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CPT > Lecture 22- Anticoagulants > Flashcards

Lecture 22- Anticoagulants Flashcards

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1
Q

What is thrombosis?

A

Pathological haemostasis within a blood vessel;

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2
Q

What is the difference between arterial and venous thrombi in terms of their platelet content?

A

Arterial = platelet rich
Venous = Lower platelets more fibrin

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3
Q

What is antithrombin III?

A

Endogenous inactivator of clotting factors

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4
Q

How do coagulation factors circulate in the blood?

A

As zymogens (inactive enzymes)

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5
Q

What is an important co facotr of the coagulation cascade?

A

Calcium (Ca2+)

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6
Q

What is the function of calcium in the coagulation cascade?

A

Needed for clotting to occur

Ca2+ in citrate tubes or EDTA tubes chelate calcium preventing coagulation

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7
Q

Where are heparins naturally produced?

A

Mast cells
Vascular endothelium

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8
Q

What are the 2 main types of heparins?

A

Unfractioned heparin

Low molecular weight heparins

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9
Q

What natural substance can we increase the levels of to prevent clotting?

A

Antithrombin III (AT-III) activity

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10
Q

How do heparins act as anticoagulants?

A

Enhance antithrombin III (AT-III) actiivty preventing clotting

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11
Q

What is the purpose of anticoagulant drugs?

A

Prevent thrombus formation and thrombus growing

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12
Q

What is the onset of action of unfractioned heparin?

A

Fast onset of action

T1/2 = 30min low dose, 2hr at higher doses

It has mixed elimination so is unpredictable

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13
Q

How is unfractioned heparin administered?

A

Normally IV bolus and infusion

Can be given s.c for prophylaxis but low bioavailability

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14
Q

How does unfractioned heparin act as an anticoagulant?

A

Binds to Antithrombin III causing conformational change and increasing actiivty of ATIII

To inhibit thrombin (IIa) heparin needs to bing to both ATIII and IIa

So inhibts Xa + Thrombin IIa

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15
Q

What does unfractioned heparin need to bind to to inhibit factor Xa?

A

just ATIII

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16
Q

How does the absorption of unfractioned heparin and low molecular weight heparin differ?

A

Unfractioned heparin = unpredictably

Low molecular weight heparin = more uniformly (dosed with certain number of units per kilo)

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17
Q

What are some examples of low molecular weight heparins?

A

Dalteparin
Enoxaparin

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18
Q

How are low molecular weight heparins likes Dalteparin and Enoxaparin normally administered?

A

Subcutaneously

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19
Q

How does the half life of low molecular heparins like Dalteparin and Enoxaparin differ to unfractioned heparin?

A

Low molecular heparins have longer t1/2 at 2hrs +

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20
Q

How do low molecular weight heparins like Dalteparin and Enoxaparin act as anticoagulants?

A

Inhibts Xa by enhancing ATIII

DOESNOT inactivate Thrombin (IIa) its too short

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21
Q

What is a synthetic low molecular weight heparin?

A

Fondaparinux

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22
Q

How does the synthetic low molecular weight heparin fondaparinux act as an anticoagulant?

A

Selectively inhibits Xa be enhancing ATIII

Given s.c

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23
Q

What type of molecules are heparins?

A

Negatively charged molecules

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24
Q

What is the difference in speed of action of Unfractioned heparin and low molecular weight heparins?

A

UF = IV infusion fast Anticoagulation

LMWH. = s.c slower onset

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25
Q

What are some indications for using heparins or fondaparinux?

A

Prevent VTE or preiopereative prophylaxis of VTE

During pregnancy since dont cross placenta

DVT
PE

Acute coronary syndromes
During Percutaenosu coronary intervention
NSTEMI

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26
Q

What are some adverse drug reactions to heparins?

A

Bruising and bleeding = Intracranial, at site of injection, GI and epistaxis

Heparin I induced thrombocytopenia autoimmune response

Osteoporosis

Hyperkalaemia (Inhibts aldosterone secretion)

27
Q

What is heparain induced thrombocytopenia?

A

Autoantibodies to heparin Platelet factor 4 complex produced, platelets depleted which can paradoxically lead to thrombosis as more platelets activated by damaged endothelium

28
Q

What are the contraindications to heparins?

A

Clotting disorders
GI ulcers
Renal impairment (LMWH and fondaparinux)

29
Q

What are the drug-drug interactions of heparins?

A

Other antithrombotic drugs

ACEi, ARBs and other K+ sparring diuretics

30
Q

What value is measured when monitoring a patient who is being dosed with unfractioned doses of heparin?

A

Activated partial thromboplastin time (aPTT)

31
Q

Why does low molecular weight heparirn require little monitoring when given to patients whereas unfractioned heparin needs lots of monitoring?

A

LMWH much more predictable in its action and elimination

32
Q

What is a drug that can reverse/inactivate heparin?

A

Protamine sulphate

33
Q

How does protamine sulphate work to reverse the Anticoagulation of heparin?

