Drugs And Haemostasis Flashcards Preview

Cardio-respiratory Physiology And Pharmacology > Drugs And Haemostasis > Flashcards

Flashcards in Drugs And Haemostasis Deck (43)
0

What is haemostasis ?

Stopping blood flow

1

What are the 3 natural mechanisms for haemostasis ?

Vasoconstriction.
Platelet plug
Coagulation

2

Describe vasoconstriction

Smooth muscle present in vessel walls spasm and constrict the vessel reducing the diameter of the vessel
It can reduce blood flow for about 30 mins

3

Describe platelet plug

Damaged vessels can expose collagen causing platelets to rapidly adhere and become sticky and irregular in shape and they swell
The activated platelets de granulate causing the release of many substances which activate more platelets and impede blood flow
Platelet surface has protease receptors which can be activated by thrombin causing de granulation

4

Describe coagulation

Uses proteolytic enzymes and cofactors
An in Vivo and an in vitro coagulation cascade

5

What factors convert prothrombin into thrombin ?

Xa and Va

6

What is Bernard-soulier syndrome ?

Rare autosomal recessive disease
Platelets don't stick to vessel wall causing bleeding

7

What is classic haemophilia ?

Haemophilia a - deficiency in factor 8
Haemophilia b - deficiency in factor 9
Causes bleeding

8

What causes hypercoagulabilty disorder ?

Factor 5 Leiden mutation

9

What acquired defects can cause coagulopathies ?

Liver disease
Vitamin k deficiency
Pregnancy - there is an increase in coagulation factors - excessive coagulability can lead to miscarriage

10

What are the 2 for a of vitamin K ?

K1 - phylloquinone, made in plants
K2- menaquinones, made in bacteria

11

What does vitamin k do ?

Converts glutamate into gamma-carboxyglutamate by adding a carboxyl group
This is important for the formation of clotting factors - prothrombin, factor 7, 9 and 10 and proteins c, s and z

12

Why do newborns get a vitamin k injection ?

Because their gut flora is not established so it improves their coagulability

13

What gastrointestinal disorders can cause a vitamin k deficiency ?

Fat malabsorption
Liver disease
Prolonged antibiotic therapy

14

What are the characteristics of an ideal anticoagulant ?

Administered orally once a day
Highly effective
Predictable dose response and kinetics
Low rate of bleeding
No routine monitoring required
Wide therapeutic window
No dose adjustments required
Little interactions - food/drugs
Low non specific pla a protein bindi
Inhibition of both free and clot bound coagulation factors

15

What is warfarin a synthetic derivative of ?

Coumarin

16

What is the mechanism of action of warfarin ?

Interferes with vit k metabolism and prevents formation of functional coagulation factors

17

What are the medical uses of warfarin ?

DVT
Pulmonary embolism

18

What are the pharmokinetics of warfarin ?

Very long half life - 20-60 hours - makes it difficult to determine dose
Delayed onset
Often co administered with heparin

19

How is warfarin controlled ?

aPTT assay - activated partial thromboplastin time
Can be reversed by vit k injection or in sever cases with prothrombin complex

20

What are the complications of warfarin ?

Narrow therapeutic range - monitoring and tailoring
Drug to drug interactions - antibiotics, aspirin, statins and antidepressants
- aspirin causes excessive bleeding and antibiotics exacerbate effects o warfarin on gut flora
Drug to diet interactions- brocolli, green leafy beg and liver - these food reduce actions of warfarin

21

What are the 2 main benefits of warfarin ?

Easily administered
Cheap to produce

22

What is heparin ?

Strongly negatively charged glycosaminoglycan made up of variably surfaced repeating disaccharide units

23

What is heparin derived from ?

Mucosal tissue of porcine intestine or bovine lungs
Large molecular mass range 3-50kDa

24

What are the 3 other examples of the drug heparin ?

Enoxaparin and dalteparin and tinzaparin

25

What is the mechanism of action of heparin ?

Prevents thrombus formation and extension of existing blood clots
Binds to antithrombim and enhances its inhibitory capacity
No effet on thrombus bounds thrombin

26

What are the medical uses of heparin ?

Myocardial infarction
Atrial fibrillation
DVT
Pulmonary embolism
During surgery for coronary bypass

27

Which antithrombim does heparin bind to ?

Antithrombim 3 inhibiting factors 7a, 2 and 2a

28

What are the pharmokinetics of heparin ?

Administered intravenously or subcutaneously - sub cuntaneous is for continuous treatment
Short half life -1hour

29

How is heparin controlled ?

Monitored by laboratory assay - aPTT

30

What is an adverse effect of heparin and how are overdoses treated ?

Haemorrhage and can transiently decrease platelet number
Protamine sulphate is used for overdoses
- used to be taken from shark sperm but now there is a recombinant form

31

What are the 2 types of thrombin inhibitors ?

Bivalent - derived from hirudin a leech anticoagulant
- leprudin, bivalirudin and desinudin
Univalent- synthetic compounds derived to fit active site of thrombin
- argatroban, melagatran, dabigatran

32

What are the advantages of direct thrombin inhibitors ?

Don't rely on interactions with endogenous anticoagulant mechanisms
Inhibit both coagulation and platelet activation by thrombin

33

How are DTIs controlled ?

No means established
Ecarin( venom of saw scaled viper which activates prothrombin) clotting time

34

Why was melagatran withdrawn from the market ?

Because it causes liver toxicity

35

What do anti platelet drugs do ?

Decrease platelet activation and thrombus formation
Very effective in arterial circulation where thrombi are platelet rich and anticoagulants are less effective
Able to act at numerous pathways

36

What are the 3 classes of anti platelet drugs ?

Cyclooxygenase inhibitors
ADP receptor antagonists
Glycoproteins 2b-3a antagonists

37

What drugs are often used to treat acute coronary syndrome ?

Clopidogrel, ABCIXIMAB and TIROFIBAN

38

What is thrombolysis ?

Breakdown of blood clots by pharmacological means - clot busting
They stimulate fibrinoloysis by infusion of proteins which generate active plasmin

39

What is the mechanism of action of thrombolytic agents ?

Stimulate conversion of endogenous plasminogen to plasmin skin lyses blood clots relaxing fibrin degradation products

40

What are the medical uses of thrombolytic agents ?

Myocardial infarction
Stroke
Pulmonary embolism

41

How is antithrombolytic agents controlled ?

Infused intravenously with heparin for 24-48 hours
Can cause haemorrhage

42

Why are antifibrinolytic agents used ?

To prevent blood loss or haemorrhage
Act to down regulate conversion of plasminogen to plasmin
Administered orally or intravenously