Anticoagulant drugs Flashcards
Heparin
- what is it used for?
- how to give it?
Uses
- acute coronary syndromes
- thromboembolism (DVT, PE, AF)
- Warfarin replacement e.g pregnancy
- IV (not absorbed well by GI tract due to negative charge)
how does heparin work?
How to measure its affects?
Binds to anti-thrombin, and promotes its activity
Antithrombin - will stop thrombin, and factor 10a
-also inhibits 9,11,12
Take blood tests to measure effects - APPT (therapeutic range is slightly higher than normal range)
Pharmacokinetics of heparin
- how long does it last?
- What is its bio-availability like? is it constant with other individuals)
- Rapid onset and offset
- bioavailability is unpredictable due to binding to cells and plasma proteins
(when stop giving it will wear of very quickly)
How we give heparin after a thrombus
- Give initial bolus
- then maintenance IV
- then measure APPT to see if rate and dose is giving therapeutic effect
Disadvantages of heparin?
- It is hard to measure and we require constant blood samples and APPT tests
- Complicated to get the right dose
- Time consuming
Adverse effects of heparin
- Can get bruising and bleeding (intracranial worst)
- can also get thrombocytopenia (need regular platelet checks and if these do fall then need to stop heparin)
- osteoporosis
Reversal of heparin - why and how do we do it?
- If we get bleeding then need to do this
- stop heparin
- give protamine - binds to heparin and stops its activity
Advantages of low molecular weight heparin and disadvantagess
Advantages
- better absorbed - higher bioavialablity
- longer half life (doesn’t bind to cells and plasma proteins)
- much more reliable than heparin as there is a strong dose-effect relationship
- dont need to monitor - can measure 10a activity
- patient can inject themself dont need to be in hospital
- lower risks of thrombocytopenia and bleeding
Disadvantages
- cannot be reversed by protamine
- is cleared by kidneys (not plasma proteins) so patient with a low GFR need to have a dose reduction
Low molecular weight heparin action
-Bind to antithrombin 3, and inhibit factor 10a
What are the LMWH used for?
what is most common one called?
-how is it given?
- non STEMI, and STEMI
- initial treatment for DVT, PE
- Enoxaparin is the main one
- give subcutaneously
- can be used in treamtnet or prevention of thrombus
Treatment for PE and DVT
- first give LMWH for 5 days
- then warfarin
- then continue these and measure INR
How does warfarin work?
how long does it take?
- Vit K antagonist (inhibits its actions)
- Liver requires vit K to make clotting factors 2,7,9,10
- takes a few days to kick in
When do we use wafarin
To treat or prevent venous or arterial thrombus
- also used in patients with metal heart valves
- also in patients with atrial fibrillation (because you have an increased risk of stroke so this decreases the risk of stroke)
how does wafarin help break down the clot?
it doesnt directly break down the clot it just stops it from breaking of and getting any bigger and your own bodies mechanisms will break it down
-means you need to be on it for a while
How to give it?
How much binds to plasma proteins
-can we give in pregnancy?
-what happens when you have other drugs?
Give it orally
- 99% binds to plasma proteins
- crosses placenta - can have anticoaulgant effect on fetus - DONT GIVE IN PREGNANCY
- other drugs - is broken down in liver by cytochrome p450, and so are other drugs
- can get other drugs inhibiting or enhacnign effects of wafarin due to increased or decreased breakdown
How do we monitor warfarin
INR - want it to be between 2-3
-for treatment of VTE, PE, atrial fibriliation
However for metal heart valves may want it to be 3-4 - or recurrent thrombus
What are things that can effect warfarin metabolism
absorption - dihorrhea, vomiting
metabolism - liver disease
nutrition/ dietary - if eat too much vit K then may not be helping as much
-Drugs
Drugs that potentiate warfarin
Antibiotics - e.g erythromycin, clarithromycin, metronidazole, ciproloaxcin, tetracyclin
Anti fungals - fluconazole
Anti lipid agents - simvastatin
Analgesics - paracetamol, NSAIDS, aspirin
Drugs inhibiting warfarin
Alcohol
rifampicin
contraceptives
Management of wafarin when the INR increases
- depends on severity of bleeding
- can give IV vit K if need or oral vit K
Practical info
Initiating - dosing - based on INR then give heparin whist it kicks in
General advice
- monitor bruising and bleeding, other medication, stopping before surgery, other medications - see influences and start or stop this
INR monitoring
Problems with warfarin
- narrow therapeutic window
- lifetime risk of haemorrhage
- drug interactions
- need to constantly test INR
What to give when someone develops side effects of heparin
- can give pentasaccharides
- will inhibit 10a
Dabigatran
- how is it activated
- what does it do?
- when can we not give it? (2 cases)
- what is the inhibitor of it
Prodrug (gut will activate this)
is a direct thrombin inhibitor
P glycoprotein substrate
Is renally excreted so cannot use if patient GFR is low
cannot be used with metal heart valves - can lead to thrombus
Idarucizumab - binds dabigatran and inhibits it (if pateint is bleeding on thsi)
