Anticoagulants Flashcards

1
Q

Describe the intrinsic pathway of the coagulation cascade

A
  • Abnormal / damaged surface
  • Kininogen released
  • Formation of XIIₐ from XII
  • Formation of XIₐ from XI
  • Formation of IXₐ from IX
  • Formation of Xₐ from X (VIIIₐ catalyst)
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2
Q

Describe the extrinsic pathway of the coagulation cascade

A
  • Trauma / tissue damage
  • Formation of VIIₐ from VII
  • Formation of Xₐ from X (tissue factor catalyst)
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3
Q

Describe the common pathway of the coagulation cascade

A
  • Formation of thrombin (IIₐ) from prothrombin (II) (Xₐ and Vₐ catalyst)
  • Formation of fibrin (Iₐ) from fibrinogen (I)
  • Formation of cross-linked fibrin clot (XIIIₐ catalyst)
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4
Q

Name 4 types of anti-coagulant drugs

A
  1. Heparin
  2. Coumarins
  3. Direct Thrombin Inhibitors
  4. Direct Factor Xₐ Inhibitors
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5
Q

Where do anticoagulants tend to target?

A

Veins

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6
Q

What are 2 types of heparin?

A
  1. Unfractionated (UFH)

2. Low molecular weight (LMWH)

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7
Q

Give an example of a LMWH drug

A

Enoxaparin sodium

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8
Q

Name 2 reasons why may LMWH drugs be preferable to UFH

A
  1. Longer duration

2. More predictable anticoagulant effect

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9
Q

Describe the mechanism of action of heparin

A
  • Binds to and activates anti-thrombin III (ATIII)
  • LMWH-ATIII complex inactivates Xₐ
  • UFH-ATIII complex inactivates Xₐ and thrombin
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10
Q

Why are heparin drugs not administered orally?

A

Large, highly charged molecules so cannot be absorbed by the GIT

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11
Q

Describe the ADME of UFH

A
  • Given IV (or subcutaneously)
  • Immediately active
  • T½ = 40-90 minutes
  • T½ increases at higher dose as metabolic pathways in liver saturate
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12
Q

Describe the ADME of LMWH

A
  • Given subcutaneously
  • Longer T½ (once or twice daily dose)
  • Renal excretion
  • Caution in renal failure
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13
Q

What 3 clinical conditions may heparin be used to treat?

A
  1. Thromboembolic disease
  2. Acute coronary system
  3. Acute peripheral arterial occlusion
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14
Q

Name 2 uses of heparin other than treatment of clinical conditions

A
  1. Prevention of thromboembolic disease

2. Extracorporeal circuits (haemodialysis)

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15
Q

Why are heparins used instead of warfarin in pregnancy?

A

Heparin molecules are too large to cross the placenta

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16
Q

What are 5 adverse effects of heparin?

A
  1. Haemorrhage
  2. Reduced aldosterone secretion (hyperkalaemia)
  3. Osteoporosis and alopecia (rarely)
  4. Hypersensitivity reactions
  5. Thrombocytopenia
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17
Q

What is thrombocytopenia?

A

Reduced platelet count

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18
Q

How is UFH monitored?

A
  • UFH given as IV bolus then infusion adjusted by activated partial thromboplastin time
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19
Q

How does APTT allow for the adjustment of UFH?

A
  • APTT uses thromboplastin with no tissue factor activity

- Tests intrinsic and final common pathways

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20
Q

How can LMWH monitoring be carried out?

A
  • LMWH does not affect APTT
  • If need to assess, effect can measure Factor Xₐ activity
  • Rarely done due to predictability
21
Q

Give an example of a coumarin drug

A

Warfarin

22
Q

Describe the mechanism of action of warfarin

A
  • Inhibitor of Vitamin K epoxide reductase
  • Prevention of regeneration of reduced Vitamin K
  • Blocks synthesis of Vitamin K-dependent clotting factors
23
Q

What are 3 uses of warfarin?

A
  1. Prophylaxis and treatment of thromboembolic disease
  2. Prophylaxis in atrial fibrillation
  3. Prophylaxis with prosthetic heart valves fitted
24
Q

What value is used to monitor warfarin?

A

International Normalised Ratio

25
Q

What are 5 adverse effects of warfarin?

