Pharmacology, use and monitoring of anticoagulant, antiplatelet, and fibrinolytic agents Flashcards
What Kind of drugs do we often look towards for haemostasis?
We are mostly concerned with preventing thrombosis.
Drugs to treat or prevent this imbalance to away from clot formation:
Anticoagulant
Pro-fibrolytic
Anti-platelet
What pathways are manipulated for antiplatelet formation?
Coagulation
Fibrinolysis
Platelets
What are anticoagulants?
Warfarin (oral)
Heparin (SC / IV)
Where does tissue factor come from?
Tissue exposure to circulation
What are new oral anticoagulants?
Direct Anti-Xa
Direct Anti-IIa
Where is warfarin derived from?
Coumarin which is a toxin occurring in plants
What is another use for warfarin?
Active component in rat poisons
What does warfarin do?
Inhibits vitamin K epoxide reductase.
It inhibits formation of vitamin K
It is a Vitamin K antagonist
Leads to reduced formation of vitamin K dependent coagulation proteins (factor II, VII, IX, and X)
Can warfarin outside of the body? Why?
No, it only works in vivo. It has a delayed onset of activity and doesn’t affect coagulation factors that are already formed.
How is warfarin taken?
Orally active and rapidly absorbed. (works through the liver.
How fast is warfarin absorbed?
Rapidly absorbed
What is warfarin’s half like like? What does this mean?
Long half life because it becomes strongly bound to plasma protein so can be taken once a day
What must we be weary of when administering warfarin?
It can interact with many other drugs and is affected by diet. This means dosage is difficult as it must be monitored
What increases warfarin anticoagulation activity?
Vitamin K deficiency (already low activity down that pathway so warfarin makes things even lower)
Hepatic diseases (already impaired synthesis of coagulation factors)
Hypermetabolic states
Drug interactions with other anti-haemostatic drugs and liver enzyme medications.
What decreases warfarin anticoagulation activity?
Pregnancy
High Vit K diet (vitamin K competitively inhibited by warfarin)
Drug interactions such as alcohol which stimulates liver to increase clearance.
Vitamin K supplements
How is warfarin tested?
Prothrombin Time (PT) [time for coagulation of plasma after stimulation of extrinsic factor pathway by addition of tissue factor and calcium]
International Normalized Ratio (INR) The PT of patient divided by a normal PT adjusted for the batch of reagents
What are the possible adverse effects of warfarin?
Haemorrhage which is difficult to reverse
How can warfarin adverse effects be treated?
Oral vitamin K (takes too long)
Fresh Frozen Plasma (FFP)
How can adverse effects of warfarin be prevented?
Dosage must be carefully titrated based on INR
Warfarin summary:
Chronically used
Delayed effect
Dosing is problematic
Difficult to reverse
Orally administered
What is heparin?
Highly suflated glycosaminoglycan derived from pig or cow mucosa.
What is heparin’s polarity?
Very strong negative charge
What is heparin’s molecular weight?
Highly variable molecular weight (60 to 100 kDa)
What does heparin mimic?
Human heparin sulphate
What is the active part of the heparin molecule?
A repeating pentasaccharide unit
How is heparin administered?
IntraVenously or subcutaneously
How does heparin work?
Binds to and increases activity of endogenous antithrombin to bind to activated factor II by 1000 fold. Heparin is reusable because complex reversibly binds to AT.
What is heparin resistance?
Effectiveness tapers of due to loss of active AT molecules and this can be reversed with subsequence AT injection following heparin administration
How long does heparin need to take effect?
Works immediately
How is heparin activity monitored?
Activated Partial Thromboplastin Time (APTT)
some controversy about this method’s effectiveness
How is heparin activity reversed?
Administration of protamine sulphate
What are the adverse effects of using heparin?
Haemorrhage
Thrombocytopenia
Osteoporosis (inhibition of vitamin D in the kidneys)
What is low molecular weight heparin?
Heparin which has been treated to remove many of the non-active parts creating a more consistent sized protein of consistent molecular weight.
Why is consistency of the low molecular weight heparin useful?
Creates more predictable pharmacokinetics.(dosing is easier)
Molecule is far more active and potent