Cardio-Thromboembolitic Flashcards
What is the mechanism of action of thrombolytic drugs
Aka fibrinolytic drugs
-Activates the endogenous fibrinolytic system, resulting in the converting of plasminogen to plasmin and the breaking up of clots
What are the agents used in prosthetic heart valves
Diphyridamole with warfarin
What class of drug is dabigatran
Oral Direct thrombin inhibitor
*Oral Anticoagulants
What is the mechanism of action of the ADP receptor antiplatelet drugs
1-Blockers of ADP receptors results in continues AC activation
2- AC results in cAMP levels to remain high
3- High cAMP results in lack of platelet aggregation
What can be given to patients with heparin-induced thrombocytopenia (HIT) to reverse the effects of the heparin
Protamine sulfate
What are the pharmokenetics of Clopidogrel
-High variability as metabolized by CYP2C19 (some nonfunctional alleles in Asians,African Americans)
Which direct thrombin inhibitor can cause anaphylactic reactions
Lepirudin
What is the state of usage of the inhibitors of phosphodiesterase inhibitors as antiplatelet drugs
Used in conjunction with other agents
What is the mechanism of action for warfarin
Inhibits the reactivation of vitamin K by inhibiting the Vitamin K epoxide reductase (inhibits carboxylation of glutamate residues cia gamma-glutamyl carboxylase)
What class of drug is rivaroxaban
Oral Factor Xa inhibitor
*Oral Anticoagulants
What are the factors and proteins involved in the use of Warfarin
Factor 2, 7, 9, 10
What is the mechanism of action for Tirofiban
Targets the RGD sequence on the GP2b/3a sequence on platelets, which prevents aggregation
What class of drug is lepirudin
Direct thrombin inhibitors
*Parenteral Anticoagulants
What is the mechanism of action of abciximab
Targets the RGD sequence on the GP2b/3a sequence on platelets, which prevents aggregation
What class of drug is reteplase
Tissue type plasminogen activator
*Thrombolytic (fibrinolytic) drug
What class of drug is urokinase
Urokinase type plasminogen activator
*Thrombolytic (fibrinolytic) drug
What are the pharmacokinetics of warfarin
- Oral administration
- 100% bioavailability
- Delayed onset of action (12 hours), but long half life (36 hours)
What are the kind of thrombus forming in the low pressure veins and heart
Red thrombus
Which of the ADP receptor antiplatelet drugs are impacted by P450
-Clopidogrel
What class of drug is Warfarin
Oral Coumarin anticoagulants
*Oral Anticoagulants
What class of drug is edoxaban
Oral Factor Xa inhibitor
*Oral Anticoagulants
What class of drug is ticlopidine
ADP receptor blocker
*Antiplatelet
What is the disadvantage of using dabigatran
80% of renal excretion, so needs to be avoided in renal failure
What are the drawbacks of warfarin
- High variability
- Bleeding compilations
- requires INR monitoring
What class of drug is cilostazol
Inhibitors of phosphodiesterase
*Antiplatelet
What are the advantages of dabigatran
- No interactions with P450 drugs
- Approved antidote
What is the characteristics of binding for bivalirudin
Reversible inhibitor of thrombin
How do red thrombus form
-Forms in low pressure veins and the heart, resulting in platelet binding and aggregation, followed by fibrin tails with RBC presence
What are the advantages of warfarin
- Oral administration
- Long duration of action
- Drug clearance is independent of renal function
- Reversal of action is developed
What is the mechanism of action for argatroban
Directly binds at the thrombin active site
When is cilostazol primarily used
Treatment of intermittent claudication (impairment of walking due to pain, numbness, discomfort or standing)
What is the mechanism of action for high molecular weight heparin
Binds to both thrombin and antithrombin 3 (inactivates thrombin)
Binds to both factor Xa and antithrombin 3 (inactivates factor Xa)
What class of drug is clopidogrel
ADP receptor blocker
*Antiplatelet
What is the mechanism of action for lepirudin
