Drugs And Haemostasis Flashcards
What are the 3 natural mechanisms for haemostasis ?
Vasoconstriction.
Platelet plug
Coagulation
What is haemostasis ?
Stopping blood flow
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
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
Describe coagulation
Uses proteolytic enzymes and cofactors
An in Vivo and an in vitro coagulation cascade
What factors convert prothrombin into thrombin ?
Xa and Va
What is Bernard-soulier syndrome ?
Rare autosomal recessive disease
Platelets don’t stick to vessel wall causing bleeding
What is classic haemophilia ?
Haemophilia a - deficiency in factor 8
Haemophilia b - deficiency in factor 9
Causes bleeding
What causes hypercoagulabilty disorder ?
Factor 5 Leiden mutation
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
What are the 2 for a of vitamin K ?
K1 - phylloquinone, made in plants
K2- menaquinones, made in bacteria
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
Why do newborns get a vitamin k injection ?
Because their gut flora is not established so it improves their coagulability
What gastrointestinal disorders can cause a vitamin k deficiency ?
Fat malabsorption
Liver disease
Prolonged antibiotic therapy
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
What is warfarin a synthetic derivative of ?
Coumarin
What is the mechanism of action of warfarin ?
Interferes with vit k metabolism and prevents formation of functional coagulation factors
What are the medical uses of warfarin ?
DVT
Pulmonary embolism
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
How is warfarin controlled ?
aPTT assay - activated partial thromboplastin time
Can be reversed by vit k injection or in sever cases with prothrombin complex
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
What are the 2 main benefits of warfarin ?
Easily administered
Cheap to produce
What is heparin ?
Strongly negatively charged glycosaminoglycan made up of variably surfaced repeating disaccharide units
What is heparin derived from ?
Mucosal tissue of porcine intestine or bovine lungs
Large molecular mass range 3-50kDa
