Anticoagulant Drugs Flashcards
what are the types of anticoagulant drugs
heparin and wafarin
why do you need to monitor heparin and warfarin
as have narrow theraputic windows
what drugs for arterial thrombosis
anti platelets
what drugs for venous thrombosis
anti coagulants
what are the indications for anticoagulant drugs
venous thrombosis
atrial fibrillation
why does AF cause venous thrombosis
as stasis of blood in LA causes clot to form on atrial wall - if this embolises it goes through carotids into brain
what do anticoagulant drugs target
the formation of fibrin clots
are platelets or coagulation cascade activated in venous thrombosis
coagulation cascade (clot is rich in fibrin)
how do you tell the type of clot causing a stroke
atheroma plaque rupture (platelet rich, need anti platelets)
AF (fibrin rich clot, need anticoagulants)
differentiated by ECG (presence of AF)
what does antithrombin do
switches of the action of thrombin (and thus its effect on factors 8 and 9 and fibrinogen)
what clotting factors do protein C and S turn off
5 and 8
what increases the activity of proteins C and S
thrombomodulin modulated thrombin
what drug affects proteins C and S
not usually targeted by drugs but can be affected by warfarin as dependent on Vit K for their synthesis
what are the naturally occurring anticoagulants
anti thrombin
proteins C and S
what is the action of heparin
potentiates the action of antithrobmin (joins to anti-thrombin and protein complex to help them stay together and act of thrombin or factor Xa)
(doesnt dissolve the blood clot (neutrophils do this) but stop it getting bigger and stabilises it to prevent embolisation
what are the forms of heparin
unfractionated (has to be given IV)
low molecular weight (IV or SC)
how long till herparin starts working
immediately effective
how is the dose of LWMH calculated
based on patient weight
does LWMH or unfractionated heparin need more monitoring
unfractionated heparin (why LMWH used more now)
when might unfractionated heparin be preferred
as effect only lasts 30 mins
can also be switched off or reversed so good if patient starts to bleed or needs operation
how long does the effect of LMWH last
12 hours
what does unfractionated heparin predominantly target
pro-thrombin (has small effect on CF Xa)
what does LMWH predominantly target
CF 10
how do you monitor heparin
APTT for unfractionated
anti Xa assay for LMWH (only needed in e.g. renal failure)
what test for monitoring warfarin
INR (ratio of PT)
why is APTT used to monitor heparin
due to positive feedback thrombin usually has on factors 8 and 9 (intrinsic pathway)
what are the potential complications of heparin use
bleeding
heparin induced thrombocytopenia
oesteoporosis with long tern use
what is heparin induced thrombocytopenia
when antibodies form against heparin complex which causes platelets to aggregate (causes numbers to drop)
this creates risk of thrombosis
(if giving heparin and get sudden stop in platelets look for antibodies)
how do you reverse heparin
stop heparin (usually enough as has short half life (30 mins)
in severe bleeding:
-protamine sulphate (reverses antithrombin effect- completely reversed unfractionated, partially reverses LMWH)
what are courmarin anticoagulants
those that work to inhibit the synthesis of vitamin K:
- warfarin
- phenindione
- acenocoumarin
- phenprocoumon
what generally are MWH and heparins used to treat
acute thrombosis situations
what are coumarin anticoagulants used to treat (warfarin)
recurrent VTE (prophylaxis, long term- lifelong)
what type of vitamine is Vit K
fat soluble (needs bile salts to be absorbed)
where is vitamin K absorbed
upper intestine
what is the role of vitamin K
final carboxylation of glutamic acid in clotting factors II, VII, IX and X (+ protein C and S)
this adds COOH group creating negative charge to CF allowing them to bind to calcium on phospholipids in platelets
what factors are dependent on vitamin K
II (prothrombin), VII, IX and X
proteins C and S
where is vit K synthesised
in the liver
which Vit K CF has the shortest half life
7
what should you always give with warfarin in an acute scenario
heparin (warfarin on its own can cause thrombosis)
what is the mechanism of action of warfarin
antagonises vit K
what are the different ways you would initiate warfarin
rapid- acute thrombosis, with heparin
slow- e.g. for AF in community, liver failure, malnourished, elderly etc
when should warfarin be taken
at same time every day
what influences warfarin metabolism
metabolised in the liver- cytochrome P450 levels
how do you monitor warfarin therapy
INR (ratio of PT that corrects it for differences in reagents in the tests- allows for comparison between labs and standardises the PT)
(both PT and APTT will be affected but PT is much more sensitive)
what is the major adverse event in warfarin therapy
haemorrhage
what factors influence the bleeding risk on warfarin
intensity of anticoagulation
concomitant clinical disorders / medications (beware drug reactions- drugs that are metabolised by cytochrome P450)
quality of management
what is the risk and benefit balance of warfarin therapy
risk- 1 in 200 with AF on warfarin have fatal ICH per year
reduced risk of stroke by 1 in 10
what is the target INR ratio
2-3
risk of what increases as the INR rises
risk of bleeding
what are the types of bleeding complications when on anticoagulants
mild: skin bruising, epistaxis, haematuria
severe: GI, ICH, significant drop in Hb
how do you reverse warfarin
for minor bruising/ bleeding with good INR= no action
high INR +/- minor bleedind/bruising= omit warfarin
non threatening bleeding, need to bring down INR= administer oral vit K (takes 6 hours)
ICH, major GI bleed, BP loss= administer clotting factors (concentrated of 2,7,8,9) (not given immediately as scarse resource
assess response (clinically and in lab- INR)
how quickly does the administration of clotting factors work to reverse warfarin
immediately
what do NOACs target
activated factor 10 (more specific)
some are direct thrombin inhibitors (dabigatran)
do you need to monitor NOACs
no
what is dabigatran
NOAC that is a thrombin inhibitor
what are Xa inhibitors
NOACs
e.g. edoXABAN, rivaroXABAN, apiXABAN
target CF Xa (Xa-ban)
are there less or more drug interactions and complication with NOACs
less
1 in 500 bleeding rate
what is now first line for AF
NOAC
what are NOACs used for
treatment of DVT/PE
AF stroke prophylaxis
when is warfarin superior to NOACs
for artificial heart valves and at preventing arterial clots (APS)
what should you give at same time as clotting factors in warfarin reversal
vit K
