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CPT > L20- Anticoagulants > Flashcards

L20- Anticoagulants Flashcards

1
Q

Intrinsic inhibitors

A

Antithrombin III
Prostacyclin
Calcium

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2
Q

Heparin mechanism

A

Inhibits coagulation in vitro and in vivo
Enhances antithrombin III activity
Target factor X - therefore less prothrombin to thrombin
Targets thrombin IIa - less fibrinogen to fibrin

Heparin simultaneously binds to thrombin (IIa) and antithrombin III
Xa inhibition only requires ATIII binding

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3
Q

Unfractionated heparin (45 polysaccharides) onset, half life and delivery

A

Onset:
Fast onset of action

Half life:
low dose- 30 mins
High dose - 2 hours

Delivery
I.v. Bolus and infusion
Subcutaneous - prophylaxis with low bioavailability

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4
Q

Low molecular weight heparin (15 polysaccharides) examples and mechanism

A

Dalteparin
Enoxaparin
Fondaparinux - synthetic polysaccharide (5) with longer half life (18 hours)

Does not inactivate thrombin IIa
Inhibits factor Xa specifically by enhancing ATIIIa

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5
Q

Low molecular weight heparin delivery, half life, bioavailability

A

Delivery:
- subcutaneous

Half life:
- 2+ hours

Bioavailability:
90% +

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6
Q

Pharmacokinetics of unfractionated heparin - metabolism and monitoring

A

Metabolism:

  • dose dependent - protein binding, depolymerisation, desulfation
  • 1st and zero order elimination

Monitor: aPTT

Use: severe renal impairment and fine control

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7
Q

Pharmacokinetics of low molecular weight heparin

A 
Dose: predictable
Bioavailability: 90% +  
Metabolism: 
- rapid liver 
- slower renal excretion

Monitoring: none
Action: slow onset

Use: most situations

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8
Q

Indications for heparin use (5)

A
  • prevention of thromboembolism
  • perioperative prophylaxis
  • used during pregnancy as does not cross placenta
  • PE or DVT
  • ACS
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9
Q

Adverse reactions of heparin

A
  • bruising and bleeding - intracranial, GI, epistaxis, site of injection
    (Hepatic and regally impaired, elderly or carcinoma patients at higher risk)
  • heparin induced thrombocytopenia - antibodies to heparin platelet factor IV complex paradoxically leads to thrombosis as more platelets activated by damaged endothelium
  • hyperkaleamia- inhibition of aldosterone secretion
  • osteoporosis - rare long term use, higher risk in pregnancy and UFH
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10
Q

Protamine sulphate

A

Heparin antidote
Positively charged
Forms irreversible inactive complex with heparin
Dissociates heparin from ATIIIa

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11
Q

Warfarin

A

Vitamin K antagonist
Inhibits activation of vitamin K dependent clotting factors
Inhibits conversion of vitamin K active reduced form
Decreases hepatic synthesis of active clotting factors II, VII,IX and X

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12
Q

Warfarin onset and half life

A

Delay in onset as active clotting factors need to be metabolised
Half life: 3 to 4 days

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13
Q

Indications for use of warfarin (6)

A
  • PE
  • DVT and superficial VT
  • Atrial fibrillation with high risk of stroke
  • heart valve replacement
  • longer term anticoagulation
  • If anticoagulation needed immediately give heparin cover
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14
Q

Warfarin pharmacokinetics -bioavailability, variability, pregnancy

A

Bioavailability: 95% + (good GI absorption)

Variability:

  • Functional CYP2C9 polymorphism
  • racemic mixture (INR)
  • effected by vitamin K intake

Pregnancy:
- crosses placenta - avoid in 1st and 3rd trimester

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15
Q

Warfarin adverse drug reaction and antidote

A

Bleeding

  • epistaxis
  • retroperitoneal bleeding

Antidote:

  • vitamin K prothrombin complex
  • stop warfarin
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16
Q

Warfarin drug interactions

A

Inhibition of hepatic metabolism:

  • amiodarone
  • clopidogrel
  • alcohol
  • quionolone
  • metronidazole

Reducing vitamin K by eliminating gut bacteria which produces it
- cephalosporin antibiotics - clarythromycin

Displacement of warfarin from plasma albumin
- NSAIDs

Acceleration of warfarin metabolism

  • barbiturates
  • phenytoin
  • rifampicin
  • St Johns Wort
17
Q

Requirements for warfarin use

A

Monitoring - highly varied response
Keep diet and lifestyle stable
INR 3 - 3.5: greater risk of bleeding

18
Q

DOACs mechanism

A

Direct activity oral anticoagulants

  • inhibit free factor Xa and factor Xa bound with ATIII
    OR
  • selectively direct competitive free and bound thrombin inhibitor
19
Q

DOAC examples

A

Direct Xa

  • apixaban
  • edoxaban
  • rivaroxaban

Direct IIa
- dabigatran

20
Q

DOAC adverse reactions

A

Bleeding
Dabigatran contraindicated in low eGFR
Effected by CYP inhibitors and inducers
Avoid in pregnancy

21
Q

Advantages of DOACs

A

Less risk of intracranial bleed

Less risk of stroke in AF patients

CPT (23 decks)

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