption, converting plasminogen to plasmin, which is capable of cleaving fibrin, a protein that forms thrombi.
Indications
Fibrinolytics are prescribed for such pathologies:
- Myocardial infarction, triggered by a thrombus.
- Ischemic stroke.
- Thromboembolism of the pulmonary artery.
- Thrombosis of any major arteries or veins.
- Intracardiac thrombi.
Drug treatment for thrombosis is advisable no later than 3 days after the formation of the thrombus. And it is most effective in the first 6 hours.
Varieties of thrombolytics
In novelty and effectiveness, the drugs of this group are divided into 3 generations.
Generation of thrombolytics:
| 1 generation | 2nd generation | 3rd generation |
|---|---|---|
| Streptokinase | Alteplase | Retaplase |
| Urokinase | Prourokinase | Tenteplase |
| Actylase |
Streptokinase was the first drug to have thrombolytic activity. This enzyme produces bacteria - beta-hemolytic streptococci. The fibrinolytic effect of this substance was first described in 1940.
Despite the effectiveness of the remedy, it very often causes allergic reactions.
Moreover, both Streptokinase and Urokinase provoke the cleavage of not only the dangerous fibrin that formed the blood clot, but also fibrinogen, prothrombin, coagulation factor 5 and coagulation factor 8. This is very fraught with bleeding.
These shortcomings of the first thrombolytics and prompted scientists to develop new, more safe for the body fibrinolytic drugs.
Thrombolytics 2 and 3 generations are more selective. They act more specifically on a thrombus and do not dilute blood so much. This minimizes bleeding as a side effect of thrombolytic therapy. However, the risk of bleeding still persists, especially if there are predisposing factors( if used, the use of drugs is contraindicated).
In modern medical practice mainly use thrombolytics of 2 generations, as they are safer than preparations of the 1st generation.
Contraindications
Do not conduct thrombolytic therapy in such cases:
- Abundant internal bleeding in the last six months.
- Surgical operations on the spinal cord or brain in the anamnesis.
- Hemorrhagic diathesis.
- Inflammatory vascular disease.
- Suspected hemorrhagic stroke
- Severe hypertension, not amenable to drug control( systolic blood pressure above 185 mm Hg or diastolic above 110 mm Hg).
- Recent traumatic brain injury.
- Postponed 10 days and later a serious injury or surgery.
- Childbirth( 10 days ago and later).
- Less than 10 days ago a puncture of the subclavian or jugular vein and other vessels that can not be pressed.
- Cardiopulmonary resuscitation, which lasted more than 2 minutes, as well as the one that caused injuries.
- Liver failure, severe liver disease( cirrhosis, hepatitis, etc.).
- Varicose veins of the esophagus.
- Hemorrhagic retinopathy( tendency to hemorrhage in the retina, often occurs with diabetes).
- Peptic ulcer exacerbation in the last 3 months.
- Pancreatitis in acute form.
- Endocarditis of bacterial nature.
- Aneurysms and other abnormalities of large arteries or veins.
- Tumors with an increased risk of bleeding, especially in the organs of the gastrointestinal tract, in the lungs, the brain. A hemorrhagic stroke in the anamnesis.
- Intracranial hemorrhage in the anamnesis.
- Severely leaking ischemic stroke, with cramps in the number of symptoms.
- Tuberculosis with hemoptysis.
- Individual intolerance of the drug.
Hemorrhagic stroke There are also contraindications regarding the state of the blood at the moment. thrombolytics are contraindicated if a blood test showed the following deviations:
- The sugar level is above 400 milligrams per deciliter or less than 50 mg / dl.
- The number of platelets is less than 100,000 per mm3.
If the drug is used for stroke, then there are age limits. Fibrinolytics are usually not administered to patients under the age of 18 and older than 80 years.
Interaction with other drugs
Drugs for thrombolytic therapy are not administered on the background of patients taking anticoagulants( such as Warfarin).
When used concomitantly with agents that affect platelet levels( antibiotics of the cephalosporin group, non-steroidal anti-inflammatory drugs, corticosteroids), the risk of bleeding increases.
Patients who have received antiaggregants on a continuous basis also increase the risk of bleeding. The doctor must take this into account when calculating the dosage of thrombolytics.
If a patient shortly before the introduction of fibrinolytics has taken ACE inhibitors, the risk of an allergic reaction increases.
Side effects of
The main side effect of all thrombolytics is bleeding:
- External. Of recently damaged vessels, for example, from which blood was taken for analysis. From gums, nose.
- Hemorrhages in the skin. In the form of petechiae( points), bruises
- Internal. From mucous gastrointestinal tract, organs of the genitourinary system. Hemorrhages in the retroperitoneal space. In the brain( manifest neurological symptoms: seizures, speech disorders, retardation).Less commonly - bleeding from the parenchymal organs( liver, adrenal, spleen, pancreas, thyroid and other glands, lungs).
Petechial hemorrhages Internal bleeding in patients without contraindications is rare.
Arrhythmias( which will require the use of antiarrhythmic drugs), lowering blood pressure, nausea, vomiting, fever may also occur.
When an allergic reaction to the drug appears rash, bronchospasm, swelling, a decrease in pressure. Allergy to medication can lead to a deadly anaphylactic shock. Therefore, it is important to apply anti-allergic drugs in time when the first symptoms appear.
Side effects are most pronounced in 1 generation drugs. With the use of fibrinolytic 2 and 3 generations, they occur less often and do not flow so hard.
When using 1st generation thrombolytics, there are so much bleeding that blood transfusion is needed.
Further treatment of
Response of the body to a sharp dilution of blood becomes increased production of thrombin - a substance that increases thrombogenesis. This can lead to a recurrence of thrombosis. For prophylaxis they can re-enter thrombolytics 2 or 3 generations( but not 1 because of higher bleeding after their use).
Instead of repeated administration of fibrinolytic, anticoagulants( heparin) or antiplatelet agents( acetylsalicylic acid) can be used to prevent the re-formation of thrombi.
Overdose
Since the drug is rapidly excreted from the body, an overdose occurs rarely. However, it is very dangerous, as it provokes heavy bleeding, after which blood transfusion is required.
To stop the overdose, stop the injection. Also can introduce antifibrinolytics( inhibitors of fibrinolysis) - drugs with the opposite effect, which restore blood coagulability and stop bleeding. The most common drug in this group is aminocaproic acid.
