Anticoagulant, Antiplatelet, and Thrombolytic Drugs

Question 1

Three major groups

Answer 1

Anticoagulants: Disrupt the coagulation cascade, thereby
suppressing the production of fibrin
u Antiplatelets: Inhibit platelet aggregation
u Thrombolytics: Promote lysis of fibrin, causing dissolution of thrombi

Question 2

Heparin and Heparin Derivatives

Answer 2

u Preferred anticoagulant during pregnancy and
when rapid anticoagulation is required u Pulmonary embolism (PE)
u Stroke evolving
u Massive deep vein thrombosis (DVT)
u Open heart surgery
u Renal dialysis
u Low-dose therapy postoperatively
u Disseminated intravascular coagulation (DIC) u Adjunct to thrombolytic therapy

u Adverse effects u Hemorrhage
u Heparin-induced thrombocytopenia (HIT) u Hypersensitivity reactions
u Contraindicated
u Thrombocytopenia
u Uncontrollable bleeding
u During and immediately after surgery of the eye, brain, or spinal cord
u Antidote for overdose (OD): Protamine sulfate u Activated partial thromboplastin time (aPTT)

Question 3

Low-Molecular-Weight (LMW) Heparins

Answer 3

u Heparin preparations composed of molecules that are shorter than those found in unfractionated heparin
u Therapeutic uses
u Prevention of DVT after surgery
u Including replacement of hip, knee
u Treatment of established DVT
u Prevention of ischemic complications
u Patients with unstable angina, non–Q-wave myocardial
infarction (MI), and ST-elevation MI (STEMI)

u Administered subQ
u Dosage based on body weight
u Antidote for toxicity: Protamine sulfate
u Costs more than unfractionated heparin
u Does not require monitoring; can be given at home u Adverse effects and interactions
u Bleeding (but less than with unfractionated heparin)
u Immune-mediated thrombocytopenia
u Severe neurologic injury for patients undergoing spinal puncture or spinal epidural anesthesia

u In the United States, three LMW heparins are available: u Enoxaparin
u Dalteparin u Tinzaparin

Question 4

Warfarin, an Oral Anticoagulant

Answer 4

u Originally discovered when cattle were observed ingesting spoiled clover silage
u Used as rat poison
u Failed suicide attempt with large dose
brought renewed clinical interest u Clinical use
u Oral anticoagulant with delayed onset
u Vitamin K antagonist
u Blocks biosynthesis of factors VII, IX, and X and prothrombin

Therapeutic uses
u Not useful in emergencies
u Long-term prophylaxis of thrombosis
u Prevention of venous thrombosis and associated pulmonary embolism
u Prevention of thromboembolism (in patients with prosthetic heart valves)
u Prevention of thrombosis during atrial fibrillation

u Monitoring treatment
u Prothrombin time (PT)
u International normalized ratio (INR)
u Adverse effects
u Hemorrhage (vitamin K for toxicity)
u Fetal hemorrhage and teratogenesis from use during pregnancy
u Use during lactation u Other adverse effects

u Drug interactions
u Drugs that increase anticoagulant effects u Drugs that promote bleeding
u Drugs that decrease anticoagulant effects u Heparin
u Aspirin
u Acetaminophen

u Warfarin overdose u Vitamin K
u Dietary vitamin K: Mayonnaise, canola oil, soybean oil, and green leafy vegetables
u Contrasts between warfarin and heparin

Question 5

Dabigatran etexilate

Answer 5

Direct inhibition of thrombin (unlike heparin, which enhances the activity of antithrombin)
u Dabigatran etexilate: Oral prodrug that undergoes conversion to dabigatran
u Advantages of dabigatran: Does not require monitoring of anticoagulation, little risk of adverse interactions, same dose can be used for all patients regardless of age or weight

u Therapeutic uses
u Atrial fibrillation
u Adverse effects u Bleeding
˜ No specific antidote to reverse dabigatran-related bleeding
˜ Gastrointestinal (GI) disturbances

Question 6

Hirudin analog: Bivalirudin [Angiomax]

