Treatment of stroke: application of anticoagulant drugs

Indirect inhibitor of thrombin

1 unfractionated heparin

Heparin sodium

【Pharmacokinetic characteristics】Bioavailability 37%-66%, protein binding rate of about 99%, blood t1/2 2-3 hours; Does not penetrate easily through the blood-cerebrospinal fluid barrier
.

【Indications】It is used for the prevention and treatment of thrombotic or embolic diseases, acute myocardial infarction, diffuse intravascular coagulation (D1C) caused by various reasons, and can also be used as an in vitro anticoagulant
.

【Dosage】

Intravenous injection: 0.

Intravenous infusion: 20,000-40,000 U
a day.

Deep subcutaneous injection: 0.

Pediatric dosage: intravenous injection or intravenous infusion, 50U/kg each time, added to sodium chloride injection
.

【Precautions】

(1) Long-term use can occur temporary hair loss, osteoporosis and spontaneous fractures
.

(2) Heparin mixed with hyaluronidase injection can not only reduce the pain of intramuscular injection, but also promote the absorption
of heparin.

(3) Use with caution when hypotension is used, and contraindicated
in shock.

(4) The elderly should use with
caution.

(5) In the case of severe bleeding, intravenous injection of protamine sulfate emergency can be given, and 1mg of protamine can neutralize 100U heparin sodium
.

Heparin calcium

【Pharmacokinetic characteristics】T1/2 is 18-22 small inches; Does not penetrate easily through the blood-cerebrospinal fluid barrier
.

【Indications】For the prevention and treatment of thromboembolic disease or thrombosis
.

【Dosage】For acute pulmonary embolism, acute hemocoagulation abnormalities and elevated diseases, 30,000 U a day, diluted with 5% glucose, sodium chloride injection or compound sodium chloride injection after intravenous infusion
.

For the treatment of DIC and thromboembolic diseases, 20,000 U a day, intravenous infusion, or subcutaneous injection
every 8-12 hours.

【Precautions】

(1) Long-term use can occur temporary hair loss, osteoporosis and spontaneous fractures
.

(2) Heparin mixed with hyaluronidase injection can not only reduce the pain of intramuscular injection, but also promote the absorption
of heparin.
Temporary compatibility before use, the drug should not be left
for a long time after mixing.

(3) Use with caution when hypotension is used, and contraindicated
in shock.
Liver and kidney function should be used with
caution.
Use with caution in
the elderly.
Use with caution in
pregnant women and postpartum women.

(4) In the case of severe bleeding, intravenous injection of protamine sulfate first aid, lmg protamine can neutralize 100U heparin calcium
.

2 low molecular weight heparin

Low Molecular Weight Heparin Sodium

【Pharmacokinetic characteristics】Bioavailability is close to 95%, the binding rate to plasma proteins is low, t1/2 is about 4.
4 hours, and the elimination of t1/2 in elderly patients is slightly prolonged
.
Does not pass through the placenta
.

【Indications】It is used to prevent venous embolic disease and venous thrombosis after surgery, to prevent coagulation in vitro circulation during hemodialysis treatment, to treat deep vein thrombosis, and to treat acute unstable angina and non-Q-wave myocardial infarction in combination with aspirin
.

For the prevention of venous embolism, 1 time a day, 20 mg
is injected subcutaneously.

【Dosage】Metallurgical treatment of acute unstable angina and non-Q-wave myocardial infarction, 120U/kg, not more than 10000U, subcutaneous injection every 12 hours, treatment course of 5-8 days, until the clinical symptoms are stable
.
Simultaneous oral administration of aspirin 75-165 mg once
a day.

【Precautions】

(1) Elderly patients for prophylaxis do not need to adjust the dose, which is not suitable for children
.
Contraindicated in pregnant women, and should be used with
caution in lactating women.

(2) Overdose can lead to severe bleeding, intravenous injection of protamine sulfate injection, per 0.
6ml of protamine protein can neutralize about 0.
1ml of nadroparin calcium
.

