Anticoagulation therapeutics Flashcards
what are anticoagulants?
They prevent the blood from clotting as quickly or as effectively as normal
what are fibrinolytics?
stimulate the breakdown/ dissolution of a thrombus/ blood clot
activate fibrinolytic pathway
what are anti-fibrinolytics?
promote clotting by preventing or slowing the process of fibrinolysis
prevent break down of blood clots
what are the stages of haemostasis?
vascular spasm formation of platelet plug conversion to a clot by reinforcement with fibrin tissue repair gradual removal of clot
what is haemostasis?
first phase of acute wound healing
what is antithrombin?
anticoagulant
inactivates thrombin
inactivates factor Xa and IXa
anticoagulants
heparin
warfarin
DOACs
how does heparin work?
affects factor Xa production through the intrinsic pathway
affects IIa
LMWH
greater effect on factor Xa than IIa
unfractionated heparin
affects factor Xa and IIa equally
what is fondaparinux?
synthetic heparin
only affects factor Xa
half life of unfractionated heparin?
short - 1 hour
half life of LMWH
4 hours - short
excretion of unfractionated heparin?
not renal
excretion of LMWH
renal
reversal of heparin and LMWH
unfractionated heparin can be completely revered by protamine
LMWH can only be partially reversed by protamine
risk associated with heparin
heparin-induced thrombocytopenia
autoimmune induced low platelets, risk of DIC
higher risk with unfractionated than LMWH
fondaparinux
longer half life - 17 hours
renally excreted
cannot be reversed
few reports of heparin-induced thrombocytopenia
administration of heparin
IV infusion
administration of LMWH
subcutaneous injection
onset of action of heparin
quick onset - minutes
onset of action of LMWH
long half life
monitoring for heparin and LMWH
heparin requires monitoring with APTR but LMWH doesn’t require any
e.g. of LMWH
dalteparin
indications for use of heparin/ LMWH
DVT PE VTE prophylaxis perioperatively during haemodialysis during open heart surgery safe for use in pregnancy
contraindications for heparin
haemorrhagic disorders thrombocytopenia severe hypertension trauma surgery lumbar puncture spinal/epidural anaesthesia liver disease renal impairment
complications of heparin
bleeding
heparin-induced thrombocytopenia - thrombotic events
can be reversed with discontinuation or protamine
hypersensitivity reactions
how does warfarin work?
vitamin K antagonist
inhibits carboxylation of factors II, VII, IX, X
administration of warfarin
loading dose - 5mg per day
must measure INR - aim for 2-3 in most cases and over 2 in all cases
needs daily administration
initially prothrombotic so give with heparin until target INR reached
pharmacokinetics of warfarin
peak effect several days later
metabolised by CYP450
initially prothrombotic
indications for warfarin
moving away from its use due to need for daily blood tests and variable doses
DVT
PE
AF
mechanical prosthetic heart valves - main use
contraindications for warfarin
pregnancy and 48 hours post-partum haemorrhagic stroke recent ischaemic stroke severe renal disease severe hepatic disease peptic ulcer GI bleed severe hypertension recent surgery
complications of warfarin
initially prothrombotic
bleeding - increased risk due to interactions
teratogenic - disordered bone development
skin necrosis
drug interactions
can increase or inhibit warfarin’s effect
what drugs potentiate warfarin’s effect?
metronidazole co-trimazole aspirin cephalosporins broad spectrum antibiotics
what drugs inhibit warfarin’s effect?
rifampicin
carbamazepine
colestyramine
examples of DOACs
rivaroxaban
apixaban
dabigatran
how does rivaroxaban work?
directly inhibits factor Xa
how does apixaban work?
directly inhibits factor Xa
how does dabigatran work?
direct thrombin inhibitor
downsides of DOACs
drug interactions
very difficult to reverse
no easy reversal
benefits of DOACs
longer term therapy
no monitoring needed
half-life of DOACs
longer than heparin
daily doses of DOACs
once daily for rivaroxaban
twice daily for apixaban and dabigatran
how are DOACs excreted?
renally
drug interactions with rivaroxaban and apixaban
potent dual inhibitors of CYP3A4 and P-gp
drug interactions with dabigatran
P-gp inducers
indications for DOACs
similar to warfarin
surgical prophylaxis
contraindications for DOACs
acute bleeding coagulopathies severe renal insufficiency pregnancy or breastfeeding severe hypertension endocarditis
complications of rivaroxban
constipation
headaches
complications of apixaban
lower risk of GI bleeds than the other DOACs
complications of dabigatran
GI disturbance
diarrhoea
GI bleed risk
fibrinolysis
tissue plasminogen activator converts plasminogen into plasmin
plasmin breaks fibrin down into fibrin degradation productions
what is plasmin
antithrombotic
how do fibrinolytics work?
increase activity of tPA
break down fibrin
examples of fibrinolytics
alteplase
streptokinase
urokinase
indications for fibrinolytics
acute MI - if no immediate surgery
acute ischaemic stroke - within 4 hours
massive PE
occluded central venous access
contraindications for fibrinolytics
aneurysm/dissection will cause bleeding if there is any predisposition/ reason for it history of cerebrovascular event history of coagulation defects GI ulcers GI bleed pancreatitis recent surgery recent trauma severe hypertension cavitating lung disease endocarditis
complications of fibrinolytics
anaphylaxis cardiac arrest cardiogenic shock heart failure CNS haemorrhage hypotension pericarditis
ischaemic stroke treatment
if presentation outside of 4 hour window - too late for fibrinolytic treatment so treat with embolectomy
risk of treating ischaemic stroke with fibrinolytics
haemorrhagic transformation
ischaemic stroke can become haemorrhage of brain
how do antifibrinolytics work?
competitively inhibit activation of plasminogen to plasmin
prevents fibrinolysis
doesn’t cause clotting just prevents break down of clots
example of antifibrinolytic
tranexamic acid
