Lecture 5 - Anticoagulant Drugs Flashcards
Anticoagulant indications?
arterial disease - coronary heart disease, cerebrovascular disease, peripheral vascular disease (combine w anti-platelets); thrombo-embolic disease - atrial fibrillation, venous thrombo-embolism, prosthetic cardiac valves
Virchow’s Triad to indicate anti-coagulant use?
hypercoagulabiltiy, vascular damage, circulatory stasis
Uses of heparin?
acute coronary syndromes, DVT, PE, AF, temporary warfarin replacement (pregnancy)
Heparin physiology?
increases activity of anti-thrombin (III) (which inactivates IIa, XIa, Xa XIa, XIIa, requires APTT monitoring, no GI absorption (IV), rapid onset and offset`
Problems with unfractionated heparin?
difficult, blood testing requirement, variable APTT control
Adverse effects - heparin?
bruising/bleeding sites, heparin-induced thrombocytopenia (auto-immune, check platelets every 2 days as early complication), osteoporosis (long term)
Reversal of UF therapy?
protamine, APTT test, protamine sulphate
Low Molecular Weight Heparins (LMWH)?
binds to III, does not inactivate iia, affects Xa specifically, reliable dose-effect relationship
LMWH advantages?
higher bioavailability (subcutaneous injection), doesn’t bind plasma proteins , macrophages or endothelial cells (no monitoring requirement), lower risk of HIT and bleeding
LMEH cons?
cannot be monitored by APTT, nor reversed by protamine
Warfarin mechanism of action?
vit K inhibitor in liver, reduces production of coagulation factors II, VII, IX, X, slow onsert of anticoagulation due to metabolism and excretion of factors
Uses of warfarin?
DVT, PE, mural thrombus, mechanical heart valves, AF
Duration of anti-coagulation action?
mechanical valves and AF - lifetime; VTE - balance between bleeding vs recurrence and cause (LMWH for cancer co-morbidity)
Internatonal Normalised Ratio?
INR = patients PT (s)/mean normal PT (s); 2-3 or 3-4 in serious cases (mechanical valves, recurrent thromboses)
Warfarin contraindication?
pregnancy, risk of haemmorhage (drugs, dementia, falls) poor concordance
Individual variability of warfarin?
absorption, metabolism, vitK in diet, co-morbidity, drugs (cytc. P450 inducers and inhibitors)
Drugs inducing warfarin (inhibiting P450)?
A drugs - antibiotics, alcohol, amniodrane, antacids, analgesics
Drugs inhibiting warfain (inducing P450?)
alcohol (chronic constant use), barbiturates, contraceptives
Initial regime?
dose loading then maintenance based on INR, LMWH cover whilst commencing warfarin (not required for AF)
Patient advice?
bruising and bleeding, other medications, INR monitoring, surgery status
Management of high iNR?
vitK admin (slow effect), IV prothrombinex
Problems with warfarin?
narrow therapeutic window, lifetime risk of haemmorrhage, interactions, INR monitoring
Other anticoagulants?
Hirudin (III independent IIa inhibitor), pentasaccharides (indirect Xa inhibitor), dabigatran
Dabigatran?
competitive, reversible inhibitor, non-P450 dependent, mechanical valve contraindication, reversed by idarucizumab
