Anticoagulants Flashcards
1
Q
Unfractionated heparin
A
- 45 polysaccharide mixture (more than LMWH)
- fast onset of action
- 30 min half life at low doses
- 2hr half life at high dose
- unpredictable (so must be titrated)
- given IV bolus and infusion
- binds to AT3 causing conformational change and increased activity of AT3
- if inhibiting IIa then needs to bind to AT3 and IIa
- if inhibiting Xa then only needs to bind to AT3
2
Q
LMWH (dalteparin and enoxaparin)
A
- 15 polysaccharides which are absorbed more uniformly
- almost always s.c.
- enoxaprin used in ACS and needs to be given IV
- > 90% bioavailability
- longer half-life +2hr
- more predictable dose response because doesnt bind to any cells
- doesnt inhibit IIa
- only inhibits Xa by enhancing AT3 activity
3
Q
Fondaparinux
A
- synthetic LMWH
- selectively inhibits Xa by binding to AT3
- given s.c.
- half life is 18hrs
4
Q
What are the indications for use of heparins?
A
- prevention of venous thromboembolism, perioperative prophylaxis with LMWH duration and dose dependant on risk
- used during pregnancy because DOESNT crops placenta but monitor with caution
- used for VTE, DVT and PE
- used for ACS becauses it reduces recurrence and extension of coronary artery
- thrombosis post STEMI in PCI and non PCI patients
- NSTEMI
5
Q
What are the adverse reactions related to heparin?
A
- bruising and bleeding intracranially, at site of injection, GI, epistaxis, hepatic and renal impairment, elderly or those with carcinoma at higher risk
- heparin-induced thrombocytopenia (1/100 in UFH vs. 1/1000 LMWH)
- allergy/autoimmune response 2-14 days after initiation of heparin
- antibodies to heparin platelet factor 4 complex
- depletion of platelets
- paradoxically can lead to thrombosis as more platelets activated by damaged endothelium
- hyperkalaemia due to inhibition of aldosterone secretion
- osteoporosis is rare but can be due to long-term use, there is higher risk with UFH and more prevalent in pregnancy
6
Q
How is heparin monitored?
A
UFH
- need APTT when using therapeutic doses
- dose is titrated against APTT
LMWH
-more predictable in its action so little monitoring required
7
Q
Protamine sulphate
A
- forms inactive complex with heparin
- given i.v. And dissociates heparin from AT3, irreversible binding amount given guided by heparin dose can cause bleeding
- do in vitro test if unsure
- greater effect with UFH then LMWH, no effect on fondaparinux
8
Q
Vitamin K antagonist (warfarin)
A
- inhibits activation of vitamin K dependant clotting factors (koagulation vitamin)
- inhibits conversion of vitamin K to active reduced form: competitive inhibition of VKOR
- hepatic synthesis of active clotting factors 2, 7, 9, 10 require active vitamin K as cofactor
- delay in onset of action as circulating active clotting factors present for several days
- must be cleared and replaced with noncarboxylated forms (inactive clotting factors)
- half life is 36-48 hours
9
Q
What are the indications for use of warfarin?
A
- venous thromboembolism
- PE
- DVT and secondary prevention
- superficial vein thrombosis
- AF with high risk of stroke
- heart valve replacement
- generally used in long term anticoagulation c.f. Heparins
- slow onset of action likely to require heparin cover if anticoagulation needed immediately
10
Q
What are the pharmacokinetics of warfarin?
A
- good GI absorption and taken orally
- +95% bioavailability
- functional CYP2C9 polymorphism contribute to significant inter-individual variability
- [plasma] does not correlate directly with clinical effect
- warfarin is a racemic mixture of 2 enantiomers (R and S which have different potency and metabolised differently)
- crosses placenta so must be avoided n 1st and 3rd trimester
- response affected by CYP2C9 and others such as vitamin K intake
- if fluctuating levels of vitamin K, then must be mindful of warfarin dose
11
Q
What are the adverse drug reactions of warfarin?
A
- principle ADR is bleeding: a patient taking warfarin is always of clinical interest
- epistaxis and spontaneous retroperitoneal bleeding
- most effective antidote is vitamin K, or prothrombin complex concentrate (given iv)
- perioperative anticoagulation needs to be considered
- BRIDGING therapy with LMWH often required when initiating or temporarily stopping warfarin (surgery, sickness)
12
Q
What are the warfarin drug-drug interactions (DDI)?
A
- high number
- majority potentiate anticoagulant action but some decrease effects
- inhibition of hepatic metabolism especially CYP2C9 by amiodarone, clopidogrel, intoxicating dose of alcohol, quinolone, metronidazole
- reduce vitamin K by elimating gut bacteria involved in production by using cephalosporin antibiotics
- displacement of warfarin from plasma albumin by using NSAIDS and drugs that decrease GI absorption of vitamin K (will likely increase INR because more warfarin present in blood)
- acceleration of warfarin metabolism will decrease INR, can be done through the use of barbiturates, phenytoin, rifampicin, St. John’s Wort
13
Q
Direct acting oral anticoagulants aka DOAC (apixaban, edoxaban, rivaroxaban)
A
- directly inhibits Xa whether it is free or bound
- does not have action on IIa
- hepatic metabolism and excreted partly by kidneys
- half life of 10hrs
- given orally once a day
14
Q
Dabigatran
A
- DOAC
- selectively direct competitive thrombin inhibitor (IIa)
- acts on free and bound IIa
- half life on 9hrs
- given orally 1-2 times a day
- need bridging therapy
- no need for monitoring
15
Q
When would monitoring of DOACS be beneficial?
A
-to see if the patient is compliant and adhering
