Anti-Thrombotic Drugs Flashcards
1
Q
What are examples of some anti-platelet drugs?
A
- NSAIDs (aspirin)
- platelet GPIIB-IIIA receptor blockers
- ADP receptor blockers
- Phosphodiesterase inhibitors
- these drugs prevent clots from even occuring
2
Q
What are the factors involved in platelet activation and aggregation?
A
- healthy endothelium releases prostacyclin which binds to platelet receptors and induces cAMP synthesis. cAMP inhibits the release of granules containing aggregating agents.
- damaged endothelium will have exposed collagen and also releases thrombin and thromboxane A2. these stimulate the synthesis of thromboxane A2 from platelets’ arachidonic acid. thromboxane A2 binds to platelet receptors to stimulate release of aggregating agents like ADP.
- balance between prostacyclin and thromboxane A2 determines whether platelets aggregate or circulate freely
3
Q
What is the MOA of NSAIDs like aspirin?
A
- irreversibly inhibit COX 1 and COX 2 enzymes. thromboxane A2 synthesis is inhibited more than prostacyclin from arachidonic acid so there is less promotion of platelet aggregation
- inhibitory effect lasts 7-10 days (lifespan of platelet) because NSAIDs irreversible inhibit cyclooxygenase enzymes on platelets
- prophylactic treatment of transient cerebral ischemia
- reduces recurrence of myocardial infarction
- decrease mortality in post myocardial infarction patients
4
Q
What are side effects of NSAIDs?
A
- above the age of 60, the risk of NSAIDs tend to outweigh the benefit of NSAIDs
- many arachidonic acid products have protective functions in gastric mucosa so NSAIDs can cause GIT bleeding due to peptic ulceration.
- there may also be allergic reactions
- can cause Reye’s syndrome if aspirin is given to a child with viral infection
5
Q
What is the MOA of GPIIB-IIIA receptor antagonists?
A
- GPIIB-IIIA receptors are where fibrinogen, vitronectin, vWF and fibronectin bind for adherence between platelets so the receptor antagonists block this final common pathway for platelet aggregation
- Abciximab
- humanized monoclonal antibody against GPIIB-IIIA receptor
- reversibly inhibit the binding of fibrinogen and other ligands for linking between platelets - Eptifibatide
- analog of fibrinogen so binds to receptor and competitively inhibits fibrinogen attachment - Tirofiban
- small molecule blocker of GPIIB-IIIA receptor
6
Q
What are GPIIB-IIIA receptor antagonists used for?
A
- used in acute coronary syndromes which often have pro-thrombotic condition
- Prevent restenosis after coronary angioplasty because some factors may still be sticky
7
Q
What is the MOA of ADP blockers?
A
eg. Clopidogrel and Ticlopidine (has alot of SE)
- prevent ADP from binding to receptor which induces more aggregate release from platelets
8
Q
What is the MOA of Phosphodiesterase blockers?
A
eg. Dipyridamole
- phosphodiesterase normally breaks down cAMP into 5-AMP but cAMP inhibits thromboxane A2 and ADP release from platelets so phosphodiesterase inhibitor allows cAMP accumulation
9
Q
What are examples of some anti-coagulants?
A
- heparin derivatives
- warfarin
- antithrombin III
*these drugs prevent coagulation cascade from occurring
10
Q
What are the functions of thrombin?
A
- activates upstream factors V, VIII and XI resulting in further thrombin generation
- cleaves fibrinogen into fibrin
- activates factor XIII to strengthen fibrin-to-fibrin links such that fibrin mesh can be formed
- causes platelet aggregation, cell proliferation and modulate smooth muscle contraction
11
Q
What is the MOA of Antithrombin III?
A
- endogenous anticlotting protein that irreversibly inactivates factors X, IX and II (thrombin) by forming complexes with them such that they cannot activate other factors in the cascade
12
Q
What is the MOA of heparin?
A
- family of sulfated glycosaminoglycans that bind to antithrombinIII and cause conformational change by exposing ATIII active sites for enhances complex formation with factors II,IX and X
- To inhibit thrombin, it is necessary for heparin to bind to factor II as well as to AT III but to inhibit factor X it is only necessary for heparin to bind to AT III.
- low molecular weight heparin have longer duration of action than regular unfractioned heparin but this longer effect only applies to ATIII inhibition of factor X and not thrombin
13
Q
What is heparin used for?
A
- treatment for DVT, pulmonary embolism, acute myocardial infarction
- combined with thrombolytics for revascularization (restoring blood flow in arteries). because heparin prevents thrombus formation but thrombolytics needed to breakdown existing thrombus
- combined with GPIIB-IIIA receptor antagonists for angioplasty and coronary stent placement
- used in pregnancy if anticoagulant needed
14
Q
What are side effects of heparin?
A
- can only be given by IV or subcutaneous bcs intramuscular causes haematoma formation
- can cause hemorrhage so stop therapy and give protamin sulfate which can chelate heparin
- ironically causes thrombosis and thrombocytopenia
15
Q
What is the MOA of warfarin?
A
- inhibits vit K epoxide reductase which reduces oxidised vitamin K. reduced vitamin K needed to carboxylate clotting factors II, VII,IX and X into their functional forms
*same clinical uses as heparin but cannot be used in pregnancy. heparin has small distribution volume because it is tightly bound to plasma albumin. metabolised by liver CYP450