A

Binds to heparin forming an inactive complex leading to heparin dissociating from ATIII

34
Q

How does protamine sulphate affect Unfractioned heparin, LMWH and fondaparinux respectively?

A

UFH = much greater effect than LMWH

Fondaparinux = no effect

35
Q

What is warfarin?

A

Vitamin K antagonist

36
Q

What is the mechanism of action of warfarin as an anticoagulant?

A

Competitively inhibits vitamin K epoxide REDUCTASE preventing vitamin K being recycled back into its active form

Therefore reduces hepatic synthesis of vitamin K dependant clotting factors

37
Q

What clotting factors require vitamin K for the liver to produce them?

A

II, VII, IX and X

38
Q

What is the time of onset of warfarin and why?

A

Delay in onset of

Since it takes several days for circulating active clotting factors to be cleared and replaced with the inactive clotting factors

39
Q

What is the rough half life for Vit K antagonists like warfarin?

A

36 - 48hr

40
Q

What are some indications for warfarin?

A

VTE
PE
DVT and seconadry prevention
Superficial vein thrombosis
AF patients where DOAC not suitable
Heart valve replacemtn bio prosthetic
Pre cardio version

41
Q

Why may you temporarily see warfarin and heparin used alongside each other?

A

Warfarin has a slow onset of action whereas heparin is much quicker

If Anticoagulation is needed immediately often give heparin as cover while waiting for the warfarin to kick in

42
Q

How is warfarin usually administered?

A

Taken orally since has good GI absorption

43
Q

What are the 2 enantiomers of warfarin?

A

R and S

44
Q

What is the major contraindication to warfarin?

A

Pregnant since crosses placenta so needs to be avoided in at least 1st trimester and early post partum

45
Q

What affects the response by warfarin?

A

CYP2C9 polymorphisms
Vit K intake (leafy vegetables)
Alcohol

46
Q

What is the major adverse drug reaction of warfarin?

A

Bleeding (epistaxis and spontaneous Retroperitoneal bleeding)

47
Q

If a patient starts bleeding who is taking warfarin what is the first option step to take?

Then following on from that;

A

1st = GIVE ACTIVE VITAMIN K

Prothrombin complex concentrate via I

Then stopp the warfarin which is inhibiting the Vit K epoxide REDUCTASE

48
Q

What is bridging therapy?

A

When you give LMWH when initiating or temporarily stopping warfarin since it takes some time for the effect of warfarin to kick in

49
Q

What are the many drug drugs interactions of Warfarin?

A

Drugs that Inhibit CYP2C9 (Amiodarone, clopidogrel, metronidazole, intoxicating dose of alcohol))

Cephalosporin Abx Elimates gut bacteria producing VItamin K so leads to reduced Vit K

Displacemtn of warfarin from plasma albumin (NSAIDs and drugs that decrease GI absorption of Vit K

Aceleration of WArfarin metabolism by barbiturates, phenytoin, Rifampicin and St John’s wart (decreasing INR)

50
Q

What is meant by a high INR and a low INR?

A

High INR = more anti coagulated so higher bleeding risk

Low INR = less anti coagulated so less bleeding I risk

51
Q

What is INR?

A

Compares prothrombin clotting time against a standardised control plasma

52
Q

Which clotting facotr is most sensitve to vitamin K deficiency?

A

Factor VII

53
Q

What does DOAC stand for?

A

Direct acting oral anticoagulant

54
Q

What are some DOACs?

A

ApiXAban
EdoXAban
RivaraoXAban

55
Q

What is the mechanism of action of ApiXAban, edoXAban and rivaroXAban acting as an anticoagulant?

A

Directly inhibits both free Xa and Xa bound to ATIII but DOES NOT effect thrombin (IIa)

56
Q

How are DOACs like ApiXAban metabolised and excreted?

A

Hepatic metbolism
Excreted partly by kidneys

57
Q

How does dabigatran act as an anticoagulant?

A

Directly and competitively inhibits Thrombin IIa

58
Q

What anticoagulant inhibts Thrombini IIa?

A

Dabigatran

59
Q

What anticoagulant inhibits factor Xa?

A

Apixaban (DOAC)
Low molecular weight heparins (Dalteparin)
Fondaparinux

60
Q

What are the adverse reactions of DOACs like Apixaban?

A

Bleeding
Skin reactions
Dose adjustments needed for GI bleed risk groups

61
Q

What are the contraindations to oDOACs?

A

Dabigatran contraindicated in low creatinine clearance

Avoid use in pregnancy and breast feeding

62
Q

What are the drug drug interactions of DOACs?

A

Affected by CYP inhibtors and inducers

Macrolides increase plasma conc of DOACs

Carbamazepine, phenytoin and barbiturates reduce plasma conc of DOACs

63
Q

What are the antidotes for Apixaban and RivaraoXAban?

A

Andexanet Alfa

64
Q

What is the antidote for dabigatran?

A

Idarucizumab

CPT (30 decks)

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