Anti-platelets & anti-thrombotics

Question 1

Examples of anti-platelet drugs

Answer 1

1. NSAIDs
2. Platelet GPIIb/IIIa receptor blockers
3. ADP receptor blockers
4. Phosphodiesterase inhibitor

Question 2

Example of NSAID

Answer 2

aspirin

Question 3

MOA of aspirin

Answer 3

Irreversible COX-1 inhibition → inhibition of thromboxane (TXA2) synthesis in platelets → inhibition of platelet aggregation (antithrombotic effect)
- Irreversible in aspirin (so the entire life of platelet – 7-10 days)

Question 4

PK of aspirin

Answer 4

inhibitory effect is rapid and last for the life of the platelet approx. 7 to 10 days

Question 5

Clinical uses of aspirin

Answer 5

1. prophylactic treatment of transient cerebral ischemia
2. to reduce the incidence of recurrent myocardial infarction
3. to decrease mortality in post-myocardial infarction patients

Question 6

Adverse effects of aspirin

Answer 6

Gastric upset and ulcers

Question 7

Examples of GPIIb/IIIa receptor blockers

Answer 7

1. Abciximab
2. Eptifibatide
3. Tirofiban

Question 8

MOA of Abciximab

Answer 8

humanised monoclonal antibody directed against the IIb/IIIa complex > reversibly inhibits the binding of fibrinogen and other ligands to GPIIb/IIIa

Question 9

MOA of Eptifibatide

Answer 9

an analog of the sequence at the extreme carboxyl terminal of the delta chain of fibrinogen, which mediates the binding of fibrinogen to the receptor

Question 10

MOA of tirofiban

Answer 10

a small molecule blocker of the GPIIb/IIIa receptor

Question 11

Clinical uses of GPIIb/IIIa receptor blockers

Answer 11

prevent restenosis after coronary angioplasty and are used in acute coronary syndromes

Question 12

MOA of clopidogrel and ticlopidine

Answer 12

prevents ADP from binding to the ADP receptor hence preventing platelet aggregation

Question 13

MOA if dipyridamole

Answer 13

Inhibits the breakdown of cAMP to 5’-AMP hence preventing platelet aggregation

Question 14

Examples of anticoagulants

Answer 14

1. Heparin derivatives
2. Coumarin derivatives (Warfarin)
3. Lepirudin, hirudin
4. Antithrombin III

Question 15

MOA of heparin

Answer 15

1. The active heparin molecules bind tightly to ATIII and cause a conformational change, which exposes its active site for more rapid interaction with the proteases
2. to inhibit thrombin, it is necessary for heparin to bind to the enzyme as well as ATIII; to inhibit factor X it is only necessary for heparin to bind to ATIII

LMWHs increase the action of ATIII on factor Xa but not its action on thrombin

Question 16

Clinical uses for heparin

Answer 16

1. treatment for DVT, pulmonary embolism and AMI
2. be used in combination with thrombolytics for revascularisation and in combination with GPIIb/IIIa inhibitors during angioplasty and placement of coronary stents
3. be used when an anticoagulant must be used in pregnancy

Question 17

PK of heparin

Answer 17

given IV or SC

NOT GIVEN IN IM AS IT CAN LEAD TO HEMATOMAS

Question 18

Adverse effects of heparin

Answer 18

1. Haemorrhage: stop heparin therapy + protamin sulfate

2. Thrombosis and thrombocytopenia

Question 19

MOA of Warfarin

Answer 19

Inhibit hepatic vitamin K epoxide reductase → ↓ hepatic synthesis (recycling) of the active, reduced form of vitamin K → ↓ γ-carboxylation of glutamate residues on coagulation factors II, VII, IX, and X as well as protein C and protein S

Question 20

Clinical uses of warfarin

Answer 20

same as heparin except in pregnant woman

Question 21

PK of warfarin

Answer 21

1. warfarin is small and lipid-soluble molecule which is given orally and absorbed quickly and totally
2. it has a small volume of distribution volume, being strongly bound to plasma albumin (>99%)
3. its elimination depends on metabolism by hepatic cytochrome P450

Question 22

Adverse effects of warfarin

Answer 22

1. bleeding
2. warfarin should never be administered during pregnancy
   - warfarin crosses the placenta readily and can cause a hemorrhagic disorder in the fetus
   - fetal proteins with gamma-carboxyglutamte residues found in bone and blood may be affected by warfarin

Question 23

MOA of vitamin K

Answer 23

reduced vitamin K is an essential cofactor in the carboxylation of glutamate residues

Question 24

Clinical uses of vitamin K

Answer 24

1. treatment and/or prevention of bleeding
   - resulting from use of oral anticoagulant drugs (eg warfarin)
   - babies: to prevent hemorrhagic disease of the newborn
2. for vitamin K deficiencies in adults

Question 25

Examples of thrombolytic agents

Answer 25

1. t-PA (alteplase)
2. urokinase
3. streptokinase
4. anistreplase

Question 26

MOA of thrombolytic agents

Answer 26

1. Fibrinolytics promote the degradation of thrombi by activating plasminogen to plasmin
2. Plasmin breaks down and deactivates fibrin and fibrinogen → release of fibrin degradation products (e.g, D-dimers)

Question 27

Clinical uses of thrombolytic agents

Answer 27

1. emergency treatment of coronary artery thrombosis

2. peripheral arterial thrombosis and emboli

Question 28

PK of thrombolytic agents

Answer 28

intracoronary injection, intravenous injection

Question 29

Adverse effects of thrombolytic agents

Answer 29

bleeding

Question 30

Contraindication of thrombolytic agents

Answer 30

1. healing wounds

2. pregnancy