Dr. Siegars, Cp2, Antiplatelets, Anticoagulants And Thrombolytics

Front 1

common risk factors for bleeding

Back 1

severe, uncontrolled HTN, aneurysm, recent surgery, recent trauma, severe hepatic disease (drug elimination, clotting factor production), severe renal disease (drug elimination) bone marrow suppression/blood dyscrasias (thrombocytopenia), intracranial mass/neoplasm, hx CVA, GI ulcers, IM or spinal injections

Front 2

what is one side effect that every antiplatelet, anticoagulant and thrombolytics will cause

Back 2

BLEEDING

Front 3

clotting factors are made

Back 3

in the liver

Front 4

monitoring therapy:
bleeding time test

Back 4

evaluates platelet FUNCTIONING (a platelet count=number of platelets, not function)

Front 5

monitoring therapy:
prothrombin time (PT)

Back 5

evaluates vitamin K factors (2,7,9 and 10) PT test goes with the drug Warfarin
normal is 10-13 seconds, goal is 15-26 seconds**know this for test**

Front 6

monitoring therapy:
international normalized ratio (INR)

Back 6

used for warfarin. better test. normal is 1.0. the goal is 2.0-3.0. UNLESS 1) pt has a mechanical heart valve 2) anybody who is in 2-3 range and throws a clot

Front 7

monitoring therapy:
activated partial thromboplastin time (aPTT)

Back 7

used with heparin. evaluates serine protease factors (2,9, 10,11, and 12) mainly 2 and 10 becaue these are the normal pathway. normal aPTT is 30-50 seconds, goal is 50-70 seconds

Front 8

assessment of choice for warfarin is:

Back 8

INR

Front 9

what 2 patients should be in 2.5-3.5 range for INR (instead of 2-3)

Back 9

1)pts with mechanical valve
2) pts who throw a clot when they are in the 2-3 range

Front 10

Activated clotting time (ACT)

Back 10

pts on high dose heparin. utilized during CABG/PCI...
normal range is 70-180, our goal with treament is 350-500 seconds. (this is how long it takes to make a clot)

Front 11

overview of platelet function

Back 11

stick together and hang on until fibrin comes around and makes a clot.

Front 12

6 receptors on platelets that are activated by what substances?.

Back 12

1)GP Ib-IX---> vWF (von Willebrands)
2)GP Ia-IIA receptor-->collagen
3) P2Y12 receptor-->plasma phospholipids
4) arachidonic acid pathway-> COX
5) Dense bodies, ATP/ADP, Ca++, 5-HT
6) GP IIb/IIIa receptor-->fibrin
These are ways the body keeps its balance and also the ways our drugs will work to affect clotting

Front 13

COX inhibitors
names and MOA

Back 13

ASA, APAP (aspirin and acetaminophen)
MOA=irreversibly inhibits COX (non-selectively, COX 1 and 2) associated with phosholipid released or platelet released arachidonic acid
at low doses COX-1 more than COX-2. Effects last life of platelet 7-10 days

Front 14

side effects of COX inhibitors and monitoring

Back 14

GI related=less frequent at low dose. Caution in asthmatics/bronchospasm. To monitor could use BT or Platelet count. (no common monitoring test)

Front 15

ADP antagonists (list the 4 drugs in this category)

Back 15

1) clopidogrel (plavix)
2) Ticlopidine (ticlid)
3) prasugrel (effient)
4) Ticagrelor (brilinta)

Front 16

MOA for ADP antagonists

Back 16

inhibition of ADP binding to the receptor P2Y12. This results in irreversible inhibition of platelets.

Front 17

what are the alternatives for pts who cant take ASA?

Back 17

ADP antagonists (clopidogrel, ticlopidine, prasugrel, ticagrelor)

Front 18

indications for ADP-Antagonists (differentiating indications from ASA)

Back 18

ASA hypersensitivity/allergic
in combination with ASA and anticoagulants (all drugs in ADP-antagonist class are prodrugs)

Front 19

side effects of ADP antagonists

Back 19

similar to ASA; clopidogrel has less GI than ASA (ticlopidine has more GI than ASA)
Ticlopidine=increased AST/ALT (liver enzymes that show liver is being damaged)
blood dyscrasias (rarely)

Front 20

monitoring ADP-antagonists

Back 20

platelet count, CBC, LFT's (liver function tests), BT plausible but not commonly used.

