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Anticoagulants Flashcards

1
Q

What clotting factors require vitamin K to be produced?

A

II, VII, IX, X

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2
Q

What does plasmin do?

A
  • It is the enzyme that breaks down a fibrin enriched clot
  • *plasmin medications are dangerous to give because they will break down clots everywhere, not just the one clot that may be causing a problem.
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3
Q

For what reasons are anti-coagulants most commonly given?

A
  • in peri-op setting for CV procedures
  • to prevent DVT (10-40% of surgical patients)
  • to pts with chronic atrial fibrillation
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4
Q

How do the different types of anticuagulanst effect clots?

anticoagulants?

anti-platelet drugs?

Thrombolytic drugs?

A
  • Anticoagulants- decrease the production of fibrin
  • Anti-platelet drugs- reduce platelet aggregation/function
  • Thrombolytic drugs- promote clot lysis/fibrinolysis
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5
Q

What are the anticoagulant drugs that decrease the production of fibrin?

A
  • Warfarin (Coumadin)
  • Heparin
  • Low molecular weight heparin
    • lovenox
  • Xa inhibitors
  • Direct thrombin inhibitors
    • Argatroban
    • Dabigatran
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6
Q

Warfarin

Use

origination

A
  • Used for long term thrombosis prophylaxis
    • DVT
    • afib
    • prosthetic heart valves
    • recurrent TIA/MI
  • Originally marketed as a rat poison, but in a much higher dose
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7
Q

If you are dealing with arterial clotting issues, you would use ___________ therapy.

If you are dealing with venous (hemostasis) issues, you would use _________ therapy.

A

anti-platelet

Anticoagulant

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8
Q

Warfarin (Coumadin) MOA?

Why do the effects differ so much from patient to patient?

A
  • Inhibits vitamin K epoxide reductase complex I (VKORC1), preventing the synthesis of vitamin K
    • decrease in vitamin K will decrease production of the clotting factors that require vit K (II, VII, IX, X)
  • The effects of this drug differ so greatly between patients because everybody has a different amount of epoxide reductase and also a different amount of the enzyme that breaks down warfarin
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9
Q

Warfarin:

absorption

peak effect

E1/2t

Pb

dosing

A
  • Absorbed in 1-2 hours, but no effect until the clotting factors you already have are depleted
  • Peak effect delayed 36-72 hours
  • E1/2t = 24-36 hours
  • 97% PB
  • Very narrow therapeutic index, but doses can range from 0.5 mg to 30 mg/day
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10
Q

How is INR calculated?

What would INR be for a pt not on warfarin?

What would INR be for pt with DVT, Afib, or PE?

A
  • (Pt’s PT/normal PT)ISI
  • ISI= international sensitivity index that is given with each batch of thromboplastin
  • Pt NOT on Warfarin = 0.8-1.2
  • Pts with DVT, Afib, or PE = 2.0-3.0
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11
Q

What is pregnancy category for Warfarin?

What are adverse reactions to Warfarin

A
  • Category X
    • Do not take while breastfeeding
  • Adverse reactions?
    • bruising
    • bloody nose
    • bleeding when brushing teeth
    • blood in urine and stool
    • pelvic pain
    • HA
    • dizziness
    • low BP
    • Tachycardia
  • **pts should wear a medical alert bracelet
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12
Q

How can dietary intake affect Warfarin?

How can medications interfere?

A
  • Foods with vit K antagonize the effect of warfarin;
    • have a consistent diet
  • Medications can increase or decrease the anticoagulation effects of Warfarin
    • alter protein binding
    • alter function of CYP enzymes
      • Acetaminophen increases risk of bleeding
      • several anti-sz medication
    • Alter the synthesis or function of clotting factors and/or platelets
      • heparin, NSAIDS, ASA, clopidogrel
    • Alter absorption of warfarin
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13
Q

How far before surgery should you have the pt discontinue their warfarin?

When should you assess how this affects them?

How can warfarin be reversed for emergent procedure

A
  • d/c at least 5 days before elective procedure
  • Assess INR 1-2 days prior to surgery
    • if >1.5, consider 1-2 mg oral Vit K
  • Reversal for urgent procedure: 2.5-5 mg oral or IV vitamin K or FFP
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14
Q

What is the best way to reverse warfarin if INR is high?

A
  • If INR is above range but less than 6.0, hold 1-2 doses of warfarin
  • If INR is higher or pt is showing signs of bleeding, administer Vit K
    • Low doses via oral route is best
    • IV may be used in pts with absorption issues
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15
Q

Unfractionated Heparin

structure?

A
  • Highly sulfated glycosaminoglycans
  • Potency varies so it is always prescribed in units
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16
Q

Heparin function is very variable, what factors cause the variablility?

Molecule size/shape?

