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

Drugs And Haemostasis Flashcards

0
Q

What are the 3 natural mechanisms for haemostasis ?

A

Vasoconstriction.
Platelet plug
Coagulation

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1
Q

What is haemostasis ?

A

Stopping blood flow

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2
Q

Describe vasoconstriction

A

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

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3
Q

Describe platelet plug

A

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

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4
Q

Describe coagulation

A

Uses proteolytic enzymes and cofactors

An in Vivo and an in vitro coagulation cascade

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5
Q

What factors convert prothrombin into thrombin ?

A

Xa and Va

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6
Q

What is Bernard-soulier syndrome ?

A

Rare autosomal recessive disease

Platelets don’t stick to vessel wall causing bleeding

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7
Q

What is classic haemophilia ?

A

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

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8
Q

What causes hypercoagulabilty disorder ?

A

Factor 5 Leiden mutation

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9
Q

What acquired defects can cause coagulopathies ?

A

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

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10
Q

What are the 2 for a of vitamin K ?

A

K1 - phylloquinone, made in plants

K2- menaquinones, made in bacteria

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11
Q

What does vitamin k do ?

A

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

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12
Q

Why do newborns get a vitamin k injection ?

A

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

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13
Q

What gastrointestinal disorders can cause a vitamin k deficiency ?

A

Fat malabsorption
Liver disease
Prolonged antibiotic therapy

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14
Q

What are the characteristics of an ideal anticoagulant ?

A 
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
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15
Q

What is warfarin a synthetic derivative of ?

A

Coumarin

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16
Q

What is the mechanism of action of warfarin ?

A

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

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17
Q

What are the medical uses of warfarin ?

A

DVT

Pulmonary embolism

18
Q

What are the pharmokinetics of warfarin ?

A

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

19
Q

How is warfarin controlled ?

A

aPTT assay - activated partial thromboplastin time

Can be reversed by vit k injection or in sever cases with prothrombin complex

20
Q

What are the complications of warfarin ?

A

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
Q

What are the 2 main benefits of warfarin ?

A

Easily administered

Cheap to produce

22
Q

What is heparin ?

A

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

23
Q

What is heparin derived from ?

A

Mucosal tissue of porcine intestine or bovine lungs

Large molecular mass range 3-50kDa

24
Q

What are the 3 other examples of the drug heparin ?

A

Enoxaparin and dalteparin and tinzaparin

25
Q

What is the mechanism of action of heparin ?

A

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

26
Q

What are the medical uses of heparin ?

A 
Myocardial infarction 
Atrial fibrillation 
DVT 
Pulmonary embolism 
During surgery for coronary bypass
27
Q

Which antithrombim does heparin bind to ?

A

Antithrombim 3 inhibiting factors 7a, 2 and 2a

28
Q

What are the pharmokinetics of heparin ?

A

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

29
Q

How is heparin controlled ?

A

Monitored by laboratory assay - aPTT

30
Q

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

A

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
Q

What are the 2 types of thrombin inhibitors ?

A

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
Q

What are the advantages of direct thrombin inhibitors ?

A

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

33
Q

How are DTIs controlled ?

A

No means established

Ecarin( venom of saw scaled viper which activates prothrombin) clotting time

34
Q

Why was melagatran withdrawn from the market ?

A

Because it causes liver toxicity

35
Q

What do anti platelet drugs do ?

A

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
Q

What are the 3 classes of anti platelet drugs ?

A

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

37
Q

What drugs are often used to treat acute coronary syndrome ?

A

Clopidogrel, ABCIXIMAB and TIROFIBAN

38
Q

What is thrombolysis ?

A

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

39
Q

What is the mechanism of action of thrombolytic agents ?

A

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

40
Q

What are the medical uses of thrombolytic agents ?

A

Myocardial infarction
Stroke
Pulmonary embolism

41
Q

How is antithrombolytic agents controlled ?

A

Infused intravenously with heparin for 24-48 hours

Can cause haemorrhage

42
Q

Why are antifibrinolytic agents used ?

A

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

Cardio-respiratory Physiology And Pharmacology (33 decks)

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