Pharm Fall Final Anticoagulants

Front 1

what are the 3 mechs for hemostasis

Back 1

1. vascular constriction
2. platelet adhesion, activation, aggregation
3. fibrin formaiton and reinforcement of platelet

Front 2

what does prostacycline do

Back 2

inhibits clot formation (PGI2)

**it is made by the endothelium that lines the cessels

Front 3

what do these things do

1. prostacycline
2. thrombomodulin
3. antithrombin
4. heparin sulfate
5. protein C/S
6. TFPI (tissue factor pathway inhibitor)

Back 3

all inhibit clotting cascade

Front 4

how does platelet adhesion and plug formation happen

Back 4

1. vascular damage to endo reveals collagen
2. Platelet binds to collagen
3. Platelets are activated and release. Thromboxane A2, and ADP
4. other platelets bind via fibrinogen and GP IIb IIIa

Front 5

what is GpIIa/IIIb used for

Back 5

binding platelets to activated platelets

**endo damage, plate binds collagen, plate is activated release thromboxane A1 and ADP, more plate bind via GpIIa/IIIb nad fibrinogen

Front 6

whats fibrinogen, fibrin

Back 6

fibrinogen, soluble. inactive

fibrin- strong rope to tie down plates. activated by thrombin

Front 7

is lots of hte clotting cascade activatd during surgery

Back 7

nope, its a clean inscision. not a lot of tissue damage

VII --> X --> thrombin

Front 8

thrombin activates fibrin, what does thrombomidulin do

Back 8

thrombomodulin inhibits thrombin so plugs arent formed

thrombomodulin inhibits clotting

Front 9

are protein C and S anticoagulatns or procoagulants

Back 9

anticoagulants

C required vit K epoxide reductase

Front 10

what are 5 anticoagulants

Back 10

1. Heparin
2. Low Moleculat Weight Heparin (Fractionated)
3. Warfarin
4. Dibigatran
5. Rivaroboxane

Front 11

what are 2 ways to monitor anticoagulants

Back 11

1. aPTT: monitor heparin

2. PT: prothrombin time. monitor warfarin

Front 12

heparin adn warfarin are both anticoagulants. how are they measured/monitored

Back 12

1. aPTT- heparin
2. PT- warfarin

Front 13

where does heparin work

Back 13

both in vivo and in vitro

**its a catalyst that enhances the association of antithrombin III and clotting factors

**recall that antithrombin is a clotting inhibitor

Front 14

what are some basics of heparin

1. administration
2. clearance
3. composition
4. monitored
5. action
6. increased effect with...

Back 14

1. IV only (no IM)
2. hepatic
3. found in mast cells endogenously and it heterogenous
4. increases aPTT
5. catalyst: enhances binding of antithrombin III and clotting factors (anticoagulant). works IMMEDIATLY
6. decreased body temp, renal/hepatic disease

Front 15

what is low molecular weight heparin

Back 15

Enoxaparin

**affects less of the clotting cascade (mainly 10a) but is just as effective as heparin

**subcutaneous (heparrin was IV only)- more available so given less often

**used for prevention of DVY

Front 16

whats the dif btwn heparin and enoxaparin (LMWH)

Back 16

the end result is the same. BUT enoxaparin has higher affinity for 10a. less is needed and it can be given subcu

enoxaoarin is used to prevent DVT

Front 17

what is enoxaparin

Back 17

low molecular weight heparin

**high affinity for factor 10a
**subcutaneous
**used to prevent DVT

Front 18

what is hte major toxicity associated with heparin, how is it tx

what are some ways to prevent

what is a side effect from long term use

Back 18

bleeding! stop the heparin, take protamine sulfate (its a basic drug that binds tight to the acidic heparin)

monitor aPTT (increaed with heparin)

osteoperosis, hypersensitivities, allergic reactions

Heparin Indiced Thrombocytopenia: decrease in platelets. new thrombus while on heparin. SWITCH

Front 19

what is heparin indiced thrombocytopenis (HIT)

Back 19

a new thrombus while on heparin. STOP HEPARIN AND SWITCH antocoagulants

Lepriudin: in pts with liver disease
Argatroban: in pts with renal failure
Bivalirudin
danaoaroid

Front 20

what is protamaine sulfate used for

Back 20

reverse action of heparin when there is hemmorage caused by heparin

**only use if its heparin induced

Front 21

osteoperosis
allergic reactions and decreased platelets are long term side effects of what