(3) Hepatic and renal insufficiency should be used with caution, and patients with severe renal failure should consider reducing the dose
.

(4) Regular monitoring of platelet juice number, severe thrombocytopenia or significantly reduced platelet count, thrombosis during treatment, should be discontinued immediately
.

(5) Can not be used for intramuscular injection
.

Low molecular weight heparin calcium (Nadroparin Calcium)

【Pharmacokinetic characteristics】The bioavailability is about 98%, the plasma protein binding rate is very low, t1/2 is 8-10 hours, and it does not penetrate the placenta
.

【Indications】It is used for the prevention and treatment of thromboembolic diseases, prevention of thromboembolic diseases
of general surgery or orthopedic surgery.
Prevention of blood clot formation
during hemodialysis.

【Dosage】Prevention of thromboembolic disease, once a day, 0.
3ml subcutaneous injection, general surgery 2-4 hours before surgery, orthopedic surgery 12 hours before surgery and 12 hours after surgery
.
The drug should be continued for 7-10 days
.

For the treatment of thromboembolic disease, 0.
01 ml/kg is injected subcutaneously every 12 hours, and the general course of treatment is 10 days
.
Oral anticoagulants
should be given as early as possible unless contraindicated.

【Precautions】See Low molecular weight heparin sodium
.

3.
Heparin analogues

Sagrel ester (Sarpogrelate)

【Pharmacological effect】Serotonin (5-HT) receptor selective antagonist
.
By selectively antagonizing the 5-HT receptor, in order to exert its inhibition of platelet aggregation, especially inhibition of platelet aggregation enhanced by 5-HT and inhibition of vasoconstriction
.

【Indications】It is used to improve ischemic symptoms
such as ulcers, pain and cold sensation caused by chronic arterial occlusion.

【Dosage】Once l00mg, 3 times a day, after meals, should be appropriate according to age, symptoms appropriate withering dose
.

【Adverse reactions】Serious adverse reactions: cerebral hemorrhage, gastrointestinal bleeding (vomiting blood, blood in the stool); thrombocytopenia; Hepatic dysfunction, jaundice, and elevated alanine aminotransferase and γ-glutamyltransferase
.

【Precautions】

(1) Disabled: (1) Bleeding patients
.
(2) Pregnant women, women who may already be pregnant, and lactating women are prohibited
.

(2) Use with caution: (1) Previous use of similar drugs caused by agranulocyte deficiency and thrombocytopenia
.
(2) Menstruating women
.
(3) Those with
bleeding tendencies.
(4) Patients
who are taking anticoagulants (such as warfarin) or inhibition of platelet aggregation drugs (such as aspirin, silotazole).
(5) Severe renal insufficiency
.
(6) Elderly patients should use this drug
with caution.

(3) Long-term use of this drug, need to monitor blood count and platelet count
.

(4) Attention should be paid to the combination of anticoagulant drugs (warfarin, etc.
) or drugs that inhibit platelet aggregation (aspirin, ticlopidine, silotazole, etc.

).

Direct inhibitors of thrombin

1 Recombinant Hirudin

【Pharmacological effect】Non-covalent compound is formed with thrombin, which directly inhibits the effect of
thrombin.
In addition to inhibiting heparin-induced platelet activation, there is no direct effect on
platelet function.

【Indications】For the treatment of type II heparin-induced thrombocytopenia (type II HIT).

【Dosage】The starting dose is 0.
4mg/kg, projectile injection, slow administration (more than 15 seconds
).
The solution concentration is 5 mg / ml, and the maximum injection volume is 8.
8 ml
.
The maintenance dose is 0.
15 mg / (kg.
h) (different concentrations of solution can be selected, infusion at different speeds), continuous intravenous infusion for 2-10 days: for patients with renal insufficiency, the initial dose and infusion rate should be reduced
.
The recommended starting dose is 0.
2 mg/kg
.

【Adverse reactions】Heart failure, pericardial effusion and ventricular fibrillation, fever (7%)
can be seen.
Multiple organ failure, cough, bronchospasm, stridor, and dyspnea
may be seen.
Anti-hirudin antibodies
can be formed in 56% of patients.

