Antithrombotic Drugs Flashcards
Define Antiplatelet drugs, anticoagulant drugs, thrombolytics, and procoagulants:
Antiplatelet drugs - prevent platelet activation
Anticoagulant - prevent fibrin formation
Thrombolytics - cause fibrinolysis
Procoagulants - enhance coagulation
Name the ADP receptor antagonists/P2Y12 inhibitors:
- Clopidogrel
- Ticlopidine
- Prasugrel
- Ticagrelor
Name Anti-thromboxane drugs:
Aspirin
Name GPIIb/IIIa antagonists:
- Abciximab
- Eptifibatide
- Tirofiban
Name Phosphodiesterase Inhibitors:
- Dipyridamole
- Cilostazol
—Clopidogrel— Why it is used: ADR: DI: Boxed warning:
PRODRUG
— Used to reduce platelet activation to reduce aggregation. (Like in reducing the rate of MI/strokes in patients with MI/stroke history or established PAD/unstable angina/acute coronary syndrome
— ADR: bleeding, GI problems
— DI: proton pump inhibitors (interaction can diminish the therapeutic effect of clopidogrel)
— Boxed warning: patients who are homozygous for nonfunctional alleles of CYP2C19 gene are poor metabolizers of CYP2C19 and therefore should consider another P2Y12 inhibitor.
Why does the clopidogrel DI with PPIs diminish its therapeutic effect?
Clopidogrel is a pro drug and it is converted to the active compound by CYP2C19, PPIs especially omeprazole inhibit this enzyme and so this reduces the conversion of clopidogrel to its active form thus reducing its therapeutic effect.
—Prasugrel— Why is it used: ADR: DI: Boxed warning:
PRODRUG
— Used to reduce platelet activation and thereby reduces aggregation
— ADR: bleeding, CVS problems, GI problems
— DI: nothing (does not interact with PPIs as the main enzyme for this prodrug is CYP3A4)
— Boxed warning: should not be used in patients with active pathological bleeding or with a history of ischemic attack or stroke
—Ticagrelor— Why is it used: ADR: DI: Boxed warning:
NOT A PRODRUG but is also metabolized by CYP3A4 into an active metabolite (means it can be taken by patients who are poor metabloizers)
— Used as a secondary prevention of thrombotic events in conjunction with aspirin.
— ADR: Dyspnea, bleeding, headache, abnormal heart rhythm.
— DI: will interact with CYP3A4 inducers and inhibitors
— Boxed warning: avoid maintenance doses of aspirin
—Aspirin—(ASA)
Mechanism:
Why is it used:
ADR:
— Mechanism: irreversible inhibitor of COX1 and COX2 which inhibits the production of TXA2 in platelets and so reduces platelet activation/aggregation and inhibits clot formation
— Used as prophylaxis of MI/stroke and used in revascularization procedures
— ADR: at low doses no reactions while on higher doses GI irritation can happen and bleeding; on overdose salicylism can occur and tinnitus (ringing in ear) happens
—Abciximab— Administered: Why is it used: ADR: Drawbacks:
Monoclonal antibody fab — Administered IV — used to reduce the risk of restenosis — ADR: increase the risk of bleeding — Drawbacks: immunogenicity limits the use to a single administration
Name the major anticoagulant drugs:
- Heparin and heparinoids
- oral protease inhibitors
- warfarin (oral)
Heparin binds with anti thrombin and inactivates which proteases:
IIa VIIa IXa Xa XIa XIIa
—Heparin— When is it used: Advantage: ADR: Antidote for overdose:
— Used for treatment of venous thrombosis and pulmonary embolism/ used for patients with unstable angina or acute myocardial infraction/ during or after coronary angioplasty or stent placement/ during surgery for cardiopulmonary bypass
— Advantage: heparin does not cross the placenta
— ADR: HIT (heparin induced thrombocytopenia) and is caused by IgM and IgG antibodies against heparin platelet factor 4 and this causes a clot
— overdoes antidote: Protamine which forms an inactive complex with heparin that can be excreted
—LMWH—
Molecular weight:
Why is it used:
Example of LMWH:
Given subcutaneously
— contain a molecular weight of less than 8000 daltons.
— used because it inhibits Xa more selectively by activating ATIII
Examples: Enoxaparin/ Dalteparin/ Ardeparin/ Tinzaparin
What is the boxed warning of Enoxaparin?
Spinal hematoma during spinal/epidural injections (and can causing paralysis)
Pentasaccharides - fondaparinux
Very similar to LMWH
Advantage: HIT is very low
Oral protease inhibitors examples:
Dabigatran
Rivaroxaban
Apixaban
Endoxaban
—Dabigatran—
PRODRUG that is a direct inhibitor of thrombin (IIa)
Orally active anticoagulant which is not a vitamin K antagonist
— used in prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
— DI: P glycoprotein inducer decrease serum conc of dabigatran
—Rivaroxaban—
Oral anticoagulant which is not a vitamin K antagonist
Inhibits factor Xa independent of anti thrombin
— used in postop thromboprophylaxis in patients who have undergone total hip or knee replacement
— ADR: bleeding
—Warfarin—
ORAL anticoagulant
— Used to prevent the progression of acute DVT or pulmonary embolism, to prevent venous thromboembolism in patients undergoing orthopedic or gynecological surgery, to prevent systemic embolism.
— ADR: contraindicated in pregnant woman and spinal puncture
Synthesis of which Vit K-dependent coagulation factors are inhibited by warfarin?
II
VII
IX
X
Warfarin is metabolized by:
CYP2C9
In warfarin overdose we give:
Vitamin K administered PO or IV
And we monitor INR
Recombinant tPAs
Alteplase - selective to fibrin bound plasminogen
Reteplase - longer half life
Recombinant tPAs are less antigenic
For strokes which thrombolytic do we use?
Alteplase
NOT streptokinase
