anticoagulants

Question 1

Anticoagulant drugs –

Answer 1

prevent thrombus formation and thrombus growing

Question 2

heparin, naturally, function

Answer 2

Produced naturally in mast cells and vascular endothelium
Inhibit coagulation
- Enhance antithrombin III (AT-III) activity

Question 3

unfractionated heparin

Answer 3

fast onset of action, t1/2 30min low dose, 2h at higher doses – mixed elimination so is unpredictable
• i.v. bolus and infusion,
To catalyse inhibition of thrombin (IIa), heparin needs to simultaneously bind ATIII AND IIa.

Question 4

Low molecular weight heparins (LMWH)

Answer 4

dalteparin enoxaparin
predictable
Almost always s.c. (enoxaparin i.v. in ACS)
• Bioavailability > 90%, longer t1/2 ~ 2+h
• Inhibition of Xa specifically – by enhancing ATIII activity
Fondaparinux – synthetic
selectively inhibits Xa by enhancing ATIII – s.c., t1/2 18h

Question 5

heparin indications

Answer 5

VTE–DVT and PE
During pregnancy used as do not cross placenta – monitored with caution
initial treatment prior to oral agents in some but now a shift towards oral agents Long term in some patient groups
• Acute Coronary Syndromes (ACS)
short term - reducing recurrence and or extension of coronary artery thrombosis post STEMI - PCI and non PCI patients
NSTEMI

Question 6

heparin #

Answer 6

Bruising and bleeding
Intracranial, at site of injection, GI, epistaxis
thrombocytopenia
autoimmune response
Hyperkalaemia – inhibition of aldosterone secretion
Osteoporosis -

Question 7

heparin x, Δ

Answer 7

X Clotting disorders, renal impairment (LMWH and fondaparinux)
• Δ Other antithrombotic drugs, ACEi/ARB, amiloride, spironolactone

Question 8

heparin reversal

Answer 8

Protamine sulphate forms inactive complex with heparin – given i.v.
dissociates heparin from ATIII,
Much greater effect with UFH than LMWH, no affect on fondaparinux

Question 9

vitamin K antagonist

Answer 9

warfarin

Question 10

vit K antagonist mechanism

Answer 10

Inhibit activation of vitamin K dependant clotting factors II, VII, IX and X

Delay in onset of action
orally ~95+% bioavailability
X It crosses the placenta
– avoided at least in 1st (teratogenic) and 3rd (haemorrhage) trimesters,
hepatic disease
• Response affected by CYP2C9 and others, vitamin K intake, alcohol

Question 11

vit K antagonist indications

Answer 11

Venous thromboembolism PE. DVT
Atrial fibrillation with high risk of stroke
Cardioversion
• Heart valve replacement

Question 12

vit K antagonist #, Δ

Answer 12

bleeding,

antidote: vitamin K
Δ : CYP2C9: Amiodarone, clopidogrel, intoxicating dose of alcohol,
Reduce vitamin K by eliminating gut bacteria involved in production
-cephalosporin antibiotics
Displacement of warfarin from plasma albumin: NSAIDs and drugs that decrease GI absorption of vitamin K -more anticoagulated
Acceleration of warfarin metabolism
barbiturates, phenytoin, rifampicin, St Johns Wort - less anti coagulated
X: pregnancy, hepatic imp
Monitoring required due to huge variation in patient response
• Keeping diet and lifestyle/medications stable is important

Question 13

direct acting oral anticoagulants DOACs

Answer 13

oral, Lower intracranial bleed risk compared to warfarin
apixaban edoxaban rivaroxaban:
direct Xa:Inhibit both free Xa and that bound with ATIII, do not directly effect thrombin (IIa) - hepatic metabolism and excreted partly by kidneys

dabigatran: Direct IIa
Selective direct competitive thrombin inhibitor, both circulating and thrombus bound IIa

Question 14

DOACs #,X, Δ

Answer 14

bleeding

X: dabigatran contraindicated in low creatinine clearance, avoid in pregnancy and breastfeeding
Δ: affected by CYP inhibitors and inducers
[plasma] reduced by carbamazepine, phenytoin and barbiturates
[plasma] increased by macrolides