Haemostasis, thrombosis and platelet function Flashcards Preview

Yr 2 - Pharmacology > Haemostasis, thrombosis and platelet function > Flashcards

Flashcards in Haemostasis, thrombosis and platelet function Deck (72):
1

Which three drug groups decrease clotting?

  • Anticoagulants
  • Antiplatelet
  • Thrombolytics

2

What is thrombosis?

unwanted haemostatic plug in a blood vessel or the heart

3

What causes deep vein thrombosis?

poor blood flow

sitting for long periods of time

 

 

4

What are the symptoms of deep vein thrombosis?

Swelling and heat in leg

Very painful

5

What can result from a failure to treat deep vein thrombosis?

Loss of a leg

6

Which two things can increase clotting?

  • Replacement factors (VIII & IX)
  • Plasminogen ihibitors

7

Which enzyme does waraffin inhibit?

Vitamin K reductase

(stops carboxylation of glutamic acid residues = cannot bind platelet = no proteolysis = no cascade and no clotting)

8

Which 3 drugs increase the action of waraffin and how?

  • Aspirin = displace it from plasma proteins
  • Sulphonamides = interferes with liver function
  • NSAIDs = interferes with platelet function

9

Which two patient factors increase the action of waraffin?

  • Liver disease (decreases factor production and clearance)
  • Reduced vitamin K availiability

10

What is the average rate of onset for warrafin use?

12-16 hours

11

How long do the effects of warrafin last once you stop taking it?

4-5 days

12

How do we measure the action of warrafin in a patient?

Prothrombin time

(the time a sample takes to clot following addition of a standardised amount of Ca = ratio = compared to healthy subjects)

 

2-2.5 = prophylaxis of deep vein thrombosis

2.5 = treatment of deep vein thrombosis/ pulmonary embolism

3.5 = recurremt deep vein thrombosis/pulmonary embolism

 

13

After starting a patient on warrafin at which intervals do we measure the action of warrafin?

Initially daily

Then at longer intervals

Then every 12 weeks

14

Which two drugs decrease the action of warrafin and how?

  • Barbituates = induce metabolising enzymes
  • Colestipol (athlerosclerosis) = decreases absorption

15

Which two patient factors decreases the action of warrafin?

  • Increased vitamin K = promoted clotting factor synthesis
  • Vomitting

16

What are the side effects of Warrafin (2)?

  • Haemorrhage in bowel or brain (stop administration & give vitamin K & replacement factors)
  • Teratogenic (damages foetus)

17

Name two injectable anticoagulants:

Heparin

Low molecular weight heparin

18

Which two factors does heparin hit?

Factor IIa 

Factor Xa

= activates antithrombin III 

n.b. Heparin also binds to factor IIa but LMW heparin is too short = only hits factor Xa!!

 

19

What is the main clinical use for heparin?

Clearing blocked IV catheters

20

What inhibits heparin?

Factor IV (LMW heparin not inhibited)

21

Can factor Xa bind to factors already bound to fibrin?

No

22

What causes heparin to be badly absorbed in the gut?

Its large size and charge

23

In which 2 ways can heparin be administered?

IV 

Subcutaneous (LMW heparin only)

24

Why is there an initial rapid removal of heparin?

Binds to plasma proteins (heparin only), endothelial cells and macrophages

 

25

How is heparin excreted?

Slowly through renal excretion

26

What are the side effects of heparin (5)?

  • haemorrhage (counter with heparin antagonist e.g. protamine sulphate)
  • Thrombosis (rare -> when antibodies against heparin cause endothelial damage)
  • Osteoporosis
  • Hypersensitivity
  • Hypoaldosteronism

27

Name 4 examples of heparin:

heparin

calciparine

minihep

monoparin

28

Name 3 types of LMW heparin:

Certoparin

Dalteparin

Enoxaparin

29

Name 3 antithrombin independant anticoagulants:

  • Hirudin (binds thrombin active site -> leeches)
  • Hirugen
  • Bivalirudin

30

Which patients may antithrombin III independant anticoagulants be useful for?

Those who produce heparin antibodies

31

What are the possible uses for antithrombin III independent anticoagulants?

Percutaneous coronary intervention (angioplasty) = rapid on/off effects = get patient out of hospital as quickly as possible

32

What are the 3 main uses of anticoagulants?

  • prevention of deep vein thrombosis (perioperatively since wound increases the liklihood of clot formation)
  • treatment of deep vein thrombosis
  • prevention of thrombosis on prosthetic heart valves

33

Which enzyme does Aspirin irreversibly activate in platelets?

