Thrombolytics And Anticoagulants

Front 1

Risk of venous thromboembolism--

Back 1

- prior history of VTE, multiple trauma, major surgery, immobility, hypercoagulable disorder

Front 2

- Platelet adhesion v. aggregation

Back 2

- adhesion means platelets adhereing to subendothelium
- activtn occurs after adhesion
- after activtn- platelet aggregation occurs

Front 3

Intrinsic system is activated with what factor?

Back 3

XII to XIIa

Front 4

The extrinsic system is activated with what factor?

Back 4

VII

Front 5

Name the natural anticoagulants

Back 5

1. Prostacyclin- PGI2- which is a metabolite of ARA
2. anti thrombin III
3. Protein C

Front 6

Heparin- clinical indications/uses

Back 6

- Tx of venous thrombosis, PE, early tx of unstable angina and acute MI
- Prev of postoperative DVTs & PE
- Prev of clotting in arterial and heart surgery, blood transfusions, extracorporeal circulation, dialysis procedure, and blood samples
- used also in pregnancy- does not cross placenta

Front 7

Heparin- MOA

Back 7

- Heparin interferes with clot formation by accelerating the reaction of antithrombin III in binding to thrombin. Antithrombin III inhibits coagulation factors of the intrinsic and common pathways
- Antithrombin III also inactivates factors IXa, Xa, XIa, XIIa, and kallikrein
- Heparin at high doses can interfere with platelet aggregation
-Increases lipoprotein lipase activity
-Inhibits smooth cell proliferation

Front 8

Heparin- PK

Back 8

- NOT absorbed through GI, must be given IV or sub q
- cleared by reticuloendothelail syst (macs)
- eliminated renally
- half life increases as dose increases b/c more binds to proteins
- follow with PTT-- should have 1.5-2.5x baseline

Front 9

Heparin- drug interxns, CI

Back 9

- Decreased effect with digoxin, tetracycline, nicotine, antihistamine
- Increased effect with anticoagulants, NSAIDs, ASA, dipyridamole, Plavix, direct thrombin inhibitors
- CI- hypersensitivity or severe thrombocytopenia

Front 10

Heparin- tox

Back 10

- bleeding, thrombocytopenia- takes about a wk so that anti platelet IgGs can be produced b/c heparin makes haptens out of platelets-- basically become antigens= HIT, HAT= 2 days, LFTs, osterporosis if > 3mos

Front 11

What is the antidote for heparin poisioning, i.e. if you wanna reverse HAT?

Back 11

- protamine sulfate

Front 12

LMWH- use (little parins-- dalteparin, enoxaparin, tinzaparin)

Back 12

- Tx/prophylax DVT, PE
- unstable angina/non Q wave MI
- ortho surgery
- hemodialysis
- preferred over unfractionated heparin in pregnancy

Front 13

LMWH- (little parins-- dalteparin, enoxaparin, tinzaparin) MOA

Back 13

- inactivates factor Xa. Reduced inactivation of thrombin, reduced binding to platelets (less HIT & HAT), osteoblasts (less osteoporosis), macrophages & plasma proteins (predictable T½, dose 1x/day)

Front 14

LMWH- (little parins-- dalteparin, enoxaparin, tinzaparin) PK, Tox

Back 14

- subq though no monitoring needed as w/ unfractionated heparin b/c more predictable
- Tox: major bleeding, minor bleeding at injection site, and thrombocytopenia

Front 15

Direct thrombin inhibitors (-argatroban, lepirudin, bivalirubin)- MOA

Back 15

- interacts directly with circulating & clot bound Thrombin to inhibit converstion of fibrinogen to fibrin & unclot

Front 16

Direct thrombin inhibitors-argatroban, lepirudin, bivalirubin- use

Back 16

- anticoagulant for ppl with HIT

Front 17

Agratroban is different from bivalirudin and lepirudin b/c, what class are these drugs?

Back 17

- direct thrombin inhibitors
- agratroban REVERSIBLY binds to thrombin while -udins irreversibly bind to thrombin
- also udins are excreted renally while agratroban is first made into inactive metabolite by liver

Front 18

- Direct thrombin inhibitors- Tox,

Back 18

- high risk of bleeding compared to heparins

Front 19

Dabigatran- MOA, PK, Tox

Back 19

- MOA- direct thrombin inhibitor (factor IIa)
- PK: ORAL, protein bound
- Tox: major bleeding

Front 20

Fondaparinux- Class, MOA

Back 20

Class: Factor Xa inhibitor
MOA: binds specifically and reversibly to antithrombin which will inactivate factor (Xa).
It accelerates antithrombin activity.

