Anti-platelet And Anti-coagulant Drugs Flashcards
GPIa/IIa and GPIb are platelet membrane proteins that bind to collagen and
-Cause platelets to adhere to subendothelium of damaged blood vessel
von Willebrand Factor (vWF)
Protease activated receptors that respond to thrombin
PAR1 and PAR4
ADP receptors that, when stimulated by agonists, these receptors activate the fibrinogen-binding protein and COX-1 to promote platelet aggregation and secretion
P2Y1 and P2Y12
The major product of COX-1 involved in platelet activation
Thromboxane A2
Highly sulfates mucopolysaccharide
Heparin (antithrombin III activator)
Specific pentasaccharide essential for binding and inducing conformational change in antithrombin
Heparin
Binds antithrombin III and increases rate of protease inhibition by 1000x
Heparin
Catalyzes the antithrombin-protease “suicide substrate” reaction
Heparin
The heparin-induced conformational change in antithrombin is sufficient to inactivate
Factor Xa
Requires heparin to bridge antithrombin and thrombin
Thrombin inactivation
Can rapidly neutralize heparin effects in a life-threatening hemorrhage
Protamine Sulfate
A basic peptide that binds to negatively charged heparin forming a stable complex devoid of anticoagulant activity
Protamine
Partially effective against LMWH but not against pentasaccharide
Protamine
Can lead to major bleeding and osteoporosis
Heparin Therapy
Typically caused by antibodies against heparin:platelet factor 4 complex
-Onset is 5-10 days after treatment
Heparin-Induced Thrombocytopenia (HIT)
Bind both the catalytic site and expo site I of thrombin to inhibit thrombin
Hirudin and Bivalirudin
Inhibits thrombin only by binding the active site
Argtroban
A recombinant form of hirudin that functions as the most potent inhibitor of thrombin
Desirudin
Can reach and inactivate fibrin-bound thrombin in thrombi
-Found in leeches
Desirudin
Desirudin does NOT cause
Thrombocytopenia
Approved prevention of DVT and post elective hip replacement
Desirudin
Synthetic peptide congeners of hirudin
-used in coronary angioplasty and patients with HIT
Bivalirudin
A small synthetic derivative of arginine that blocks catalytic site of soluble and clot-bound thrombin
Argatroban
FDA approved for use as an anticoagulant in patients with HIT
Argatroban
Monitored by aPTT and also prolongs PT
-aPTT returns to normal two hours after discontinuing treatment
Argatroban
Inhibits vitamin K epoxied reductase (VKOR) and biosynthesis of vitamin K-dependent zymogens
Warfarin
Does not inhibit existing functional clotting factors
-Delayed onset of action (4-5 days)
Warfarin
Prothrombin and Factors VII, IX, and X are all
Procoagulants
Protein C and protein S are both
Anticoagulants
Contains 9-13 gamma-carboxylated Glu residues that are required for activity
-Binds Ca2+
Gla domains
Protein C and Factor VII both have short
Half-lives
Cause an increased risk for venous thrombosis
Protein C or S deficiency
We can treat adverse bleeding effects caused by warfarin w/
Vitamin K
May occur in patients with heterozygous protein C or S deficiency if a high initial dose of warfarin is used
Microvascular thrombosis
Warfarin can cause nephrotic syndrome in the form of low plasma
Albumin
Can cause decreased cytochrome P450 metabolism
Warfarin
Can cause increased target reductase sensitivity (VKORC1)
Warfarin
What are the three new/novel direct oral anticoagulants?
-Called the Xa inhibitors
Rivaroxaban, Apixaban, and Edoxaban
Cause less intracranial bleeding than warfarin (by at least 50%)
Xa inhibitors
Cause higher rates of GI bleeding than warfarin
Xa inhibitors
The Xa inhibitors have similar uses to warfarin, but are contraindicated in patients with
Mechanical Heart Valves
An antidote to da bigot ran
Idarucizumab
Recombinant modified human factor Xa decoy protein is an antidote for
Andexanet alfa
Process of breaking down fibrin. Particularly urgent when a clot has inappropriately formed or has broken free into the general circulation
Fibrinolysis
The central process of fibrinolysis is conversion of inactive plasminogen to plasmin by
Tissue Plasminogen Activator (t-PA)
Rapidly lose thrombi by catalyzing the formation of plasmin from plasminogen
Fibrinolytic Drugs
A recombinant tissue plasminogen activator
Alteplase (Activase)
Physiologically, t-PA activates plasminogen that is bound to fibrin of
Thrombus
Has a half-life of 5 minutes and is typically given as an IV bonus and then infusion
Alteplase
An anti-platelet drug that functions as a cyclooxygenase (COX) inhibitor
Aspirin
Works because platelets have no nucleus and thus can not resynthesize
COX
Endothelial cells can regenerate COX and restore antithrombotic effect by producing
PGI2
A low dose of aspirin (70-325 mg/day) can selectively inhibit
- Spares endothelial COX
- sustains antithrombotic effect
Platelet Cox
Serves as the primary prophylaxis of MI and as a secondary prevention of vascular events following heart disease
Aspirin
Irreversibly inhibits binding of ADP to its receptor on platelets and inhibits platelet aggregation
Clopidogrel and Prasugrel
Reversible inhibits the binding of ADP to its receptor on platelets and inhibits platelet aggregation
Ticagrelor (Brilinta)
Dual antiplatelet therapy is typically an
ADP inhibitor + Aspirin
A platelet membrane receptor which binds to the fibrinogen and vitronectin and also to fibronectin and vWF
GPIIb/IIIa
Facilitates formation of the platelet plug
GPIIb/IIIa
What are the three platelet GPIIb/IIIa receptor blockers?
Abciximab, eptifibatide, and tirofiban
