ANTIPLATELETS, ANTICOAGULANTS, THROMBOLYTICS
I. Process of blood coagulation & thrombus formation
Blood vessel injury
Vasoconstriction
Blood loss into tissues
Intrinsic pathway to clot formation
Extrinsic pathway to clot formation
Platelet adhesion to injured wall of bv & platelet aggregation
decrease blood flow at site of injury
compression of injured bv
platelet plug
blood clot
thrombus
Decrease blood loss at site of injury
Final step of clot formation:
Prothrombin thrombin
Fibrinogen
Fibrin
clot
Clot dissolution:
Plasminogen plasmin (fibrinolysin)
Fibrin clot
dissolution of clot
II. Drugs affecting Blood Coagulation A. Antiplatelets aspirin * clopidrogel (Plavix) ticlopidine (Ticlid) dipyridamole B. Anticoagulants (blood thinners)
heparins* o o Heparin sodium Low- molecular weight heparins ( LMWH ) danaparoid hirudin daltaparin
warfarin (Coumadin)* Dicumarol
C. Thrombolytics ( clot busters)
streptokinase* Urokinase Altepase (tissue plasminogen activator )
A. Antiplatelets aspirin * MOA: suppress platelet adhesion& aggregation ---> prevent thrombosis in ARTERIES Indications: 1. prevent MI or stroke in pxs with familial history 2. prevent repeat MI 3. prevent stroke in pxs with transient ischemic attacks (TIAs) other uses: peripheral arterial disease after angioplasty & stent replacement after coronary artery bypass graft (CABG) atrial fibrillation SE: 1. bleeding (MC) petechiae ecchymosis epistaxis 2. 3. 4. 5. headache, dizziness & weakness GI distress skin rash tinnitus, hearing loss tarry stools hematemesis bloody urine
Contraindications (CI): pregnancy & lactation bleeding disorders o blood dyscrasias o peptic ulcer dse (PUD) o CVA o severe hypertension recent surgery closed head injuries
:
Drug interactions: anticoagulants, thrombolytics, herbs (garlic , gingko)
B. Anticoagulants (blood thinners) heparin* warfarin (Coumadin)* MOA: interfere with clotting cascade & thrombin formation ---> prevent formation of new blood clots & keep existing blood clots from grower larger. Heparin MOA: heparin binds with antihthrombin Prothrombin thrombin
fibrinogen
Fibrin
clot
poorly absorbed orally --->IV (for acute thrombosis) or SC ( for prophylaxis) onset of action : immediate t1/2 = 1-2 hrs donot cross placenta Indications: 1. deep vein thrombosis (DVT) 2. pulmonary embolism 3. coronary artery disease (CAD) CI: hemophilia peptic ulcer severe HPN severe renal / liver dse dissecting aneurysm
4. atrial fibrillation 5. TIAs 6. prevent clotting in blood samples & in dialysis & venous tubing
prolongs clotting time: monitor activated partial thromboplastin time (aPTT) – 1.5 to 3x control value (60-70sec) monitor partial thromboplastin time (PTT) – 1.5 -2x control value (60-70 sec) antidote for heparin overdose : protamine sulfate
warfarin (coumadin) MOA: inhibit liver synthesis of Vitamin K --> decrease clotting factors --> decrease clot formation well absored orally onset of action : 3 days t1/2= 3 days effects last for 4 – 5 days cross placenta & breastmilk
Indications: 1. 2. 3. 4. atrial fibrillation artificial heart valves valvular heart disease tx & prevent thrombosis & embolization after acute MI or pulmonary embolism
prolongs clotting time: monitor prothrombin time (PT) - 1.5 – 2.5 x control value (11- 15 sec) monitor PT/ International normalized ratio (INR) – 2 – 3 (1.3-2.0) antidote for warfarin overdose: Vitamin K1 (phytonadione)
SE/ Adverse effects of anticoagulants: 1. bleeding/ hemorrhage 2. GIT upset 3. alopecia, dermatitis, BM depression, priapism CI of warfarin:: bleeding tendencies pregnancy Severe Liver /kidney dse Acute MI alcoholism
Drug interactions: esp with warfarin Aspirin NSAIDS Phenytoin Cimetidine Antibiotics Some antidysrhythmics Grapefruit juice
C. Thrombolytics ( clot busters) streptokinase* MOA: Plasminogen thrombolytics plasmin (fibrinolysin)
Fibrin clot
dissolution of clot
Indications: 1. 2. 3. 4. acute MI pulmonary embolism ischemic stroke to open clotted IV catheters
SE/adverse effects: 1. bleeding tendencies 2. cardiac arrhythmias 3. hypotension 4. fever CI: same as anticoagulants Drug interactions: antiplatelet , anticoagulants Antidote for thrombolytic overdose: aminocaproic acid