Pharmacology - ACS (Acute Coronary Syndrome)

Question 1

name 2 different classes of drugs used for ACS

Answer 1

antiplatelets
fibrinolytics

(also 2 miscellaneous - dipyridamole and cilostazol)

Question 2

name 3 classes of antiplatelet agents used for ACS

Answer 2

aspirin
adenosine receptor inhibitors
GpIIb/IIIa inhibitors

Question 3

hemostasis is a balance of what 2 things

Answer 3

blood loss and thrombosis

Question 4

what are zymogens

Answer 4

inactive enzymes. activated when balance needs to be maintained.

ie - balance between blood loss and thrombosis

Question 5

define thrombosis

Answer 5

blood clots in vessels

Question 6

“white clots” are also called…

Answer 6

arterial clots

Question 7

atherosclerosis really only causes what kind of clots

Answer 7

ARTERIAL

Question 8

2 types of venous clots

2 complications of arterial clots

Answer 8

venous – DVT, PE

arterial - heart attack, stroke

Question 9

fibrinolytics degrade ___

Answer 9

fibrin

Question 10

antiplatelets inhibit platelet ___ or ____

Answer 10

activation or aggregation

Question 11

as platelets become activated, what do they do?

Answer 11

they release chemical mediators that promote AGGREGATION

(ie - ADP)

Question 12

true or false

the clotting cascade is a positive feedback loop

Answer 12

true

Question 13

how are zymogens activated

Answer 13

proteases break them to activate them

Question 14

fibrin is the main meshwork of a clot

how is it produced

Answer 14

from fibrinogen

Question 15

name 3 mediators that activated platelets secrete to promote aggregation

Answer 15

ADP TXA2 serotonin

these bind to receptors on adjacent platelets to promote aggregation

Question 16

true or false

normal endothelial cells (not injured) release PGI2

Answer 16

true

Question 17

what is the ligand for GpIa receptor on platelets

Answer 17

collagen

Question 18

what is the ligand for Gp Ib receptor on platelets

Answer 18

von willebrand factor

Question 19

what is the ligand for IIb / IIIa (integrin) receptor on platelets

Answer 19

fibrinogen, macromolecules (ADP)

Question 20

name 3 classes of antithrombotics

Answer 20

anticoagulants
antiplatelets
fibrinolytics

Question 21

what does t-PA stand for and what drug is it

Answer 21

tissue plasminogen activator

alteplase

Question 22

how does plasmin affect fibrin

Answer 22

ultimately, plasmin will decrease fibrin levels because it inhibits fibrinogen (activator of fibrin)

and also breaks down fibrin clots themselves

Question 23

true or false

plasmin is an enzyme that causes blood to clot

Answer 23

FALSE - breaks clots
by inhibiting fibrinogen and breaking down fibrin clots

Question 24

true or false

streptokinase causes blood to clot

Answer 24

FALSE

dissolves clots by activating plasminogen, which activates plasmin

Question 25

what does urokinase do

Answer 25

dissolves blood clots by converting plasminogen into plasmin

Question 26

what is the fibrin-specific protease that digests fibrin and thus breaks down clots?

Answer 26

plasmin

Question 27

what is the inactive form of plasmin

Answer 27

plasminogen

Question 28

true or false plasmin and alteplase both break down clots

Answer 28

true

Question 29

what activates plasminogen?

Answer 29

t-pa (secreted by endothelial cells)

Question 30

name 2 inhibitors of t-pa and ultimately inhibitors of plasmin formation

Answer 30

a2-antiplasmin plasminogen activator inhibitor

Question 31

what is DIC (disseminated intravascular coagulation) 3 drugs that can be used. name 1 thing that inhibits and is used in the case of bleeding

Answer 31

when the coagulation and fibrinolytic systems are pathologically activated due to something like massive tissue injury, cancer, sepsis, etc clots basically form everywhere and it's very dangerous drugs - t-pa, urokinase, streptokinase used to reverse if bleeding - aminocaproic acid

Question 32

name 3 fibrinolytic drugs

Answer 32

t-pa (recombinant alteplase) urokinase and streptokinase (not used a lot)

Question 33

true or false alteplase can be given PO

Answer 33

FALSE - it's a protease (enzyme) cannot be given PO - given IV

Question 34

alteplase is a ___ protease

Answer 34

serine

Question 35

true or false alteplase is highly specific for plasminogen that is FIBRIN BOUND

Answer 35

true

Question 36

true or false alteplase has a short half life

Answer 36

true - 5mins need continuous infusion for prolonged action

Question 37

reteplase and tenectaplace are slightly modified versions of alteplase how are they different

Answer 37

they have longer half lives (just different pharmacokinetics)

Question 38

when alteplase is administered the body is in a systemic ___ state. what does this mean

Answer 38

lytic state the body is breaking down clots everywhere due to high levels of plasmin

Question 39

the drug that alteplase is contraindicated with

Answer 39

heparin - serious hemorrhage!

