Drugs for anti thrombotics

Question 1

outline the mechanism of thrombosis

Answer 1

Clotting is based on the balance between prothrombotic- thromboxane A2, and antithrombotic- prostacyclin
Baseline normal endothelium:
Normal endothelium produces prostacyclin prevents the release of prothrombotic factors and changes
DAmaged endothelium: release of arachidonic acid which causes thromboxane A2, then the platelets change morphology, secretion of ADP to become sticky, increased release of thromboxane and homing for fibrinogen and platelets

Question 2

What classes of drugs are used to reduce risk of thrombotic events

Answer 2

1. Platelet blocker 
NSAIDs
Gp IIb/IIIa glycoprotein 
ADP blocker 
PDE inhibitor

2. Anticoagulation
   Heparin
   Warfarin
3. Thrombolytics
   tissue plasminogen activator

Question 3

NSAIDs MOA

Answer 3

NSAIDs, aspirin
binds to COX , reduces formation of Prostacyclins and thromboxanes,
-thromboxane only produced by platelets, the inhibitory effects last for a week

Question 4

Indications and adverse effects of NSAIDs

Answer 4

Indications:

• Previous MI
• TO prevent recurrence of thrombotic events
• Cerebral vascular disease/high risk of stroke

Adverse effects

• Bleeding tendency
• haemorrhage
• Hepatotoxicity
• Gastric ulcers due to reduced prostaglandin secretion

Question 5

Glycoprotein IIb/IIIa inhibitors

Answer 5

GpIIb/IIIa binds fibrinogen to the platelets, and fibrinogen to VWF

abciximab
- Anti Gp IIb/IIIa

tirofiban
- Anti Gp IIb/IIIa receptor

Eptifibatide
pseudofibrinogen that binds to the receptors and competitively inhibits

Question 6

Indications and adverse effects of Gp inhibitors

Answer 6

Indications:

coronary artery angioplasty, in acute coronary syndromes

Question 7

ADP antagonist

Answer 7

Clopidogrel

Inhibits the binding of ADP to the receptor

Question 8

Anti phosphodiesterase

Answer 8

Dipyridamole

- Inhibits PDE, increase cAMP which is anticoagulatory in intracellular signalling of platelet

Question 9

Name 2 anticoagulants

Answer 9

Heparin and warfarin

Question 10

What is thrombin and its function

Answer 10

1. thrombin is protease coagulatory factor,
2. Promotes V, VIII, XI and hence causes self production
3. activation of thrombin is necessary to cleave fibrinogen to active fibrin thread
4. cross linking of fibrin threads with factor XIII release

Question 11

WHat is antithrombin and its function

Answer 11

binds to heparin sulfate, inactivates proteases II, IX, X

mainly II and X

Question 12

Heparin MOA

Answer 12

two types of heparin: Unfractionated heparin and low molecular weight heparin

Heparin is a mix of sulfated glycosaminoglycan

Binds to Antithrombin III and causes the inactivation of clotting factor II, IX and X.

Question 13

Difference between LMWH and Unfractionated heparin

Answer 13

Unfractionated binds to both ATIII and clotting factor II and X. Causes inactivation of them in equimolar ratio

LMWH binds to AT III only and only inactivates factor X

Question 14

indications and adverse effects of heparin

Answer 14

used in dvt, PE
used in coronary angioplasty with Gp IIb/IIIa inhibitors or revascularisation after embolism- with thrombolytics

ADverse effects:
- haemorrhage
- Thrombocytopenia, thrombosis (formation of immune complexes causes platelet aggregation and thrombosis, use clotting factors)
can be used in pregnancy

Question 15

What to do in heparin toxicity

Answer 15

protamine sulfate intravenously

Question 16

How is heparin administered and why

Answer 16

Can only be administered subcut or intravenously, intramuscular will cause hematoma

Question 17

Vitamin K role in blood clotting?

Answer 17

Involved in the carboxylation of glutamate residues of proteases
- Vitamin K reduced causes carboxylation
prescribed in haemorrhage disorder
vitamin K deficiency

Question 18

Warfarin and its moa

Answer 18

warfarin prevents reduction of vitamin K, hence preventing the carboxylation of glutamate residues
- Decrease II, VII, IX, X

Question 19

Route of administration and indications of warfarin

Answer 19

orally, for dvt, PE, in instances of prevent recurrences of restenosis of coronary disease

Question 20

adverse effects of warfarin

Answer 20

1. Teratogenic in pregnancy, causes bleeding disorder also causes issues of post translational modification of protein in bones and other tissue
2. Hepatically cleared / metabolised CYP 450 enzyme
   - carbamezapine, phenytoin induce CYP450
   - cimetidine, amilodarone inhibit CYP450
3. narrow therapeutic window, may cause haemorrhage

Question 21

Thrombolytic agent

Answer 21

tissue plasminogen activator
Alteplase,urokinase, streptokinase, anistreplase
Causes breakdown of fibrinogen/fibrin into products

Question 22

Indications and Adverse effects of tpa

Answer 22

• arterial blood clot in periphery, coronary blood clot
• Administration: IV, intracoronary injection
• adverse effects: haemorrhage , contraindicated in pregnancy or healing