Anti-platelet and anti-coagulant drugs Flashcards
What is Heparin’s Mechanism of action?
Catalyzes the anti-thrombin-protease “suicide substrate” reaction
- Inactivation of factor IIa is mediated by the formation of ternary complex heparin, ATIII, thrombin **unfractionated heparin
- LMWH-> inadequate to form ternary complex-> little antithrombin activity
How do we administer heparin?
- not oral
- Does not cross the placenta or accumulate in brest milk
- ** IV-> pts w/ active thrombosis or PE
- ** Activated partial thromboplastin time (aPTT) should be measured before next admin. of heparin to adjust the dose
- SubQ-> pts requiring low dose prophylaxis
- Antidote for excess heparin: Protamine sulfate
Adverse effects of heparin?
- Major bleeding-> incre. risk w/ aPTT > 2.5x norm
- Osteoporosis, vertebral fractures
- Heparin resistance* -> elevated factor VIII, antithrombin def, increased clearance, monitor w/ antiXa assay
- Heparin-induced thrombocytopenia (HIT)
a. ) immune-onset after 5-10 days, Abs present, thrombosis
b. ) non-immune, immediate onset, Abs present; no thromb
Describe the characteristics of Enoxaparin
- LMWH
- inhibit factor Xa
- longer half life (-4.5h)
- Less frequent dosing
- Increased bioavial when admin subQ-> no blood tests
- Less HIT-> but don’t give to ppl with HIT
When do we use Enoxaparin?
- Prevention of deep venous thrombosis in postop
- Tx of acute venous thromboembolic disease & acute coronary syndromes
Describe the characteristics of Fondaparinux
- LMWH
- Synthetic analog of the pentasaccharide binding sequence of heparin
- Pharmacokinetics: long 1/2 life: 17-21H
- Renal clearance
- SubQ
- No HIT
- No blood test
What are the adverse effects of LMWH?
-Severe uncontrolled HTN and bleeding
What are the Direct thrombin inhibitors?
Desirudin, Bivalirudin, Argatroban
What are the characteristics of Desirudin?
- Recombinant form of hirudin
- Independent of antithrombin III
- Reach and inactivate fibrin-bound thrombin to thrombi
- Does not cause thrombocytopenia
- t1/2-2 hours following subQ admin
- Renal clearance
When do we use Desirudin?
-DVT post elective hip replacement
Describe Bivalirudin
- synthetic peptide congener of hirudin
- short 1/2 life- 25 minutes
- renal and metabolic clerance
When do we use Bivalirduin?
-Coronary angioplasty, Patients w/ HIT
Describe Argatroban
- synth. deriv. of arginine
- blocks catalytic site of soluble and clot-bound thrombin
- admin. IV
- Used in pts w/ heparin-induced thrombocytopenia (HIT)
- 1/2 life: 40-50 minutes
- monitored by aPTT
Adverse effects of argatroban
- Hemorrhage
- Allergic reactions
- Prolongs PT-when used with Warfarin
What are the Oral anitcoagulants?
-Warfarin
Describe warfarin
- Binds vit. K reductase -> blocks 2,7,9,10 Vit. K dependent coag factors(procagulant factors) and (protein C and S-anticoagulant)
- Peaks 2-8 hours after an oral dose
- 1/2 life 25-60 hours
What VIt. K dependent coagulation factor is affected first by Warfarin and what effects can it have?
- Earliest inhibition in anticoagulant protein C (anticoagulant factor) -> moves into procoagulant state-> pro clotting (not what we want)
- Narrow therapeutic window-> monitor with INR/prothrombin time
What are the adverse effects of warfarin??
- Bleeding-> INR >4,
- Treat with vit K (delayed response)
- Birth defects + abortion (use heparin)
- Skin necrosis
What are the new direct oral anticoagulants?
Dabigatran (thrombin inhibitor)
-Xa inhibitors (Rivaroxaban, Apixaban, Edoxaban)
Dabigatran
Direct thrombin inhibitor
Rivaroxaban, Apixaban, Edoxaban
Thrombin inhibitor
What are the fibrinolytic drugs?
Ateplase (activase)
What is the MOA of ateplase?
Physiologically t-PA activates plasminogen to plasmin that is bound to fibrin of thrombus -> dissolution of the clot
Characteristics of Ateplase?
- recombinant tissue plasminogen activity
- 1/2 life 5 minutes in plasma
- IV bolus then infusion
- contraindications for pregnant women, uncontrolled HTN
When do we use Ateplase?
- acute MI
- Acute ischemic stroke
- PE
- central venous catheter occlusion
What are the anti-platelet agents?
-Aspirin, Clopidogrel, Prasgrel, Abciximab, Tirofiban, Eptifibatide
What is the MOA of aspirin?
- Cyclooxygenase (COX) inhibitor -> prevents the TXA2 from forming
- Platelets have no nucleus and cannot regenerate COX-> effects lasts the life of the platelet (7-10 days)
- Endothelial cells-> regenerate COX -> PGI2-> restoring anti-thrombtic effect
- Low dose -> selectively inhibit platelet COX, sparing endothelial COX
What do we use aspirin for?
- primary prophylaxis for MI
- 2ndary prevent for vascular events following heart disease
What are the adverse effects of aspirin?
-Bleeding, increase risk of peptic ulcer disease
What are the ADP receptor antagonists?
-Clopidogrel, Prasugrel, Ticarelor
Describe the MOA for the ADP receptor antagonists that end in -grel
-Irreversibly inhibits the binding of ADP to its receptor on platelets, inhibits platelet aggregation
Describe the MOA for Ticarelor
-Reversibly inhibits the binding of ADP to its receptor on platelets, inhibits platelet aggregation
Adverse effects for ADP receptor antagonists
- Bleeding
- Dual anti-platelet therapy: ADP inhibitor + aspirin
- Triple therapy: Oral anticoagulant + ADP inhibitor + aspirin
What are the platelet GP IIb/IIIa receptor blockers
-Abciximab, Tirofiban, Eptifibatide
Describe Abciximab and what it’s used for
- monoclonal ab directed against GPIIb/IIIa complex
- Used for coronary angioplasty and acute coronary syndrome
Describe Tirofiban and what it’s used for
-non-peptide analog main recognition seq of GPIIb/IIIa receptors -> occupies receptor inhibits binding
Eptifibatide
-Analog of the sequence -> mediates the binding of fibrinogen to the receptor -> occupies receptor inhibits binding
adverse effects of GP IIb/IIIa receptor blockers
Bleeding