Back 21

heparin

**more common is hemmorage. tx with protamine sulfate

**can also cause heparin induced thrombocytopenia

Front 22

when is heparin CI

Back 22

1. when pt is bleeding
2. hypersenstiviteies
3. heophilia, thrombocytopenia, purpura, HTN, intracranial hemmorage
4. infections: infective endocarditis, TB, ulcers, threatened abortion, visceral carcinoma
5. liver/kidney disease
6. during or after surgery of brain, spine, eye. lumbar puncture

Front 23

which anticoagulant is good for use in preggers

Back 23

heparin

**when a person is preg and taking warfarin, replace with heparin

Front 24

what is heparin used

Back 24

1. Anticoagulant, operations (CI in brain, spine, eye surgery)

2. preggo (replace warfarin)

3. LMWH (enoxaparin) used subcu after MI. lett heparin indiced thrombocytopenia

Front 25

what is the state of coagulability in preggo, what drug can we use

Back 25

hypercoagulable

**use heparin as an anticoagulatn

Front 26

whats the deal if a pt is on heparin and bleeds

Back 26

well heparin is used to decrease clotting so bleeding is a natural side effect

**use with protamine sulfate, but only if the person is heperanized. with out heparin protamine sulfate will just be MORE anticoagulant and make the bleed worse

Front 27

is protamine sulfate good to use in ALL cases of inappropriate bleeding

Back 27

no! its antagonizes heparin so only use when pt is bleeding who is heparinized

**alone it will be anticoagulant and further the bleed

Front 28

what are hte toxicities associated with protamine sulfate

Back 28

**this stops bleeding in heparinized pts

**hypotension 2 to histamine release
**Pulm HTN
**allergic reactions

Front 29

what is lepirudin

Back 29

*recombinant leech spit (hirudin)
**specific DIRECT inhibitor of thrombin (doesnt use thrombin III like heparin)

**used IV as an alternate in HIT (heparin indiced thrombocytopenia)

Front 30

what is used IV as an alternative antocoagulant in heparin indiced thrombocytopenia (HIT)

Back 30

lepirudin

**its a DIRECT inhibitor of thombin (its an antocoagulant)

**its recombinant leech spit

Front 31

who works immediatly warfarin or heparin

what works in vovto aND vitro, warfarin or haparin

Back 31

heparin (uses antothrombin III to inhibit the action of clotting factors) IMMEDIATE. vito and vitro. IV vivo only. oral (lepirudin was the DIRECT thombin inhibitor)

Warfarin: takes some time, it inhibits vit K reduction so the clotting factors that require vit K dont work. vivo only. Oral. interacts with EVERYTHING

Warfarin:

Front 32

when is the max effect of warfarin seen

Back 32

48 hrs

**inhibits vit K reduction so clotting factors dont work right (they NEED vit K)

Front 33

what drug exerts is anticoagulant effect by inhibiting clotting factor fomraiton by decreasing K

Back 33

warfarin

Front 34

heparin and warfarin. what inhibits the contact activated (intrinisic path) what inhibits the Tissue factor activated path (extrinsic)

Back 34

Intirisic: heparin (aPTT to monitor) inhibit VII X prothrombin & IX

Extrinsic: warfarin (PT to monitor)

Front 35

warfarin inhibits synthesis of what

Back 35

II
VII
IX
X
protein C/S

**all the ones that are dependint on vit K

**works ONLY in vivo, takes some time to have an effect
**monitor PT

Front 36

what inhibits synthesis of II VII IX X Protei n C/S

Back 36

warfarin

**works in vovo only
**oral
**monotor PT time

Front 37

how is warfarin administered

Back 37

its an oral that ppl can take long term

**initiate over about a week. GO SLOW (inhibits II, VII, IX, X, c/s)

*The therapeutic range is defined in terms of an international normalized ratio (INR), which is a function of the prothrombin time
–
The target INR should be 2 to 3 for most indications (INR=3 is equivalent to a prothrombin time ratio of about 1.6)

Front 38

what is the INR (international normalized ratio)

Back 38

fx of prothrombin time to determine theraputic range of warfarin

Front 39

ok so like everything interacts with warfarin, what are 5 big categories.

Back 39

1. Asprin: increases bleeding
2. Drugs that affect liver enzymes: cemetidine
3. Chronic EtOH (tear up liver and slow clotting factor formation) Acute EtOH (
4. oral contraceptives (make you hypercoagulable-warfarin causes birth defects, use heparin)
5. Barbituates

Front 40

what do drugs that decrease K do with anticoagulants

Back 40

decrease K (like thiazides and loops) will alter clotting. Warfarin decreased K availability to act as an anticoagulant

Front 41

what happens to a pt on warfarin that has asprin

Back 41

asprin inhibits platelet aggregation adn warfarin inhibits coagulation factors so increased bleed risk