PB

Metabolism

Indications

A
  • Variability:
    • Baseline antithrombin activity can influence pt response
    • Temperature dep: more active at higher temps
  • Size/shape:
    • Higly polar and large molecular weight (3,000-30,000 daltons- does not cross biologic membranes)
      • IV/SQ only
      • Good choice in pregnancy and breast feeding
  • Non-specific protein binding = variable free drug/unpredictable dose response
  • Metabolism:
    • Onset in minutes; 1-2 hours SQ
    • 1/2 live about 1 hour; mechanism unclear, renal excretion
  • Indications:
    • PE, DVT (&prevention) acute MI, stroke, dialysis, cardiopulm bypass, DIC
17
Q

Heparin MOA?

A
  • Heparin binds to antithrombin, a normally circulating anti-coagulant, once bound to heparin, the antithrombin’s effect is enhanced about 1,000x
  • Antithrombin/heparin inactivate: thrombin, IX, X, XI, XII
18
Q

What test is used to measure the efficacy of heparin?

What is the goal?

A
  • aPTT
    • goal: 1.5-2x normal (normal = 30-35 seconds)
  • ACT used for higher doses
    • get baseline, then check 3-5 minutes after administration, then every 30 minutes
19
Q

What are the adverse effects of Heparin?

A
  • Hemorrhage
  • HIT (heparin induced thrombocytopenia)
    • 50% decrease in plt count with thrombosis
  • Osteoporosis
  • hypersensitivity- d/t being extracted from animals
20
Q

What is the reversal agent for heparin?

How does it work?

DOA?

dose?

SE?

A
  • Protamine
  • Protamine is alkaline with + charge and heparine is acidic wth - charge, so they are very attracted to each other, together they have no anticoagulant effects
    • removed by macrophages
  • DOA: 2 hours (may need to redose)
  • Dose: 1 mg protamin per 100 units heparin
    • give slowly!
    • consider how much of the dosed heparin has already been metabolized
  • SE:
    • anaphylaxis (made from fish, in insulin)
21
Q

How is Heparin induced thrombocytopenia caused?

A
  • Platelets produce/release platelet factor 4, which the heparin can bind to
  • This creates a new surface that antibodies might bind to, forming a heparin-PF4-antibody complex
  • The antibody will then bind to the Fc receptor on platelets
    • this activates the release of more PF4, further enhancing the aggregation
  • These platelets form clots that are removed by the spleen, causing thrombocytopenia
22
Q

When is heparin contraindicated or should be used cautiously?

A
  • liver and kidney disease
  • indwelling epidural catheter
  • traumatic placement of epidural or spinal anesthetic
  • other anti-platelet or anti-coagulation medications
  • peri-surgical: eye, brain or spinal cord
  • patients at high risk of bleeding
    • hemophilia, aneurysm, severe HTN, GI bleed, thrombocytopenia
23
Q

How does the relative risk of spinal hematoma change with these situations? (table)

  • No heparin
    • no trauma
    • trauma
    • ASA
  • Heparin
    • no trauma
    • trauma
    • heparin > 1 hr after puncture
    • heparin < 1 hour after puncture
    • ASA
A
24
Q

Low molecular weight heparins:

prototype?

use?

efficacy?

A
  • Enoxaparin
  • Use
    • 1st line therapy for DVT prophylaxis and tx
    • unstable angina, MI, coronary ischemia
  • efficacy:
    • equal with heparin- inactivates 10a
    • not as effective in inactivating thrombin
25
Q

LMWH pharmacokinetics?

compared to heparin

A
  • Higher bioavailability
  • longer half life (up to 6x longer)
  • No aPTT monitoring required
  • no hospitalizatin required
26
Q

LMWH

adverse effects?

Contraindications?

A
  • adverse effects:
    • bleeding- lower risk than with unfractionated hep
    • HIT
  • Contraindicatins:
    • effect greatly prolonged in renal failure- use unfractionated heparin instead
    • spinal or epidural- hold for 24 hours
    • Anti-pld or anti-coagulant drugs
    • delay surgery 12 hours after last dose
27
Q

How does Fondaparinux (Arixtra) work?

Half life?

A
  • Exclusively inactivates Xa by enhancing antithrombin III activity
    • no direct effect on thrombin activity
  • Chemically identical to the 5 sugar active site of heparin and LMWH, but much smaller than them
  • Half life is over 3x longer than LMWH
    • E1/2 t = 15 hours
    • effect onset 2 hours, lasts 2-4 days after last dose
    • eliminated unchanged in kidneys
28
Q

Fondaparinux

reversal agent?

Contraindications?

Caution?

A
  • No reversal agent
  • Contraindications:
    • severe renal impairment (CrCL <30ml/min)
    • Weight <50 kg for pts undergoing hip fracture, hip replacement, or knee replacement surgery
  • Caution:
    • HIT does not occur but thrombocytopenia does (3%)
    • elderly
    • CrCl 30-50 ml/min
    • epidural or spinal (d/t long half life)
29
Q
A

Advanced Pharm (27 decks)

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