drugs Flashcards
aspirin MoA
antiplatelet agent
inhibits cyclooxygenase 1+2 which is necessary to produce thromboxane A2
(a platelet agonist released from granules on activation)
-> reduced ability of platelets to aggregate
who should aspirin not be given to?
under 16s -> risk of Reyes
Exception = Kawasaki disease
adverse effects of aspirin
bleeding
- affect platelet function for their 7-10day lifespan - STOP 7 days prior to operations
- if serious can reverse with platelet transfusion
blocks production of prostaglandins - GI ulceration, bronchospasm
clopidogrel MoA
antiplatelet agen
MoA = ADP receptor antagonist
same adverse effects as aspirin, stop 7days befoer op
1st line pharma Mx for ACS, TIA, ischaemic stroke, peripheral arterial disease
ACS - aspirin (life) + ticagrelor (12months)
TIA - clopidogrel (life)
ischaemic strke - clopidogrel (life)
PAD - clopidogrel (life)
dipyridamole MoA
antiplatelet
MoA = phosphodiesterase inhibitor - increases production of cAMP which inhibits platelet aggregation
same adverse effects as aspirin, stop 7days befoer op
heparin
acts by activating antithrombin III
parenternal - IV (unfractioned) or IM (LMWH)
- unfractioned
- LMWH
unfractionated heparin vs LMWH
unfractionated - useful in situs where high risk of bleeding as anticogulation can be terminated rapidly, also in renal failure, short acting, IV
LMWH - long acting, SC, standard use
MoA of unfractionated + LMWH
unfractionated -> forms a complex which inhibits thrombin, factors Xa, IXa, XIa, and XIIa (mostly intrinsic)
LMWH -> increases only action of antithrombin III on factor Xa
adverse effects of heparin
bleeding
thrombocytopenia (HIT)
osteoporosis with long term use
hyperkalaemia - due to inhibition of aldosterone secretion
-> lower risk of HIT + osteoposrosis with LMWH
heparin induced thrombocytopenia
a prothrombotic condition despite reduced platelets
usually develops 5-10days after treatment
features
- >50% decrease in platelets
- thrombosis
- skin allergy
reversal of heparin
stop heparin (short half life)
in severe bleeding = protamine sulphate
- reverses antithrombin effect
— complete reversal for unfractionated
— partial for LMWH
how is unfractionated + LMWH monitored
unfractionated = APPT
LMWH = anti-Xa assay - but usually not monitoring required, more predictable response
vitamin K dependent factors
factors II (prothrombin), VII, IX + X
- carboxylation of glutamic acid in these as well as protein C + S
systhesised in liver (healthy, working liver)
require vit K for final carboxylation step essential for function
warfarin MoA
anticoagulant, long half life
MoA = blocking vit K thereby reducing clotting factors
maintenance of warfarin
dose should be taken at the same time every day - 6pm recommended
monitor INR
INR
patients PT in secs/mean normal PT in secs
international normalised ratio, ratio of prothrombin time
due to warfarins long half life, achieving a stable INR may take several days
adverse effects of warfarin
haemorrhage
teratogenic - can be used in breastfeeding mothers
skin necrosis - reduced biosynthesis of protein C
purple toes?
factors that may potentiate warfarin
liver disease
P450 enzyme inhibitors - amiodarin, ciprofloxacin
cranberry juice
drugs which displace warfarin from plasma albumin - NSAIDs
inhibit platelet function - NSAIDs
management of bleeding on warfarin
depends on severity + INR
speed of action
- vit K - 6hrs
- clotting factors - immediately
in major
- stop warfarin
- give IV vit K 5mg
- prothrombin complex concentrate - if not available then FFP
direct Xa inhibitors
edoxaban, rivoroxaban, apixaban
no monitoring, less interections
dabigatran
- Oral anticoagulant
- Direct thrombin inhibitor
- Alternative to warfarin, does not require regular monitoring
- Rapid reversal = idarucizumab