Front 21

GP IIb/IIIa receptor antagonists (list the 3 drugs)

Back 21

1) abciximab (reopro)
2) eptifibatide (integrillin)
3) tirofiban (aggrastat)

Front 22

MOA for GP IIb/IIIa receptor antagonists

Back 22

inhibits the receptor. results in inhibition of activation and platelet binding with fibrinogen, vWF, platelets

Front 23

Abciximab

Back 23

a monoclonal antibody (mab)
look for drugs that end in mab.

Front 24

indications for GP IIb/IIIa receptor antagonists

Back 24

prophylaxis of thromboembolic events in ACS or those pts going to PCI (use abcix)
prophylaxis in PCI and tx for unstable angine or non Q wave infaction (use eptifibatide and tirofiban)

Front 25

effect of GP!!b/IIIa receptor antagonists

Back 25

administered IV infusion, effect primarily seen during infusion and goes away between 4-48 hours. (opposite of ASA)

Front 26

side effects of GP IIb/IIIa receptor antagonists

Back 26

hypotension (all 3 drugs)
GI/Myalgia is seen with Abciximab
thrombocytopenia with abciximab and tirofiban (rare)

Front 27

monitoring GP IIb/IIIa receptor antagonists

Back 27

platelet count and
Scr/BUN= (renal secretion for eptifibatide and tirofiban)

Front 28

PDE3 inhibitors (list the 3 drugs)

Back 28

1) anagrelide (agrylin)
2) cilostazol (pletal)
3) dipyridamole (persantine)

Front 29

MOA of PDE3 inhibitors

Back 29

inhibit PDE3 receptors causes decreased destruction of cAMP, thereby increasing cAMP levels. also inhibits A.Acid release, indirect vasodilatory properties (cAMP)

Front 30

PDE inhibitors have unigue indications

Back 30

1)anagrelide= thrombocytopenia associated with myeloproliferative disorders
2) cilostazo=used for intermittent claudication
3)dipyridamole= adjuctive prophylaxis of thromboembolism

Front 31

warfarin

Back 31

affects vitamin K dependent factors before they get turned on.

Front 32

what is the one drug in the extrinsic pathway that warfarin is used to target

Back 32

Factor 7

Front 33

PT test monitors

Back 33

extrinsic pathway (has one T excluded PT vs PTT)

Front 34

PTT test monitors

Back 34

intrinsic pathway (has extra T included PTT vs PT)

Front 35

classifications of anti-coagulants

Back 35

1)anti-thrombin III enhancers
2)vitamin K inhibitors
3)thrombin inhibitors
4) factor Xa inhibitors

Front 36

what is the anecdote for giving too much heparin?

Back 36

protamine sulfate

Front 37

what is the anecdote for giving too much warfarin (vitamin K inhibitor)

Back 37

phytonadione (vitamin K)

Front 38

MOA for all forms of AT III enhancers

Back 38

binds to AT III and induces a conformational change enhancing binding to serine protease clotting factors (2,9,10,11,12 plasmin and kallikrein) length requirement=at least 18 units.

Front 39

Where do antiplatelet medications work?

Back 39

they are COX inhibitors

Front 40

what kind of drug is ASA

Back 40

COX inhibitor, irreversibly inhibits

Front 41

side effects of COX inhibitors

Back 41

GI upset. use caution is athmatics/broncospasm

Front 42

What is an important kinetic principle to consider for cilostazol

Back 42

the platelet effects of this antiplatelet drug continue for several days after D/C-ing the drug. Consider scheduled surgery

Front 43

Which Antiplatelet-PDE3 inhibitor is used for intermittent claudication?

Back 43

Cilostazol

Front 44

Which Antiplatelet-PDE3 inhibitor is used for thrombocytopenia associated with myeloproliferative disorders (polycythemia vera adn CML)

Back 44

Anagrelide (antiplatelet effect only at higher doses)

Front 45

Which Antiplatelet PDE3 inhibitor is used as an adjunctive prophylaxis of thromboembolism

Back 45

Dipyridamole

Front 46

which PDE3 inhibitor is not recommended for pts in CHF? (MI, valvular HD, arrythmias...)

