Drug Interactions and Clotting

Question 1

In drug-drug interactions, what is the:

1) object drug
2) precipitant drug

Answer 1

1) drug already on

2) new drugs added

Question 2

If paracetamol is the object drug, name a potential precipatant drug.

Why is this the case?

Answer 2

Alcohol!

Decreases glutathione levels = leads to NAPQI build up and hepatotoxicity

Question 3

Name an object drug that can be affected by NSAIDS.

Why is this the case?

What does this result in?

Answer 3

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

Question 4

What clotting factors does vitamin K act as a co-factor for?

Answer 4

2, 7, 9 and 10

Question 5

How does warfarin work?

Answer 5

It is a vitamin K antagonist

Question 6

What 3 mechanism/phases are at play to maintain haemostasis after bleeding?

Answer 6

1) vascular phase
2) platelet plug formation phase
3) coagulation phase (fibrin deposition, as platelet plug alone is not strong enough)

Question 7

What happens in the vascular phase of haemostasis?

What is released?

Answer 7

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?

Question 8

What are the 2 pathways in the clotting cascade?

What does each mean?

Answer 8

1) intrinsic = in the blood stream

2) extrinsic = in the vessel wall

Question 9

What are the first 3 steps of the intrinsic pathway?

Answer 9

Exposed collagen = trigger
12 - 12a
11 - 11a
9 -9a

Question 10

What happens to 9a in the intrinsic pathway once it is formed?

Answer 10

Binds with factor 8a (which was cleaved by thrombin from VWF:8 complex found circulating in the blood)

Question 11

What is the complex formed of factor 9a and 8a called?

What does this do?

Answer 11

Tenase

This activates factor 10 to form 10a

Question 12

How does the extrinsic clotting cascade pathway start?

Answer 12

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)

Question 13

What is the first step in the common clotting cascade pathway?

What factors/complexes activate this step?

Answer 13

10 - 10a

Tenase (9a:8a)

AND

Tissue factor 3:7a complex

Question 14

What does factor 10a do?

Is another factor required for this step?

Answer 14

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

Question 15

What does thrombin do?

Answer 15

Activates fibrinogen (factor 1) to fibrin (1a)

Question 16

What factor when activated helps helps fibrin to cross link?

Which factor activates the above factor?

Answer 16

13a helps fibrin cross linking

Thrombin activates factor 13 - 13a

Question 17

What is tissue factor 3 also called?

Answer 17

Thromboplastin

Question 18

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?

Answer 18

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

Question 19

What is a advantage of LMHW?

Answer 19

Does not require timed monitoring therefore is an outpatient treatment

Question 20

How is LMWH given?

Answer 20

Subcut

Question 21

What anticoagulation is the preferred choice for DVT and ACS prevention?

Answer 21

LMWH

Question 22

Name some LMWH’s.

Answer 22

Enoxaparin
Dalteparin
…they end in ‘parin’

Question 23

Which type of anticoagulation is good for those with renal problems?

Out of these, which is best for rapid onset?

Answer 23

Unfractionated

Warfarin

(Warfarin has a delayed onset)

Question 24

Which anticoagulant can be taken at home?

Which do not require monitoring?

Which of these is taken by injection without monitoring?

Answer 24

Warfarin
DOACs
LMWH

DOACS
LMWH

LMWH

Question 25

Which anticoagulants are taken orally?

Answer 25

Warfarin

DOACs

Question 26

What antocoagulant comes with dietary advice and why?

Answer 26

Warfarin - green leafy vegetables

Too much vit K can prevent it from working as it can not overpower the vit K levels

Question 27

What may NSAIDs and steroids interact to cause?

Answer 27

GI bleeding

Question 28

What can NSAIDS cause in the kidneys by a drug-drug interaction?

Answer 28

NSAIDs plus ACEi or ARB AND diuretic

Can see serum creatinine rise with the kidney unable to compensate

Question 29

What interaction may occur between weak opioids linked to the way they are metabolised, what is the reason and what are the precipitant drugs?

Answer 29

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

Question 30

Which drug inhibits the metabolism of morphine?

Answer 30

Cimetidine (H2 antagonist used in GORD)

Question 31

Explain some OTC things that interfere with CYP3A4 and how they do this.

Answer 31

Grapefruit juice = potent inhibitor

St. John’s Wort = potent inducer

Question 32

What is ranitidine?

Answer 32

A cimetidine analogue

Question 33

What effect do tricyclics have when they are the object drug to a precipitant morphine?

Answer 33

They both cause respiratory depression and therefore the effect is accumulated