S10) Anti-Coagulant and Anti-Platelet Therapy Flashcards

1
Q

What is warfarin’s mechanism of action?

A

Warfarin inhibits the production of Vitamin K dependent clotting factors by stopping the conversion of Vit K to active reduced form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Warfarin is the preferred drug choice for long term anti-coagulation.

How is warfarin administered?

A

Orally – due to good GI absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Briefly, describe the pharmacokinetics of warfarin

A
  • Slow onset of action (needs Heparin initially)
  • Slow offset (t1/2 48 hrs)
  • Heavily protein bound
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is warfarin metabolised and what is the clinical significance of this?

A

Mixed function Oxidase cytochrome p450 system:

  • Caution with liver disease
  • Caution if used with drugs that affect p450 system
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Warfarin crosses the placenta.

What is the clinical signicance of this?

A
  • Do not give in 1st Trimester → Teratogenic
  • Do not give in 3rd Trimester → Brain Haem
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How can one monitor the effects of warfarin?

A
  • Extrinsic Pathway Factors
  • Prothrombin Time
  • INR (International Normalised Ratio)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Provide some examples of drugs which potentiate the actions of warfarin

A
  • Amiodarone, quinolone, metronidazole – inhibit hepatic metabolism
  • Aspirin – inhibit platelet function
  • Cephalosporin antibiotics – reduce Vitamin K from gut bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Provide some examples of drugs which inhibit the actions of warfarin

A

Inducing hepatic enzymes, thus increasing metabolism of warfarin:

  • Anti-epileptics (except Na+ valproate)
  • Rifampicin
  • St Johns Wort
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the usual indications for warfarin?

A
  • DVT (3-6 months)
  • PE (6 Months)
  • Atrial fibrillation (Until risk > benefit)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the adverse drug reactions of warfarin?

A
  • Teratogenic
  • Bleeding/bruising (intracranial, epistaxis, injection, GI loss)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

In seven steps, describe the clinical approach one takes before prescribing warfarin

A

⇒ Indication

⇒ PMH e.g PUD, SAH, bleeding disorder

⇒ Medications (interactions)

⇒ Age, Mobility (blood tests and clinics)

⇒ Review blood tests (LFTs, Plt, INR),

⇒ Consider loading dose and heparin cover

⇒ Prescribe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does one manage a patient on warfarin with increasing INR levels of 3.0 < INR < 6.0 (no bleeding)?

A
  • Reduce warfarin dose and stop
  • Restart warfarin when INR < 5.0
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does one manage a patient on warfarin with increasing INR levels of 6.0 < INR < 8.0 (no bleeding / minor bleeding)?

A
  • Stop warfarin
  • Restart warfarin when INR < 5.0
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does one manage a patient on warfarin with increasing INR levels of INR > 8.0 (no bleeding / minor bleeding)?

A
  • Stop warfarin
  • Restart warfarin when INR < 5.0
  • If other risk factors for bleeding, give patient oral Vitamin K
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does one manage a patient on warfarin who experiences major bleeding?

A
  • Stop warfarin
  • Give prothrombin complex
  • Give oral Vitamin K
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the mechanism of action of heparin

A
  • Activate Anti-Thrombin III (ATIII) via unique pentasaccharide sequence
  • Deactivates thrombin, Factor Xa, IIa, IXa, (probably VIIa, XIa, XIIa)
17
Q

Identify and describe the two different types of heparin molecules

A
  • Unfractionated Heparin (intravenous for continuous or subcutaneous for prophylaxis) 20 kDa
  • Low molecular weight Heparins (subcutaneous) 3-4 kDa
18
Q

Compare and contrast the varying effects of LMW heparin and Unfractionated heparin on Factor Xa and thrombin

A
19
Q

Compare and contrast UFH and LMWH based on the following factors:

  • Dose-response
  • Bio-availability
  • Action
  • Administration
  • Initiation
A
20
Q

How is heparin administered?

A

Parenterally – due to poor GI absorption

21
Q

Briefly, describe the pharmacokinetics of heparin

A
  • Rapid onset of action (heparin cover)
  • Rapid offset of action
22
Q

Describe the uses of heparin

A
  • Prevention of thrombo-embolism during operation in those normally on warfarin (stopped for surgery)
  • Heparin cover for DVT/PE and AF
  • Pregnancy in place of warfarin
  • Reduces recurrence/extension of acute coronary syndromes
23
Q

Identify some adverse drug reactions of heparin

A
  • Bruising/bleeding sites (intracranial, GI loss, epistaxis, injection sites)
  • Osteoporosis
  • Thrombocytopenia
24
Q

Describe the reversal therapy for heparin (what is used, how?)

A

Protamine sulphate:

  • Dissociates heparin from anti-thrombin III
  • Irreversible binding to heparin
  • Used for major bleeding, allergy / anaphylaxis
25
Q

Identify some anti-platelet drugs and their mechanism of action

A
  • Aspirin – COX-1 inhibition
  • Dipyridamole – Phosphodiesterase Inhibitors
  • Clopidogrel – Inhibit ADP dependent aggregation
  • Glycoprotein IIb / IIIa Inhibitors – decreases platelet crosslinking by fibrinogen