Back 46

Cilostazol. It has CV and vascular bed effects

Front 47

What kind of drug is heparin

Back 47

anti-thombin III enhancer

Front 48

What kind of drug is warfarin

Back 48

vitamin K inhibitor

Front 49

What kind of drugs are: dalteparin, enoxaparin and tinzaparin

Back 49

low molecular weight heparins

Front 50

what is the MOA for all forms of heparin

Back 50

binds to AT-III and induces a conformational change enhancing binding to serine protease clotting factors. Length requirement at least 18 units

Front 51

When is the only time you will use anagrelide

Back 51

in pts with thrombocythemia (too many platelets)

Front 52

indications for cilostazol*** (and also dipyridamole)

Back 52

"angina of the calf" claudication associated with PVD

Front 53

what factors do we look at to be affected with warfarin?

Back 53

2, 7, 9, 10

Front 54

What is the only drug that effects the extrinsic pathway

Back 54

Warfarin (the only drug that effects factor 7)

Front 55

what substance works in collaboration with heparin to keep us from completely clotting uncontrollably

Back 55

antithrombin 3 (works natrually with heparin in our bodies)

Front 56

primary factors in the intrinsic pathway

Back 56

2, 9, 10, 11, 12

Front 57

PTT test

Back 57

has an extra T included (vs PT) so it evaluates primarily intrinsic pathway

Front 58

PT test

Back 58

monitors extrinsic pathway (has the extra T, EXcluded)

Front 59

heparin works in which pathway? Warfarin works in which pathway?

Back 59

heparin=intrinsic pathway (PTT)
warfarin=extrinsic pathway (PT/INR)
(they BOTH effect the common pathway)

Front 60

Will see a tiny nudge in PT test when we stop heparin...why?

Back 60

because heparin effects the common pathway, so we will see some change in the test

Front 61

Which factors are anti-thrombin III impacted?

Back 61

2, 9, 10, 11, 12

Front 62

When do you anticoagulants clinically?

Back 62

When a pt on antiplatelets is still having problems with clotting

Front 63

what is the antadote for giving too much heparin

Back 63

protamine sulfate

Front 64

antadote for warfarin

Back 64

vitamin K (phytonadione)

Front 65

Drugs that end in Rudin are what class?

Back 65

thrombin inhibitors

Front 66

drugs that end in parin are....

Back 66

all low molecular weight heparin (PARIN)

Front 67

MOA for antithrombin III enhancers

Back 67

binds to antithrombin III and provides anti-coagulant activity. Must be 18 units at least

Front 68

What are main factors in common pathway we look at in antithrombin III drugs

Back 68

factor 2 and 10

Front 69

How does unfractionated heparin work?

Back 69

It's long enough to bind factor 2a which has 3 binding points. Low molecular weight heparins are much less likely to block factor 2a.

Front 70

Factor 2a requires how many binding points? Factor Xa requires how many?

Back 70

2a requires 3 binding points
Xa requires 1 binding point

Front 71

heparin can bind to AT-III and still inhibit factor Xa

Back 71

the longer the heparin chain the more likely it will bind in a tri-binding aspect to factor 2a

Front 72

If we want to focus on blocking factor 2a which heparin will we use?

Back 72

unfractionated because the low molecular weight heparins are too short to have much of an effect.

Front 73

what is the ratio of factor Xa to factor IIa inhibited by unfractionated heparins

Back 73

1:1 (inhibits one of each)

Front 74

What is the ration of factor Xa to Factor 2a inhibited by LMWH?

Back 74

2-4:1 (it will effect 2-4 of factor Xa for every 1 factor 2a)

Front 75

when do we use AT III enhancers?

Back 75

to prevent forming clots or if pt has had clots. Can be given IV, or SQ

Front 76

Why did they invent low molecular heparins?

Back 76

unfractionated heparin is eliminated through kidneys (slow) and through endothelial cells and macrophages (fast) Before LMWH pts had to take 1000 Units/hour=but had different effect on different pts. Some would clot and some would bleed!
Low molecular weight heparins only use the first order slow process for elimination. safer and easier to use and longer half-lives.

