CVS - Anti-thrombotic Agents

Question 1

Classes of anti-thrombotic drugs & examples

Answer 1

Anti-Platelet Drugs

1. Aspirin (NSAID)
2. Thienopyridine (Ticlopidine, Clopidogrel)
3. GPIIb/IIIa Antagonist (Abciximab, Eptifibatide, Tirofiban)
4. Phosphodiesterase Inhibitors (Dipyridamole, Cilostazol)

Anticoagulants

1. Heparin (HMW, LMW)
2. Warfarin

Fibrinolytics

1. Streptokinase
2. Urokinase
3. Tissue Plasminogen Activator

Question 2

Mechanism of action of aspirin

Answer 2

Inhibits COX-1 permanently (irreversible acetylation)

- Inhibits TXA2 synthesis in platelets + inhibits PGI2 in endothelial cells - affects platelet activation & aggregation

Question 3

Uses of aspirin

Answer 3

1. Prevention of arterial thrombosis eg MI, stroke

Question 4

Toxicity of aspirin (3)

Answer 4

1. Peptic Ulcer
2. GI Bleeding
3. Allergy

Question 5

Mechanism of action of clopidogrel

Answer 5

Inhibits ADP-induced platelet aggregation, platelet is inhibited throughout its lifespan

Question 6

Uses of clopidogrel

Answer 6

1. Prophylaxis to arterial thrombosis, alternative to aspirin

Question 7

Toxicity of clopidogrel (5)

Answer 7

1. Nausea
2. Dyspepsia
3. Diarrhea
4. Skin rash
5. Hemorrhage

Ticlopidine has more - Neutropenia, thrombotic thrombocytopenic purpura

Question 8

Mechanism of action of abciximab

Answer 8

Antagonizes GPIIb/IIIa receptor, prevents binding of fibrinogen - prevents platelet aggregation

Question 9

Uses of abciximab

Answer 9

Angioplasty regime in high risk patients - less ischemic complications & restenosis (aspirin + heparin + abciximab)

Question 10

Toxicity of abciximab (3)

Answer 10

1. Bleeding
2. Thrombocytopenia
3. Human anti-mouse antibody reactions

Question 11

Mechanism of action of heparin

Answer 11

1. Binds & activates anti-thrombin III (plasma protease inhibitor) - enhanced ATIII interaction with clotting factors IIa, VIIa, IXa, XA to form inactive complexes - inhibits action of clotting factors
2. Stimulates tissue factor pathway inhibitor (TFPI) release from endothelium - inhibits extrinsic pathway

Question 12

Uses of heparin (3)

Answer 12

1. Treatment & Prophylaxis of venous thromboembolism (DVT, PE) (HMW, LMW)
2. Arterial thrombosis (MI) (HMW)
3. Pregnant women at risk of thrombosis (HMW)

Question 13

Toxicity of heparin (6)

Answer 13

1. Bleeding (8-10%)
2. Allergy
3. Heparin-induced Thrombocytopenia (Transient 25%, Severe 5%) (less in LMW)
4. Osteoporosis/Spontaneous fractures (long term) (less in LMW)
5. Transient reversible alopecia (long term)
6. Mineralocorticoid deficiency (long term)

Question 14

Mechanism of action of warfarin

Answer 14

1. Inhibits vitamin K epoxide reductase (converts inactivated vit K to active form, which is req in the activation of factors II, VII, IX, X, protein C)
2. Blocks regeneration of activated Vit K - inhibition of synthesis of clotting factors

Action takes longer as it does not inhibit activity of factors that have already been synthesised

Question 15

Uses of warfarin (4)

Answer 15

1. Maintenance of anti coagulant therapy
2. Prophylaxis & treatment of venous thromboembolism (DVT, PE)
3. Patients who suffered MI, stroke, transient ischemic attack
4. Potent rodenticide

Question 16

Toxicity of warfarin + Contraindications (3+1)

Answer 16

1. Bleeding
2. Cutaneous necrosis
3. Infarction of breast, buttock, intestine, extremities

Crosses placenta
1. Pregnancy - Fetal warfarin syndrome - teratogenic - Bone/CNS defects, hemorrhagic fetus, abortion

Question 17

Overdose of anticoagulants

Answer 17

1. Discontinue
2. Antidotes
   - Heparin - Protamine sulfate
   - Warfarin - Vitamin K (phytonadione)

Question 18

Uses of fibrinolytics (3)

Answer 18

1. AMI
2. Acute ischemic stroke
3. Acute pulmonary embolism

Question 19

Toxicity of fibrinolytics (3)

Answer 19

1. Hemorrhage
2. Allergy (SK)
3. Anti-SK Ab (SK)