Anti-clotting drugs Flashcards
Warfarin pharmacokinetics
Good GI absorption, can be given PO
Slow onset-give heparin cover for the first few days
Slow offset (T1/2 ~48 hrs)
Crosses placenta-teratogenic in first trimester, brain haemorrhage in 3rd trimester
Heavily protein bound
CYP450 metabolism
Warfarin mechanism
Prevents reduction of vitamin K
Inhibits production of vitamin K dependent clotting factors (7,9,10,2)
Gla residues can’t form so no localisation of clotting factors.
Warfarin monitoring
Prothrombin time
INR
Warfarin uses
AF
Thromboses associated with inherited conditions
DVT (3-6 months)
Mechanical prosthetic valves
Warfarin ADRs
Teratogenic
Haemorrhage
Give anticoagulant card
Warfarin DDIs
Aspirin
CYP450 inhibitors
Cephalosporins (inhibit vitamin k production by colonic bacteria)
All potentiating
Heparins mechanism
Glycosaminoglycan produced by mast cells
Activate anti thrombin 3
Deactivates factors 10a, 2a, 9a, possibly also 8a, 11a, 12a)
Warfarin reversal
Vitamin k
Unfractionated heparin
Chains of 12-15 kd
Loading dose, then IV
Monitor APTT
Is large enough to bind factor 2a (unlike LMWH)
Low molecular weight heparins
Smaller chains -4-5 kd Long T1/2 Subcutaneous Higher bioavailability (~90%) More predicable dose response - usually no monitoring required Cleared by kidneys Less risk of thrombocytopenia
Heparin reversal
Stop heparin
Protamine sulphate - dissociates heparin from AT3 - if actively bleeding
Heparin uses
Immobility Perioperative (low dose LMWH) DVT/PE/AF Acute coronary syndromes Warfarin cover -operations, pregnancy
Heparin ADRs
Bruising/bleeding-GI, intracranial, epistaxis, injection sites
Osteoporosis
Thrombocytopenia - can be autoimmune as platelets activated and used up. (PF4 receptor)
Clopidogrel
Prascigrel
ADP antagonists
Inhibit ADP dependent platelet aggregation
Indicated in ACS or PCI
Can be given with aspirin - bleeds more serious but not more life threatening.
Not long term
Dipyridamole
Probably a phosphodiesterase inhibitor
Positive isotrope, vasodilatory
Secondary prevention of stroke
Glycoprotein 2b/3a receptor antagonists
Fibrinogen usually binds here, resulting in platelet aggregation
Used in high risk ACS and post PCI-increased bleeding risk but reduced thrombosis and re stenosis.
Streptokinase mechanism
Converts plasminogen to plasmin
Thrombolysis occurs when plasmin >alpha 2 anti plasmin
Streptokinase pharmacokinetics
T1/2 ~ 15 mins
Streptokinase/plasminogen complex T1/2 ~3 mins
IV infusion
Cleared by liver
Streptokinase ADRs
Hypotension
Fibrinolytic reversal
Tranexamic acid
Inhibits plasminogen binding
Recombinant TPA advantages
Non immumogenic
Fibrin specific - less systemic disturbance
Recombinant TPA pharmacokinetics
Reteplase + tenecteplase T1/2 ~14-17 mins
Renal and hepatic clearance
Alteplase T1/2 ~ 3 mins
Hepatic clearance
Recombinant TPA issues
May stimulate thrombin and platelet activation
Give heparin alongside
Alteplase
Recombinant TPA
Reteplase
Recombinant TPA
Tenecteplase
Recombinant TPA
Contraindications to thrombolysis
History of haemorrhagic stroke Peptic ulcer or other potential bleeding source Recent trauma or surgery CNS neoplasm Aortic dissection Uncontrolled hypertension Known bleeding disorder
Indications for thrombolysis
MI in last 12 hours
Stroke in last 3 hours (up to 4.5)
Bivalrubin
Desirubin
Direct thrombin inhibitors
Fondaparinux
Idaparinux
Specific factor Xa inhibitors
