Anticoagulants Flashcards
The _____________ is non-thrombogenic.
Endothelial lining
Name the 5 Procoagulants: T T T A S
Thrombin Tissue factor Thromboxane ADP 5-HT
Name the 5 Anticoagulants: H P N A P
Heparan sulfate Prostacyclin Nitric Oxide Antithrombin Proteins C and S
What is found on the surface of endothelial cells and in the extracellular matrix, that interacts with circulating antithrombin to provide a natural antithrombotic mechanism?
Heparan Sulfate
What drugs target Platelet clumps (initial clot) ?
antiplatelet drugs
What drugs target Fibrin mesh formation around platelet clot?
Anticoagulant drugs (block single or multiple steps in coagulation cascade)
What drugs dissolve formed clots ?
fibrinolytic drugs
What are the Anticoagulant Drug classes? A H O F
Antiplatelet agents
Heparin & derivatives
Oral anticoagulants
Fibrinolytic agents
Streptokinase & Tissue plasminogen activator belong to which drug class?
Fibrinolytic agents
Warfarin belongs to which drug class?
Oral anticoagulants
Antithrombin belongs to which drug class?
heparin & derivatives
Asprin and Clopidogrel belong to which drug class?
Antiplatelet agents
Hypercholesterolemia, diabetes, hypertension can all cause _____________, platelet ___________, and plaque formation, which can rupture and activate coagulation.
endothelial dysfunction
platelet activation
plaque formation
4 Steps of Coagulation V P F R
Vasospasm
Platelet plug
Fibrin plug
Recanalization
__________ initiates the coagulation cascade.
Tissue Factor
What platelet function takes place following Disruption of endothelium?
Platelet adhesion
What platelet function takes place following platelet activation?
Platelet release
During the platelet release function , what Proaggregator mediators are released? S A T VWF P4
Serotonin ADP Thromboxane Von Willebrand Factor Platelet Factor 4
Which Proaggregatory mediator activates platelets?
Thrombin (from prothrombin)
Which drug inhibits platelet COX and prevents formation of thromboxane and Arachidonic acid?
Asprin
Which drugs block platelet purinergic P2Y receptors for ADP and increase cyclic AMP ?
Clopidogrel and ticlopidine
Which drug inhibits platelet phosphodiesterase and prevents breakdown of cAMP?
Dipyridamole
What 3 drugs block the GPIIb-IIIa receptor for fibrinogen on platelets and prevent platelet aggregation?
Eptifbatide
Abciximab
tirofiban
Aspirin is therapeutically used for what 2 things?
Prophylaxis for Myocardial infaction (MI)
Prophylaxis for Ischemic attacks (TIA)
What are the 4 Aspirin Contraindications: V H H P
Vitamin K deficiency
Hemophilia
Hypoprothrombinemia
Pregnancy/Childbirth
What Antiplatelet prodrug is used in combination with asprin that has CYP enzyme related drug interactions? (less neutropenia)
Clopidogrel
What Antiplatelet prodrug is used in combination with asprin and is potent. It has no CYP related drug interactions
Prasugrel
What Antiplatelet drug is potent and has CYP enzyme related drug interactions?
Ticagrelor
What Antiplatelet prodrug may cause severe neutropenia in 1% of patients?
Ticlopidine
Heparin is a _______ly charged molecule. This causes it to not cross the cell membrane easily.
negatively
Heparin is found in what type of cells?
mast cells
______________ circulates in the plasma and rapidly inhibits activated clotting factors: IIa (thrombin), Xa, IXa, XIa, and XIIa. Heparin acts as a catalyst to increase the rate of the reaction
Antithrombin III
Heparin toxicity leads to ________. this can be treated using _____________.
Hemorrhage
Protamine sulfate
HIT = ______________
heparin-induced thrombocytopenia.
___________ is when there is more than 50% decrease in platelet count due to antigen antibody reaction.
Thrombocytopenia
HIT incidence can be lowered by the use of what 2 alternative anticoagulants?