Front 21

Fondaparinux- Class, PK, Use

Back 21

Class: Factor Xa inhibitor
PK: SubQ, long half life
Use: indicated for pts with HIT

Front 22

Warfarin- Use, MOA

Back 22

Use: proph & tx of VT & PE
- atrial fib w/ risk of embolism
- prosthetic heart valve and rheumatic heart disease
MOA: inhibits gamma carboxylation of vitamin K dependent clotting factors : 2, 7, 9, 10, and also anticoagulants protein C & protein S.

Front 23

Warfarin- PK

Back 23

- half life 36-42 hrs but DURATION of action is 2-5 days, highly protein bound
- follow with PT-- want INR 2-3 or 2.5-3.5 if prosthetic heart valve

Front 24

Warfarin- AE

Back 24

- b/c protein C which is an anticoagulant has a half life of 8 hrs the pt may first be hypercoagulable
- give heparin to pt while waiting for warfarin to kick in
- warfarin/coumadin associated skin necrosis (due to knocking out protein S and C..causes microthrombosis in superficial vessels)

Front 25

Warfarin- CI, Drug/food interxns

Back 25

CI:pregnancy, uncontrolled bleeding, GI ulcers, hypersensitivity
Drug/food interxns:
- cant have large amts of vit K rich foods at once, be consistent
- Increased warfarin activity with NSAIDs, thyroid hormone, phenytoin, gingko, broad spectrum abx (gut bacteria help activate vitamin K, if you kill them you get decreased vitamin K), lots of other herbs & medicines
o Decreased warfarin activity with EtOH, estrogen (decreased antithrombin III activity and hence procoaguable), phenytoin, St. John’s Wort, etc. (the inducers)

Front 26

Aspirin- class, MOA

Back 26

Class: anti platelet agents
MOA: irreversible binding of COX enzymes-which prevents thromboxane A2 which would have promoted platelet aggregation and vasoconstriction- lasts for life of platelet- 7-10 days

Front 27

Dipyridamole- Class, MOA

Back 27

Class: antiplatelet agent
MOA: uncertain, possibly inhibits phosphodiesterase (allows cAMP accumulation and reduction in platelet aggregation) and stimulates prostacyclin synthesis to stop platelet aggregation. Often given with warfarin or ASA for prosthetic heart valves or for pts with thrombotic disease

Front 28

Ticlopidine- Class, MOA, Tox

Back 28

Class: anti platelet
MOA:irreversibly binds adenosine diphosphate (ADP) to its receptor on the platelet to competitively inhibit the ADP dependent activation of the glycoprotein IIa/IIIb receptor that is necessary for platelet aggregation.
Tox: neutropenia, tummy aches

Front 29

Clopidogril- Class, MOA, PK/DI

Back 29

Class: anti platelet
MOA: Blocks ADP receptors to inhibit platelet aggregation
PK: prodrug which is activated by the liver using cyp2c19 which is inhibited by PPI like prilosec

Front 30

Glycoprotein IIa/IIIb receptor antagoniststs (Eptifibatide, tirofiban, ABCIXIMAB)- class, MOA, Tox, Use

Back 30

Class: Anti platelet
MO: block receptor necessary for platelet aggregation. IIa/IIIb binds fibrinogen
Use: acute MI, refractory myocardial ischemia, and during cardiac catheterization

Front 31

Prasugrel- MOA, Class, PK, TOx

Back 31

MOA: blocks platelet ADP receptor irreversibly to prevent platelet aggregation
Class: anti platelet agent
PK: prodrug metab by liver but less drug interactions than clopidigrel b/c uses 2 enzyme systems
Tox: life threatening bleeding risk-- black box warning

Front 32

- Kinase drugs- MOA, Class, CI

Back 32

MOA: converts plasminogen to plasmin to dissolve an already formed clot-- leads to fibrin digestion
CI: recent surgery, ulcer, aortic dissection, previous stroke

Front 33

- kinase drugs include both kinase and ____ drugs like alteplase and reteplase which are recombinants.

Back 33

- tPA drugs, other kinase drugs are urokinase