A
  1. Haemorrhage
  2. GI upset
  3. Teratogen
  4. Alopecia
  5. Skin necrosis
26
Q

Name 5 contraindications of warfarin

A
  1. Pregnancy
  2. Active bleeding
  3. Recent peptic ulcer
  4. Uncontrolled severe hypertension
  5. Bacterial endocarditis
27
Q

What 4 things can cause variation in warfarin effects?

A
  1. Diet
  2. Disease
  3. Genetic variation
  4. Drug interactions
28
Q

What 3 diseases can cause a variation in warfarin effects?

A
  1. Acute liver disease
  2. Congestive heart failure
  3. Small bowel disease
29
Q

What 2 results of genetic variation can cause a variation in warfarin effects?

A
  1. Vitamin K epoxide reductase

2. Cytochrome P450-2C9

30
Q

Name 4 drugs which increase the effects of warfarin

A
  1. Metronidazole
  2. Erythromycin
  3. Fluconazole
  4. Cimetidine
31
Q

Name 3 drugs which reduce the effect of warfarin

A
  1. Rifampicin
  2. Barbiturates
  3. Carbamazepine
32
Q

Name a type of drug which is used as a safer alternative to coumarin drugs

A

Direct Acting Oral Anticoagulants (DOAC)

33
Q

Name 2 examples of DOAC drugs and their targets

A
  1. Dabigatran - Thrombin IIₐ inhibitor

2. Apixaban - Direct Xₐ inhibitor

34
Q

What are 3 clinical uses of DOAC drugs?

A
  1. Treatment of thromboembolic disease
  2. Prophylaxis of thromboembolic disease
  3. Prophylaxis of stroke in non-valvular atrial fibrillation
35
Q

What are 5 adverse effects of DOAC drugs?

A
  1. GI upset
  2. Abdominal pain
  3. Dyspepsia
  4. Thrombocytopenia
  5. Haemorrhage
36
Q

Name 5 drugs which interact with DOAC drugs

A
  1. Other anticoagulants (Warfarin)
  2. Significant enzyme inhibitors (Fluconazole)
  3. NSAIDs (Naproxen)
  4. P-gp1 enzyme inhibitors (clarithromycin)
  5. P-gp1 enzyme inducers (carbamazepine)
37
Q

Name 3 advantages of DOAC drugs compared to warfarin

A
  1. Orally available with faster onset
  2. No need for monitoring INR
  3. Less toxicity and interactions
38
Q

Name 3 disadvantages of DOAC drugs compared to warfarin

A
  1. More frequent dosing required
  2. Lack of reversal agents
  3. Less known about efficacy and safety
39
Q

What are 4 contraindications of DOAC drugs?

A
  1. Pregnancy
  2. Artificial heart valve present
  3. Liver disease
  4. Malignancy
40
Q

How do fibrinolytic drugs function?

A

Activate conversion of plasminogen to plasmin which dissolves fibrin strands of clot

41
Q

Name 2 examples of fibrinolytic drugs

A
  1. Streptokinase

2. Alteplase

42
Q

What are 2 clinical indications of fibrinolytic drugs?

A
  1. Given IV for acute pulmonary embolism

2. Reduce mortality early post myocardial infarction or ischaemic stroke

43
Q

Name 4 side effects of fibrinolytic drugs

A
  1. Bleeding
  2. Breakaway embolus formation
  3. Reperfusion arrhythmias
  4. Hypersensitivity reactions
44
Q

How do anti-fibrinolytic (pro-coagulant) drugs function?

A

Inhibit the activation of plasminogen to plasmin and/or stabilise fibrin clot

45
Q

Name 2 examples of anti-fibrinolytic drugs

A
  1. Tranexamic acid

2. Desmopressin

46
Q

What is the mechanism of action for tranexamic acid?

A

Synthetic analogue of lysine which binds to plasminogen preventing plasmin from binding to and degrading fibrin

47
Q

What is the mechanism of action of desmopressin?

A

Modified form of vasopressin which activated V₂ receptor coupled to stimulation of van Willibrand’s factor release from endothelium

48
Q

What are 2 side effects of anti-fibrinolytic drugs?

A
  1. GI upset

2. Hypotension

49
Q

What are 2 clinical indications of anti-fibrinolytics?

A
  1. Control persistent haemorrhage after tooth extraction

2. Given with Factor VIII as standard therapy for haemophilia