Cyclo-oxygenase

 

34

How long does it take platelets to replace COX?

7-10 days

35

Why is it that platelet cells cannot replace COX immediately but endothelial cells can?

Platelets do not have a nucleus!! 

36

When are antiplatelet drugs used?

In acute MI (myocardial infarction) in combination with fibrolytic drugs

37

Tell me the following about Triclopine:

Is it reversible or irreversible?

What is its onset like?

Which other drug does it have a similar efficacy to in reducing stroke?

Irreversible

Slow (3-7 days)

Aspirin

 

38

What are the 3 main side effects of triclopidine?

Rash

Diarrhoea

neutropenia (loss of wbc)

39

Tell me the following about clopidogrel:

Is it reversible or irreversible?

How is it administered?

Irreversible

Oral prodrug

 

40

Which group of individuals does clopidogrel not work in?

Those with a cytochrome p450 mutation

41

When is clopidogrel given?

Given after heart surgery & after an MI

42

Tell me the following about prasugrel:

Is it reversible or irreversible?

What is its onset like?

What is its metabolism like?

Irreversible

Faster onset (hours)

More easily metabolised to its active metabolite

43

Tell me the following about Ticagrelor:

Is it reversible or irreversible?

Which other two antiplatelet drugs does it have a similar efficacy to?

Reversible = stays in body for a couple of days only = can release patients faster!

Clopidogrel & prasugrel

 

44

Why can abciximab only be used once?

It is an antibody fragement directed against the receptor, repeated use = provokes immune response

45

After use of abciximab how quickly does platelet function recover?

in days

46

When is abciximab used?

IV

in high risk coronary angioplasty patient on herparin & aspirin

47

What is tirofiban/eptifibatide?

A cyclic peptide that resembles the IIb/IIIc ligands

48

How is tirofiban/eptifibatide administered?

IV 

n.b. long term oral administration may be harmful

49

How quickly is platelet function regained following use of tirofiban/eptifibatide?

hours

50

Why are the prostaglandin agonists (epoprostenol) given intravenously?

It is chemicallly unstable

51

When is Epoprostenol and other prostaglandin agonists used?

In patients undergoing haemodialysis (cannot use heparin)

52

What is the effect of using the phosphodiesterase inhibitor dipyrimidole?

it increases platelet cAMP levels

53

What are the 5 clinical uses of antiplatelet drugs?

  • Following acute MI
  • Those at risk of MI
  • Following coronary bypass/angioplasty
  • Unstable coronary syndromes
  • following a cerebral stroke

54

Name 3 plasminogen activators:

  • Streptokinase
  • Recombinant tPA
  • Urokinase

55

What do plasminogen activators do?

they produce plasmin = degradation of clot

56

After administering streptokinase what must be done to block the function?

Give antistreptococcal after 4 days

57

How long must you wait before reuse after giving a streptokinase?

1 year

58

Which is the most commonly used plasminogen activator?

recombinant tPA

59

What are the 3 types of recombinant tPA:

Anteplase/duteplase (short half life = IV infusion)

Reteplase (longer half life = IV bolus)

60

At which sites are recombinant tPA more active?

At fibrin bound plasminogen (clot specific!)

61

What are the contraindications of Fibrolytic agents (7)?

  • Active/recent internal bleeding
  • Recent cerebrovascular incident
  • Invasive procedures (where haemostasis is important)
  • Pregnancy (can cause loss of child)
  • If had cardipulmonary rescissitatopm for hours before
  • Trauma
  • Bacterial endocarditis

62

What are the side effects of fibrolytic agents (3)?

  • GI haemorrhage
  • Allergic reaction (/fever)
  • Hypotension (burst of plasmin by streptokinase)

63

What are the clinical uses of fibrolytic agents (4)?

  • Acute MI
  • Acute thrombotic stroke
  • Clear thrombosed shunts/cannulae
  • Acute arterial thromboembolism

64

What are anti-thrombolytic drugs used for?

To stabilise a clot

65

Name two antithrombolytic drugs:

  • Tranexamic acid
  • Aprotinin

66

How does tranexamic acid work?

Inhibits activation of plasminogen (stabilises clot)

67

How is tranexamic acid administered?

Oral/IV

68

When is tranexamic acid used clinically?

when increased risk of bleeding (e.g. dental extraction, prostoectomy etc)

69

What are the side effects of tranexamic acid?

Nausea & vomitting

70

How does aprotinin work?

Proteolytic inhibitor of plasmin/kallikrein

71

How is aprotinin administered?

slow IV

72

When is aprotinin used clinically?

patients of high risk of blood loss (e.g. open heart surgery)