11. Anticoagulants Flashcards
What do anticoagulant drugs do?
Prevent thrombus formation and thrombus growing
What is an important cofactor in many of the coagulation cascade steps?
Calcium
What is the role of heparin?
Inhibit coagulation in vitro and in vivo- enhance antithrombin III activity
How is unfractionated heparin given?
IV bolus and infusion
SC for prophylaxis with low bioavailability
What is the action of unfractionated heparin?
Binding to antithrombin III causing conformational change and increased activity of ATIII
To catalyse inhibition of thrombin (IIa), heparin needs to simultaneously bind ATIII and IIa
Xa inhibition only needs ATIII binding
Name some low molecular weight heparins (LMWH)
Dalteparin
Enoxaparin
How are LMWH administered?
Almost always SC
What is the action of LMWH?
Inhibition of Xa specifically - by enhancing activity of ATIII
What are the indications for heparin?
Prevention of venous thromboembolism, perioperative prophylaxis with LMWH
During pregnancy used - monitored with caution
DVT and PE - initial treatment, long term in some patients
Acute coronary syndromes
What are the ADR of heparins?
Bruising and bleeding - intracranial, at site of infection, GI, epistaxis
Heparin induced thrombocytopenia
Hyperkalaemia - inhibition of aldosterone secretion
Osteoporosis
What are the contraindications for heparins?
Clotting disorders, renal impairment
What are the DDI for heparins?
Other anti thrombotic drugs
ACEi/ARB and spironolactone
Name a reversal for heparin
Protamine sulphate - dissociates heparin from ATIII, irreversible binding
Name a vitamin K antagonist
Warfarin
What is the action of warfarin?
Inhibit activation of vitamin K dependent clotting factors
Inhibits conversion of vitamin K to active reduced form - competitive inhibition of VKOR
Which clotting factors require vitamin K as cofactor for activation?
II, VII, IX, X
What are the indications for warfarin?
Venous thromboembolism PE DDVT and secondary prevention Superficial vein thrombosis Atrial fibrillation with high risk of stroke Heart valve replacement Longer term anti coagulation
What are the contraindications for warfarin?
Avoided at least in 1st and 3rd trimesters of pregnancy
Hepatic disease
What is the response of warfarin affected by?
CYP2C9 and others
Vitamin K intake
Alcohol
What are the ADR of warfarin?
Bleeding
Epistaxis and spontaneous retroperitoneal bleeding
What are the DDI for warfarin?
Inhibition of hepatic metabolism esp. CYP2C9 - amiodarone, clopidogrel, intoxicating dose of alcohol
Cephalosporin antibiotics - reduce vit K
NSAIDs, drugs that decrease GI absorption of vit K
Barbiturates, phenytoin, rifampicin, St Johns wort - acceleration of warfarin metabolism
What must be monitored in patients taking warfarin?
INR - clotting time against a standard
DVT, PE, AF - INR 2.5
Recurrent DVT or PE - INR 3-3.5
Name some direct acting oral anticoagulants (DOAC)
Apixaban (Xa)
Edoxaban (Xa)
Rivaroxaban (Xa)
Dabigatran (IIa)
What is the action of direct Xa DOACs?
Inhibit both free Xa and that bound with ATIII, do not directly effect thrombin (IIa)
What is the action of direct IIa DOACs?
Selective direct competitive thrombin inhibitor, both circulating and thrombus bound IIa
What are the ADR of DOACs?
Bleeding
What are the contraindications of DOACs?
Dabigatran contraindicated in low creatinine clearance, others are at ver low creatinine clearance
Avoid in pregnancy and breastfeeding
What are the DDI of DOACs?
Affected by CYP inhibitors and inducers
Carbamazepine, phenytoin, barbiturates
Macrolides
