Topic 13 Bloooood Flashcards by Rachel ramella

Anticoagulants indirect thrombin inhibitors

Warfarin (Coumadin)
Unfractionated heparin Low-molecular-weight heparin -Lovenox
Fondaparinux-Arixtra

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Warfarin

Coumadin

Anticoagulants indirect thrombin inhibitors

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Coumadin

Warfarin

Anticoagulants indirect thrombin inhibitors

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Unfractionated Low-molecular-weight heparin

Lovenox

Anticoagulants indirect thrombin inhibitors

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Fondaparinux

Arixtra

Anticoagulants indirect thrombin inhibitors

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Lovenox

Unfrac Low MW Heparin

Anticoagulants indirect thrombin inhibitors

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Arixtra

Fondaparinux

Anticoagulants indirect thrombin inhibitors

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Anticoagulant: Direct Thrombin Inhibitor

Lepirudin (Refludon)
Argatroban
Bivalirudin (Angiomax)

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Lepirudin

Refludon

Anticoagulant: Direct Thrombin Inhibitor

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Argatroban

Anticoagulant: Direct Thrombin Inhibitor

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Bivalirudin

Angiomax

Anticoagulant: Direct Thrombin Inhibitor

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Refludon

Lepirudin

Anticoagulant: Direct Thrombin Inhibitor

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Angiomax

Bivalirudin

Anticoagulant: Direct Thrombin Inhibitor

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How do Anticoagulants work?

inhibit one or more steps in the clotting cascade that lead to fibrin formation…
*They do NOT dissolve clots

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Heparin chemistry

It is a mix of straight-chain polymers consisting of extremely anionic repeating dissacharide units.

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Heparin pH?

most acidic molecules in a critter’s body because so many carboxyl and sulfate groups are attached

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Heparin lives where?

“lives” in mast cells and basophils (which are essentially circulating mast cells.)

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Unfractionated Heparin size?

5000-30,000 Daltons

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One (1) Unit of Heparin?

~0.002 mg of heparin/unit

“The quantity of heparin required to keep 1 milliliter of cat’s (sheep) blood fluid for 24 hours at 0°C”

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Porcine intestinal- derived heparin may be better in preventing what complications ?

HIT

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Heparin administration

ALWAYS Parentally

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Fractionated LMW Heparin size

5,500 daltons

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Heparin + AT-III > _____ more active anticoagulant activity than AT-III by itself

1000X

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Heparin and LMWH:

Intravenous half life

Heparin: 2 hrs
LMWH: 4hrs

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Heparin and LMWH: | Anticoagulant response

Heparin: Variable LMWH: predicable

Heparin and LMWH: | Bioavailibility

Heparin: 20% LMWH: 90%

Heparin and LMWH: | Major adverse effect

Heparin: Frequent Bleeding LMWH: Less Frequent bleeding

Heparin and LMWH: | Setting for therapy

Heparin: Hospital LMWH: Hospital and outpatient

Heparin Time to effect: –Intravenous: –Subcutaneous:

(IV): a few minutes | (SQ): 1-2 hours

Heparin is cleared by what?

cleared by binding to macrophages and being depolymerized and desulfonated in the liver...and the metabolites are excreted in the urine

Unfractionated heparin’s half-life?

~1-2 hours

*Fractionated (LMWH) half-life

3-7 hours

heparin’s half-life is prolonged by what dysfunctions?

either renal &/or liver dysfunction

Heparins process is saturable (implied) - what does this mean?

Lower doses of heparin are cleared at a faster rate than higher higher doses

Heparin is a metabolic process? how do we know this?

heparin clearance is (naturally) slower at lower temps and accelerated at higher temps

Heparin side effects

excessive bleeding | HIT

Fondaparinux

sunthetic LMWH (pentasaccharide)

Fondaparinux t1/2

~20 hours and eliminated unchanged in the urine

Major advantage of Fondaparinux?

eliminated risk of HIT type II

Warfin sponsored by?

Wisconsin Alumni Research Foundation

Warfin works by inhibiting what?

Works by inhibiting Vitamin K

Vitamin K aka

phytonadione/Mephyton

Warfarin blocks an enzyme named what?

named Vitamin K epoxide reductase

Vitamin K epoxide reductase is required to allow the liver to do what?

“recycle” spent (oxidized) Vitamin K so eventually stores of Vitamin K are simply depleted

Giving Vitamin K readily reverses the effects of what?

warfarin

Warfin requires vitamin K to produce factors: (4)

II: Prothrombin VII: Proconvertin IX: Plasma Thromboplastin Component X: Stuart-Prower Factor

Warfin Blocks the γ-carboxylation sites of what factors? (which are also anticoagulants via their ability to block factors Va and VIIIa)

factors II, VII, IX, & X as well as Proteins C and S

Takes a while for Warfarin to exert its clinical effect, why? when is peak effect?

(8-24 hours) since those Vitamin K stores have to be depleted. Peak effects occur~2-4 days (once those stores are completely empty

Warfarin side effects?

``` #1 bleeding birth/fetal deformities/death warfarin necrosis (bc involves CNS) ```

Warfarin typical dose

Typical dose is 5-7mg/day with adjustments made after ∽ one week

Warfarin typically monitored via what?

prothrombin time (PT)

What is added to plasma to monitor Warfarin?

``` Tissue Factor (Factor III) Calcium (Factor IV) ```

INR

= “International Normalized Ratio” | = Critter’s PT / Laboratory “normal” PT mean

Hirudin

Irreversibly binds to and deactivates thrombin

Lepirudin

Refludan

Lepirudin (Refludan) - how does it work?

synthetic, purified form of hirudin Bivalently and irreversibly binds to thrombin One molecule of lepirudin binds one molecule of thrombin

Lepirudin (Refludan) how does it work differently than Heparin?

not dependent on interactions with AT III for its function

Lepirudin (Refludan) T1/2

~ 1 hour, but can increase to several days in renal insufficiency/failure patients

Lepirudin (Refludan) - ~50% of patients who receive this courses of therapy develop what?

Very antigenic. - develop antibodies to the lepirudin-thrombin complex. - These antibodies prevent Lepirudin’s clearance by the kidneys and increases its anticoagulant effect &/or can cause an anaphylactic reaction.

Lepirudin - reversal ?

Unlike heparin, NO REVERSAL AGENT EXISTS!

Bivalirudin what?

(Angiomax) completely synthetic yet chemically smaller “cousin” of hirudin a bivalent direct thrombin inhibitor, operates independent of AT III, and is given parenterally

Bivalirudin (Angiomax) can be removed by what?

hemoconcentrators

Drug that is also commonly used for anticoagulation for patients with HIT

Bivalirudin (Angiomax)

Very commonly used during PTCAs to prevent platelet activation also commonly used for anticoagulation for patients with HIT

Argatroban

A parenterally-administered small molecule direct thrombin inhibitor. Short half-life (~40-50 minutes).

Argatroban monitored with what?

Monitored with aPTTs

Argatroban eliminated how?

*Eliminated by hepatic clearance

Argatroban or Bivalirudin (Angiomax) how do you choose which one to use?

whether the patient has intact renal or hepatic function and ease of monitoring the anticoagulation Bivalirudin - ok with liver failure

Apixiban (Eliquis) and Rivaroxaban (Xarelto)

–Both are oral anticoagulants that directly inhibit Factor Xa Both are cleared renally and used for a-fib

Apixiban

Eliquis Both are oral anticoagulants that directly inhibit Factor Xa

Rivaroxaban

Xarelto Both are oral anticoagulants that directly inhibit Factor Xa

Topic 13 Bloooood Flashcards

(71 cards)