【Precautions】

(1) Cross-allergy: patients who are allergic to low-molecular weight heparin may also be allergic
to this drug.

(2) It is forbidden
for those who are allergic to this drug.

(3) For (1) vascular or organ malformations (increasing the risk of bleeding
).
(2) Patients with bacterial endocarditis (increased risk of bleeding
).
(3) Patients with
signs of bleeding.
(4) Patients with
severe and uncontrolled hypertension.
(5) Those who have recently had cerebrovascular events and have undergone intracranial surgery
.
(6) Those who
have recently undergone large vascular puncture and organ biopsy.
(7) Patients with hepatic and renal insufficiency
.
All are disabled
.

2Argatroban

【Pharmacological effect】 It has a strong inhibitory effect on thrombin, inhibits platelet aggregation caused by thrombin, and has a weak inhibition effect on fibrinolysis
.
In vitro tests have shown inhibitory effects
on thrombosis produced by various thrombotic models.

【Indications】For chronic arterial occlusion
.

【Dosage】Intravenous infusion: 2 times a day, 10mg once, diluted with infusion solution within 2-3 hours, adjust the dose
according to age and symptoms.

[Adverse reactions] Common: digestive tract reactions, such as belching, vomiting, loss of appetite, abdominal pain and diarrhea
.

Occasionally: increased bleeding, prolonged clotting time, hematuria, erythrocytopenia, leukopenia, serum white egg reduction; rash, vascular pain, abnormal liver function, bilirubin, elevated BUN; Headache, chest pain, arrhythmias, dyspnea, etc
.

【Precautions】

Contraindications: Contraindicated
in women with bleeding disorders (eg, intracerebral hemorrhage, hemophilia, menstrual period, gastrointestinal bleeding, urinary tract bleeding, hemoptysis), preterm birth, pregnancy, and lactation.

Other: blood clotting tests should be carried out during medication, and continuous use of this product should not exceed 4 weeks
.

3 tirofibans

【Pharmacological effect】By selectively inhibiting the final common pathway of platelet aggregation (plasma coagulation factor I binding to glycoprotein IIb/IIIa), the ischemic state
caused by thrombosis can be reversed.

【Indications】

(1) It is used for coronary artery angioplasty or coronary artery plaque resection in patients with coronary syndrome to prevent and treat related cardiac ischemic complications
.

(2) It is used in patients with unstable angina or non-Q-wave myocardial infarction to prevent the occurrence
of cardiac ischemic events.

【Dosage】

(1) Coronary angioplasty or coronary intra-artery plaque resection: it should be combined with heparin, the starting dose of this drug is 10 μg / kg, after intravenous injection within 3 minutes, then maintain intravenous infusion at 0.
15 μg / (kg.
min) for 36 hours, and then stop heparin
.

(2) Unstable angina or non-Q-wave myocardial infarction: in combination with heparin, start 30 minutes, inject intravenously at 0.
4 μg / (kg.
min), and then maintain intravenous infusion
by 0.
1 μg / (kg.
min).

【Adverse reactions】

(1) The most common is bleeding, such as intracranial hemorrhage, retroperitoneal hemorrhage, etc
.

(2) Systemic: acute and/or severe platelet count reduction with chills, mild fever or bleeding complications
may be seen.
Nausea, headache, rash, or urticaria
.

(3) Platelet count, hemoglobin, hematocrit decrease
.

【Precautions】

(1) Prohibited: (1) Those who are
allergic to this drug.
(2) Patients
with a history of active visceral hemorrhage and intracranial hemorrhage.
(3) Patients with
intracranial tumors, aneurysms, arteriovenous malformations.
(4) Vital
organ surgery or serious trauma requiring surgical treatment.

(2) Use with caution: (1) Patients with
a history of bleeding within 1 year.
(2) Those with a history of coagulation disorders, platelet abnormalities or thrombocytopenia
.
(3) Platelet count is less than 150/l09/L
.
(4) Patients with
recent epidural surgery, major surgery or a history of severe physical trauma in the past 1 month.
(5) Patients with
intermural aneurysm.
(6) Control of patients with
severe hypertension who are not satisfied.
(7) Patients with acute pericarditis (8) patients with
hemorrhagic retinal disease.