Front 42

is warfarin bound to plasma protein

Back 42

ya, this means that it interacts with all oghtet drugs that bind to plasma proteins

ex phenylbutazone, ethacrynic acid

Front 43

if microsomal enzymes are inhibited (cimentidine, chloramphenicol, imipramine, metronidazole) what happens to warfarin

Back 43

when enzymes are inhibited the conc of warfarin increased

Front 44

if microsomal enzymes are induced (barbiturates) what happens to warfarin

Back 44

decreased

Front 45

what does preggo & oral contraceptives do to warfarin

Back 45

decrease effects

Front 46

what do AB do to warfarin

Back 46

alter warfarin bc bacteria make vit K

Front 47

what is the toxicity of warfarin

Back 47

1. hemmorage: tx with vit K (takes a while) or fresh frozen plasma (has already made coagulation pfactors)

2. hyperthyroidism, hepatic disease, increased effect of warfarin

3. preg decreases effect of warfarin (teratogenic, dont use if preggo)

Front 48

ok so we know warfarin decreases clotting factors, which one is affected first

Back 48

decrease vit C first! this is an anticoagulant so we can get clots (warfarin indiced thrombosis) that can cause cutaneous necrosis and infarct during early therapy use

Front 49

what is a risk of warfarin in the beginnins (recall you give is slowely over a week)

Back 49

warfarin induced thrombosis

**vit C is the first to go and its an ANTIcoagulant so we can get some coagulation---> skin necrosis

Front 50

how can the effects of warfarin be reduced

Back 50

vit K (takes some time)

fresh frozen plasma is immediate bc coagulation factors are already made

Front 51

what are the uses of warfarin

Back 51

prevent emboli formation

DVT

thromboembolism

given chronically (oral)

WARN PTS ABOUT INTERACTIONS

Front 52

does warfarin act on already formed emboli

Back 52

nope! just prevents formation of NEW emboli. prevent DVT after bed rest or surgery

Front 53

what is Dabigratran

Back 53

oral anticoagulant:
direct thrombin inhibitor. p
used to prevent stroke, non valvular atrial fibrilation
toxicity: bleeding, duh its an anticoagulant

Front 54

what is Rivaroxaban

Back 54

oral antocoagulant,
inhibits facot 10a
*prevent DT after orthopedic procedure
*toxicity is bldding

Front 55

what are hte 2 new oral anticoagulants

Back 55

1. Dabigratran: inhibit thrombin directly, prevent stroke.

2. Rivaroxaban: inhibits factor 10a. prevent DVT after orthopedics

**toxicity for both is bleeding

Front 56

what is fibrinolysis

Back 56

breaking the clot

plasmin is activated to destroy fibrin adn fibrinogen

**thrombolytics increase normal fibrinolysis

Front 57

what are plasminogen activators

Back 57

activate plasmin so it can destroy fibrin and break up clots

**plasmnin degrades both fibrin and fibrinogen

Front 58

what does stim of protein C do

Back 58

thrombin stim protein c for fibrinolysis

**increase normal fibrinolysis is a thrombolytic

Front 59

whats a thrombolytic

Back 59

increase normal fibrinolysis

*act to activate plasmin so it can break up fibrin(ogen)
*lyse clots to reestrablish perfusion, good to reduce mortality in MI

Ex tPA (tissue plasminogen activator, alteplase, activase)

Front 60

what are some great uses of antithrombolytics

Back 60

after MI for reperfusion (be careful, not too much or you may induce stroke)

PE

SVT

Arterial thrombosis
**tPA is a thrombolytic

Front 61

what is the "clot selective" thrombolytic

Back 61

tPA

Streptokinase is another thrombolytic agent but can cause allergies and is used only once bc of this (its a protein and we may make AB to it)

Front 62

what is a great way to lyse a clot after MI to get reperfusion

Back 62

thombolytic, an anticoagulant wont break the clot

Front 63

what else besides thrombolytics (tPA, streptokinase) are given post MI

Back 63

asprin
b blocker
ACEi

thrombolytics also good for: PE, DVT, arterial thombus. stroke- be cautious!!!