Front 77

side effects of heparins (both low and high molecular weight)

Back 77

heparin induced thrombocytopenia or thrombotic cytopenia. (less risk with LMWH) If platelet counts plummet you HAVE to take them off heparin

Front 78

how do we monitor pts on heparin?

Back 78

With a PTT test. We want it to be 50-70 seconds. or blood level 0.3-.7 IU/mL (PTT not used on LMWH) also check serum creatinine because they are renally eliminated. (cut dose or extend interval if renal function is redulced)

Front 79

toxicity treatment/antedote for too much heparin?

Back 79

protamine, whole blood or fresh frozen plasma

Front 80

what is the one vitamin K inhibitor

Back 80

Warfarin. Inhibits factors 2,7,9 and 10 (vitamin K dependent clotting factors)

Front 81

How quickly of an anticoagulant effect with the pts body get after swallowing first dose of Warfarin?

Back 81

Not too quickly because some factors are already activated and it has no effect on those factors, only not activated factors. depends on half-life of factors 2,7,9 and 10. (4-5 half lives to establish new equilibrium)
Factor 7 has shortest half life, factor 2 has half life of one day. Takes 4-7 days to establish new equilibrium

Front 82

how quickly does heparin work compared to warfarin

Back 82

heparin works right away, warfarin takes about a week. so pts get put on warfarin AND heparin at same time.

Front 83

warfarin is what class drug
heparin is what class drug

Back 83

warfarin=vit K inhibitor
heparin is Antithrombin III enhancer

Front 84

side effects of vit K inhibitor (warfarin)

Back 84

skin necrosis/gangrene (remember pic of necrotic breast tissue from path?)

Front 85

How does vitamin K work

Back 85

vitamin K reductase activates vit K-->reduced form of vit K forms vitamin K epoxide. (II becomes IIa) once vitamin K is used it's done, but our body uses vitamin K epoxide reductase back to original vitamin K. (our body recycles vitamin K and warfarin blocks both of these enzymes)

Front 86

drug-drug interactions and warfarin

Back 86

there are HUGE drug-drug interactions. LOOK them up. It is metabolized by CYP450 enzyme

Front 87

What test is used to monitor warfarin?

Back 87

INR. our goal range for INR is 2-3

Front 88

when is our range goal for INR not 2-3?

Back 88

if the pt throws a clot when INR is 2-3 or if pt has mechanical valves

Front 89

What anticoagulant will we use with pregnant pts?

Back 89

Use heparin

Front 90

IIa inhibitors work on which pathway

Back 90

common pathway...already activated factors

Front 91

drugs that end in RUDIN come from

Back 91

leach spit

Front 92

IIa inhibitors are...

Back 92

anticoagulants that also have antiplatelet activity

Front 93

MOA for IIa inhibitors

Back 93

reversibly (irreversibly for lepirudin) factor 2a

Front 94

What is the latest and greatest drug in class 2a inhibitors

Back 94

Dabigatran...because its ORAL and convenient and blocks 2a

Front 95

monitoring for 2a inhibitors

Back 95

look for risk of bleeding. Hematocrit, platelets, renal function, there is no antidote for 2a inhibitors, but they have short half-lives.

Front 96

Xa inhibitors

Back 96

fairly nes...Fondaparinux

Front 97

MOA for Fondaparinux

Back 97

blocks factor 10a. Also in the common pathway. administered SQ. side effects=thrombocytopenis. watch kidneys because it's renally eliminated

Front 98

How do thrombolytics work

Back 98

aids in conversion of plasminogen to plasmin which inititiates breakdown of the clot

Front 99

what drugs are in thrombolytics class

Back 99

alteplase, reteplase, streptase, tenexteplase (ASE)

Front 100

steptokinase

Back 100

a purified strep of bacterial proteinfrom group C Beta hemolytic streptococci

Front 101

urokinase

Back 101

produced fromhuman kidney tissue cells (uro=urinary)

Front 102

side effects of thrombolytics

Back 102

hemorrhagic CVA, reperfusion arrhytmias, hypotension, hypersensitivity reactions, resistance (Abs develop to streptokinase)

Front 103

contraindications for thrombolytics

Back 103

recent bleeding, uncontrolled HTN and cerebral tumors