Antiplatelets and Antithrombotics Flashcards
Name 3 classes of anti clotting drugs
- Antiplatelets
- Anticoagulants
- Thrombolytics
Name 4 classes of antiplatelets
- NSAIDs
- Platelet GPIIB/IIIA receptor blockers
- ADP receptor blockers
- Phosphodiesterase (PDE) inhibitors
Name an example of a NSAID antiplatelet
Aspirin
Name 3 examples of platelet GPIIB/IIIA receptor blockers
- Abciximab
- Tirofiban
- Eptifibatide
Name 2 examples of ADP receptor blockers
- Ticlopidine
- Clopidogrel
Name a PDE inhibitor
Dipyridamole
MOA of aspirin
COX 1 and COX 2 inhibitor, which reduces conversion of arachidonic acid to eicosanoids. Acts as an anti platelet
3 clinical uses of aspirin
- Prophylactic treatment for transient cerebral ischemia
- Reduce the incidence of recurrent myocardial infarction
- Decrease mortality in patients with post myocardial infarction
2 ADRs of aspirin use
- Bleeding (PGI2)
- GI effects: gastric upset, ulcers, GI bleeding (PGE2)
State the normal function of GPIIb/IIIa receptor
A platelet membrane surface protein.
GPIIb/IIIa complex functions as a receptor for mainly fibrinogen and vitronectin, and also fibronectin and vWF.
Activation of the complex is the final common pathway for platelet aggregation
Structure of abciximab
Chimeric monoclonal antibody that reversibly inhibits the GPIIb/IIIa receptor complex
Structure of eptifibatide
Structural analogue of the carboxyl terminal of fibrinogen, thus binds reversibly to the GPIIb/IIIa receptor complex
2 clinical uses of platelet GPIIb/IIIa receptor blockers
- Prevent restenosis after coronary angioplasty
- Treatment of acute coronary syndrome
MOA of clopidogrel and ticlopidine
ADP receptor inhibitor. Prevent binding of ADP, reduce platelet aggregation
MOA of dipyridamole
Inhibits PDE which prevents conversion of cAMP to AMP, thus reducing platelet aggregation
Name the 4 drug classes for anticoagulants
- Heparin derivatives
- Coumarin derivatives (Warfarin)
- Lepirudin, Hirudin
- Antithrombin III
Outline 4 physiological actions / effects of thrombin
- Activates upstream proteins (esp factor V, VIII and XI) which increases thrombin generation
- Cleaves fibrinogen into fibrin which polymerises
- Activates factor XIII to factor XIIIa which stabilises the fibrin-fibrin linkages
- Increases platelet aggregation, stimulates smooth muscle contraction and increases cell proliferation
MOA of antithrombin III
Endogenous anticlotting protein that irreversibly binds and inactivates clotting factor proteases, especially IIa (thrombin), IXa and Xa by forming equilimolar stable complexes with them
Heparin is a family of sulfated…
Glycosaminoglycans
State 2 PK advantages of low molecular weight heparin (LMWH) compared to regular heparin
- Higher bioavailability
- Longer half-life
MOA of heparin on factor IIa (thrombin)
Binds tightly to ATIII, causing a conformational change which exposes its active site for more rapid interaction with the protease
Must bind to BOTH ATIII and factor IIa to inhibit thrombin
MOA of heparin on factor Xa
Binds tightly to ATIII, causing a conformational change which exposes its active site for more rapid interaction with the protease
Only needs to bind to ATIII to inhibit factor Xa
LMWHs increase the action of ATIII on factor ___ but not on factor ___
Increase action on factor Xa but not on factor IIa
State 4 clinical uses of heparin
- Treatment of DVT, pulmonary embolism, acute myocardial infarction
- Combine with thrombolytics for revascularisation
- Combine with GPIIb/IIIa blockers during angioplasty and inserting coronary stents
- Used as an anticoagulant in certain pregnancies for treating venous thromboembolism (VTE)
Is heparin / LMWH safe to use in pregnant patients?
Yes
2 routes of administration for heparin
- Intravenous
- Subcutaneous
Heparin must NEVER be administered ___ as it can cause ___
Intramuscularly
Hematomas
State 2 ADRs of heparin use
- Haemorrhage
- Thrombocytopenia
Outline the treatment for heparin induced haemorrhage
Stop heparin therapy
Give protamine sulfate (cationic peptide): Forms an inactive ionic complex with heparin
Name the 4 clotting factors that require vitamin K
Factors II, VII, IX, X
Functioning / activated vitamin K needs to be in the reduced or oxidised state?
Reduced state
Name the enzyme that reduces oxidised vitamin K into its reduced form
Vitamin K reductase
Name the type of reaction that reduced vitamin K is used in activating factors II, VII, IX, X
Carboxylation of glutamate residues in clotting factors
State 3 clinical uses of vitamin K
- Treatment and prevention of bleeding from the use of oral anticoagulants
- Babies: Used to prevent haemorrhagic disease of the newborn
- Adults: For patients with vitamin K deficiency
MOA of warfarin
Vitamin K reductase inhibitor.
Inhibits the reduction of oxidised vitamin K, thus reduces the carboxylation of glutamate residues in clotting factors II, VII, IX, X, thus inhibiting their coagulation function
State 3 clinical uses of warfarin
*same as heparin
1. Treat DVT, PE, AMI
2. Combine with thrombolytics for revascularisation
3. Combine with GPIIb/IIIa during angioplasty and for inserting coronary stents
Warfarin is administered
Orally
Does warfarin bind to albumin in the blood?
Yes
Where is warfarin metabolised?
Liver by CYP450
State an adverse effect of warfarin use
Bleeding
Warfarin is contraindicated in ___ because ___
Pregnancy
Crosses the placental barrier readily and causes haemorrhagic disease of the foetus.
It also affects fetal proteins containing gamma-carboxyglutamate residues
Name 4 thrombolytic agents
- tPA (alteplase)
- Urokinase
- Streptokinase
- Anistreplase
MOA of thrombolytic agents
Plasminogen activators which increase the conversion of plasminogen to plasmin, and thus increases fibrinolysis of fibrin clots / mesh, thus dissolving blood clots
State 3 clinical uses of thrombolytics
- Emergency treatment in coronary artery thrombosis
- Peripheral artery thrombosis and emboli
- Ischaemic stroke
Administering thrombolytics for ischaemic stroke must be done within (time window)
Less than 4.5 hours
Can thrombolytics be used in haemorrhagic stroke?
No
State 2 routes of administration for thrombolytics
- Intracoronary
- Intravenous
State an adverse effect of thrombolytics
Bleeding
Thrombolytics are contraindicated in 2 kinds of patients
- Healing wounds
- Pregnancy
