Drugs used in coagulation disorders Flashcards
1
Q
Antiplatelet drugs
A
- Inhibition of COX-1 (Aspirin)
- Inhibitors of phosphodiesterase 3 (Dipyridamole, Cilostazol)
- ADP receptors antagonists (Ticlopidine, Clopidogrel, Prasugrel)
- Glycoprotein IIb/IIIa receptor inhibitors (Abciximab, Tirofiban, Eptifibatide)
2
Q
Aspirin
A
- Block COX-1 –> inhibit thromboxane A2 synthesis (platelet aggregation stimulator) from arachidonic acid by irreversible acetylation of a serine
- Used to prevent further infarcts in patients that have had 1 or more MI, and reduce incidence of first infarcts
- Used to prevent TIA, ischemic strokes, and other thrombotic events
- Adverse effects; GI and CNS
3
Q
Clopidogrel, Ticlopidine, Prasugrel
A
- Irreversible inhibition of ADP receptor, thereby inhibit the activation of GP IIb/IIIa
- Prevent TIAs and ischemic strokes, especially in patients who can not tolerate aspirin
4
Q
Abciximab
A
- Reversible inhibits the binding of fibrin and other ligands to GP IIb/IIIa
- A monocona antibody
- Prevent restenosis after coronary angioplasty and used in acute coronary syndrome
5
Q
Eptifibatide and Tirofiban
A
- Reversible block GP IIb/IIIa
- Bind to the site that interacts with the arginine-glycine-aspartic acid sequence of fibrinogen
- Prevent restenosis after coronary angioplasty and used in acute coronary syndrome
6
Q
Dipyridamole and Cilostazol
A
- Increase intracellular cAMP by inhibiting cyclic nucleotide phosphodiesterase 3 –> decreased thromboxane A2 synthesis
- Coronary vasodilators, used to treat intermittent claudication
- Dipyridamole: used prophylactically to treat angina pectoris
- Cilostazol: treat Buerger disease, vascular sclerosis complicating DM, chronic cerebral ischemia
7
Q
Thrombolytic agents
A
- Forms of tissue plasminogen activator (t-PA) (Alteplase, Tenecteplase, Reteplase)
- Plasminogen activation (Urokinase)
- Plasminogen-complex (Streptokinase)
- Anisoylated plasminogen-streptokinase activator complex (APSAC) (Anistreplase)
8
Q
Alteplase, Reteplase, Tenecteplase
A
- Active tissue plasminogen activator (t-PA)
- Converts plasminogen to plasmin
- Results in hydrolyzing of fibrin –> breakdown and dissolution of clots
- Alteplase: IV, normal human plasminogen activator
- Reteplase, Tenecteplase: bolus doses, mutated form of human t-PA
9
Q
Thrombolytic agents; indication
A
- Used in emergency treatment of coronary artery thrombosis
- Better outcome in ischemic strokes
- Used in multiple PE
- Cerebral hemorrhage must be ruled out before use
10
Q
Streptokinase
A
- Combine with plasminogen. The complex converts plasminogen into plasmin
- IV infusion
- May cause allergic reactions
- Antibodies may neutralize its fibrinolytic properties
11
Q
Urokinase
A
- Directly converts plasminogen to plasmin
- Extracted from cultured human kidney cells
12
Q
Anistreplase
A
- Prodrug
- Slowly releases streptokinase-activated plasminogen
13
Q
Anticoagulants
A
- Antithrombin III activatiors (Heparin, Enoxaparin, Fondaparinux, Dalteparin)
- Direct thrombin inhibitors (Lepirudin, Biyalirudin, Argatroban)
- Vitamin K antagonist (Warfarin, Dicumarol)
14
Q
Heparin can be neutralized by…
A
Protamine
- Heparin is highly acidic and can be neutralized by basic molecules
15
Q
Mechanism of Heparin
A
- Bind to endogenous ATIII
- The heparin-ATIII complex combines with and irreversible inactivates thrombin (factor II) and factor Xa
- ATIII proteolysis factor II and Xa, 1000-fold faster when combine to heparin
16
Q
Differences between Heparin and LMWH
A
- Heparin weight 15,000-20,000, LMWH weight 2000-6000
- Heparin inhibit factor II and Xa, LMWH selectively inhibit factor Xa
- LMWH have higher bioavailability and longer duration of action
- Heparin is monitored with aPTT, LMWH is not reliably measured
- Heparin is administrated IV or subcutaneously, LMWH is administrated subcutaneously
- Heparin cause moderate transient thrombocytopenia and osteoporosis when long-term therapy
17
Q
Heparin; indications
A
- Treatment of DVT, PE, and acute MI
- Used in combination with thrombolytics for revascularization
- Used in combination with GP IIb/IIIa inhibitors during angioplasty and placement of coronary stents
- Prophylactically to prevent postoperative DVTs
- Anticoagulant drug of choice in pregnancy
18
Q
Anticoagulants
A
- Antithrombin III activatiors (Heparin, Enoxaparin, Fondaparinux, Dalteparin)
- Direct thrombin inhibitors (Lepirudin, Biyalirudin, Argatroban, Dabigatran etexilate)
- Vitamin K antagonist (Warfarin, Dicumarol)
19
Q
Mechansim of direct thrombin inhibitors
A
- Lepirudin and Bivalirudin bind simultaneously to the active site of thrombin and to thrombin substrates
- Argatroban bind solely to thrombin
- Bivalirudin also inhibit platelet activation
- Monitored with aPTT (dabigatran etexilate does not require INR)
20
Q
Direct thrombin inhibitors; indications
A
- Lepirudin and Argatroban; used as alternatives to heparin in patients with heparin-induces thrombocytopenia
- Bivalirudin used in combination with Aspirin during percutaneous transluminal coronary angioplasty
- Dabigatran etexilate approved for prevention of stroke and systemic embolism in patients with AF
21
Q
Vitamin K antagonists; mechanism
A
- Site of action: liver
- Interfere with the normal post translational modification of clotting factor that requires vitamin K; II, VII, IX and X
- Prevent -carboxylation by inhibiting vitamin K epoxide reductase
- The factor is produced with diminished activity (10-40% of normal)
- Monitored with the prothrombin time (PT)
22
Q
Warfarin; indications
A
- Used to prevent progression or recurrence of acute DVT or PE after initial Heparin treatment
- Used to prevent venous thromboembolism during orthopedic or gynecologic surgery
- Used prophylactically in patients with acute MI, prosthetic heart valves, and chronic AF
- Contraindicated in pregnancy - can cause bone defect and hemorrhage
23
Q
Drugs used to treat bleeding disorders
A
- Vitamin K deficiency (Phyotonadione)
- Hemophilia (factor VIII and IX)
- Inhibiton of plasminogen activation (Aminocaproic acid, Tranexamic acid)
- Plasmin inhibitor (Aprotinin)
