Cell and Tissue Bio 1

Term
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-Aspirin
-Clopidogrel (Plavix®) and Ticlopidine (Ticlid®)
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Terms in this set (29)
-Aspirin
-Clopidogrel (Plavix®) and Ticlopidine (Ticlid®)
Anti-platelet agents:
ØDirect Thrombin Inhibitors
Dabigatran (Pradaxa®)

Ø Antithrombin III Enhancers
-Heparin
-Low molecular weight heparins: Enoxaparin (Lovenox®)

ØSelective Factor Xa Inhibitors

Ø Vitamin K Antagonists
Warfarin sodium (Coumadin®)
Anticoagulants
Aspirin

Platelets cannot synthesize new COX enzyme (halted for the lifetime of the platelet (7-10 days)

given orally

Nonselective COX inhibitor
•COX-1 predominates in platelets. Also in GIT
•COX-2 presents at the site of inflamation

Reducing pain and fever
Reducing gastric mucous secretion
Thromboxane A2 Pathway Inhibitors
Clopidogrel- once daily, less toxic
Ticlopidine- twice daily, agranulocytosis

Given orally

Irreversibly inhibit the ADP receptor (for the life span of platelets)- stop aggregation

They are often prescribed for patients that have an aspirin allergy or are intolerant of aspirin (usually stomach upset).
ADP (Adenosin diphosphate) Receptor Pathway Inhibitors
activated by CYP2C19 ,and genetic variation in expression of this enzyme exists

•Avoid NSAIDs - may increase risk of bleeding

•should NOT be stopped for dental surgery, especially in those patients with recently placed cardiac stents
Clopidogrel side effects
Dabigatran (Pradaxa)

•Oral anticoagulant (came out with one dose )

Bind to the active sites on the thrombin molecule

NOT a substrate inhibitor or inducer of CYP

rapidly hydrolyzed by esterases

does not require blood monitoring

fewer DDIs, unaffected by food

•FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin
Direct Thrombin Inhibitors:
Heparin

More specific: Just Xa and IIa
Enoxoparin (Lovenox)
Dalteparin (Fragmin)
Anti Thrombin III enhancers
Rivaroxaban (Xarelto®)
Apixaban (Eliquis)

avoid anti fungals
Selective Factor Xa inhibitor
Warfarin (Calmodulin)

competitive inhibitor of vitamin K epoxide reductase

DDIs:
2C9 inhibitors
antibiotics
Vit K antagonist
Inducers of CYP2C19 will increase the effect of Plavix

Inhibitorsof CYP2C19 willdecreasethe effect of Plavix
Clopidogrel (Plavix) prodrug Activated by CYP2C19
Dabigatran (Pradaxa) is NOT a substrate of CYP enzymesDabigatran (Pradaxa) is _______________Inducers of CYP3A4 will decrease the effect of Xeralto Inhibitorsof CYP3A4 willincreasethe effect ofXeraltoXeralto is metabolized to inactive metabolites by CYP3A4Inducers of CYP3A4 will decrease the effect of Xeralto Inhibitorsof CYP3A4 will increasethe effect of XeraltoXeralto is metabolized to inactive metabolites by CYP3A4Inducers of CYP2C9 will decrease the effect of Warfarin Inhibitors of CYP2C9 will increase the effect of WarfarinWarfarin is metabolized to inactive metabolites by CYP2C9Immediate Skin, mucosalPlatelet/vascular disordersThrombocytopenia (low platelet count) -Increased consumption (DIC) -Decreased production (marrow disease, chemo) Defective platelet function (drugs most common cause) Von Willebrand disease (defective platelet adhesion) ******** Most common inherited bleeding disorder. *******Defects in Platelet Plug FormationDelayed Deep tissueCoagulation factor deficiencyTests the EXTRINSIC and final common pathways Prolongation in: -Liver disease -vitamin K antagonism (i.e. warfarin) and deficiency -Disseminated intravascular coagulation -Factor VII, X, V, II and fibrinogen defectProthrombin time (PT)Tests the INSTINSIC and common pathways Prolongation in: -Liver disease -Disseminated intravascular coagulation- Heparin therapy -Vitamin K antagonism -Factor XII, XI, IX, VIII, X, V, II, and fibrinogen defectActivated Partial Thromboplastin Time (PTT)Evaluate for fibrinogen and for inhibition of thrombin action Prolongation in: - Hypofibrinogenaemia - Heparin therapy - Disseminated intravascular coagulationThrombin TimePlatelet aggregation allows more light transmission than platelet suspension in PRP (platelet rich plasma)Light Transmission Platelet Aggregometry (LTA)Defective clot formation: Platelet plug Fibrin clot -Excessive fibrinolysis -Vascular fragilityCauses of Bleedinginherited deficiency of single clotting factor (hemophilia A or B) Acquired deficiency of multiple clotting factors -Liver disease - Vitamin K deficiency/warfarin -DIC (Disseminated intravascular coagulation) Circulating inhibitor -Antibody to factor VIII -Heparin Defective fibrin crosslinking (factor XIII deficiency - very rare)Defects in Fibrin Clot FormationDIC (Disseminated intravascular coagulation)Excessive FibrinolysisConsumption of platelet and clotting factors clotting factor deficiency excessive bleedingDIC (Disseminated intravascular coagulation)Inherited deficiency or dysfunction of von Willebrand factor • Defective platelet adhesion********** • Mild or moderate bleeding tendency in most patients • Diagnosis: Measure the amount of von Willebrand factor antigen in the blood, and platelet function analysis • Treatment: Desmopressin, Amicar, replacement therapiesVon Willebrand DiseaseInherited deficiency of factor VIII (Hemophilia A) or IX (Hemophilia B) • Sex-linked inheritance: almost all patients male • Bleeding into joints, soft tissues; mucosal/skin/CNS bleeding rare • Severity inversely proportional to factor level • Treatment includes injections of a clotting factor or plasma.HemophiliaDeficiency of factors II, VII, IX, X, protein C, protein S • Causes: -Decreased vitamin K intake -Decreased production of vitamin by gut flora (antibiotics) -Poor absorption - sprue, biliary obstruction, etcInhibition of vitamin K action (warfarin, certain antibiotics • Treatment: vitamin K (oral or parenteral); FFP (Fresh Frozen Plasma)Vitamin K DeficiencyPathophysiology: - Diminished synthesis of most clotting proteins and inhibitors -platelet sequestration ********* • Bleeding due to impaired fibrin formation and (in some cases) increased fibrinolytic activity • Treatment: FFP, platelets, AmicarLiver Disease