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MCC > Wk 3 Drugs Affecting Hemostasis > Flashcards

Wk 3 Drugs Affecting Hemostasis Flashcards

1
Q

What is INR?

A

International Normalized Ratio
-calculated from PT to standardize results to be compared across labs

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2
Q

How is warfarin monitored?

A

PT testing

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3
Q

MOA warfarin

A

Anticoagulates by acting as a vitamin K antagonist, reducing [] of F II, VII, IX, and X

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4
Q

Therapeutic range of warfarin

A

INR of 2-3

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5
Q

What does it mean to be vitamin K dependent?

A

IMP to create Ca2+ binding sites so the factors can participate in Ca-dependent rxns in the coagulation cascade

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6
Q

What factors in the thrombolysis pathway does warfarin affect?

A

Protein C and S

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6
Q

What factors in the thrombolysis pathway does warfarin affect?

A

Protein C and S

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7
Q

What is heparin for?

A

Anticoagulant (naturally occurring)
-Indirect thrombin inhibitor

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8
Q

Heparin MOA

A

potentiates antithrombin (makes antithrombin better at doing its job of inactivating certain coagulation factors)
anti FII and FXa activity paired w/ antithrombin

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8
Q

Heparin MOA

A

potentiates antithrombin (makes antithrombin better at doing its job of inactivating certain coagulation factors)
-either IV or subcutaneous injection (parenteral administration)

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9
Q

Heparin key things to know

A

tx for blood clots, maintain vascular access
-large (heparin hunter)
-monitored w/ aPTT or anti-Xa activity (measures heparin paired w/ antithrombin)
-LMWH does not require monitoring
-either IV or subcutaneous injection (parenteral administration)
-indirect mechanism b/c requires antithrombin for action

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10
Q

What is the difference b/w unfractionated heparin (UFH) and low molecular weight heparin (LMWH)

A

UFH = lots of big sticky molecules w/ long polysaccharide tails. Good activity against IIa and Xa
LMWH = more purified w/ fewer big sticky molecules. Mostly active against Xa, less so IIa

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11
Q

Fondaparinux

A

synthetic
-binds to antithrombin to change its confirmation
-only has anti-Xa activity
-fragment of heparin

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12
Q

What are the direct oral anticoagulants (DOACs)?

A
  1. dabigatran - direct thrombin inhibitor
  2. rivaroxaban - direct Xa inhibitor
  3. apixaban -“
  4. edoxaban - “
  • do not require lab monitoring
  • avail in pill form
  • newer (approved 2010-2015)
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13
Q

What is the class of drugs that affect platelet fxn?

A

Antiplatelet agents:
COX-1 inhibitor - aspirin

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14
Q

What are the LMWHs?

A
  1. dalteparin
  2. enoxaparin
  3. tinzaparin
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15
Q

What is HITS?

A

=heparin-induced thrombocytopenia syndrome
-life-threatening

16
Q

What happens to cause HITS?

A

formation of antibodies that recognize complexes of heparin and PF4 on the surface of platelets, and complexes of heparin-like molecules and PF4-like proteins on endothelial cells

17
Q

What are 3 direct thrombin inhibitors?

A
  1. bivalirudin
  2. argatroban
  3. dabigatran
18
Q

3 direct F Xa inhibitors

A
  1. rivaroxaban
  2. apixaban
  3. edoxaban
19
Q

What are 2 antiplatelet agents that work as thienopyridine P2Y12 inhibitors?

A
  1. clopidogrel
  2. prasugrel
20
Q

What are reversal agents to anticoagulants?

A

Vitamin K
Desmopressin
Plasma fractions
protamine
idarucizaumab (dabigatran reversal)
andexanet alfa (rivaroxaban and apixaban reversal)

21
Q

2 Antiplatelet agents, non-thienopyridine P2Y12 inhibitors

A

ticagrelor
cangrelor

22
Q

Antiplatelet agents - glycoprotein IIb/IIIa inhibitors

A

abciximab
eptifibatide
tirofiban

23
Q

Antiplatelet Agent - glycoprotein IIb/IIIa inhibitor

A

abciximab

24
Q

Sketchy F II

A

Thrombin = throm-beaver w/ 2 front teeth

25
Q

How is F II activated?

