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Life Sciences - Sem 2 > 1.4 Drugs Affecting Haemostasis > Flashcards

1.4 Drugs Affecting Haemostasis Flashcards

1
Q

What are the 4 key steps of haemostasis?

A
  1. Adhesion
  2. Activation
  3. Aggregation of platelets
  4. Fibrinolysis
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2
Q

What is thrombosis?

A

Haemostasis in the wrong place

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3
Q

What is Virchow’s triad?

A
  1. Injury to vessel wall
  2. Altered blood flow
  3. Abnormal (hyper) blood coagulability
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4
Q

What are the differences between an arterial thrombus and venous thrombus?

A

Arterial thrombus = white thrombus, mainly platelets in fibrin mesh

Venous thrombus = red thrombus + red tail than can break away to form an embolus

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5
Q

How does the formation of a thrombus (clot) work?

A
  1. Rupture = activation mechanism
  2. Platelet reactions (3As) + coagulation cascade (fibrin mesh to catch platelets)
  3. Thrombus (clot)
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6
Q

The coagulation cascade works by activating factors via extrinsic + intrinsic pathways. What are the factors involved and their effects?

A

Extrinsic = tissue pathway = tissue factor
Intrinsic = contact pathway = factor XII + XI

Causes proteolysis of prothrombin (II) into thrombin (IIa = active thrombin)

Active thrombin converts fibrinogen to fibrin to stabilise mesh

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7
Q

Heparin is an injectible anticoagulant. How does heparin influence the coagulation cascade?

A

Counteracts lots of reactions in coagulation cascade

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8
Q

Ruptures cause ahesion of platelets to thrombogenic surfaces which leads to activation. What are the products of platelet activation?

A
  1. Thrombin + direct thrombin inhibitors (leads coagulation cascade)
  2. Releases ADP
  3. Produces the ezyme cyco-oxygense (COX) + arachidonic acid (AA)
  4. COX + AA = prostaglandins + thromboxanes (TXa2 = activated thromboxanes)
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9
Q

What are the 3 agonists and corresponding platelet receptors that induce platelet aggregation?

A
  1. Thromboxane A = TPa receptors
  2. Thrombin = PAR 4 (protease activator receptors)
  3. ADP = P2Y receptors
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10
Q

What is the mechanism behind platelet aggregation?

A
  1. Thromboxane A, Thrombin + ADP activate receptors on platelet
  2. G-Protein intracellular signalling shift integrins to a high-affinity state
  3. Integrins boost adhesion to collagen + VWF in endothelium
  4. GpIIb/GpIIIa receptors activate to adhere other platelets via integrins + fibrogen
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11
Q

How does aspirin interfere with platelet aggregation?

A

Inhibits cyco-oxygenese (COX)

COX 1 = platelet inhibitor, but aspirin is non-selective between COX 1 + 2

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12
Q

What are the 4 different classes of injectable (parenteral) anticoagulants?

A
  1. Heparins
  2. Low molecular weight heparins (LMWH)
  3. Direct thrombin inhibitors
  4. Factor Xa inhibitors
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13
Q

Whar are examples of LMWH classed inhectable anticoagulants?

A

“-parins” (not heparin itself)

  1. Dalteparin
  2. Nadroparin
  3. Danaparoid
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14
Q

What is an example of a direct thrombin inhibitor classed injectable anticoagulant?

A

Bivalirudin

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14
Q

What is an example of a direct thrombin inhibitor classed injectable anticoagulant?

A

Bivalirudin

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15
Q

What is an example of a Factor Xa inhibitor classed injectable anticoagulant?

A

Fondaparinux

16
Q

Why is antithrombin III (AT III) important?

A

Inactivates thrombin (factor IIa) which stops factor Xa production

So, inactivation of thrombin STOPS blood from clotting = needed to keep blood flowing

17
Q

How does heparin and LMW heaprins work as anticoagulants?

A

Potentiates the effects of antithrombin III by increasing the affinity of AT III to specific clotting factors

Heparin binds to both AT II + factor IIa (thrombin), but to inhibit factor Xa heparin + LMWH must bind ONLY to factor III

LMWHs = more predictable, needs less monitoring

18
Q

What are the 3 classes of oral anticoagulants?

A
  1. Vitamin K antagonists
  2. Direct thrombin inhibitors (hirudins)
  3. Factor Xa inhibitors
19
Q

What is an example of a vitamin K anatagonist class of oral anticoagulant?

20
Q

What is an example of a direct thrombin inhibitor class of oral anticoagulant?

A

Dabigatran

21
Q

What is an example of a factor Xa inhibitor class of oral anticoagulant?

A

“-abans”

Apixaban
Rivaroxaban

22
Q

What are three examples of clinical use for oral anticoagulants?

A
  1. Venous thromboembolism (VTE)
  2. Deep vein thrombosis (DVT)
  3. Pulmonary embolism
23
Q

What is the role of vitamin K in the coagulation cascade?

A

Essential for carboxylation of glutamic acid residues in factors II, VI, IX, and X but works in a reduced form only produced by reductase (VKOR)

24
How does warfarin, as a vitamin K antagonist, work as an anticoagulant?
Inhibits vitamin K epoxide reductase = prevents vitamin K changing into its reduced (activated) form Requires careful monitoring, acts in vivo after several days
25
How does non-VKAs (non-vitamin K antagonist) act as oral anticoagulants?
Either direct thrombin inhibitor or factor Xa inhibitors As a group, target multiple coagulation factors with faster onset + offset than warfarin
26
What are the 3 classes of antiplatelet drugs?
1. P2Y12 antagonists 2. Glycoprotein IIb/IIIa inhibitors 3. Other
27
What is an example of a P2Y12 antagonist class antiplatelet drug?
1. Clopidogrel 2. Ticagrelor
28
What are 3 examples of a glycoprotein IIb/IIIa inhibitor class antiplatelet drugs?
1. Abciximab 2. Eptifibatide 3. Tirofiban
29
What are examples of other classified antiplatelet drugs?
1. Aspirinn (NSAID) 2. Dipyridamole
30
What are examples of clinical use for antiplatelet drugs?
1. Managing arterial thrombosis 2. Prevention of treatment of myocardial infarction, unstable angina, and ichemic stroke + transient ischemic attack (TIA)
31
How does clopidogrel work as an antiplatelet drug?
P2Y12 receptor antagonist = inhibiting ADP induced platelet aggregation
32
How does tirofiban, abcixmab, and eptifibatide work as an antiplatelet drug?
GP IIb/IIIa receptor antagonists = prevent fibrinogen from binding to these receptors inhibiting platelet aggregation
33
How does aspirin work as an antiplatelet drug?
Irreversible inhibitor of COX = inhibits thromboxane A2 synthesis Effective at low doses (80 - 300mg daily) (Low dosage = blood thinner, high doses = pain relief)
34
How does dipyridamole work as an antiplatelet drug?
Inhibitor of phosphodiesterase = increases cAMP + decreases platelet function Hinhibits adenosine uptake = vasodilation
35
Oral aspirin has a half-life of 15-20 minutes, BUT irreversibly acetylates, inactivating the enzymes COX-1 and COX-2. How does this work?
Irreversible binding = lasts as long as platelet lifespan (7-10 days) As little as 30mg a day = near-complete suppression of platelet-derived thromboxane A2
36
What are thrombolytics or fibrinolytics?
"Clot busters" that catalyse breakdown of fibrin Plasmin is formed from plasminogen, which breaks down fibrin (last step in clot formation)

Life Sciences - Sem 2 (27 decks)

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