Bivalent binding-directly binds to thrombin at the substrate recognition spot, as well as the active site
What class of drug is apixaban
Oral Factor Xa inhibitor
*Oral Anticoagulants
What is the mechanism of action for streptokinase
Binds to plasminogen and forms a complex, which converts it plasmin without being cleaved
What are the adverse effects of heparin
- Bleeding
- Heparin induced thrombocytopenia (HIT), which includes thrombosis
What is the mechanism of action of tPA
Cleaves plasminogen into plasmin, but requires fibrin
What is is the drug used to break a clot and what is the time frame it should be used
tPA, generally needs to be used within 3 hours of emboli stroke
What is the mechanism of pathogenesis of heparin-induced thrombocytopenia (HIT)
-Complex formation of heparin, IgG, platelet with PF4 (platelet factor 4) leading to thrombocytopenia, along with formation of thrombi
What class of drug is enoxaparin
Low molecular weight heparin, an indirect thrombin and factor Xa inhibitor
*Parenteral Anticoagulants
Which drugs tend to increased the prothrombin time
- Azoles
- Aspirin
- cephalosporins
- Hyperthyroidism
What is the main general function of thrombolytics
Destroying blood clots after they have formed to re-establish blood flow
What is the cause of the white thrombus
Forming in high pressure arteries as a result of the platelet forming on the damaged endothelium with little fibrin
What is the clinical use for the direct oral anticoagulants
- Prevention, treatment of thromboembolism
- Prevention of stroke in patients in atrial fibrillation
What is the mechanism of action of dabigatran
Direct thrombin inhibitor
What class of drug is alteplase
Tissue type plasminogen activator
*Thrombolytic (fibrinolytic) drug
Which patients population is less resistant to warfarin
Asian Americans
*Low dose haplotype VKORC1 (vitamin K epoxide reductase complex)
Which patient population is more resistant to warfarin
African Americans
*High does haplotype VKORC1 (Vitamin K epoxide reductase complex 1)
Clinically, how is fondaparinux different from heparin
- Does not inhibit thrombin formation
- Rarely induces HIT
- Not reversed by protamine sulfate
What are the agents used in prevention cerebrovascular ischemia
Diphyridamole with aspirin
What are the clinical indications for direct thrombin inhibitors
HIT
Coronary angioplasty
What are the pathological conditions associated with white thrombus
Local ischemia due to arterial occlusion, especially in the coronary arteries leading to MI and unstable angina
What class of drug is dalteparin
Low molecular weight heparin, an indirect thrombin and factor Xa inhibitors
*Parenteral Anticoagulants
What is the main general function of anticoagulants
Regulation in the synthesis of clots, primarily prevention in the venous system or heart (red thrombus)
What class of drug is abciximab
Platelet glycoprotein receptor
*Antiplatelet
What are the tests used to monitor patients on heparin
- Activated partial thromboplastin time (aPTT)
- Anti-Xa assay
What is the general mechanisms of action for indirect thrombin and factor Xa inhibitors
-Bind plasma serine protease inhibitor antithrombin 3
What is the mechanism of action for aspirin
Inhibition of cyclooxygenase and decreased TxA2 production
What class of drug is tenecteplase
Tissue type plasminogen activator
*Thrombolytic (fibrinolytic) drug
What class of drug is tirofiban
Platelet glycoprotein receptor
*Antiplatelet
What is the antidote in the case of dabigatran overdose
-Idarucizumab (directly binds to drug)
What are the adverse effects of the direct thrombin inhibitors
Bleeding, there is no antidote so should be used with caution
What is the mechanism of action of bivalirudin
Bivalent binding-directly binds to thrombin at the substrate recognition spot, as well as the active site
What class of drug is bivalirudin
Direct thrombin inhibitors
*Parenteral Anticoagulants
