Pharmacology - ACS (Acute Coronary Syndrome) Flashcards
name 2 different classes of drugs used for ACS
antiplatelets
fibrinolytics
(also 2 miscellaneous - dipyridamole and cilostazol)
name 3 classes of antiplatelet agents used for ACS
aspirin
adenosine receptor inhibitors
GpIIb/IIIa inhibitors
hemostasis is a balance of what 2 things
blood loss and thrombosis
what are zymogens
inactive enzymes. activated when balance needs to be maintained.
ie - balance between blood loss and thrombosis
define thrombosis
blood clots in vessels
“white clots” are also called…
arterial clots
atherosclerosis really only causes what kind of clots
ARTERIAL
2 types of venous clots
2 complications of arterial clots
venous – DVT, PE
arterial - heart attack, stroke
fibrinolytics degrade ___
fibrin
antiplatelets inhibit platelet ___ or ____
activation or aggregation
as platelets become activated, what do they do?
they release chemical mediators that promote AGGREGATION
(ie - ADP)
true or false
the clotting cascade is a positive feedback loop
true
how are zymogens activated
proteases break them to activate them
fibrin is the main meshwork of a clot
how is it produced
from fibrinogen
name 3 mediators that activated platelets secrete to promote aggregation
ADP TXA2 serotonin
these bind to receptors on adjacent platelets to promote aggregation
true or false
normal endothelial cells (not injured) release PGI2
true
what is the ligand for GpIa receptor on platelets
collagen
what is the ligand for Gp Ib receptor on platelets
von willebrand factor
what is the ligand for IIb / IIIa (integrin) receptor on platelets
fibrinogen, macromolecules (ADP)
name 3 classes of antithrombotics
anticoagulants
antiplatelets
fibrinolytics
what does t-PA stand for and what drug is it
tissue plasminogen activator
alteplase
how does plasmin affect fibrin
ultimately, plasmin will decrease fibrin levels because it inhibits fibrinogen (activator of fibrin)
and also breaks down fibrin clots themselves
true or false
plasmin is an enzyme that causes blood to clot
FALSE - breaks clots
by inhibiting fibrinogen and breaking down fibrin clots
true or false
streptokinase causes blood to clot
FALSE
dissolves clots by activating plasminogen, which activates plasmin
what does urokinase do
dissolves blood clots by converting plasminogen into plasmin
what is the fibrin-specific protease that digests fibrin and thus breaks down clots?
plasmin
what is the inactive form of plasmin
plasminogen
true or false
plasmin and alteplase both break down clots
true
what activates plasminogen?
t-pa (secreted by endothelial cells)
name 2 inhibitors of t-pa and ultimately inhibitors of plasmin formation
a2-antiplasmin
plasminogen activator inhibitor
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
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
name 3 fibrinolytic drugs
t-pa (recombinant alteplase)
urokinase and streptokinase (not used a lot)
true or false
alteplase can be given PO
FALSE - it’s a protease (enzyme)
cannot be given PO - given IV
alteplase is a ___ protease
serine
true or false
alteplase is highly specific for plasminogen that is FIBRIN BOUND
true
true or false
alteplase has a short half life
true - 5mins
need continuous infusion for prolonged action
reteplase and tenectaplace are slightly modified versions of alteplase
how are they different
they have longer half lives (just different pharmacokinetics)
when alteplase is administered the body is in a systemic ___ state.
what does this mean
lytic state
the body is breaking down clots everywhere due to high levels of plasmin
the drug that alteplase is contraindicated with
heparin - serious hemorrhage!
