浙江大学医学院：《药理学 Pharmacology》课程教学资源（PPT讲稿）作用于血液和造血系统药物 Drugs affecting blood and blood-forming organs

Drugs affecting blood and blood-forming organs (作用于血液和造血系统药物 Tang Huifang(汤慧芳) Email:tanghuifang@zju.edu.cn

Drugs affecting blood and blood-forming organs (作用于血液和造血系统药物) Tang Huifang (汤慧芳) Email: tanghuifang@zju.edu.cn

General concept s affecting the ble gs lood and blood-forming organs Coagulation Anticoagulant drugs(抗凝血药) bleedin Antiplatelet drugs(抗血小板药) Fibrinolytic dr~ug(纤维蛋白溶解药) Hemostatic drugs(止血药) Blood cell Antianemic drugs(抗贫血药) growth Hematopoietic growth agents agents(促白细胞生长药 Blood volume Drugs for treatment of hypovolemia(血容量扩充剂)

Drugs affecting the blood and blood-forming organs Coagulation￾bleeding Anticoagulant drugs(抗凝血药) Antiplatelet drugs(抗血小板药) Fibrinolytic drugs(纤维蛋白溶解药) Hemostatic drugs(止血药) Blood cell growth Blood volume Antianemic drugs(抗贫血药) Hematopoietic growth agents agents (促白细胞生长药) • Drugs for treatment of hypovolemia (血容量扩充剂) General concept

Par1. Anticoagulants抗凝血药 凝血酶间接抑制剂: > Heparin(肝素) Low molecular weight heparin(低分子量肝素) > Fondaparinux(磺达肝癸钠) Oral direct Factor X inhibitors: Apixaban(阿派沙班)、 Rivaroxaban(利伐沙班 >凝血酶直接抑制剂( direct thrombin inhibitors,DTIs): ORAL DTIS: Dabigatran(达比加群) > Factor II inhibitor: Lepirudin(重组水蛭素/来匹卢定) desirudin(地西卢定)、 bivalirudin(比伐卢定)、 Argatroban (阿加曲班) Vitamin K antagonists: Coumarins香豆素类 Warfarin(华法林)、 dicoumarol(双香豆素) acenocoumarol(醋硝香豆素)

➢ 凝血酶间接抑制剂： ➢ Heparin（肝素） ➢ Low molecular weight heparin （低分子量肝素） ➢ Fondaparinux (磺达肝癸钠) ➢ Oral direct Factor X inhibitors：Apixaban （阿派沙班）、 Rivaroxaban(利伐沙班) ➢ 凝血酶直接抑制剂（direct thrombin inhibitors，DTIs)： ➢ ORAL DTIs: Dabigatran (达比加群) ➢ Factor II inhibitor: Lepirudin（重组水蛭素/来匹卢定）、 desirudin （地西卢定）、bivalirudin(比伐卢定)、Argatroban （阿加曲班） ➢ Vitamin K antagonists: Coumarins 香豆素类 Warfarin（华法林）、dicoumarol（双香豆素）、 acenocoumarol（醋硝香豆素） Part 1. Anticoagulants 抗凝血药

ANTICOGO山crcr山c Heparin(肝素) H2COSO3 CO0 HCOSO H2COSO3 o、KoH OH 0、K0 0、KQH O HOCH OH NHSO 3 OSo NHSO3 (or -SO3) N-acetyl N-sulfated Iduronic N-sulfated glucosamine Glucuronic glucosamine acid fucosamine 6-0-sulfate acid 3.6-0-disulfate 2-0-sulfate 6-0-sulfate MW of 530 kD(mean 12 kD) 化学:强酸性,具强负电荷(抗凝作用基础) 特效解毒剂:鱼精蛋白(碱性,强正电荷

Anticoagulant drugs MW of 5～30 kD(mean 12 kD). Heparin（肝素） 化学：强酸性，具强负电荷（抗凝作用基础） 特效解毒剂：鱼精蛋白（碱性，强正电荷）

Unraced Xa oD Ooooo Antiroman cOp ronⅪa、Ⅸa、Xa、Ⅻa Heparin accelerates inactivation of coagulation factors by antithrombin

• Heparin accelerates inactivation of coagulation factors by antithrombin. Ⅺa、Ⅸa、Ⅹa、Ⅻa