Answer 6

Direct Thrombin Inhibitors

u Prevents clot formation (combined with aspirin) in patients with unstable angina undergoing coronary angioplasty
u Mechanism of action
u Facilitates the actions of antithrombin
u Prevents conversion of fibrinogen to fibrin u Prevents activation of factor XIII
u Adverse effects u Bleeding
u Back pain
u Nausea, headache

Question 7

Desirudin [Iprivask]

Answer 7

u Indicated for prevention of DVT in patients undergoing
elective hip replacement surgery u Adverse effect
u Bleeding

Question 8

Argatroban

Answer 8

u IV anticoagulant
u Direct inhibition of thrombin
u Indicated for prevention of DVT in patients undergoing
elective hip replacement surgery
u Prophylaxis and treatment of thrombosis in patients with HIT

Question 9

Rivaroxaban [Xarelto]

Answer 9

Produce selective inhibition of factor Xa

u Binds directly with factor Xa to cause inactivation
u Oral
u Prevention of DVT and PE after total hip or knee replacement surgery
u Prevention of stroke in patients with atrial fibrillation
u Treatment of DVT and PE unrelated to orthopedic surgery

Question 10

Apixaban [Eliquis]

Answer 10

Selective inhibition of factor Xa
u Oral
u Inhibits free and clot-bound factor Xa, as well as prothrombinase activity
u Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation

Question 11

Antithrombin (AT)

Answer 11

Endogenous compound that suppresses coagulation, primarily by inhibiting thrombin and factor Xa
u Used to prevent thrombosis in patients with inherited AT deficiency
u Two preparations, marketed as ATryn and Thrombate III

Question 12

Aspirin (ASA)

Answer 12

Therapeutic uses u Ischemic stroke
u Transient ischemic attack (TIA) u Chronic stable angina
u Unstable angina
u Coronary stenting
u Acute MI
u Previous MI
u Primary prevention of MI

Adverse effects u Bleeding
u GI bleeding and hemorrhagic stroke
u Enteric-coated tablets may not reduce the risk of GI
bleeding

Question 13

Clopidogrel [Plavix]

Answer 13

u Therapeutic uses
u Block P2Y12 ADP receptors on the platelet
surface, preventing ADP-stimulated aggregation
u Prevents blockage of coronary artery stents
u Reduces thrombotic events in patients with acute coronary syndromes
u Prevents stenosis of coronary stents; also for secondary prevention of MI, ischemic stroke, and other vascular events
u Adverse effects similar to those of aspirin u Use with caution in combination with other
drugs that promote bleeding

Question 14

Abciximab [ReoPro]

Answer 14

Binds to platelets in the vicinity of GP IIb/IIIa receptors, thereby preventing the receptors from binding fibrinogen
u Used in conjunction with aspirin and heparin
u Approved for IV therapy of ACS and for patients undergoing
PCI
u Can accelerate revascularization in patients undergoing thrombolytic therapy for acute MI
u Antiplatelet effects persist for 24 to 48 hours after the infusion is stopped

Question 15

Eptifibatide [Integrilin]

Answer 15

u Small peptide that causes reversible and highly selective inhibition of GP IIb/IIIa receptors
u ACS
u Patients undergoing PCI
u Antiplatelet effects reverse within 4 hours of stopping the infusion

Question 16

Tirofiban [Aggrastat]

Answer 16

Selective and reversible inhibition of GP IIb/IIIa receptors
u Used to reduce ischemic events associated with ACS and PCI
u Platelet function returns to baseline within 4 hours of stopping the infusion
u Bleeding is the primary adverse effect
u Risk of bleeding can be increased by other drugs that
suppress hemostasis

Question 17

Thrombolytics: Alteplase (tPA)

Answer 17

u Binds with plasminogen to form an active complex
u Alteplase-plasminogen complex then catalyzes the conversion of other plasminogen molecules into plasmin, an enzyme that digests the fibrin meshwork of clots

u Therapeutic uses
u Myocardial infarction
u Ischemic stroke
u Massive pulmonary emboli

u Adverse effects
u Bleeding
u Risk for intracranial bleeding higher than with streptokinase
u Whole blood or blood products (packed red blood cells, fresh- frozen plasma)
u Aminocaproic acid [Amicar] u Fever
u Advantages
u Does not cause allergic reactions u Does not induce hypotension