Pharm 23: Clots and bleeds Flashcards
How does aspirin thin the blood
Inhibits the synthesis of prostaglandins, thereby inhibiting the platelet granule release reaction and interfering with normal platelet aggregation.
Aspirin inhibits (enzymes)
COX 1/2 non selective
In platelets, an increase in the concentration of intracellular ____ leads to a decrease in platelet _____
In platelets, an increase in the concentration of intracellular cAMP leads to a decrease in platelet aggregability
Inhibitors of platelet phosphodiesterase decrease platelet aggregability by inhibiting __________
Inhibitors of platelet phosphodiesterase decrease platelet aggregability by inhibiting cAMP degradation
Dipyridamole MOA
platelet phosphodiasterase inhibitor
decreased platelet aggregation
Dipyridamole is administered with _________
Why?
Warfarin/aspirin
kinda weak
Dipyridamole side effect
Vasodilation leading to angina
Drugs that inhibit ADP-dependent platelet activation
clopidogrel
ticlopidine
prasugrel
aka thienopyridines
Ticlopidine indications
1) Secondary prevention of strokes when aspirin allergy
2)Post stent thrombosis prophylaxis (with aspirin)
Clopidogrel metabolism
Prodrug via P450
Clopidogrel indications
Secondary stroke prevention post MI
Clopidogrel dosing considerations
Loading dose to achieve effect then maintanance
Prasugrel use
Acute coronary syndromes during PCI
Cath lab drug
Prasugrel major AE cosideration
Dont give to stroke bc of head bleed risk
Ticagrelor MOA
competitive P2Y12 ADP receptor antagonist
Tricagelor use
Acute coronary syndromes
Tricagelor route
Oral with no hepatic activation needed
Eptifibatide MOA
GPIIb–IIIa receptor antagonist
Platelet inhibition
Abciximab MOA
Chimeric mouse–human monoclonal antibody directed against the human GPIIb–IIIa receptor.
Tirofiban MOA
nonpeptide tyrosine analogue that reversibly antagonizes fibrinogen binding to the platelet GPIIb–IIIa receptor.
Eptifibatide, tirofiban and abxcimab how to reveres
Abxicimab: give more platelets
Others: Wait
Vorapaxar MOA
protease-activated receptor 1 (PAR-1) antagonist one of two major thrombin receptors
Warfarine MOA
Epoxide reductase inhibitor
vitamin K cant regenerate
Warfarin dosing considerations
Delayed action takes many doses to reach effect
Warfarin kinetics
100% orally bioavailable, peak 1-4 hours, 99% albumin bound
Warfarin drug drug interactions
Inhibitted by P450 enzyme activators
Increased by P450 inhibittors or antibiotics (less vit K availability)
γ-carboxilated antiguaolant think
warfarin
Warfarin contraindications
Pregnancy (cross placenta and bleed fetus)
With warfarin monitor
PT/INR
Heparin MOA
Cofactor for antithrombin III
-it serves as a catalytic surface to which both antithrombin III and the serine proteases bind
-induces a conformational change in antithrombin III that makes the reactive site of this molecule more accessible to the attacking protease
LMW Heparin are more efficient in ___ and less efficient in _______.
More efficient: Catalyze factor Xa inactivation
Less efficient: catalyze inactivation of thrombin
Unfractionated heparin
Less selective.. catalyzes both thrombin and factor Xa inactivation
Heparin structure
Pentasacchiride structure… super acidic
fondaparinux
Binds antithrombin III to indirectly inhibit Xa
Heparin effect monitored via
aPTT
LMW heparin names
Enoxaparin
Dalteparin
Tinzaparin
Rivaroxaban and apixaban MOA
Direcltly inhibit factor Xa by competitive inhibition
do not require antithrobin III
Lepidurin MOA
Direct thrombin inhibitor
Heparin Induced Thrombocytopenia HIT MOA
Antibodies to hapten when heparin molecules bind to platelet. Platelets then removed by body
Desirudin use
DVT prophalaxis in hip replacement
HIT treatment
lepirudin
Bivalirudin MOA and use
Inhibits thrombin activity. Use in cath lab
Argatroban MOA and use
Thrombin inhibitor. Used for patients wtih HIT.
Biliary excretion, use with bad kidneys
No exosite activity
Dabigatran MOA and use
Oral direct thrombin inhibitor
Use in non valve afib, and as warfarin substitute for mechanical valve pts
Dabigratan mechanics /monitoring
Prodrug… does not need to be monitored
Recombinant activated protein C (r-APC) MOA and use
Used in septic shock by cleaving factors Va and VIIIa
Streptokinase moa and use
1) Forms complex with plasminogen, exposing active site
2) Now active, plasminogen cleaves other plasminogens to plasmin
STEMI and PE
t-PA MOA and use
Binds to fresh thrombus, causing fribinolysis. After binding, t-PA is conformationally changed and it can now activate plasminogen
Use in stroke, STEMI, PE
Tenecteplase vs tPA
More resistant to plasminogen activator inhibitor 1
Longer half life
Admin as single weight based bolus
Reteplase what to know
Re- use (2 boluses 30 min apart)
Protamine MOA and use
Chemical antagonist to heparin. used when too much heparin
Aprotinin MOA and use
Serine protease inhibitor: Plasmin, thrombin t-pa
not really used bc anaphylaxis