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Clinical Pharmacology > 15) Anticoagulant Therapy > Flashcards

15) Anticoagulant Therapy Flashcards

1
Q

What are the constituents of Virchow’s triad?

A

Hypercoagulability
Endothelial damage
Stasis

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2
Q

What factors/conditions can affect hypercoagulability?

A 
Smoking
OCP
Heart valves
Malignancy
Protein C and S deficiency
SLE
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3
Q

What factors/conditions can cause endothelial damage?

A

Atheroma
HTN
Toxins (cigarettes)

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4
Q

What factors/conditions cause stasis?

A

Venous - immobility

Arterial - cardiac abnormality (AF)

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5
Q

What is the mechanism of action of warfarin?

A

Inhibits production of vitamin K dependent clotting factors

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6
Q

What are the vitamin K depending clotting factors?

A

Prothrombin (II), VII, IX, X

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7
Q

Describe the onset and offset time of warfarin:

A 
Slow onset
Slow offset (need to stop 3 days before surgery)
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8
Q

Describe the pharmacokinetics of warfarin (ADME):

A

Good GI absorption
Heavily protein bound
Metabolised in liver by cytochrome P450

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9
Q

What are some adverse effects of warfarin?

A

Teratogen (trimester 1) and can cause brain haemorrhage (T3)

Excessive bleeding - intracranial, epistaxis, GI

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10
Q

How can warfarin be monitored?

A

Prothrombin time

INR

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11
Q

What is the prothrombin time?

A

Citrated plasma clotting time

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12
Q

What is the INR?

A

Standard value of PT between labs

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13
Q

What drugs can inhibit the hepatic metabolism of warfarin?

A

Amiodarone, quinolone, metronidazole, alcohol

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14
Q

What drugs increase warfarin’s effect?

A

Aspirin
Cephalosporins (reduce vit K from gut bacteria)
NSAIDs

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15
Q

What drugs are inhibitors of warfarin?

A

Anti-epileptics
Rifampicin
St John’s Wort

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16
Q

When is warfarin used?

A

DVT, PE, AF, prosthetic valves

17
Q

How can the action of warfarin be reversed?

A

Stop warfarin and give: IV vit K, fresh frozen plasma or prothrombin complex concentrate

18
Q

Describe the structure of heparin:

A

Glycosaminoglycan with a glucose backbone

19
Q

What is the mechanism of action of unfractionated heparin?

A

Activate anti-thrombin III that de-activates factors Xa, IIa, IXa

20
Q

What clotting factor is affected by low molecular weight heparin?

A

Xa

21
Q

How do unfractionated and LMWH heparin vary in structures?

A

Unfractionated: variable length heparin chains (20kDa)
LMWH: small chains (4kDa)

22
Q

How do unfractionated and LMWH heparin vary in route of administration?

A

Unfractionated: IV
LMWH: SC

23
Q

Why is unfractionated heparin able to inhibit thrombin, when LMWH can’t?

A

To catalyse inhibition of thrombin by ATIII, heparin has to bind to molecules simultaneously and only unfractionated is large enough to do this

24
Q

Describe the onset and offset time of heparin:

A

Rapid onset and offset of action

25
Q

Describe the pharmacokinetics of LMWH (ADME):

A

Poor GI absorption
High bioavaliability
Long half life

26
Q

How can unfractionated heparin be monitored?

A

Activated partial thromboplastin time

27
Q

When is heparin used?

A

Prevention of thromboembolsim (post op, immobility)
DVT/PE and AF
Acute coronary syndromes
Pregnancy

28
Q

What are some of the adverse effects of heparin?

A

Bruising/bleeding
Heparin induced thrombocytopenia
Osteoporosis

29
Q

Explain heparin-induced thrombocytopenia:

A

Heparin and PF4 on platelets are immunogenic, IgG complexes form activating more platelets until platelets are depleted and get thromboses in area

30
Q

How should heparin induced thrombocytopenia be managed?

A

Stop heparin and add hirudin

31
Q

How can heparin be reversed?

A

Stop heparin and if actively bleeding give protamine sulphate

32
Q

Name some antiplatelet drugs:

A

Aspirin
Clopidogrel
Dipyridamole
Glycoprotein IIb/IIIa inhibitors

33
Q

What is the mechanism of action of aspirin?

A

Inhibition of thromboxane A2 production by COX enzymes

34
Q

What is the mechanism of action of clopidogrel?

A

Inhibits P2Y12 ADP receptor involved in platelet activation

35
Q

When is clopidogrel given?

A

ACS and PCI

36
Q

What is the mechanism of action of dipyridamole?

A

Phosphodiesterase inhibitor - positive ionotrope and vasodilator

37
Q

When is dipyridamole given?

A

Secondary prevention of stroke

38
Q

How do glycoproteins IIb/a receptor antagonists work?

A

Block fibrinogen from binding to these receptors which causes platelet aggregation

39
Q

When are glycoprotein IIa/b receptor antagonists used?

A

High risk ACS, post PCI

Clinical Pharmacology (24 decks)

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