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510 - Pharmacology > S2L1 - Coagulation and Anticoagulants > Flashcards

S2L1 - Coagulation and Anticoagulants Flashcards

1
Q

What initiates the clotting sequence of events?

A

Tissue injury and platelets

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2
Q

What is the final event in the coagulation cascade?

A

Fibrin deposition

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3
Q

What retracts clots?

A

Plasminogen –> Plasmin degrades fibrin and releases fibrin degradation products (FDPs)

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4
Q

What substances promote coagulation?

A

ADP and Thromboxane (TXA2)

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5
Q

What substances inhibit coagulation?

A

Prostacyclin

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6
Q

How does TXA2 transport?

A

Via platelets with membrane-bound fatty acids

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7
Q

What generates TXA2?

A

COX

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8
Q

What is TXA2 involved in?

A

Platelet aggregation, release response, arterial constriction

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9
Q

What generates prostacyclin and where is it located?

A

COX, endothelial cell walls

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10
Q

What does prostacyclin do?

A

It acts as a negative feedback mechanism to inhibit platelet aggregation and relax blood vessels

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11
Q

What is the order of the intrinsic coagulation cascade?

A

12 - 11 - 9 - 10 - prothrombin - thrombin - fibrinogen

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12
Q

What is the order of the extrinsic coagulation cascade?

A

7 - 10 - prothrombin - thrombin - fibrinogen

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13
Q

What is fibrinolysis and what causes it?

A

The breaking of a clot - plasminogen becoming plasmin degrades the fibrin that creates the clot

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14
Q

How is coagulation maintained in hemostasis?

A

Platelets circulate ready to be activated and are stabilized by the presence of prostacyclin

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15
Q

What triggers the coagulation cascade?

A

Exposure to collagen from injury causes platelet aggregation and then release of tissue factor that signals for the cascade

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16
Q

What is heparin and what are the types? Where do they work?

A

It is a rapid anticoagulant - unfractionated (nonspecific for Xa and thrombin IIa) and a low molecular weight version (specific for Xa)

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17
Q

What reverses UFH action and how?

A

An infusion of protamine - it is a weak base that neutralizes the weak acid of UFH

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18
Q

How do you monitor heparin dosing and what is a common side effect?

A

aPTT - side effect is thrombocytopenia or HIT

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19
Q

Where do immune complexes bind to platelets?

A

Fc Receptor

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20
Q

What are the ways to monitor HIT in a patient?

A

4T score from clinical manifestation and antibody immunoassay

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21
Q

How is type II HIT managed?

A

Patient taken off heparin and put on other anticoagulant such as Fondaparinux, Argatroban, Bivalirudin

22
Q

What are the LMWH drugs?

A

Tinzaparin, Enoxaparin, Dalteparin - “TED”

23
Q

What are the LMWH drugs used for and why?

A

DVT, PE, AMI, TIA - long acting so don’t need monitoring and easier dosing, more predictable activity

24
Q

When should you not use heparin/contraindications?

A

Bleeding, recent surgery, hypersensitivity, aortic aneurysm, but can be given during pregnancy

25
Q

What are the direct thrombin inhibitors (DTI)?

A

Argatroban and bivalirudin

26
Q

What are DTIs used for and why?

A

HIT or narrowing arteries - they are expensive and less studied which is why heparin is used first - can cause bleeding as an ADE

27
Q

When is there paradoxical bleeding related to heparin use?

A

When large doses of protamine are given for reversal of heparin induced toxicity

28
Q

What is the difference in type I and II HIT?

A

Type I is only thrombocytopenia and will resolve on it’s own
Type II can lead to thrombocytopenia and thrombosis giving a hyper-coagulated state and takes longer to come up and requires therapy - more severe and immune mediated

29
Q

Why are heparins used over DTIs?

A

DTIs are expensive and less studied

30
Q

What does warfarin do and how?

A

It works by inhibiting the hepatic synthesis of vitamin K dependent clotting factors - II, VII, IX and X - inhibits reduced form of vitamin K via carboxylation

31
Q

How do you reverse the action of warfarin?

A

Giving vitamin K

32
Q

What drug interactions does warfarin have?

A

CYP 450 2C9 and 3A4 which can effect the blood level of warfarin

33
Q

What can be a result of use of warfarin?

A

Protein c deficiency which is a natural anticoagulant

34
Q

What are contraindications of warfarin?

A

pregnancy, bleeding, aneurysm, surgery and hypersensitivity

35
Q

What are the new oral anticoagulants?

A

Dabigatran, apixaban, rivaroxaban “RAD”

36
Q

What is used to treat bleeding secondary to newer anticoagulant drugs?

A

Prothrombin protein concentrates (PCCs)

37
Q

What do fibrinolytic/thrombolytic drugs do?

A

Break clots by activating the conversion of plasminogen to plasmin which breaks down fibrin to potentiate clot breakdown

38
Q

What are fibrinolytic drugs used for?

A

short-term emergency management of DVT, thromboembolism, thromboses in MI and stroke

39
Q

How are fibrinolytic drugs eliminated?

A

Hepatic clearance and reversed by cryoprecipitate a blood product

40
Q

What are the fibrinolytic drugs?

A

Streptokinase, tPA/alteplase, reteplase, tenecteplase, urokinase, anistreplase

41
Q

What are reteplase and tenecteplase mostly used for?

A

heart attacks

42
Q

How is tPA different from streptokinase?

A

It selectively lyses clots giving less hemorrhage and allergic response and has a shorter half-life so can be reversed easier

43
Q

How do platelets aggregate together?

A

Fibrinogen adheres two platelets together via the GPIIb/IIIa receptor and platelets release TXA2 in response to elevated calcium levels to stimulate clotting

44
Q

What are the antiplatelet drugs?

A

Aspirin, ADP antagonist, Dipyridamole, Glycoprotein IIb/IIIa receptor inhibitors

45
Q

How does aspiring work?

A

Irreversibly inhibits COX1 and TXA2 synthesis to prevent platelet aggregation

46
Q

What is aspirin used for and what are it’s side effects?

A

Aspirin is used to prevent thrombosis in IHD, strok patients and to treat and prevent MI and TIA – can cause GI bleeding and ulcers and salicylism at toxic doses

47
Q

How do ADP antagonists work?

A

Interfere with binding of ADP to platelet receptor which inhibits GPIIb/IIIa receptor activation for fibrinogen binding for aggregation

48
Q

What are the ADP antagonist drugs and when are they used?

A

Ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor - used as alternative to aspirin or after stent placement

49
Q

What do ADP antagonists cause as side effects?

A

GI bleeding and neutropenia but this is rare - ticlopidine can lead to thrombocytopenia and bruising

50
Q

How does dipyridamole work?

A

Acts as coronary vasodilator to inhibit cellular uptake of adenosine - Inhibits phosphodiesterase enzyme which results in decreased TXA2 synthesis

51
Q

When is dipyridamole used?

A

It is the weakest anti-platelet so it is used in combination with aspirin or warfarin as a prophylactic treatment

52
Q

What are the glycoprotein IIb/IIIa receptor inhibitors?

A

Abciximab,eptifibatide, tirofiban

510 - Pharmacology (7 decks)

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