Antithrombotic Drugs Flashcards

1
Q

What are the two major anticoagulant drugs?

A

Warfarin

Heparin

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2
Q

What is the mechanism of action of warfarin?

A

Blocks vitamin K epoxide reductase, preventing reduction of vitamin K back to its acted form which is needed as a cofactor for coagulation factor synthesis.

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3
Q

Why might you give heparin alongside warfarin initially?

A

Warfarin has a slow onset of action - heparin covers you for the first few days

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4
Q

List 4 uses of warfarin

A
  • Prevention of recurrence of VTE
  • Prevention of AF
  • Prevention of thrombosis in mechanical heart valves
  • Prevention of thrombosis in thrombophilic conditions
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5
Q

Why isn’t warfarin used to prevent stroke/MI

A

These are arterial and caused by platelet aggregation - therefore anti-platelet drugs more efficacious

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6
Q

What is the main ADR associated with warfarin?

A

Bleeding

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7
Q

List two circumstances in which Warfarin use is contraindicated

A
  • Liver disease

- Pregnancy

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8
Q

List two major groups of DDI associated with warfarin use. Give examples.

A
  • CYP450 inducers reduce warfarin levels - e.g. Rifampicin, St John’s Wort
  • CYP450 inhibitors increase warfarin levels - e.g. Macrolides, alcohol
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9
Q

How would you monitor warfarin levels? Give the full name.

What would the ideal range be

A

International normalised ratio (INR)

In most conditions, 2 - 3, but in mechanical heart valves 3 - 6

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10
Q

List the steps taken to reverse warfarin in the case of bleeding

A
Reduce warfarin
Stop warfarin
Oral vitamin K
IV vitamin K
Fresh frozen plasma
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11
Q

What are the two types of heparin and how do they differ in administration/monitoring?

A

Unfractionated heparin - IV, non-linear PK - needs monitoring via aPTT
Low molecular weight heparin - subcutaneous injection - more predictable PK - no monitoring needed.

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12
Q

Give an example of a low molecular weight heparin

A

Dalteparin

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13
Q

Describe the mechanism of action of heparin (both unfractionated and LMW)

A

Binds to antithrombin III (ATIII) which activates it.
ATII in turn inhibits:
- Xa
If heparin is unfractionated, also binds to IIa - inhibits this too.
End result is prevention of fibrin plug formation

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14
Q

List 3 major uses of heparin

A
  • VTE prophylaxis
  • First-line treatment of VTE
  • Safe in pregnancy
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15
Q

List 3 important ADRs of heparin

A
  • Bleeding
  • Injection site reactions
  • Heparin-induced thrombocytopenia (autoimmune)
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16
Q

How is heparin reversed?

A

Stop heparin

Give protamine sulphate

17
Q

List the 3 anti-platelet drugs on the PPE drug list

A
  • Aspirin
  • Dipyridamole
  • Clopidogrel
18
Q

Briefly outline the mechanism of action of aspirin

A
  • Inhibits COX-1 by binding irreversibly
  • Therefore inhibits conversion of arachadonic acid to prostaglandin H2
  • In turn, this prevents production of thromboxanes which promote platelet aggregation - hence decreased aggregation
19
Q

List the 2 major uses of aspirin as an antiplatelet

A
  • Acute coronary syndrome - prevents clot progression

- Prevention of thrombosis in CVS disease

20
Q

List 3 ADRs associated with aspirin

How could you overcome one of these?

A
  • GI irritation +/- ulceration/haemorrhage - use PPI
  • Bronchospasm
  • Tinnitus
21
Q

In whom should aspirin be used with caution? (4 examples)

A
  • Children under 16
  • Asthmatics
  • Peptic ulcers
  • 3rd trimester of pregnancy
22
Q

What is the mechanism of action of dipyridamole?

A
  • Phosphodiesterase inhibitor - increases cAMP, therefore decreases Ca2+.
  • Therefore decreased thromboxane synthesis and hence decreased platelet aggregation
23
Q

What is the major use of dipyridamole?

List 2 ADRs - why do they occur?

A

Secondary prevention of stroke

Can cause flushing and headaches - positive inotropic effect and vasodilatory

24
Q

What is the mechanism of action of Clopidogrel? (And therefore what is its class?)

A
  • ADP Antagonist
  • Binds irreversibly to the P2Y12 ADP receptor on the platelet surface - therefore decreases platelet aggregation due to decreased downstream signalling.
25
Q

When is Clopidogrel most often used?

A

In conjunction with aspirin for same conditions

26
Q

List 3 important ADRs associated with Clopidogrel

A
  • Bleeding
  • GI upset
  • Thrombocytopenia
27
Q

What is significant in terms of DDIs with Clopidogrel?

Why is this particularly relevant given its common usage?

A
  • Pro-drug - requires activation by CYP450 enzymes
  • Therefore inhibited by CYP450 inhibitors
  • These include Omeprazole - commonly used for gastroprotection with aspirin, which Clopidogrel is usually used alongside
  • Lansoprazole is a better bet
28
Q

What is alteplase?

A

Thrombolytic drug - recombinant tissue plasminogen activator

29
Q

How does alteplase work?

A

Generates plasmin itself - therefore dissolves fibrin

Works preferentially in the presence of fibrin, so clot-specific

30
Q

Give another example of a thrombolytic drug

A

Reteplase

31
Q

Give 4 uses of thrombolytic drugs

A
  • Acute MI
  • PE
  • Major VTE
  • Stroke (if clearly infarction)
32
Q

It’s not on the drug list, but what is streptokinase? Why is its usage unique?

A

Another thrombolytic drug - bacterial protein which binds to and activates plasminogen
As its bacterial, it’s antigenic - cannot be used more than once in same patient as body produces antibodies against it

33
Q

What is the major ADR associated with thrombolytic drugs?

List 2 specific to streptokinase

A
  • Bleeding

- Anaphylaxis, hypotension during IV infusion

34
Q

List 4 contraindications to using thrombolysis

A
  • Trauma
  • History of cerebral haemorrhage
  • Coagulation defect
  • Uncontrolled hypertension