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Clinical pharmacology and therapeutics > Anticoagulant and antiplatelet drugs > Flashcards

Anticoagulant and antiplatelet drugs Flashcards

1
Q

Describe the coagulation cascade

A

Extrinsic pathway - Tissue factor (3), 7
Intrinsic pathway - 12, 11, 9, 8

Prothrombin (2) - Thrombin (2a)

Fibrinogen (1) - Fibrin monomer - 13 - fibrin clot formation

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2
Q

Name some anticoagulants

A 
Warfarin
Heparin
Direct oral anticoagulants 
Antiplatelets
Antifibrinolytics
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3
Q

List the two types of heparin

A

Unfractionated

Low molecular weight

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4
Q

List some direct oral anticoagulants and state what they inhibit

A

Dabigatran - Thrombin (2a)

Rivaroxaban - 10a

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5
Q

What is warfarin?

A

Vitamin K antagonist
Prevents gamma carboxylation of factors 2, 7, 9 and 10
Prolongs the extrinsic pathway

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6
Q

How is warfarin use monitored?

A

International normalised ration (INR)

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7
Q

What is the target INR for DVT/PE/AF?

A

2.5

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8
Q

What is the target INR for recurrent VTE or metal heart valves?

A

3.5

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9
Q

Describe how warfarin is metabolised

A

Hepatically metabolised by CYP2C9

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10
Q

How many days does it take warfarin to reach therapeutic levels?

A

> 3 days

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11
Q

What does warfarin inhibit?

A

Natural anticoagulants - Protein C and protein S

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12
Q

What is the half life of clotting factor 7?

A

6 hrs

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13
Q

What is the half life of clotting factor 9?

A

24 hrs

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14
Q

What is the half life of clotting factor 10?

A

40 hours

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15
Q

What is the half life of clotting factor 2?

A

60 hours

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16
Q

Describe how warfarin is prescribed?

A

Patient usually loaded with LMW heparin cover
10mg, 10mg, 5mg

Fall in protein C and S within hours may result in a temporary pro-coagulant state

LMW heparin continued till INR> 2.0 for 2 consecutive days

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17
Q

Why does warfarin interact with other drugs?

A

Cytochrome P450

Beware of interaction with alcohol

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18
Q

List some enzyme inhibitors that potentiate warfarin

A 
Carbamezepine 
Azathioprine
Allopurinol 
Erythromycin 
Ciprofloxacin 
Metronidazole 
Fluconazole
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19
Q

List some enzyme inducers which inhibit warfarin

A

Rifampicin
Amiodarone
Citalopram
Phenytoin

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20
Q

List some side effects of warfarin

A

Haemorrhage risk - intracranial bleeds, increased risk in elderly
Skin necrosis
Alopecia

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21
Q

Is warfarin safe to use in pregnancy?

A

No

teratogenic effects

22
Q

Which anticoagulant is used in pregnancy?

A

LMW heparin

23
Q

How do you reverse warfarin?

A

If life threatening bleed - give activated prothrombin complex (octaplex) containing factors 2, 7, 9 and 10 (25-50 units per kg)

Give vitamin K 2-10mg iv/po depending on INR level

Fresh frozen plasma can also be used

24
Q

Describe heparin

A

Mucopolysaccharide that potentiates antithrombin

Irreversibly inactivates factors 2a (thrombin) and 10a

25
Q

How is heparin administered?

A

Parentally
LMW - Sc injections
Unfractionated - iv infusion

26
Q

Describe the use of unfractionated heparin

A

Given with iv 5000bolus and 1000U/hour infusion

27
Q

How is unfractionated heparin monitored?

28
Q

What is the APTT target range of unfractionated heparin?

A

1.5-2.5 x normal

29
Q

Is unfractionated heparin safe in renal failure?

30
Q

How can unfractionated heparin be partially reversed?

A

Protamine sulphate

31
Q

List two rare complications of using unfractionated heparin

A

Thrombocytopenia

VTE

32
Q

Describe the use of low molecular weight heparin

A

Once daily sc injections
Prescribed according to the patients weight
Not usually monitored - can use Xa assay
Patient must have creatinine clearance of over 30ml/minute

33
Q

List the LMW heparin formulations

A

Tinzaparin 175U/Kg
Enoxaparin 1.5mg/Kg
Dalteparin

34
Q

What is LMW heparin commonly used for in hospital patients?

A

Thromboprophylaxis

35
Q

Describe the dose of LMW heparin used in thromboprophylaxis in hosptial patients

A

3500 U or 4500 U Tinzaparin

20 or 40mg Enoxaparin

36
Q

Describe a Hirudin and give an example

A

Snake venom derived
Argatroban - direct thrombin inhibitor
Used in place of heparin in patients with HIT

37
Q

Describe a heparinoid and give an example

A

Danaparoid - heparin like compound

38
Q

Describe a fondaparinux and ive an example

A

Arixtra - potentiates anti thrombin - inhibits factor Xa

39
Q

Give the two classes of direct oral anticoagulant and Give examples

A 
Direct thrombin (2a) inhibitor - dabigatran
Direct factor 10a inhibitor - rivaroxaban
40
Q

Give the indications of rivaroxaban

A

VTE prophylaxis
Treatment of DVT and PE
Stroke prevention in AF

41
Q

Give the dosing of rivaroxaban

A

15mg bd for 3 weeks

then 20mg od

42
Q

Give the indications for dabigatran

A

VTE prophylaxis
Treatment of DVT and PE
Stroke prevention in AF

43
Q

Give the dosing of dabigatran

A

Treatment dose - 150mg bd

Prophylactic dose 110mg bd

44
Q

What must you do before prescribing dabigatran?

A

Confirm creatinine clearance > 30ml/min

45
Q

How can dabigatran be reversed?

46
Q

List the types of antiplatelet drugs

A 
Aspirin
Clopidogrel
Dipyridamole
Prostacyclin 
Glycoprotein 2b/3a inhibitors
47
Q

How does aspirin work?

A

Cyclooxygenase inhibitor

48
Q

How does clopidogrel work?

A

ADP receptor blocker

49
Q

How does dipyridamole work?

A

Inhibits phosphodiesterase

50
Q

How does Prostacyclin work?

A

Stimulates adenylate cyclase

51
Q

Name some glycoprotein 2a/3b inhibitors

A

Abciximab - monoclonal antibody
Eptifibatide - snake venom derivative
Tirofiban - blocks platelet aggregation

52
Q

Describe fibrinolytic agents

A

Thrombolytic agents used to lyse fresh thrombi (arterial) by converting plasminogen to plasmin

Tissue plasminogen activator (alteplase, tap) and streptokinase

Administered systemically in acute MI, recent thrombotic stroke, major PE or iliofemoral thrombosis

Aim to use within 6 hrs

Clinical pharmacology and therapeutics (27 decks)

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