Question 40

2 alternatives to alteplase in a patient who has a serious clot

Answer 40

mechanical reperfusion mechanically extracting the clot

Question 41

name some disease states in which alteplase is contraindicated

Answer 41

any bleeding liability ie - peptic ulcer, intracranial hemorrhage, history CVA, metastatic cancer, etc

Question 42

true or false alteplase is not contraindicated in pregnancy

Answer 42

false - it is

Question 43

name an antiplatelet agent that is a prostaglandin synthesis inhibitor

Answer 43

aspirin

Question 44

name 5 antiplatelets that are adenosine receptor inhibitors

Answer 44

clopidogrel prasugrel ticlodipine ticagrelor cangrelor

Question 45

name 3 antiplatelets that are glycoprotein receptor inhibitors

Answer 45

tirofiban epifibatide abciximab

Question 46

name of the antiplatelet that prevents thrombin from binding to its PAR-1 receptor

Answer 46

vorapaxar

Question 47

true or false aspirin IRREVERSIBLY inhibits COX-1

Answer 47

true

Question 48

why is aspirin taken QD for prevention

Answer 48

bc repeated doses produce a cumulative effect on platelets

Question 49

true or false aspirin is bound to platelets for the entire lifetime of the platelet

Answer 49

true - irreversible

Question 50

true or false aspirin is very little protein bound

Answer 50

false - 50-90% - pretty high

Question 51

aspirin metabolic pathway

Answer 51

glucuronidation

Question 52

name some AE of aspirin

Answer 52

GI ulcer and bleeding heartburn prolonged bleeding time (thrombocyto, leukopenia - rare)

Question 53

*true or false aspirin can be given to children

Answer 53

FALSE - CANNOT BE GIVEN TO INFANTS AND CHILDREN!!!! RISK OF REYE'S SYNDROME (swelling in liver and brain)

Question 54

name 2 drugs that interact with aspirin and state the effect

Answer 54

NSAIDS - low dose aspirin wont work (unless you separate) probenecid - decreased effects of probenecid

Question 55

name 6 drugs whose effects are ENHANCED when given with aspirin, and thus side effects are more likely

Answer 55

NSAIDS anticoagulants digoxin methotrexate valproic acid sulfonylurea hypoglycemics

Question 56

what are some other names for the P2Y12 receptor antagonists

Answer 56

ADP/adenosine/purinergic receptor antagonists

Question 57

name 3 thienopyridine P2Y12 receptor antagonists are they prodrugs? reversible or irreversible binding?

Answer 57

clopidogrel prasugrel ticlodipine IRREVERSIBLE prodrugs

Question 58

which class of P2Y12 receptor antagonists are standard therapy for coronary stent? the thienopyridines or the ATP mimics?

Answer 58

Thienopyridines are the standard

Question 59

name the 2 P2Y12 antagonists that are reversible blockers

Answer 59

ticagrelor cangrelor

Question 60

explain the MOA of clopidogrel

Answer 60

P2Y12 antagonist blocks Gi receptor this increases AC and increases cAMP, VASP-P stays phosphorylated due to increased PKA, leading to the inhibition of platelet aggregation under normal circumstances, ADP would bind to the receptor and do the opposite of these events by activating Gi

Question 61

true or false clopidogrel is a prodrug

Answer 61

true

Question 62

true or false clopidogrel is an irreversible inhibitor

Answer 62

true

Question 63

clopipdogrel response is affected by mutations in what enzyme

Answer 63

cyp2c19

Question 64

true or false when clopidogrel is given, the platelets are not affected for their entire lifespan

Answer 64

false - they are. irreversible inhibitor

Question 65

true or false clopidogrel has slow offset of action

Answer 65

true

Question 66

true or false clopidogrel is commonly used with baby aspirin

Answer 66

true

Question 67

name 3 specific DDI considerations with clopidogrel

Answer 67

1. omeprazole and PPIs inhibit CYP2C19 therefore, there will be decreased activation of clopidogrel to its active metabolite 2. opioids slow GI emptying, so plavix remains in the stomach longer. this decreases its absorption bc its mainly absorbed in the INTESTINE 3. NSAIDS, warfarin, and SSRIs increase bleeding risk

Question 68

true or false prasugrel is not a prodrug

Answer 68

FALSE - it is

Question 69

explain metabolism of prasugrel how is this an advantage of clopidogrel

Answer 69

esterases convert it to a thiolactone which spontaneously falls apart (sometimes with 3a4) to the active metabolite no DDI with proton pump inhibitors bc not bioactivated by CYP2C19 like clopidogrel

Question 70

true or false prasugrel has lower efficacy and higher toxicity than clopidogrel

Answer 70

FALSE - both efficacy and toxicity is higher in prasugrel

Question 71

which 2 enzymes metabolize prasugrel

Answer 71

3a4 and 2b6 (very small extent 2c19 - not nearly as much as clopidogrel)

Question 72

DDI concern with prasugrel

Answer 72

no issue with PPIs - but its metabolized by 3a4 so there's a lot

Question 73

true or false rifampin is a CYP3A4 inhibitor

Answer 73

FALSE - inducer

Question 74

true or false ticlodipine has more AE than clopidogrel

Answer 74

true

Question 75

true or false ticlodipine is inferior to clopidogrel in terms of safety and efficacy

Answer 75

true

Question 76

true or false ticagrelor is a competitive, reversible inhibitor of ADP binding to P2Y12

Answer 76

FALSE - noncompetitive and reversible even tho adenosine-like structure, it binds the allosteric site and NOT the active ADP binding site - so non competitive

Question 77

true or false ticagrelor is not a prodrug

Answer 77

true

Question 78

true or false ticagrelor has a more rapid onset and offset of action than clopidogrel

Answer 78

TRUE - REVERSIBLE!!!

Question 79

Route administration ticagrelor

Answer 79

oral tablet

Question 80

CYP that metabolizes ticagrelor

Answer 80

CYP3A4

Question 81

true or false both the drug itself and the metabolite of ticagrelor are active

Answer 81

true

Question 82

3 major AE of ticagrelor

Answer 82

dyspnea (shortness of breath - pretty significant amt of people will have) bleeding (duh) bradycardia

Question 83

DDI concerns with ticagrelor

Answer 83

metabolized by CYP3A4!! any strong CYP inhibitors or inducers are a concern (remember - SAL acronym statins metabolized by 3A4!)

Question 84

ticagrelor + digoxin interaction

Answer 84

digoxin toxicity ticagrelor is weak P-Gp inhibitor - increase digoxin levels