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d. Aspirin
Anticoagulant, except
a. Heparin
b., Warfarin
c. Dalteparin
d. Aspirin
b. Argatroban
A direct thrombin blocker
a. Dalteraparin
b. Argatroban
c. Dipyridamote
d. Heparin
a. Idarucizumab
Antidote for dabigatran toxicity
a. Idarucizumab
b. vitamin K
c. protamine sulfate
d. fresh plasma
a. cilostazole
A drug used to treat intermittent claudication
a. cilostazole
b. hydralazine
c. nitroglycerin
d. aspirin
c. abciximab
GP2b/GP3a blocker
a. Nestiride
b. aspirin
c. abciximab
d. enoxaparin
von Willebrand factor
When the vascular endothelium is damaged, the exposed collagen binds to what factor?
TXA2
ADP
Serotonin
Activating platelets can can release the aggregation mediators:
Synthesis of TXA,
Release of platelet granules,
Activation of the GPIIB/GPIIIA receptors
Mediators evoke intracellular Ca+2 release. Elevated Ca2+ causes:
Fibrinogen
GPIIB/GPIIIA binds to a receptor to further solidify the platelets together.
Injury to blood vessel → Vasospasm (vasoconstriction) → platelet plug formation → fibrin clot formation → fibrinolysis
NORMAL HEMOSTASIS:
Thrombus
clot that adheres to a vessel wall
Thrombosis→ blood clot in the blood vessel
ischemic stroke
Thrombus blockage in the brain
heart attack
Thrombus blockage in the heart
Embolus
intravascular clot that float in the blood
Pulmonary embolism
Fibrin
stronger clot
Aspirin
Dipyridamole
Cilostazol
Adenosine Diphosphate (ADP) inhibitors
GP-IIb/GP-IIIa Antagonists
Vorapaxar
Anti-platelets
Aspirin
MOA: inhibits platelet aggregation by blocking the synthesis of Prostacyclin (PGI2) & Thromboxane (TXA2)
Prevention of thrombosis, Prevention of second attack of MI
Low dose
At __ dose, Aspirin can selectively inhibit the synthesis of TXA2
Dipyridamole
vasodilator & Weak antiplatelet drug
combined with aspirin (+ anti-platelet act)
MOA: blocks platelet uptake of adenosine = dec platelet aggregation
Use: vasodilator during myocardial perfusion imaging (Thallium imaging), stroke prevention
Cilostazol
(antiplatelet + vasodilator)
MOA: inhibits PDE3 → decrease degradation of cAMP
Result: inc cAMP = dec platelet agrregation
Use: treatment of intermittent claudication (pain and weakness in a limb)
Adenosine Diphosphate (ADP) inhibitors
MOA: block platelet ADP P2Y12 receptors
Result: decrease GP2B/GP3A receptor activation → no platelet-platelet aggregation
Clopidogrel
Prasugrel
Irreversible Adenosine Diphosphate (ADP) inhibitors
Cangrelor
Ticagrelor
Reversible Adenosine Diphosphate (ADP) inhibitors
GP-IIb/GP-IIIa Antagonists
MOA: block GP2B/GP3A receptor (adhesion R)
Result: decrease cross-linking of platelets by fibrinogen = dec platelet-platelet aggregation
Abciximab
Tirofiban
Eptifibatide
GP-IIb/GP-IIIa Antagonists drugs:
Abciximab
first platelet GP-2b/3a antagonist to be developed
Eptifibatide
a GP-IIb/GP-IIIa that is a cyclic heptapeptide from rattlesnake venom
Vorapaxar
protease-activated receptor-1 (PAR-1) antagonist
approved for patients with a history of MI
Intrinsic Pathway
activation is inside
slower, but efficient
starts at activation factor XII → XI → IX → VIII → X → Fibrin
Extrinsic Pathway
needs tissue factor (for clotting factor)
needs activator something outside
faster cascade' less efficient
starts at activation factor III → VII → X → Fibrin
Factor X
Common factor pathway
Warfarin
Vitamin K antagonists (inhibits factors IX, X, VII, II)
Inhibits the synthesis of proteins C and S (endogenous anticoagulants)
factors IX, X, VII, II
Warfarin inhibits the factors:
transient pro-coagulation effect
Initial effect of Warfarin:
Low MW Heparin
If there’s a transient pro-coagulation effect, add __ until anticoagulant effect has developed
pregnant woman
Warfarin is C/I to:
Phytonadione (Vit.K), Fresh Plasma, Factor IX concentration
Warfarin toxicity antidote:
Warfarin
Heparin and Related Drugs
Active Factor X inhibitors (-xaban)
Direct Thrombin Inhibitors (Heparin Alt)
Anti-Coagulants:
Heparin
safe to pregnant women
MOA: potentiates
immediate onset (parenteral)
bleeding
Heparin’s Toxicity:
Protamine Sulfate
Heparin toxicity antidote:
aPTT
Heparin is measured with:
INR
Warfarin is measured with:
heparin induced thrombocytopenia
A/E Heparin:
direct thrombin inhibitors
Alternative for Heparin
Low MW Heparin
Dalteparin, Enoxaparinn
Inactivate Xa
Less affinity to thrombin
aPTT does not need to be monitored
Fondaparinux
more selective inhibitor of Xa
does not affect thrombin
direct thrombin inhibitors
MOA: directly inhibits IIa
Based on protein present in saliva of medicinal leech
Use: if px has HIT
Toxicity: Bleeding
Idarucizumab
direct thrombin inhibitors toxicity antidote:
Argatroban
Bivalirudin
Dabigatran
direct thrombin inhibitors:
Argatroban
Tx for prophylaxis and treatment of thrombosis in patients with HIT
Dabigatran
1st oral direct thrombin inhibitor
alternative to warfarin for patients who have been poorly controlled or not well monitored
Apixaban, Edoxaban, Rivaroxaban
Active Factor X inhibitors:
THROMBOLYTIC DRUGS
Dissolve clot
Use: Acute MI
MOA: (+) tPA (an enzyme used to convert plasminogen → plasmin; dissolves clot)
Aminocaproic acid
Thrombolytic drugs toxicity antidote:
Urokinase
Streptokinase
1st Generation THROMBOLYTIC DRUGS
Alteplase
Reteplase
Tenecteplase
2nd Generation THROMBOLYTIC DRUGS
ASA + Clopidogrel
GPIIb/GIIIa blockers
Tx for Unstable angina & Non-STEMI
Thrombolytic, LMWH, ASA
Tx for STEMI
LMWH, ASA
Tx for Acute Thrombolytics
Clopidogrel, ASA + Dipyridamole
Tx for Prophylaxis
Thrombolytics, LMWH
Tx for Pulmonary Embolism