Front 64

can thrombolytics be used to treat stroke

Back 64

ya but be careful

Front 65

what are 4 thrombolytics

Back 65

1. tPA- clot selective
2. Streptokiase- allergic reactions
3. Urokinase
4. Anistreplase- plasminogen/streptokinase

Front 66

tell me some stuff about tPA

Back 66

1. breaks clots by activating plasmin
2. made in endo cells or give recombinant as drug
3. "clot selective"
4. more effective than streptokinase (the other thrombolytic) BUT higher risk of stroke!!!
5. $$$$$$$$$

Front 67

tell me about streptokinase

Back 67

1. thrombolytic- its a clot buster
2. complexes with plasminogen to increase fibrinolysis
3. IV
4. can cause allergic anaphylaxis
5. less effective than tPA (less risk for stroke) but when combined with asprin its just as good
6. can only use once bc its a protein and elicits AB response

Front 68

what is anistreplase

Back 68

thrombolytic

**mixture of plasminogen and streptokinase that is inert (takes care of the allergic reaction problem see in streptokinase alone)

**long duration
**clot selective

Front 69

what is aminocarproic acid

Back 69

1. inhibits fibrinolysis by inhibiting plasminogen formation

**used in bleeding disordrs (hemophilia)
**used to reverse thrombolytics (tPA, streptokinase)

Front 70

what is the drug that inhibits thrombolytic activity by preventing formation of plasmin

Back 70

aminocaproic acid

**used in bleeding disorders (hemophilia)
**used to reverse thrombolytic therapy (tPA, streptokinase)
**used to prophylax against rebleedin in aneurysns

Front 71

what is tranexamic acid

Back 71

similiar to aminocaproic acid- prefents fibrinolysis by inhibiting plasmin

**used to treat bleeding or when there is a risk of bleeding

**good for upper GI hemmorage

Front 72

what is aminocaproic acid
what is tranexamic acid

Back 72

simliar both inhibit fibrinolysis by inhibiting plasmin

**both used in bleeding disorders and to treat over kill of tPA/streptokinase

**tranexamic is used for upepr GI bleed

Front 73

what is lysteda

Back 73

oral antifibrinolytic

**used to help heavy menstural bleeding

Front 74

what is teh toxicity of aminocaproic acid and tranexamic acid

Back 74

**these are ANTIfibrinolytics (opposite of clot busters, they are clot savers. they inhibit plasmin fomraiton)

**thombus
**hypotension, myopathy, GI discomfort, nasal stuffyness

Front 75

what are 3 drugs that inhibit thrombogenesis

Back 75

asprin
clopidogrel
abciximab

**regulate platelet fx by:
inhibit PG metabolism
inhibit ADP mediated platelet aggregation
block GpIIa/IIIb

Front 76

tell me about asprin, and clopodogrel and where they act

Back 76

well when endo is damaged we have plateletes that bind to the exposed collagen.

the platelets are then activated and release:
1. Thomboxane A2- inhibited by asprin (irreversible)
2. ADP- inhibited by clopidogrel (plavix)

**both are antithrombotics, dont let thrombus form.

Front 77

what antithrombic blocks thromboxane A2, what inhibits ADP

Back 77

Thromboxane A2- aspirin (Acetylsalicylic acid)

ADP- plavix (clopodogrel)

Front 78

what is Acetylsalicylic acid

Back 78

1. Aspirin
2. inhibits thromboxane A2 from activated platelets (inhibits more platelets from being recruited) this is IRREVERSIBLE! will be inhibited til teh platelet dies ---> a single dose can prolong bleeding for DAYS

3. good for pts at risk for embolus
4. taken to prevent MI (50mh-325 mg)

5. DOnt take before dental procedure
6. adjust warfarin if taking together

Front 79

why can a single dose of Acetylsalicylic acid prolong bleeding for DAYS!

Back 79

bc is IRREVERSIBLY inhibits thromboxane A2 so it lasts the lifetime of the platelet

**dont use before dental procedures

Front 80

what is clopidogrel

Back 80

1. antithrombolic
2. inhibits platelet addregation by blocking ADP release from initial platelets that bind to exposed endo
3. no effect on PG
4. givein during MI
5. good for pts allergic to asprin

**plavix

Front 81

what is abciximab

Back 81

inhibits binding of lots of platelets bu inhibiting GpIIa/IIIb

**antiplatelet
**orginally from mouse. Humanized Fc with only FAB (no variable region)

Front 82

what drug inhibits Gp IIa/IIIb

Back 82

Abciximab- prevents binding of vWF with fibrin

*used along with heparin in pts undergoing percutaneous coronary intervention
**used in pts having angioplasty/atherectomy, stent placement
**used in unstable angina
**used in AMI

Front 83

when is abciximab used (inhibits Gp IIa IIIb)

Back 83

1. along with heparin in pts undergoing percutaneous coronary intervention

2. pts having: angioplasty, atherectomy, stent placement

3. Unstable angina not responding to other therapy

4. AMI

**always given IV
**toxic: bleeding. $$$$$$$$

Front 84

what drug is an AB (himanized FAB) that is give IV when pts have angio, stent, unstable angina etc

Back 84

abciximab

**inhibits Gp IIa IIIb. its an antiplatelet