Week 5 Pharmacology Flashcards
How does Heparin work?
Induces antithrombin
–> accelerates inhibition of thrombin and Factor Xa
Heparin has binding sites for both antithrombin and thrombin.
Thrombin cleaves part of antithrombin which causes antithrombin to wrap around and inhibit thrombin.
How do coumarol drugs work?
Inhibit reduction of Vit K in liver.
Vit K
What cleaves fibrin?
Plasmin
What holds fibrin together?
Covalent and non-covalent bonds.
Fibrin is crosslinked by what?
Factor XIIIa
What are fibrinopeptides?
Peptides released from the alpha and beta chains of fibrinogen. This allows for the terminal ends to now bind to other fibrin monomers.
What are D2E fragments?
Products resulting from plasmin breaking down of fibrin.
Elevated with liver disease.
How does the body respond to blood vessel injury?
Platelets aggregate at injury site
- -> platelets are activated
- -> platelets release granules
- -> extrinsic clotting cascade begins
What is Protein C?
Vitamin K-dependent plasma protein anticoagulant
- aka. Clotting Factor XIV (xymogen)
- plays a role in preventing clotting, inflammation, cell death, and permeability of capillary membrane
What happens in Protein C deficiency?
Blood tends to clot more
ex. DVT
Risk of recurrent thrombotic diseases
How does warfarin effect Protein C?
Warfarin decreases the anticoagulant activity of Protein C.
What activates Protein C?
Thrombin
What is serum?
The liquid portion of blood that is leftover after the blood has been allowed to clot.
Therefore does not contain clotting factors.
Name some chelating agents.
Citrate
EDTA
What do chelating agents do?
Removes Calcium from Gla proteins in blood.
Prevents clotting!
What does thrombomodulin do?
Changes the substrate specificity of Thrombin
Thrombin-thrombomodulin complex activates Protein C.
–> Inactivates Factor Va, VIIIa
–> Fibrin production is inactivated
–> Anticoagulant activity
What is thrombin?
A pro-coagulant
What does thrombin do?
Converts fibrinogen to fibrin.
Activates platelets, Factor V, VIII, (XI), & XIII
Activates Protein C
What is standard treatment of DVT and PE?
Anticoagulant therapy.
What are some typical clinical features of PE?
Dyspnea Pleuritic pain Hemoptysis Loud P2 Heart sound Rigors
What increases the likelihood of peripheral venous thrombosis?
Virchow’s Triad:
- Stasis
- Hypercoagulability
- Endothelial damage
Polycythemia
Oral contraceptives
Dehydration
What is the most common heart rhythm in pts with PE?
Sinus tachycardia
Is hemoptysis associated with pneumonia?
No; very rarely.
Compare fibrinolytic therapy to heparin.
Fibrinolytic Therapay:
- more expensive
- more likely to bleed
- more rapid decrease in pulm HTN for large PE
After PE, what is the typical length of time that warfarin (coumadin) is given for?
3-6 months
How long does it take for PE’s to dissolve?
Days to weeks after starting on anticoagulation Tx.
What are some targets for anticoagulation?
- Anti-platelet
- Chelate Ca++
- Inhibit carbox’n of Gla proteins
- Anti-thrombin
- Directly inhibit thrombin
- Thrombolytic agent
Name examples and describe anti-platelet agents.
ASA
- inhibits COX
- prevents synthesis of TXA2
- prevents platelet activation and aggregation
Coumarol drugs are also know as…
Name one.
blood thinners
ex. Warfarin
What are couramol drugs used for?
How are they administered?
Long-term anti-coagulation in thrombosis-risk pts.
Can be taken orally (100% bioavailability)
How can the action of coumarol be reversed?
Additional Vit K intake
Therefore must monitor INR continuously
What is INR?
INR = [ Prothrombin(test) / Prothrombin(control) ] ^ ISI
How does warfarin affect PT (prothrombin time)?
Warfarin prolongs prothrombin time.
When is warfarin indicated?
- prophylaxis and Tx of VTE
- prophylaxis and Tx of atrial fib
- valvular stenosis
- heart valve replacement
- MI
- Antiphospholipid syndrome
Name some Gla proteins.
Which has the longest half-life? shortest?
Prothrombin –> longest half-life
Factor VII –> shortest half-life
Factor IX
Factor X
What initiates the extrinsic pathway?
External damage to blood vessel
- -> releases Tissue Factor
- -> binds to Factor VIIa
What converts prothrombin to thrombin?
Factor Xa and Factor Va
Why does warfarin need to be monitored so closely?
Narrow therapeutic index
Can increase risk of bleeding
Effectiveness altered by diet
How is warfarin use monitored?
INR and PT
What is the target INR for someone with previous VTE?
Target INR range: 2.0 - 3.0
What does an INR < 2 suggest?
Increased risk of thromboembolism (& stroke & MI)
What does an INR > 4.5 suggest?
Increased risk of bleeding
What is a serpin?
SERPIN = SERine Protease INhibitor
ex. antithrombin
What is PTT?
What does it measure?
PTT = Partial Prothromboplastin Time
Measures clotting factors in pt who is taking Heparin
How does size of the Heparin chain affect fxn?
Factor Xa can be inhibited (via antithrombin) with any size Heparin chain.
Thrombin can be inhibited (via antithrombin) ONLY with Heparin chain > 18 sugars.
What are some advantages of LMWH over UFH?
- Decreased Heparin resistance
- Don’t need lab monitoring
- Higher bioavailability (90% vs 30%)
- Longer plasma half-life (4-6 hrs vs 0.5-1 hr)
- Less inhibition of platelet fxn
- Lower incidence of thrombocytopenia and thrombosis
- Less interaction with platelet factor 4
How is Heparin administered?
IV
- Must be injected becuase it is highly charged.
How can Heparin action be reversed?
Administration of protamine sulfate
protein that forms a complex with Heparin
What is a serious risk of Heparin?
Fatal thrombocytopenia
What is a type of synthetic Heparin?
Fondaparinux
What agent directly inhibits Factor Xa?
Rivaroxaban
What agent directly inhibits Thrombin?
Dabigatran
How can the action of direct Thrombin/Factor Xa inhibition be reversed?
It can’t.
There’s no known antidote.
What is an advantage of direct Thrombin/Factor Xa inhibitors?
Patient does not require close monitoring.
How do Thrombolytic agents work?
Activate plasminogen to plasmin
How are Thrombolytic agents administered?
IV
What are some examples of thrombolytic agents?
Urokinase
Streptokinase (bacterial)
Tissue Plasminogen Activator “TPA” (recombinant)
What are thrombolytic agents indicated for?
Ischaemic stroke caused by blood clot