AnTicoagulant drugs 1. Pharmacological effects (1)Anticoagulation 1)Heparin increase the activity of AT Il The aT Il may inhibit the activity of the activatedⅡa、Ⅺa、Ⅸa、Ⅹa、Ⅻa. to cause anticoagulation 2)Characteristics of anticoagulation OIt is effective in vitro and in vivo @Its effects are rapid (iv)( < 10min)and short(3-4 h): activated partial thromboplastin time(APTT)↑

1. Pharmacological effects (1)Anticoagulation: 1)Heparin increase the activity of AT Ⅲ The AT Ⅲ may inhibit the activity of the activated Ⅱa、Ⅺa、Ⅸa、Ⅹa、Ⅻa, to cause anticoagulation. 2)Characteristics of anticoagulation ①It is effective in vitro and in vivo ; ②Its effects are rapid(iv) (<10min)and short(3～4 h): activated partial thromboplastin time(APTT) ↑ Anticoagulant drugs

ANTICOGO山crcr山c (2)Anti-atherosclerosis: rEgulating blood li ipds: VLDLL 2)Protecting endothelial cells; 3)Inhibiting the proliferation of smooth muscle cells 4)Inhibits platelet aggregation (3other effects Anti-complement, anti-inflammation and↓ blood viscosity(血液粘度)

(2)Anti-atherosclerosis: 1)Regulating blood lipids: VLDL 2)Protecting endothelial cells; 3)Inhibiting the proliferation of smooth muscle cells. 4)Inhibits platelet aggregation (3)Other effects: Anti-complement, anti-inflammation, and  blood viscosity（血液粘度）. Anticoagulant drugs

AaTiCoac山 ani drug 2. Pharmacokinetics Heparin and LMWH are mostly (1)Heparin is not absorbed confined to the vascularsystem by GI t need iv. or sc Partially degraded Heparin heparin and IV, deep sc (2)pl asma proTein binding LMWHs LMWHs: SC rate: 80% appear in the urine (3)t1/2:1~2hr It's metabolised in liver, and partially degraded heparin appears n the urine Heparin and LMWHs

2. Pharmacokinetics (1)Heparin is not absorbed by GI. It need iv. or sc. (2)plasma protein binding rate: 80% (3)t1/2: 1～2 hr. It’s metabolised in liver, and partially degraded heparin appears in the urine. Anticoagulant drugs

ATICOaCI山cruc 3. Clinical uses (1)Anticoagulation Such as: pulmonary emboli; deep vein thrombosis cardiac infarction, etc (2)Heart ischemia Prevent emboli in coronary artery early use (DIC(disseminated intravascular coagulation,弥散性血管内凝血) Such as: certain surgical procedures hemodialysis, cardiac catheterization, etc 4)Prevent coagulation in vitro

Anticoagulant drugs 3. Clinical uses (1)Anticoagulation Such as: pulmonary emboli; deep vein thrombosis; cardiac infarction, etc. (2)Heart ischemia Prevent emboli in coronary artery—— early use. (3)DIC(disseminated intravascular coagulation, 弥散性血管内凝血) Such as: certain surgical procedures, hemodialysis, cardiac catheterization, etc. (4)Prevent coagulation in vitro

AnTICoagu山 r drugs 4. Adverse effects (1) Bleeding(5%~10%) Protamine sulfate(硫酸鱼精蛋白) is the antagonist of heparin. 1 mg protamine=100U heparin. (2) Heparin- induced thrombocytopenia(血小板减 少症)(HIT) 5%6%, Warfarin should be substi-tuted if the platelet count fall ()Others Allergy(过敏反应) Local necrosis((局部坏死), when sc Increased loss of hair and reversible alopecia(B2) Osteoporosis(骨质疏松) (4)Contraindicated in patients with bleeding risk

4. Adverse effects (1)Bleeding(5%～10%) Protamine sulfate（硫酸鱼精蛋白）is the antagonist of heparin. 1mg protamine=100U heparin. (2) Heparin-induced thrombocytopenia(血小板减 少症) (HIT) 5%～6%, Warfarin should be substi-tuted if the platelet count falls. (3)Others Allergy(过敏反应); Local necrosis(局部坏死), when sc; Increased loss of hair and reversible alopecia(脱发); Osteoporosis(骨质疏松). (4) Contraindicated in patients with bleeding risk Anticoagulant drugs