Pharm 23: Clots and bleeds

Question 1

How does aspirin thin the blood

Answer 1

Inhibits the synthesis of prostaglandins, thereby inhibiting the platelet granule release reaction and interfering with normal platelet aggregation.

Question 2

Aspirin inhibits (enzymes)

Answer 2

COX 1/2 non selective

Question 3

In platelets, an increase in the concentration of intracellular ____ leads to a decrease in platelet _____

Answer 3

In platelets, an increase in the concentration of intracellular cAMP leads to a decrease in platelet aggregability

Question 4

Inhibitors of platelet phosphodiesterase decrease platelet aggregability by inhibiting __________

Answer 4

Inhibitors of platelet phosphodiesterase decrease platelet aggregability by inhibiting cAMP degradation

Question 5

Dipyridamole MOA

Answer 5

platelet phosphodiasterase inhibitor

decreased platelet aggregation

Question 6

Dipyridamole is administered with _________

Why?

Answer 6

Warfarin/aspirin

kinda weak

Question 7

Dipyridamole side effect

Answer 7

Vasodilation leading to angina

Question 8

Drugs that inhibit ADP-dependent platelet activation

Answer 8

clopidogrel

ticlopidine

prasugrel

aka thienopyridines

Question 9

Ticlopidine indications

Answer 9

1) Secondary prevention of strokes when aspirin allergy
2)Post stent thrombosis prophylaxis (with aspirin)

Question 10

Clopidogrel metabolism

Answer 10

Prodrug via P450

Question 11

Clopidogrel indications

Answer 11

Secondary stroke prevention post MI

Question 12

Clopidogrel dosing considerations

Answer 12

Loading dose to achieve effect then maintanance

Question 13

Prasugrel use

Answer 13

Acute coronary syndromes during PCI

Cath lab drug

Question 14

Prasugrel major AE cosideration

Answer 14

Dont give to stroke bc of head bleed risk

Question 15

Ticagrelor MOA

Answer 15

competitive P2Y12 ADP receptor antagonist

Question 16

Tricagelor use

Answer 16

Acute coronary syndromes

Question 17

Tricagelor route

Answer 17

Oral with no hepatic activation needed

Question 18

Eptifibatide MOA

Answer 18

GPIIb–IIIa receptor antagonist

Platelet inhibition

Question 19

Abciximab MOA

Answer 19

Chimeric mouse–human monoclonal antibody directed against the human GPIIb–IIIa receptor.

Question 20

Tirofiban MOA

Answer 20

nonpeptide tyrosine analogue that reversibly antagonizes fibrinogen binding to the platelet GPIIb–IIIa receptor.

Question 21

Eptifibatide, tirofiban and abxcimab how to reveres

Answer 21

Abxicimab: give more platelets

Others: Wait

Question 22

Vorapaxar MOA

Answer 22

protease-activated receptor 1 (PAR-1) antagonist one of two major thrombin receptors

Question 23

Warfarine MOA

Answer 23

Epoxide reductase inhibitor

vitamin K cant regenerate

Question 24

Warfarin dosing considerations

Answer 24

Delayed action takes many doses to reach effect

Question 25

Warfarin kinetics

Answer 25

100% orally bioavailable, peak 1-4 hours, **99% albumin bound**

Question 26

Warfarin drug drug interactions

Answer 26

Inhibitted by P450 enzyme activators Increased by P450 inhibittors or antibiotics (less vit K availability)

Question 27

γ-carboxilated antiguaolant think

Answer 27

warfarin

Question 28

Warfarin contraindications

Answer 28

Pregnancy (cross placenta and bleed fetus)

Question 29

With warfarin monitor

Answer 29

PT/INR

Question 30

Heparin MOA

Answer 30

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

Question 31

LMW Heparin are more efficient in ___ and less efficient in _______.

Answer 31

More efficient: Catalyze factor Xa inactivation Less efficient: catalyze inactivation of thrombin

Question 32

Unfractionated heparin

Answer 32

Less selective.. catalyzes both thrombin and factor Xa inactivation

Question 33

Heparin structure

Answer 33

Pentasacchiride structure… super acidic

Question 34

fondaparinux

Answer 34

Binds antithrombin III to indirectly inhibit Xa

Question 35

Heparin effect monitored via

Answer 35

aPTT

Question 36

LMW heparin names

Answer 36

Enoxaparin Dalteparin Tinzaparin

Question 37

Rivaroxaban and apixaban MOA

Answer 37

Direcltly inhibit factor Xa by competitive inhibition do not require antithrobin III

Question 38

Lepidurin MOA

Answer 38

Direct thrombin inhibitor

Question 39

Heparin Induced Thrombocytopenia HIT MOA

Answer 39

Antibodies to hapten when heparin molecules bind to platelet. Platelets then removed by body

Question 40

Desirudin use

Answer 40

DVT prophalaxis in hip replacement

Question 41

HIT treatment

Answer 41

lepirudin

Question 42

Bivalirudin MOA and use

Answer 42

Inhibits thrombin activity. Use in cath lab

Question 43

Argatroban MOA and use

Answer 43

Thrombin inhibitor. Used for patients wtih HIT. Biliary excretion, use with bad kidneys No exosite activity

Question 44

Dabigatran MOA and use

Answer 44

Oral direct thrombin inhibitor Use in non valve afib, and as warfarin substitute for mechanical valve pts

Question 45

Dabigratan mechanics /monitoring

Answer 45

Prodrug… does not need to be monitored

Question 46

Recombinant activated protein C (r-APC) MOA and use

Answer 46

Used in septic shock by cleaving factors Va and VIIIa

Question 47

Streptokinase moa and use

Answer 47

1) Forms complex with plasminogen, exposing active site 2) Now active, plasminogen cleaves other plasminogens to plasmin STEMI and PE

Question 48

t-PA MOA and use

Answer 48

Binds to fresh thrombus, causing fribinolysis. After binding, t-PA is conformationally changed and it can now activate plasminogen Use in stroke, STEMI, PE

Question 49

Tenecteplase vs tPA

Answer 49

More resistant to plasminogen activator inhibitor 1 Longer half life Admin as single weight based bolus

Question 50

Reteplase what to know

Answer 50

Re- use (2 boluses 30 min apart)

Question 51

Protamine MOA and use

Answer 51

Chemical antagonist to heparin. used when too much heparin

Question 52

Aprotinin MOA and use

Answer 52

Serine protease inhibitor: Plasmin, thrombin t-pa not really used bc anaphylaxis