ANTIPLATELETS, ANTICOAGULANTS, THROMBOLYTICS

I. Process of blood coagulation & thrombus formation

Blood vessel injury

Vasoconstriction Blood loss into tissues Intrinsic pathway Extrinsic pathway

to clot formation to clot formation

Platelet adhesion
to injured wall of bv &
platelet aggregation

decrease blood flow compression of platelet plug blood clot

at site of injury injured bv

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 Heparin sodium
o 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 • tarry stools
• ecchymosis • hematemesis
• epistaxis • bloody urine

2. headache, dizziness & weakness

 3. GI distress
4. skin rash
5. tinnitus, hearing loss

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 4. atrial fibrillation
(DVT) 5. TIAs
2. pulmonary embolism 6. prevent clotting in blood samples & in
3. coronary artery disease dialysis & venous tubing
(CAD)

• CI:
 hemophilia  peptic ulcer
  severe HPN  dissecting aneurysm
 severe renal / liver dse

 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. atrial fibrillation
2. artificial heart valves
3. valvular heart disease
4. 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: thrombolytics

Plasminogen plasmin (fibrinolysin)

Fibrin clot dissolution of clot

Indications:
1. acute MI
2. pulmonary embolism
3. ischemic stroke
4. 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