antiplatelet Flashcards
What are the 3 ways of using drugs to achieve anti-clotting
anti platelet drug
anti coagulant drug
thrombolytics
How does prostacyclin result in antiplatelet effect
prostacyclin binds to platelet membrane receptors causing synthesis of cAMP, cAMP inhibits release of granules containing aggregating agents
what does the aggregating agents include
serotonin and ADP
How does thromboxane A2 cause platelets to aggregate
thromboxane A2 and exposed collagen cause the release of AA from the platelet membrane. TXA2 is synthesized from AA and released from platelet. TXA 2 binds to receptors on other platelets thereby initiating release of additional aggregating agents
What is the pathway of AA synthesizing more TXA2 inhibited by
aspirin
What are some examples of anti-platelet drugs
- platelet GP2B/3A receptor blocker
- NSAIDS
- ADP receptor blockers
- PDE inhibitor
What is NSAIDS like aspirin used for clinically
a. prophylactic treatment of transient cerebral ischemia
- reduce incidence of recurrent myocardial infarction
- decrease mortality of postmyocardial infarction patient
What are the adverse effect of NSAIDS
bleeding (PGI2)
gastric upset and ulcers
what is the GP2B/3A receptor
It is a platelet membrane surface protein, activation of receptor complex is the final common pathway for platelet aggregation
How does GP2B/3A receptor result in platelet aggregating effect
Receptor complex anchor on fibrinogen allowing crosslinking to become fibrin
What are some example of GP2B/3A receptor blocker drugs
Epitifibatide
-mediates binding of fibrinogen to receptor
Abciximab
- is a monoclonal antibody, taken IV, reversibily inhibit binding of fibrinogen and other ligands to the 2B/3A receptor
Tirofiban
- taken orally, small molecule blocker of 2B/3A receptor
What are some example of ADP receptor blockers
Clopidogrel, Ticlopidine
How does PDE inhibitor help with anti-platelet
Prevents cAMP from degradation. cAMP inhibits degranulation
How does PDE inhibitor help with anti-platelet
Prevents cAMP from degradation. cAMP inhibits degranulation, lesser aggregating agents produced, resulting in antiplatelet effect
What is an example of a PDE inhibitor
Dipyridamole
What are some examples of anticoagulant drugs
warfarin, heparin
What is heparin
a family of sulfated glycosaminoglycans
how does heparin work
○ Active heparin molecules bind tightly to AT3 and cause a conformational change which exposes its active site for more rapid interaction with the proteases
○ To inhibit thrombin, necessary for heparin to bind to enzyme and AT3. Where as for factor 10 it is only necessary to bind to AT3
○ LMWH increase action of AT3 on factor 10a, but not action on thrombin. Because LMWH cannot allow binding of AT3 and thrombin together
what are the clinical uses of heparin
○ Treat deep vein thrombosis, pulmonary embolism, acute myocardial infarction
○ Used in combination with thrombolytics for revascularisation and in combination with GPIIb/IIIa inhibitors during angioplasty and placement of coronary stents
Can be used in pregnancy if really bobian
what would happen if heparin is given intramuscularly
hematoma
What are the adverse effect of heparin
haemorrhage, thrombosis and thrombocytopenia
how is vitamin K important in the coagulation pathway
reduced vitamin K is an essential cofactor in gamma carboxylation of glutamate residues found in factor 2,7,9,10
What is vitamin K used for clinically
used to treat and prevent bleeding resulting from the use of anticoagulant drugs like warfarin
for babies to prevent haemorrhagic disease
for vit K deficiencies in adults
What does warfarin do
inhibit vitamin K reductase, inhibits quinone( oxidised form of Vit K) from reducing to hydroquinone ( the reduced form of Vit K). without hydroquinone, y- carboxylation of glutamate residues cannot occur, thrombin and other coagulation pathway is limited
What are the adverse effect of warfarin
bleeding,,, warfarin crosses placenta readily, can cause hemorrhagic disorder in the fetus,,, fetal proteins with gamma carboxyglutamate residues found in bone and blood may be affected by warfarin
drug interaction that affect availability of cy450 can affect how much warfarin get metabolised and eliminated
What are the pharmacokinetics of warfarin
warfarin given orally absorbed quickly and totally
small distribution volume as it is strongly bounded to albumin
elimination depends on metabolism by hepatic cytochrome p450
what can increase cyp450
barbiturates, carbamezepine, phenytoin increase cyp450, can result in underdosing of warfarin
what can decrease cyp450
amiodarone, cimetidine, disulfiram, imipramine
What are the 4 main type of thrombolytic agents
t-pa, urokinase, streptokinase, antistreplase
what does thrombolytic agents do
activate plasminogen to form plasmin. Plasmin tries to break down fibrin into fibrin degradation products
what are the clinical uses of anti-thrombotic agents
emergency treatment of coronary artery thrombosis, peripheral arterial thrombosis and emboli, ischaemic stroke
