Anti-Platelets & Anti-Thrombotics Flashcards
Review the process of haemostasis
- Vasoconstriction, vascular spasm
- Primary haemostasis (platelet adhesion, activation, aggregation)
- Secondary haemostasis (coagulation cascade, fibrin clot formation)
What are the 3 main classes of anti-clotting drugs?
- Anti-platelet
- Anti-coagulants
- Thrombolytics
What are the 4 classes of anti-platelet drugs?
- NSAIDs
- GPIIb/IIIa receptor blockers
- ADP receptor blockers
- Phosphodiesterase inhibitor
Briefly explain the events involved in platelet activation and aggregation, starting from what the healthy endothelium produces
- Healthy endothelium releases prostacyclin (activates adenylyl cyclase, cAMP, inhibits platelet degranulation)
- Thrombin, thromboxane A2, exposed collagen of damaged endothelium releases arachidonic acid from platelet membrane (synthesise more TXA2)
- TXA2 binds receptors on other platelets (stimulate degranulation)
- Balance btwn levels of prostacyclin & TXA2 determines platelet aggregation or free circulation
What is the MOA of aspirin?
Irreversibly inhibit COX enzymes
- Decrease conversion of arachidonic acid to PGG2 (early PGE2)
- Decrease TXA2, PGI2, PGE2
- Decrease degranulation of other platelets by TXA2
How long does the inhibitory effect of aspirin last? Why?
Rapid and lasts for life of the platelet (irreversible) approx. 7-10d
What are the clinical uses of aspirin?
- Prophylactic treatment of transient cerebral ischaemia
- Reduce incidence of recurrent MI
- Decrease mortality in post MI pt
What are the adverse effects of aspirin?
Gastric upset & ulcers (decreased protective fn of gastric mucosa by PGE2)
What are the GP IIb/IIIa receptor blockers?
Abciximab
Eptifibatide
Tirofiban
What is the general function of GP IIb/IIIa receptor blockers?
Blocks platelet aggregation with fibrinogen
What is the MOA of abciximab? Can it be overcome?
(Humanized monoclonal Ab against GP IIb/IIIa complex)
Reversibly inhibits binding of fibrinogen & other ligands to GP IIb/IIIa
- Can be overcome by increased fibrinogen
What is the MOA of eptifibatide?
(Analog of fibrinogen)
Mediates binding of fibrinogen to the receptor
- Prevents actual fibrinogen from binding
What is the MOA of tirofiban?
Small molecule blocker of GP IIb/IIIa
What are the clinical uses of GP IIb/IIIa receptor inhibitors?
- Prevent restenosis after coronary angioplasty
2. Used in acute coronary syndromes
What are the ADP receptor blockers?
Clopidogrel
Ticlopidine
What is the MOA of ADP receptor blockers?
Prevent binding of ADP to ADP receptor
- Prevent platelet degranulation
What is the phosphodiesterase (PDE) inhibitor?
Dipyridamole
What is the MOA of PDE inhibitors?
Inhibits PDE
- Inhibits breakdown of cAMP to AMP
- Accumulation of cAMP (negative, “everything’s fine!!!” signal)
- Inhibits platelet degranulation
What are the types of anti-coagulants?
Heparin
Warfarin
Antithrombin III
What is the MOA of heparin?
Active heparin binds ATIII and cause a conformational change
- Exposes active site for more rapid interaction w proteases (potentiates ATIII fn)
- To inhibit IIa (thrombin): must bind IIa + ATIII
- To inhibit Xa: only need to bind to ATIII
What is the MOA of low molecular weight heparin? How is it different from normal heparin?
Low molecular weight heparin (LMWH) increase action of ATIII only on Xa but NOT on IIa (thrombin)
- LMWH have longer durations of action than heparin
How is heparin administered?
Given IV or S.C
Which method of administration cannot be used for heparin?
NEVER GIVEN IM (CAUSE HEMATOMAS!!)
What are the clinical uses of heparin? What other drugs is it used in combination with?
- Treatment of DVT, PE, AMI (prevent further worsening & spread but does not resolve the existing thrombus)
- Used in combination w thrombolytics for revascularization
- Used in combination w GP IIb/IIIa inhibitors during angioplasty & placement of coronary stents
- Used when an anti-coagulant must be used in pregnancy
