6.1 - Blood Flashcards
What kind of drug is acetylsalicylic acid?
Antiplatelet Drug
–> Inhibits cyclooxygenase enzymes (COX) that produce thromboxane A2, resulting in:
Reduction of platelet aggregation and prolonged bleeding time
What are the functions of ADP and thromboxane A2?
Substances that stimulate the activation and aggregation of platelets to form a plug
What are the adverse effects of acetylsalicylic acid?
Most common are gastric irritation (Heartburn), and risk of gastric ulceration
What is low dose (81mg/day) aspirin used for?
Used to prevent complications related to thromboses
–> Also effective in circumstances where there is an increased risk of arterial thrombosis (such as during angioplasty)
What kinds of drugs are clopidogrel, prasugrel, and ticagrelor?
ADP Receptor Antagonists
–> decreases platelet aggregation results in inhibition of ADP released from activated thrombocytes
–> Used to prevent thrombus formation (e.g., following angioplasty)
Which clotting factors are vitamin K dependent?
II, VII, IX, X
What is antithrombin III?
An anticoagulant in our body responsible for inactivation of factors:
Xa
IIa (thrombin)
IXa
XIa
XIIa
Which test will measure the speed of the intrinsic pathway?
aPartial Thromboplastin Time
What test measures the speed of the extrinsic pathway?
Prothrombin Time
How do anticoagulants work?
They reduce the ability of blood to form clots.
What is heparin?
Anticoagulant
–> Activates ATIII, resulting in inactivation of Xa, IIa, XIIa, XIa, and IXa.
Results in reduced coagulation
How is heparain administered?
IV
–> Effective immediately
Sub-Q
–> 1-2 hours
Administration of heparin requires close monitoring using which test?
Activated partial thromboplastin time aPTT OR Anti-Factor Xa
How is the dose of heparin adjusted?
aPTT/ newer way: Anti-Factor Xa
With a goal of obtaining a coagulation time of 1.5-2.5 times the normal value of this patient
What are the clinical uses of heparin?
–> Prevention or treatment of venous and arterial clots (DVT, PE, Acute coronary syndrome)
–> During extracorporeal circulation (Bypass, hemodialysis)
What are the adverse effects of heparin?
Bleeding
–> Nose, gums, bruising, petechiae
–> Menorrhagia, GI bleed, hematuria
–> HypoTN, tachycardia, Decreased LoC
–> Headache, confusion, change in vision
–> Abdominal or pelvic pain
–> Heparin-induced thrombocytopenia
–> Osteoporosis
What is heparin induced thrombocytopenia?
An immune reaction to heparin that results in platelets being pulled from the blood stream.
How can heparin toxicity be treated?
Protamine
What kinds of drugs are delteparin and enoxaparin? What are its advantages?
Low molecular weight heparin
–> Acts more on factor X than on II (2-4x more selective)
–> More predictable anticoagulant response and fewer hemorrhagic complications
What is fondaparinux? How is it administered?
A indirect specific factor Xa inhibitor
–> activates ATIII specifically such that is only increases desctruction of factor Xa
–> s.c.
What kind of drugs are apixaban and rivoroxaban?
Direct factor Xa inhibitors
–> inhibits Xa specifically by binding directly to it
–> p.o.
How does warfarin work? What is its route of administration and onset of action?
Oral anticoagulant
–> Vit K antagonist, decreasing synthesis of factors II, VII, IX, X
–> Treatment requires 3-4 days before it has reached full efficacy as only newly synthesized factors will be affected
Which test is used to monitor levels of warfarin therapy? What are the normal and therapeutic goal ranges for this test?
Prothrombin Time (INR)
INR = pt’s PT / ave pop PT
Normal range: 0.8-1.2
Therapy aim: 2.0-3.5
What is warfarin used for?
Long-term prophylaxis of thrombosis
–> a-fib, mechanic heart valves
What are the adverse effects of warfarin?
–> Bleeding, bruising
–> Can cross placenta; known teratogen
–> Very sensitive to dietary vitamin K intake (Vit K reduces warfarin’s efficacy)
–> Multiple drug-drug interactions, and other drugs that affect CYP levels or compete for binding to plasma proteins
How do you treat warfarin toxicity?
–> Vitamin K (p.o./i.v.)
–> Prothrombin complex concentrate (II, VII, IX, X)
–> Fresh-frozen plasma
What kind of drug is dabigatran? Why would you use it instead of warfarin?
A direct thrombin inhibitor (p.o)
–> Not sensitive to vit K intake, fewer drug-drug interactions like warfarin. Therefore more predictable and less frequent monitoring is required.
What are the adverse effects of dabigatran?
bleeding & dyspepsia
How do you treat toxicity due to dabigatran?
idarucizumab
What are the clinical uses of fribin/thrombolytics?
MI, PE, ischemic stroke
What is tPA?
Tissue plasminogen activator
–> thrombin/fibrinolytic
What is tenecteplase?
A synthetically modified tPA
What is streptokinase?
a thrombin/fibrinolytic of bacterial origin
What is the mechanism of action of thrombolytics?
Increase conversion of plasminogen to plasmin, which destroys fibrin within blood clots.
What are the adverse effects of thrombolytics?
Plasmin can destroy pre-existing clots and promote recurrence of bleeding at sites of recently healed injury - this is especially problematic if this leads to intracranial hemmorhage
What is something to be aware of when administering streptokinase?
Due to its bacterial origin, pt’s often mount an immune response against the enzyme of the first use. Therefore, it can usually only be used once.
What kind of drug is tranexamic acid?
An antifibrinolytic
–> Reduces fibrinolysis by inhibiting binding of plasminogen to fibrin
Why would you use an antifibrinolytic such as tranexamic acid?
Reduce bleeding
–> Menorrhagia
–> Hemophilia
–> During some surgery
What are the adverse effects of antifibrinolytics such a tranexamic acid?
Thromboembolic events and allergic skin reactions.
Which coagulation factors are associated with the intrinsic pathway? Which test tests their efficacy?
XII, XI, IX, VIII
–> aPartial Thromboplastin Time
Cascade to activate factor X –> II (thrombin) –> I (fibrin)
Which factors are associated with the extrinsic pathway? Which test tests their efficacy?
Tissue factor & factor VII
–> Tested with Prothrombin Time
Cascade to activate factor X –> II (thrombin) –> I (fibrin)
What are the adverse effects of clopidogrel?
–> Must be activated by CYO 2C19 (so may not be activated enough in slow metabolizers)
–> Agranulocytosis
–> Bleeding
What are the adverse effects of prasugrel?
–> Must be activated by hepatic enzymes (so may not be fully activated by slow metabolizers)
–> Bleeding
What are the adverse effects of ticagrelor?
Bleeding