A

Thrombin activated by F X (fox) -> F Xa (a= activated)
Converts F II -> IIa

26
Q

What does thrombin do?

A

Builds damn w/ fibrin (sticks) monomers cross-linked w/ F XIII (aided by platelet phospholipids and Ca2+)

27
Q

What does antithrombin target?

A

-endogenous, floating around
-inactivates F II (thrombin), F IXa, Xa, XIa, and XIIa by forming stable complexes with them (usually slow, but heparin accelerates them)
-think of anti-thrombin as heparin hunter’s trap to capture the throm-beaver
-specifically binds anti-thrombin III (think trap bars)

28
Q

What happens when heparin binds anti-thrombin III?

A

A complex is formed that irreversibly inactivates thrombin and factor Xa

29
Q

How is heparin monitored?

A

aPTT b/c the heparin-anti-thrombin complex inhibits most of the instrinsic pathway factors
-eliminated by liver
-does not cross placenta

30
Q

Is heparin a clot-buster?

A

No, it prevents clots from forming. Used in acute setting to prevent further clotting, often for venous thrombosis - DVT and then PE, or acute MI
-can also be used prophylactically for conditions that may predispose to thrombosis- major surgery, pregnant, lying in hospital, malignancy, hx of oral contraceptives -> subcutaneous heparin

31
Q

What causes acute MI?

A

Usually due to piece of thrombotic plaque that breaks off
-immediately start pt on anti-platelet therapy

32
Q

What are adverse effects of heparin?

A
  1. bleeding
  2. heparin-induced thrombocytopenia (HIT)
33
Q

What is HIT?

A

-hypercoaguable state
-occurs in up to 5% of pts tx w/ heparin (usually over 7 days)
-body makes antibodies against heparin bound to platelet F IV
-heparin is most common cause of thrombocytopenia (think of broken clay plates) in hospital that paradoxically happens w/ thrombosis

34
Q

What are 2 rare effects w/ heparin?

A
  1. Hyperkalemia
    -due to toxic effect on adrenal cells that produce aldosterone (mineralcorticoid that -> increased Na+ retention at expense of increased K+ excretion) -> hypoaldosteronism
    -heparin-induced hypoaldosteronism causes hyperkalemia
  2. osteoporosis: heparin can decrease bone formation
35
Q

What is protamine?

A

Heparin reversal agent
-reverses anticoagulant effect (less effective for LMWH and fondaparinux)
-sketchy protective fence that blocks heppy hunter from hunting in an area
-a (+) charged molecule that binds to negatively charged unfractionated heparin

36
Q

How do LMWH work?

A

LMWH-antithrombin complex inhibits F Xa w/ less effect on thrombin (think smaller cage can only fit foX, no space for throm-beaver)
-IV or commonly subcutaneous
-acute setting an prophylactically
-small, so can sneak through protamine protective fence and is not effectively reversed by protamine
-longer half-life, less frequent dosing
-no routine monitoring
-eliminated renally (if renal insufficiency, half-life cound be extended)
-does not cross placenta

37
Q

What is fondaparinux?

A

-synthetic heparin derivative
-fido w/ foxes (F Xa) in pair of tiny cages that snuck by the protective protamine
-binds anti-thrombin III
-lowest risk of HIT (fido cannot shoot at clay platelets)

38
Q

Direct Thrombin inhibitors

A

Sketchy:
no “intrudin” (bivalirudin) to gator area - arGATROban and dabiGATRAN where gator is about to bite into throm-beaver

39
Q

Direct F Xa Inhibitors

A

FoXes are banned from chicken coup - rivaroXaBAN and apiXaBAN and edoXaBAN
-fixed oral dosing, no monitoring
-a-fib

MCC (44 decks)

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