Hemolytic Drugs Flashcards
What is a red thrombus?
Fibrin rich. large RBCs; venous
What is a white thrombus
Platelet rich; arterial
What is Virchow triad?
Local vessel injury (Endothelial injury)
Abnormal blood flow (stasis/turbulence)
Altered blood coagulability (hyperactivity of hemostatic factors of hypoactivity of fibrinolytic mechanisms)
What are the drug classes of thromboembolic disease?
Systemic, Antithrombic drugs, and Fibrinolytic drugs
What is an ideal systemic anticoagulant
Prevent pathological thrombosis
Allow normal response to vascular injury and limit bleeding
What are the systemic anticoagulants?
Antithrombin
Fibrinolytic
Heparin (unfractioned heparin; generic)
Enoxaparin (Lovenox) - low molecular weight
Warfarin (Coumadin)
Rivaroxaban (Xalrelto)
Antithrombic drugs
Asprin
Clopidogrel
Fibrinolytic drugs
Tissue Plasminogen Activator
Erythropoietin (Epogen or Procrit)
Heparin
- Mechanism of action
Mixture of sulphated mucopolysaccharides
MOA: Enhances the action of antithrombin III - forms ATIII-heparin complex
ATIII - inhibits activated clotting factors especially thrombin (IIa) and Xa
Heparin
- Uses
Initial treatment of thrombosis and thromboembolic disease.
Rapid onset of action renders it useful as an acute anticoagulant.
Prevents thrombosis formation ONLY - does not lyse pre-existing thrombus
Adverse effects of Heparin
Bleeding tendencies
Protamine sulfate can neutralize heparin in overdose.
Enoxaparin - what is it?
MOA?
Low molecular weight heparin.
Fractioned from standard heparin or chemically synthesized.
Inactivates Xa well, but not thrombin.
Advantages of enoxaparin over heparin?
Less bleeding
Less risk of thrombocytopenia
Improved pharmacokinetics - SQ, longer half life
Warfarin
- MOA
Oral anticoagulant, antagonizing vitamin K actions.
Reduces clotting factors (10, 9, 7, 2); factor 7 has shortest half life.
Clotting not affected until existing factors are used up.
Warfarin adverse effects
Bleeding tendencies
Serious bleeding requires fresh blood/plasma
Warfarin crosses the placenta - do not use during pregnancy
NEED to MONITOR - PT and INR values (international normalized ratio)
Rivaroxaban
- MOA
- Pharmacokinetics
Inactivate factor Xa directly
Does not interact with ATIII and no thrombin activity
Quick action
Predictable pharmacokinetics - don’t need to monitor like Warfarin or heparins
Rivaroxaban
- Adverse effects
Bleeding can occur
Aspirin
MOA
Less commonly
Cyclooxygenase inhibitor
Irreversibly binds acetylates (COX1)
COX1 selective at lower doses, selectivity lost at higher doses.
Prevents TXA2 production in platelets reducing platelets aggregation.
Prevents thrombus and re-thrombus formation.
Adverse effects of aspirin
Bleeding
GI ulceration
Renal damage
Clopidogrel
MOA
Reduce platelet aggregation by inhibiting ADP pathways.
Act as P2Y12 receptor antagonist; prevent binding of ADP to receptors.
Can be synergistic with aspirin as it has different MOA.
Clopidogrel is irreversible inhibitor of receptor.
Pro drug - must be activated by the liver by P450 enzyme.
What is a fibrinolytic drug?
Rapidly lyse thrombi by activating plasmin from clot bound plasminogen.
Angioplasty may be superior to drugs though.
Tissue plasminogen Activator
MOA
Pharmacokinetics
Proteases that bind fibrin
Can preferentially activate clot bound plasminogen
Limits activation of systemic plasmin
Short half life - use CRI
Tissue plasminogen activator
Adverse effects
Reperfusion injury
Bleeding tendencies
Erythropoietin
What is it ?
Glycoprotein made by the kidneys in response to hypoxia
Stimulates proliferation and differentiation of red cell progenitors and release of reticulocytes.
Drug used in Anemia.
What is RhuEPO?
used primarily in chronic anemia, due to erythropoietin production in chronic renal failure.
Increase in hematocrit and hemoglobin in 2-4 weeks.
Iron supplementation is advised in EPO therapy.
Adverse effects of RhuEPO?
Hypertension and seizures are possible.
Therapeutic failure due to AB formation common.
