Unit 05: Thromboembolic Disease Flashcards
What are thombembolic diseases?
- encompasses two interrelated conditions from similar pathologies
- involves thrombus (formation of a blood clot) and emboli formation (detached travelling intravascular mass
*thrombeombolism = blood clot that pbstructs a blood vessel and later beomes disloged and migrates in the body
what is the difference between a red and white thrombus
red = fibrin rich, containing a large number of RBCs and typically occurs in venous vessels
- White = platelet rich and usually found in arterial vessels
-
descirbe the pathogenesis of thrombosis
- requires the presence of various prothrombic factors
- can be released due to local vessel injury, circulatory stasis or altered blood coagulability - namely hyperactivity of hemostatic mechanisms (hypercoagulability) or hyperactivity of fibrinolytic mechansims
what are the main classes of drugs for treatment of thromboembolic disease
anticoagulants, antithrombotic drugs and fibrinolytic drugs
what are systemic anticoagulants?
- ideally should prevent pathologic thrombosis, limit reperfusion injury, allow for a normal response to vascular injury and limit bleeding
what is Heparin
- mixture of sulfonated mucopolysaccharides (or glycosaminoglycans = long unbrached polysaccharides)
- widely used anticoagulant
- isolated from mast cells in bovine lung or procine GI mucosa - usually stored in secretory granules
how does heparin work?
- enhances or accelerates (approx 100x fold) the action of antithrombin III (AT-III) which forms a heparin AT III complex
- AT III inhibits activated clotting factors, especially thrombin (IIa) and factor Xa by means fo irreversible binding
onset of action of heparin and averse effects
heparin has rapid onset - usefula cute anticoagulant
- oral version usually taken concurrently
*keparin will only prevent new thrombus formation will not lyse an eisiting thrombus
- adverse effects = increase bleeding tendencies and possible thrombocytopenia
what can be ued for overdose from heparin
protamine sulfate
how should patients taking haparin be monitored?
- activated partial thromboplastin time (aPTT)
- measures the anticoagulant effect
what is heparin used to treat?
- primarily for initial treatment of thrombosis and thromboemolic disease
can also be used for venous thrombosis, pulmonary embolism, unstable angina, atrial fibrillation, acute myocardial infarction and various cardiovascular surgeries
what is enoxaparin
aka lovenox
- low mol weight heparin that is fractioned from standard unfractionated heparin
- anticoagulant no used more commonly due to advantages over unfractionated heparin
- fewer bleeding tendencies, less risk of thrombocytopenia and imporved pharmacokinetics like longer 1/2 life
what is warfarin
aka coumadin
- oral anticoagulant (injectible formulas also available
- antagonises the actions of vitamkin K to reduce clotting factors (II, VII, IX and X)
- used as chronic preventative anticoagulant therapy
- dosing usually begins w/ heparin administration
how are indiivduals on warfarin monitored?
- using international normalized ratio (INR) as opposed to a PTT (used for those on heparin)
- tests for patients prothombin (PT) measured over average PT for the lab
what toxicities are associated with warfarin
- bleeding tendencies which cna be combated with vitamin K1
- series bleeding however requires fresh blood and plasma transfusion
*warfarin crosses the placenta therefore it should nto be taken during pregnancy- heparin does not cross so should be taken instead
what are antithombotic drugs
target platelet activators -> reduce formation of blood clots
- can act on platelt membrane or produced within granules and act on the membrane once they are released
- can also be produced and act within platelet itself
what is collagen
- antithrombotic drug
- agents outside of the platelet that act on the platelet membrane
what is thrombin
- antithrombotic drug
- agents outside of the platelet that act on the platelet membrane
what is ADP, 5-HT and Tx A2
produced within the granules and act on the platelet membrane once they are released
what are cyclooxygenase cAMP, cGMP and calcium ions used for
antithrombotic drugs
-produced in the platelet and act within the platelet itself
what is aspirin
cyclooxygenase inhibitor
- coomonly used as an antiplatelet drug
- irreversibly binds and acetylates cyclooxygenase-1 which prevents TxA2 production in platelets and reduces platelet aggregation
- *other NSAIDs can also inhibits cyclooxygenase-1 but are not irrevesible and therefore have a shorter duration of action
- prevents thrombus formation as re-thrombosis formation which can contribute to myocardial infarcts, stroke and peripheral vascular disease
adverse effects of aspirin
gastrointestinal ulceration, renal damage and bleeding tendencies
what is clopidogrel
- ADP inhibitor to treat thrombosis
- reduced paltelet aggregation by inhibiting ADP pathways
- act as P2Y12 (found on surface ofpaltelets) receptor antagonists and prevent bindign of ADP to receptors
- actions might also be synergistic with aspirin as they work through different mechanisms of aciton
*prodrug needs to be acivated by CYP 250
*ADP inhibits are indicated to reudce or prevent the recurrence of strokes, myocardial infracts in affetced individuals
*considered safe
what is ticlopidine
aka ticlid
- ADP inhibitor to treat thrombosis
- reduced paltelet aggregation by inhibiting ADP pathways
- act as P2Y12 (found on surface ofpaltelets) receptor antagonists and prevent bindign of ADP to receptors
- actions might also be synergistic with aspirin as they work through different mechanisms of aciton
*prodrug needs to be acivated by CYP 250
*ADP inhibits are indicated to reudce or prevent the recurrence of strokes, myocardial infracts in affetced individuals
*considered safe
what is glycoprotein IIb/IIa
- platlet surface integrin receptor for fibrinogen and von willebran factor
- PLA2 (activated by TxA2) and platelet glycoprotein VI (GPVI: activated by collagen)
- subsequently activate this integrin receptor which binds and anchors paltelets to each other via fibrinogen and to exposed vessel matric via con vollebran factor
- inhibtsi the receptor so used as antithrombotic drug
what is Abciximab
aka ReoPro
- Glycoprotein Iib/Iia receptor antagonist that acts as platelet aggregation inhibitro
- Indicated in percuraneous angioplasty that is associated with coronary thrombosis
- Similar to toher antithrombotic drugs the major toxicity = bleeding tendencies
what are fibrinolytic drugs
rapidly lyse thrombi by activating plasmin from plasminogen
-
what is tissue plasminogen activator
aka t-PA (Alteplase)
- serine protease invovled in the breakdown of a clot
- bidns fibrin and preferentially activates clot-bound plasminogen and limits activation of systemic plasmin
- T-PA has fairly short half-life which necessitates delivery via constant infusion
- can be used to treat coronary thrombosis in actue mycardial infraction, deep venous thrombosis, stroke and pulmonar embolism
- toxicites are also bleeding tendencies