What class of drug is fondaparinux
Synthetic pentasaccharide, and indirect thrombin and factor Xa inhibitor
*Parenteral Anticoagulants
What are the kind of thrombus the form in the high pressure arteries
White, platelet rich thrombus
What class of drug is diphyridamole
Inhibitors of phosphodiesterase
*Antiplatelet
What is the mechanism of action for fondaparinux
Inhibits factor Xa and antithrombin 3
*no affects on thrombin
What class of drug is prasugrel
ADP receptor blocker
*Antiplatelet
What are the adverse effects of aspirin
- Peptic ulcer
- GI bleeding
What is the mechanism of action of Eptifibatide
Targets the RGD sequence on the GP2b/3a sequence on platelets, which prevents aggregation
What class of drug is streptokinase
Streptokinase preparations
*Thrombolytic (fibrinolytic) drug
What are the clinical uses for warfarin
- Used to prevent thrombosis or thromboembolism
- Atrial fibrillation
- Prosthetic heart valves
What is the main general function of antiplatelet drugs
Inhibits platelet function, primarily in the formation of white thrombi (arteries)
What class of drug is Aspirin
Inhibitor of thromboxane A2 synthesis
*Antiplatelet
Which enzyme is responsible for the dose variation in Caucasian patients
CYP2C9
What class of drug is eptifibatide
Platelet glycoprotein receptor
*Antiplatelet
What class of drug is ticagrelor
ADP receptor blocker
*Antiplatelet
How does fondaparinux act as a antithrombin 3 catalyst
Binds directly to antithrombin 3, which causes as a conformational change that increases the binding to factor Xa and its inactivation
The activated partial thromboplastin time (aPTT) looks at which pathway and factors
- Intrinsic and common pathway
- Evaluates serine proteases 2,9,10,11,12 (are affected by heparin)
What are the adverse affects of warfarin
- Teratogenic effects (bleeding and abnormal bone formation in fetus)
- Skin necrosis, infarction of breasts, intestine and extremities
- Osteoporosis
- Bleeding
What are the clinical uses for fondaparinux
- Prevention of DVT
- Treatment of acute DVT
- Treatment of a PE
What is the mechanism of action for edoxaban
Direct factor Xa inhibitor
What class of drug is tinzaparin
Low molecular weight heparin, an indirect thrombin and factor Xa inhibitors
*Parenteral Anticoagulants
What is the mechanism of action for low molecular weight heparin
Inhibits factor Xa with antithrombin 3
*No affect on thrombin
What are the advantages of direct oral anticoagulants
- Orally administered
- doesnt need to be monitored
- rapid onset
What class of drug is heparin sodium
Parenteral unfractionated heparin, an indirect thrombin and factor Xa inhibitors
*Anticoagulants
What is the clinical use for aspirin
-Primary and secondary Prevention of heart attack and vascular events (white thrombosis)
What is the characteristic of the binding of lepirudin
Irreversible binding to thrombin
What is the mechanism of apixaban
Direct factor Xa inhibitor
What can heparin be used to treat
- Protects against emboli stroke (red, fibrin rich), Pulmonary emboli
- Patients with DVTs, arrhythmias, other conditions with increased with red thrombi
- Prevention of emboli with surgery or hospitalized patients
What is the mechanism of action of rivaroxaban
Direct factor Xa inhibitor
What is the S-warfarin metabolized by
CYP2C9
What is the mechanism of action of the phosphodiesterase inhibitor antiplatelet drugs
1-Inhibits phosphodiesterase
2-cAMP levels remain high
3- cAMP levels prevent the platelet aggregation
What are the pathological conditions associated in red thrombus
Pain, swelling, embolism with potential for stroke
Which drugs tend to decrease prothrombin time
- Diuretics
- Vitamin K
- Hypothyroidism
- Barbituates
What are the disadvantages of direct oral anticoagulants
Excreted by kidneys, need to be monitored and dose adjustments
What is R-warfarin metabolized by
CYP3A4
What class of drug is argatroban
Direct thrombin inhibitors
*Parenteral Anticoagulants