(3) There is a contraindication
to compatibility with diazepam.

Vitamin K antagonist

1 Warfarin

【Pharmacological effect】There is no anticoagulant effect in vitro, and it plays a role
in vivo by inhibiting the synthesis of vitamin K-dependent coagulation factors II, VII, IX, X and anticoagulant proteins C and S.

【Indications】For the treatment and prevention of thromboembolic diseases, pulmonary embolism; Adjunctive medication
for the prevention and treatment of thrombosis after cardiac surgery, myocardial infarction.

【Dosage】General usage: 1-3 days, 3-4mg / d, 3 days after maintenance of 2.
5-5mg for deep vein thrombosis or pulmonary embolism, orally, 3-4.
5mg on the 1-2nd day, 3-4.
5mg from the 3rd day, 2-8mg a day, and later adjusted
according to the prothrombin time or prothrombin activity.

【Adverse reactions】Overdose is easy to cause bleeding
.
In the early stage, there may be ecchymosis, purpura, gum bleeding, menorrhagia and other excess-excessive bleeding and sometimes hemorrhagic skin necrosis, and allergic reactions are rare
.
A large number of oral administrations have even been reported with bilateral breast necrosis, microangiopathy or hemolytic anemia, and extensive skin necrosis, which is easy to be dangerous
when the amount is too large.

【Precautions】

(1) Patients with bleeding tendencies are disabled
.
Patients with cachexia, fever, menorrhagia, threatened miscarriage and other patients should use with
caution.
The dose should be reduced in
the elderly.

(2) If the anticoagulant effect is too large, with or without bleeding, it can be treated by stopping the drug, and can be corrected
by oral administration or injection of appropriate amounts of vitamin K1.
In patients with severe bleeding, fresh whole blood or fresh lyophilized plasma 200-500 ml may be given, or coagulation factor IX complex may be given
.

(3) The prothrombin time
should be measured regularly during the medication.
If the prothrombin time exceeds 2.
5 times normal (12 seconds normal), the prothrombin activity drops below 15% of normal, or bleeding occurs, the drug
should be discontinued immediately.

2 acetic nitrate

【Pharmacological effect】The action of bicoumarins is the strongest, and the speed of effect is comparable to that of
warfarin.
Compete with vitamin K, thereby significantly reducing the synthesis of vitamin K-dependent coagulation factors II, VII, IX, X, etc.
, and prolonging prothrombin time
.
Similarly, in vivo anticoagulation does not take effect
until the synthesized coagulation factors are depleted.

【Indications】For the prevention and treatment of intravascular thrombotic diseases, especially for long-term maintenance of anticoagulation, for acute arterial occlusion, it is necessary to first use heparin to control symptoms, and then use this product
.

【Dosage】8-12mg on the first day, 2-8mg the next day, taken in divided doses, and then maintained the amount of 1-6mg, or adjust the dose
according to the prothrombin time.

【Adverse reactions】Bleeding caused by oral overdose, the most common bleeding sites are skin, mucous membranes, gastrointestinal tract, urinary tract, but also gum bleeding, nosebleeds, ecchymosis and hemoptysis
.
Occasionally, dizziness, nausea, diarrhea, skin irritation, severe persistent headache, back pain, abdominal pain, etc
.

【Precautions】

(1) It is contraindicated in patients with bleeding tendencies, gastrointestinal ulcers, severe renal insufficiency, within 3 days of childbirth or surgery, in the third trimester of pregnancy and lactating women
.

(2) Overdose can cause obvious bleeding tendency, and vitamin K1 can be rescued
by oral administration or injection.
In case of emergency, fresh blood can be given intravenously or fresh frozen plasma
.

(3) During treatment, any tissue trauma should be avoided, and the prothrombin time should be monitored regularly, as well as fecal occult blood and urinary occult blood
.