Drug Interactions and Clotting Flashcards
In drug-drug interactions, what is the:
1) object drug
2) precipitant drug
1) drug already on
2) new drugs added
If paracetamol is the object drug, name a potential precipatant drug.
Why is this the case?
Alcohol!
Decreases glutathione levels = leads to NAPQI build up and hepatotoxicity
Name an object drug that can be affected by NSAIDS.
Why is this the case?
What does this result in?
Warfarin
Can be be displaced by NSAIDS (both drugs are plasma bound, but NSAIDS are more HIGHLY plasma bound)
Only unbound drug is active, which usually for warfarin is 3%, this can increase heavily in the presence of NSAIDS which can cause increase risk of bleeding/haemorrhage
What clotting factors does vitamin K act as a co-factor for?
2, 7, 9 and 10
How does warfarin work?
It is a vitamin K antagonist
What 3 mechanism/phases are at play to maintain haemostasis after bleeding?
1) vascular phase
2) platelet plug formation phase
3) coagulation phase (fibrin deposition, as platelet plug alone is not strong enough)
What happens in the vascular phase of haemostasis?
What is released?
Vasoconstriction due to various factors being released from the damaged endothelial cells (endothelins)
Tissue factor 3 (will eventually start the extrinsic pathway of the clotting cascade?
What are the 2 pathways in the clotting cascade?
What does each mean?
1) intrinsic = in the blood stream
2) extrinsic = in the vessel wall
What are the first 3 steps of the intrinsic pathway?
Exposed collagen = trigger
12 - 12a
11 - 11a
9 -9a
What happens to 9a in the intrinsic pathway once it is formed?
Binds with factor 8a (which was cleaved by thrombin from VWF:8 complex found circulating in the blood)
What is the complex formed of factor 9a and 8a called?
What does this do?
Tenase
This activates factor 10 to form 10a
How does the extrinsic clotting cascade pathway start?
Damaged vessels release tissue factor 3 which activates 7 to 7a
These combine to form a tissue factor 3:7a which also activates factor X (like tenase)
What is the first step in the common clotting cascade pathway?
What factors/complexes activate this step?
10 - 10a
Tenase (9a:8a)
AND
Tissue factor 3:7a complex
What does factor 10a do?
Is another factor required for this step?
It complexes with 5a to form prothrombinase
This activates factor 2 - 2a (prothrombin to thrombin)
Factor 5 is not activated until it comes into contact with thrombin itself, therefore it is not a requirement for thrombin activation but when activated and complexed with 10a it AMPLIFIES this process
What does thrombin do?
Activates fibrinogen (factor 1) to fibrin (1a)
What factor when activated helps helps fibrin to cross link?
Which factor activates the above factor?
13a helps fibrin cross linking
Thrombin activates factor 13 - 13a
What is tissue factor 3 also called?
Thromboplastin
What is prothrombin time (medical test)?
What does it measure and how does it work?
What are normal values for those both on and not on anticoagulation?
Thromboplastin (factor 3) is added to a blood sample to test the speed of the extrinsic clotting pathway
Gives you an INR value
= 0.8-1.2 is normal
= 2-3 is the target range for those on anticoagulation
What is a advantage of LMHW?
Does not require timed monitoring therefore is an outpatient treatment
How is LMWH given?
Subcut
What anticoagulation is the preferred choice for DVT and ACS prevention?
LMWH
Name some LMWH’s.
Enoxaparin
Dalteparin
…they end in ‘parin’
Which type of anticoagulation is good for those with renal problems?
Out of these, which is best for rapid onset?
Unfractionated
Warfarin
(Warfarin has a delayed onset)
Which anticoagulant can be taken at home?
Which do not require monitoring?
Which of these is taken by injection without monitoring?
Warfarin
DOACs
LMWH
DOACS
LMWH
LMWH
Which anticoagulants are taken orally?
Warfarin
DOACs
What antocoagulant comes with dietary advice and why?
Warfarin - green leafy vegetables
Too much vit K can prevent it from working as it can not overpower the vit K levels
What may NSAIDs and steroids interact to cause?
GI bleeding
What can NSAIDS cause in the kidneys by a drug-drug interaction?
NSAIDs plus ACEi or ARB AND diuretic
Can see serum creatinine rise with the kidney unable to compensate
What interaction may occur between weak opioids linked to the way they are metabolised, what is the reason and what are the precipitant drugs?
Fluoxetine and paroxetine (SSRI’s)
Ketaconazole (antifungal)
These drugs are CYP2D6 and CYP3A4 inhibitors
CYP2D6 and CYP3A4 are important as weak opioids (codeine/tramadol) are pro-drugs which are converted by these enzymes
Which drug inhibits the metabolism of morphine?
Cimetidine (H2 antagonist used in GORD)
Explain some OTC things that interfere with CYP3A4 and how they do this.
Grapefruit juice = potent inhibitor
St. John’s Wort = potent inducer
What is ranitidine?
A cimetidine analogue
What effect do tricyclics have when they are the object drug to a precipitant morphine?
They both cause respiratory depression and therefore the effect is accumulated
