PMT, Konorev - Drugs Used in Thromboembolic Disorders Flashcards
What is a white thrombus, where do they form, and what pathologic conditions are associated with it?
Drug class used to prevent this.
- A platelet-rich thrombus
- Form in high-pressure arteries.
- Associated with local ischemia due to arterial occulsion - MI/unstable angina in coronary a.) Little fibrin involvement.
- ANTIPLATELET drugs to inhibit platelet function
What is a red thrombus, where do they form, and what pathologic conditions are associated with it?
Drug class used to prevent this.
- A fibrin rich with trapped RBCs.
- Form in low pressure veins.
- Associated with embolic stroke - pain and severe swelling, embolism, distal pathology. Fibrin involvement.
- ANTICOAGULANTS to regulate function and synthesis of clotting factors
What class is used to destroy clots?
THROMBOLYTICS - reestablish flow through vessel
MOA of indirect thrombin and FXa inhibitors (anticoag) (3)
Overall: Bind plasma serine protease inhibitor ANTITHROMBIN (III)
- HMW Heparin - inhibits activity of thrombin and FXa.
- LMW Heparin - inhibits FXa, little effect on thrombin.
- Fondaparinux - inhibits FXa (indirectly), no effect on thrombin.
Admin route and indications/use of HMW v. LMW heparin.
Anticoagulants.
LMW requires less frequent injections from SC injection site.
Route: IV and SC
Use:
1) protects against pulm. emboli;
2) DVT, atrial arrhythmias»_space;any condition that will PREDISPOSE TOWARDS RED THROMBI
What is a heparin lock?
Prevents clot formation in catheters.
What are two ways to monitor patients of heparin?
- Activated Partial Thromboplastin Time (aPTT) - normal range is 30-50sec; goal in heparin-patients is 50-75sec
- Anti-Xa assay - therapeutic range is 0.3-0.7units/mL
AE of heparin.
- Bleeding
- Heparin Induced Thrombocytopenia (HIT)
Mechanism of HIT.
Tx for HIT
MOA: immunogenicity of the complex of heparin with platelet factor 4 (PF4).
Tx: discontinue hep and administer DTI
What are two things to look for in a patient on heparin?
1) Thrombocytopenia due to platelet removal by macrophages.
2) Thrombosis due to platelet activation and aggregation.
CI of Heparin.
Severe HTN, active TB, ulcers of GI, patients with recent surgery.
What do you use to reverse heparin action?
Protamine sulfate.
What is fondaparinux, its admin, and its MOA.
Synthetic pentasaccharide
SC admin
MOA - binds antithrombin to indirectly inhibit FXa by being and antithrombin III catalyst
How is fondaparinux different than heparins and what are its clinical indications?
Different bc - does not inhibit thrombin actiivty, rarely induces HIT, action NOT reversed by Protamine Sulfate.
Indications - DVT prevention, tx of acute DVT, tx of pulmonary embolism
Name the Parenteral anticoagulants:
1) Indirect thrombin and FXa-i: HMW, LMW, and synthetic pentasaccharide
2) Direct thrombin inhibitors
1)
- HMW: heparin sodium
- LMW: enoxaparin, tinzaparin, dalteparin
- Synthetic - fondaparinux
2) Lepirudin, bivalirudin, argatroban
MOA of Direct thrombin inhibitors
Directly inhibit protease activity of thrombin.
Lepirudin, bivalirudin - bind both active site and substrate recognition site.
Argatroban - bind only at thrombin active site.
Which Direct thrombin inhibitors are irr/reversible.
Lepirudin - irreversible thrombin inhibitor
Bivalirudin - reversible thrombin inhibitor (also inhibits platelet aggregation
Argatroban - IV, short acting
Indications and AE of Direct thrombin inhibitors.
Indications - HIT, coronary angioplasy (BIVALIRUDIN and ARGATROBAN).
AE - bleeding, anaphylactic reaction in repeated LEPIRUDIN use.
Name to oral anticoagulants
1) coumarin anticoags - Warfarin
2) Novel Oral AntiCoagulants - FXA-I (Rivaroxaban, Apixaban, Edoxaban); Direct thrombin inhibitor (Dabigatran)
MOA of Warfarin
Proteins affected
Inhibits vitK-epoxide reductase whic inhibits reactivaiton of vitK»_space; inhibiting carboxylation of gamma-glutamyl-carboxylase.
Proteins affected - factor 2 (protrombin). factors 7/9/10 (hemostatic)
What is the normal function of carboxylation of glutamate residues - what is warfarin effective at preventing?
Converts hypofunctional hemostatic factors into functional ones.
Warfarin - Pharmacokinetics, indications, AE
Kinetics - oral, long half life, dose varies in each person.
Indications - prevent thrombosis or tx thromboembolism afib, prosthetic heart valve
AE - TERATOGENIC (bleeding in fetus), skin necrosis/breasts, intestins, osteoperosis, bleeding
Warfarin dose titration - INR Normal? High chance of thrombosis? High chance of bleeding? Range for patients on warfarin?
- 5 - high chance of thrombosis
- 9-1.3 - normal
- 0-5.0 - high chance of bleeding
- 0-3.0 - range for patients on warfarin.
What is VKORC1? What race is high dose v. low dose haplotype more common in?
What is CYP2C9 responsible for?
VKORC1 - responsible for 30% of variation in dose: high dose haplotype = more warfarin resistant = African American; low dose haplotype = less warfarin resistant = Asian Americans
CYP2C9 - responsible for 10% of variation in dose, Caucasians
