Lecture 6: Anticoagulant drugs Flashcards
What are some anti-platelet drugs?
- Aspirin
- Clopidogrel
- Ticagrelor
What are some anti-coagulants?
- Warfarin
- Heparin
- Dabigatran
- Rivaroxaban
What are anti-coagulant indications?
Arterial disease (anti-platelets + anti-coagulants
i.e CAD, Cerebrovascular disease, peripheral vascular dsiease
Thromboembolic disease (anti-coagulants)
- Atrial fibrillation
- Venous thrombo-embolism (DVT, PE)
- Prosthetic cardiac valves
How are the anti-coags and anti-platelets adminsitered?
Parenteral: Heparin
Oral: Warfarin, dabigatran, rivoraxaban
What is unfractionated heparin used for?
- Acute coronary syndromes
- Thromboembolism (propholaxis and treatment) (DVT, PE)
- Temporary heparin replacement
- Extracorpereal units i.e dialysis.
How does heparin function?
Binds and increases the activity of antithrombin 3.
Inactivating:
- Thrombin 2a and factor 10a
- also IXa, XIa, XIIa
Requires APTT monitoring blood test.
What are the pharmacokinetics of unfractionated heparin?
Think T1/2, Bioavail etc
- Parentally, no GI absorb
- T1/2 60 mins
- Variable bioavailability
- Needs APTT monitoring
Whats the therapeutic APTT range of UH?
Normal adults: 25-37s
Therapeutic: 50-80s
What are the main points when it comes to unfractionated heparin?
Unfractionated heparin therapy
- Difficult
- Complicated
- Time consuming
- Blood tests
- Variable APTT control
What are the side effects of UH?
- Bruising and bleeding sites
- Thrombocytopenia
- Osteoporosis (long term)
How do you reverse UH therapy?
- Stop heparin
- Give protamine to reverse immediately.
What is good about LMWH and how does it differ?
- Binds anti-thrombin 3 specifically.
- Impacts factor Xa specifically.
- Doesnt impact thrombin 2a
- No monitoring required
What are the advantages of LMWH?
- Better absorbed, higher bioavailability.
- Does not bind to proteins etc
- SC injection
- Lower risk of thrombocytopeania and bleeding.
Whats the downside to LMWH?
- Cant be monitored by APTT
- Not fully reversible by protamine
- Care in renal failure. Dose reduction.
Whats the action of warfarin?
Vit K antagonists - Prevents formation of vit k dependent clotting factors; 10,9,7,2 and substance P+S
What is warfarin used for?
- Treatment of venous or arterial thrombosis
- Prevention of venous or arterial thromboembolism
-> Mechanical heart valves (only licensed anti-coagulant for this) - Atrial fibrillation
How long are patients on warfarin following mechanical heart valve or VTE?
Mechanical heart valve - Life long
VTE (DVT/PE)
- Difficult
- Balance between bleeding vs VTE recurrence
Write some notes on warfarin metabolism:
- Orally
- 99% bound to plasma proteins
- Completely absorbed (Crosses placenta so C/I in pregnancy)
- Metabolised in liver
- Huge variance in individual dosing requirements
How do you monitor warfarin?
INR : Patients PT / mean normal PT
How does INR change for different indications?
Treating: venous thrombosis, PE, atrial fibrillation. INR ~ 2-3.
Treating mechanical prosthesis, recurrent thromboses, anti-phospholipid syndrome. INR 2.5-4.5
What are the potential unwanted side effects of warfarin?
Haemorrhage
Tetarogenic if pregnant
What are the relevant contraindications to warfarin therapy?
- Pregnancy
- Situations where the risk fo hemorrhage is greater than the potential clinical benefits of therapy i.e uncontrolled alcohol/drugs, falls risk
What are the drug interactions of warfarin?
Effects on anticoagulation
Majority increase anticoagulant effect i.e inc. INR (Cyto P450 inhibitors)
Some decrease effect (Dec. INR)
Cyto P450 inducers
Interactions with warfarin are highly significant
What drugs potentiate warfarin by inhibiting P450?
- Chronic alcohol
- Analgesics i.e paracetamol, NSAIDS
- Antacids i.e omeprazole
What drugs inhibit warfarin by inducing P450?
- Acute alcoholic binge
- Barbituates
Whats the practical advice when initiating warfarin?
- Dosing: Loading then maintenance based on INR (day 4-5 before therapeutic)
- LMWH cover whilst commencing warfarin.
How do you manage a patient on warfarin who has had their INR increase too much?
Depending on severity of bleeding:
- Vit K (slow onset, long acting)
- IV prothrombinex (contains factors)
Less life threatening cases:
- Withold warfarin and recheck INR daily, lower dosage
What are the problems of warfarin?
- Narrow therapeutic window
- Lifetime risk fo haemorrhage
- Drug interactions
- Regular INR
Where do dabigatran and rivaroxaban act?
Dabigatran: 2a inhibitor
Rivaroxaban: 10a inhibitor
What is dabigatran?
Competitive, reversible inhibitor of thrombin (v predictable in action)
What is dabigatran used for?
- Atrial fibrillation
- VTE
NOT used for mechanical heart valves
How can you reverse dabigatran?
IV monoclonal AB ; Idarucizumab
Binds dibigatran:Thrombin complex and sperates them
How does rivaroxaban work?
Selective direct inhibitor of 10a
Renally excreted, cant be used in those with very low GFR
Dont use for heart valves.
Use for Afib/DVT/PE
