Which three drug groups decrease clotting?
What is thrombosis?
unwanted haemostatic plug in a blood vessel or the heart
What causes deep vein thrombosis?
poor blood flow
sitting for long periods of time
What are the symptoms of deep vein thrombosis?
Swelling and heat in leg
What can result from a failure to treat deep vein thrombosis?
Loss of a leg
Which two things can increase clotting?
- Replacement factors (VIII & IX)
- Plasminogen ihibitors
Which enzyme does waraffin inhibit?
Vitamin K reductase
(stops carboxylation of glutamic acid residues = cannot bind platelet = no proteolysis = no cascade and no clotting)
Which 3 drugs increase the action of waraffin and how?
- Aspirin = displace it from plasma proteins
- Sulphonamides = interferes with liver function
- NSAIDs = interferes with platelet function
Which two patient factors increase the action of waraffin?
- Liver disease (decreases factor production and clearance)
- Reduced vitamin K availiability
What is the average rate of onset for warrafin use?
How long do the effects of warrafin last once you stop taking it?
How do we measure the action of warrafin in a patient?
(the time a sample takes to clot following addition of a standardised amount of Ca = ratio = compared to healthy subjects)
2-2.5 = prophylaxis of deep vein thrombosis
2.5 = treatment of deep vein thrombosis/ pulmonary embolism
3.5 = recurremt deep vein thrombosis/pulmonary embolism
After starting a patient on warrafin at which intervals do we measure the action of warrafin?
Then at longer intervals
Then every 12 weeks
Which two drugs decrease the action of warrafin and how?
- Barbituates = induce metabolising enzymes
- Colestipol (athlerosclerosis) = decreases absorption
Which two patient factors decreases the action of warrafin?
- Increased vitamin K = promoted clotting factor synthesis
What are the side effects of Warrafin (2)?
- Haemorrhage in bowel or brain (stop administration & give vitamin K & replacement factors)
- Teratogenic (damages foetus)
Name two injectable anticoagulants:
Low molecular weight heparin
Which two factors does heparin hit?
= activates antithrombin III
n.b. Heparin also binds to factor IIa but LMW heparin is too short = only hits factor Xa!!
What is the main clinical use for heparin?
Clearing blocked IV catheters
What inhibits heparin?
Factor IV (LMW heparin not inhibited)
Can factor Xa bind to factors already bound to fibrin?
What causes heparin to be badly absorbed in the gut?
Its large size and charge
In which 2 ways can heparin be administered?
Subcutaneous (LMW heparin only)
Why is there an initial rapid removal of heparin?
Binds to plasma proteins (heparin only), endothelial cells and macrophages
How is heparin excreted?
Slowly through renal excretion
What are the side effects of heparin (5)?
- haemorrhage (counter with heparin antagonist e.g. protamine sulphate)
- Thrombosis (rare -> when antibodies against heparin cause endothelial damage)
Name 4 examples of heparin:
Name 3 types of LMW heparin:
Name 3 antithrombin independant anticoagulants:
- Hirudin (binds thrombin active site -> leeches)
Which patients may antithrombin III independant anticoagulants be useful for?
Those who produce heparin antibodies