2 alternatives to alteplase in a patient who has a serious clot
mechanical reperfusion
mechanically extracting the clot
name some disease states in which alteplase is contraindicated
any bleeding liability
ie - peptic ulcer, intracranial hemorrhage, history CVA, metastatic cancer, etc
true or false
alteplase is not contraindicated in pregnancy
false - it is
name an antiplatelet agent that is a prostaglandin synthesis inhibitor
aspirin
name 5 antiplatelets that are adenosine receptor inhibitors
clopidogrel
prasugrel
ticlodipine
ticagrelor
cangrelor
name 3 antiplatelets that are glycoprotein receptor inhibitors
tirofiban
epifibatide
abciximab
name of the antiplatelet that prevents thrombin from binding to its PAR-1 receptor
vorapaxar
true or false
aspirin IRREVERSIBLY inhibits COX-1
true
why is aspirin taken QD for prevention
bc repeated doses produce a cumulative effect on platelets
true or false
aspirin is bound to platelets for the entire lifetime of the platelet
true - irreversible
true or false
aspirin is very little protein bound
false - 50-90% - pretty high
aspirin metabolic pathway
glucuronidation
name some AE of aspirin
GI ulcer and bleeding
heartburn
prolonged bleeding time
(thrombocyto, leukopenia - rare)
*true or false
aspirin can be given to children
FALSE - CANNOT BE GIVEN TO INFANTS AND CHILDREN!!!! RISK OF REYE’S SYNDROME (swelling in liver and brain)
name 2 drugs that interact with aspirin and state the effect
NSAIDS - low dose aspirin wont work (unless you separate)
probenecid - decreased effects of probenecid
name 6 drugs whose effects are ENHANCED when given with aspirin, and thus side effects are more likely
NSAIDS
anticoagulants
digoxin
methotrexate
valproic acid
sulfonylurea hypoglycemics
what are some other names for the P2Y12 receptor antagonists
ADP/adenosine/purinergic receptor antagonists
name 3 thienopyridine P2Y12 receptor antagonists
are they prodrugs? reversible or irreversible binding?
clopidogrel
prasugrel
ticlodipine
IRREVERSIBLE prodrugs
which class of P2Y12 receptor antagonists are standard therapy for coronary stent? the thienopyridines or the ATP mimics?
Thienopyridines are the standard
name the 2 P2Y12 antagonists that are reversible blockers
ticagrelor
cangrelor
explain the MOA of clopidogrel
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
true or false
clopidogrel is a prodrug
true
true or false
clopidogrel is an irreversible inhibitor
true
clopipdogrel response is affected by mutations in what enzyme
cyp2c19
true or false
when clopidogrel is given, the platelets are not affected for their entire lifespan
false - they are.
irreversible inhibitor
true or false
clopidogrel has slow offset of action
true
true or false
clopidogrel is commonly used with baby aspirin
true
name 3 specific DDI considerations with clopidogrel
- omeprazole and PPIs inhibit CYP2C19
therefore, there will be decreased activation of clopidogrel to its active metabolite - opioids slow GI emptying, so plavix remains in the stomach longer. this decreases its absorption bc its mainly absorbed in the INTESTINE
- NSAIDS, warfarin, and SSRIs increase bleeding risk
true or false
prasugrel is not a prodrug
FALSE - it is
explain metabolism of prasugrel
how is this an advantage of clopidogrel
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
true or false
prasugrel has lower efficacy and higher toxicity than clopidogrel
FALSE - both efficacy and toxicity is higher in prasugrel
which 2 enzymes metabolize prasugrel
3a4 and 2b6 (very small extent 2c19 - not nearly as much as clopidogrel)
DDI concern with prasugrel
no issue with PPIs - but its metabolized by 3a4 so there’s a lot
true or false
rifampin is a CYP3A4 inhibitor
FALSE - inducer
true or false
ticlodipine has more AE than clopidogrel
true
true or false
ticlodipine is inferior to clopidogrel in terms of safety and efficacy
true
true or false
ticagrelor is a competitive, reversible inhibitor of ADP binding to P2Y12
FALSE - noncompetitive and reversible
even tho adenosine-like structure, it binds the allosteric site and NOT the active ADP binding site - so non competitive
true or false
ticagrelor is not a prodrug
true
true or false
ticagrelor has a more rapid onset and offset of action than clopidogrel
TRUE - REVERSIBLE!!!
Route administration ticagrelor
oral tablet
CYP that metabolizes ticagrelor
CYP3A4
true or false
both the drug itself and the metabolite of ticagrelor are active
true
3 major AE of ticagrelor
dyspnea (shortness of breath - pretty significant amt of people will have)
bleeding (duh)
bradycardia
DDI concerns with ticagrelor
metabolized by CYP3A4!! any strong CYP inhibitors or inducers are a concern
(remember - SAL acronym statins metabolized by 3A4!)
ticagrelor + digoxin interaction
digoxin toxicity
ticagrelor is weak P-Gp inhibitor - increase digoxin levels
