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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?

A

Warfarin

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
Q

How does warfarin, as a vitamin K antagonist, work as an anticoagulant?

A

Inhibits vitamin K epoxide reductase = prevents vitamin K changing into its reduced (activated) form

Requires careful monitoring, acts in vivo after several days

25
Q

How does non-VKAs (non-vitamin K antagonist) act as oral anticoagulants?

A

Either direct thrombin inhibitor or factor Xa inhibitors

As a group, target multiple coagulation factors with faster onset + offset than warfarin

26
Q

What are the 3 classes of antiplatelet drugs?

A
  1. P2Y12 antagonists
  2. Glycoprotein IIb/IIIa inhibitors
  3. Other
27
Q

What is an example of a P2Y12 antagonist class antiplatelet drug?

A
  1. Clopidogrel
  2. Ticagrelor
28
Q

What are 3 examples of a glycoprotein IIb/IIIa inhibitor class antiplatelet drugs?

A
  1. Abciximab
  2. Eptifibatide
  3. Tirofiban
29
Q

What are examples of other classified antiplatelet drugs?

A
  1. Aspirinn (NSAID)
  2. Dipyridamole
30
Q

What are examples of clinical use for antiplatelet drugs?

A
  1. Managing arterial thrombosis
  2. Prevention of treatment of myocardial infarction, unstable angina, and ichemic stroke + transient ischemic attack (TIA)
31
Q

How does clopidogrel work as an antiplatelet drug?

A

P2Y12 receptor antagonist = inhibiting ADP induced platelet aggregation

32
Q

How does tirofiban, abcixmab, and eptifibatide work as an antiplatelet drug?

A

GP IIb/IIIa receptor antagonists = prevent fibrinogen from binding to these receptors inhibiting platelet aggregation

33
Q

How does aspirin work as an antiplatelet drug?

A

Irreversible inhibitor of COX = inhibits thromboxane A2 synthesis

Effective at low doses (80 - 300mg daily)
(Low dosage = blood thinner, high doses = pain relief)

34
Q

How does dipyridamole work as an antiplatelet drug?

A

Inhibitor of phosphodiesterase = increases cAMP + decreases platelet function

Hinhibits adenosine uptake = vasodilation

35
Q

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?

A

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
Q

What are thrombolytics or fibrinolytics?

A

“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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