Anticoagulant drugs Flashcards
What are three indications for anticoagulants
Coronary artery disease
Cerebrovascular disease
Peripheral vascular disease
What are three thrombo-embolic disease indications for anticoagulants
Atrial fibrillation
Venous thrombo embolism (PE, DVT)
Prosthetic cardiac valves
Three indications for heparin use
Acute coronary syndromes (MI)
Thromboembolus (prophylaxis and treatment)
Warfarin replacement (pregnancy)
What is the mechanism of action of unfractionated heparin
Binds to and increases the activity of Anti-Thrombin III.
Anti-Thrombin III inactivates Thrombin and factor Xa. Also IXa, XIa and XIIa.
What test is used to monitor UH and why is it necessary to do so vigilantly
aPPT.
Because UH has variable bio-availability due to unpredictable patterns of binding to cells and plasma proteins.
What biometric measurement should UH dosage be titrated against
Weight
How do you reverse UH therapy
Protamine sulphate
Irreversibly binds to heparin
Mechanism of action of LMWH
Binds to anti-thrombin. Smaller chains and more predictable structure c/w UH.
Does not inactivate Thrombin, specifically affects Xa.
Three advantages and three disadvantages of LMWH compared with UH
- Higher bioavailiability
- More predictable- monitoring not usually required
- Less thrombocytopenia
- Community SC administration
- Cannot be monitored with aPPT
- Not fully reversible with protamine
- Care in renal failure (different metabolism)
What is an adverse effect related to UH use and platelet count
Thrombocytopenia. Due to an autoimmune phenomenon.
Prophylaxis dosing of LMWH (e.g. post C/S)
2o-40mg SC OD
Treatment regime of PE/DVT
Initially give LMWH, then warfarin, continue LMWH until INR therapeutic (5-7 days)
Mechanism of action of Warfarin
Antagonist of Vitamin K synthesis in the liver. Vitamin K required for synthesis of clotting factors II, VII, IX, and X.
Uses of warfarin
Treatment of venous or arterial thrombosis- DVT/ PE.
Prevention of venous or arterial thromboembolism- mechanical heart valves, AF.
Describe two instance when lifelong warfarin therapy is indicated
If more than one episode of DVT/ PE
If mechanical valves of AF (preventative)
How is warfarin metabolised and what is the clinical relevance of this
In the liver by cytochrome P450 enzyme. Many drugs decrease P450 efficacy and thus subject to drug interactions.
Describe the half life and clinical implications
Very long half life- takes several days for the drug to have clinical effect so in treatment requires initial dual therapy with another anti-coagulant
Two unwanted effects of warfarin
Haemorrhage (intracranial and GI)
Teratogenic in pregnancy (first trimester bone and CNS, third intracranial bleeds)
Contraindications to warfarin
Situations where the risk of bleeding is greater than potential clinical benefits of therapy: substance abuse, dementia, falls.
Pregnancy
Describe monitoring of warfarin
Use the INR. PR which adjusts for lab differences in thromboplastin. Initially monitor INF every 2-3 days. Long term therapy every 4-12/52.
Describe target INR
Rx of VTE/ PE/ AF 2-3
Rx heart valve replacement/ anti-phospholipid syndrome/ recurrent thrombosis 3-4.5
Four factors that affect warfarin metabolism
Absorption- diarrhoea and vomiting
Metabolism- liver disease
Nutrition/dietary (Vit K reduction)
Drugs
Name five drugs that are inhibitors of the P450 enzyme and describe what effect this has on warfarin therapy.
Amioderone
Antimicrobials (erythromycin, metronidazole, ceprofloxacin)
Sodium valporate
Simvistatin
NSAIDs
Omeprazole
Decrease warfarin metabolism/excretion so potentiate its effects.
Drugs that inhibit warfarin
Barbituates
OCP
Carbamazepine
Azithioprine
Describe management of high INR coupled with bleeding
Stop warfarin
Give FFP/Prothrombin X and blood PRN
Give Vitamin K (slow onset so clotting factors need to be given PRN)
Describe the mechanism of action and PK of dabigatran
Direct thrombin inhibitor
Prodrug; liver and gut enzymes cleave it to its active form.
Renal excretion
Uses of dabigatran
Similar to warfarin- PE/DVT/AF. Not used in metal prosthetic heart valves.
What drug is used to reverse the effects of dabigatran
Idarucizumab