Thrombin
factor Xa Inhibitors
What are the 4 main Therapeutic uses for Heparin? V P H P
Venous thrombosis
pulmonary embolism
Any Heart surgery
DRUG OF CHOICE - during pregnancy (does not cross placenta)
LMWH have no space to bind _________. But can still inactivate _________.
thrombin IIA
factor Xa
What are the 3 major advantages of LMWHs?
A
O
T & H
Better absorbed (higher bioavailability)
Given subcutaneously without lab monitoring (outpatients)
Lower risk of thrombocytopenia and bleeding (hemorrhage)
What are the 2 disadvantages of LMWHs?
more expensive
cleared unchanged by kidney (DO NOT USE IN KIDNEY FAILURE)
Which parenteral anticogulant drug promotes inhibition of Xa by antithrombin, is a nonheparin glycosaminoglycan, and is used in patients with heparin-induced thrombocytopenia?
Danaparoid
What parenteral Anticoagulant drug is a direct thrombin (IIa) inhibitor- a derivative of hiruden(in leech). ?
Lepirudin
What oral anticoagulant inhibits vitamin K epoxide reductase in the liver where clotting factors are synthesized?
Coumarins (Warfarin)
How long does it take for Coumarins to become effective?
4-5 days. (active carboxylated factors must be cleared before inactive factors in the liver predominate)
Coumarins have a _______ (steep or shallow) D-R curve, and a ______ (large/small) Vd
Steep
small
can easily become toxic with a small increase in dose.
Warfarin is Teratogenic. This means what?
it crosses the placenta and causes birth defects and abortion.
What is the use of Warfarin?
treats thrombo-embolic conditions
Coumarins (warfarin) are metabolized by _____ and _____ enzymes.
CYP1A & CYP2C9
What two main drug interactions should be watched for when taking Warfarin ?
- Reduced effect in case of induction of enzymes
- Increased effect (hemorrhage) in case of reduced metabolism and/or displacement from protein binding.
In the case of Warfarin overdose, what can be used as an antidote?
Excess Vitamin K uses the enzyme Diaphorase (not inhibited by warfarin) but cannot reduce vit K epoxide.
Warfarin acts by blocking what enzyme?
Vitamin K epoxide reductase
Direct Thrombin (IIa) inhibitors (Dabigatran) are useful in patients with ____________.
HIT - heparin-induced thrombocytopenia
Comparison of Warfarin and newer Oral Anticoagulants:
Which has a slow onset and offset of action?
Warfarin
Comparison of Warfarin and newer Oral Anticoagulants: what has a predictable anticoagulant effect?
Newer oral anticoagulants
Comparison of Warfarin and newer Oral Anticoagulants:
What has a narrow therapeutic index?
Warfarin
Comparison of Warfarin and newer Oral Anticoagulants:
What has a specific coagulation enzyme target so there is a low risk of other side effects?
Newer oral anticoagulants
Comparison of Warfarin and newer Oral Anticoagulants:
Which has higher food and drug interactions? (lab tests needed)
warfarin
Comparison of Warfarin and newer Oral Anticoagulants:
Which reduce synthesis of ALL vitamin K dependent proteins? (many side effects)
Warfarin
Comparison of Warfarin and newer Oral Anticoagulants:
Which varies more in dose requirements and anticoagulant effect?
Warfarin
What fibrinolytic drug dissolves clots after myocardial infarction, thrombosis, and pulmonary emboli?
Streptokinase
Streptokinase may cause increased bleeding as a side effect because its believed to cause __________ (not just at sites of clot formation)
systemic plasmin formation
Streptokinase side effects include : B A Hypo F
Bleeding
Allergic Reactions
Hypotension
Fever
Streptokinase Contraindications:
Any type of tissue or brain damage.
Tissue plasminogen activator (t-PA) activates ________________ and therefore theoretically is believed to act only at sites of clot formations but clinically does not turn out to be more specific than streptokinase. More expensive than streptokinase.
fibrin bound plasminogen. (less systemic plasmin formation)
Tissue plasminogen activator is used in which 3 situations?
Myocardial infarction, thrombosis, pulmonary emboli
