Anticoagulants

Question 1

NOACs (novel anticoagulants)- examples

Answer 1

Dabigatran- THROMBIN INHIBITOR (Tran inhibits Thrombin

Apixaban/rivaroxaban- FACTOR XA INHIBITORS (XAban)

Question 2

Indications of NOACs

Answer 2

Newly diagnosed DVT/PE- does not need covered with heparin (warfarin)
AF where CHA2DS2 score suggests need
Prevention of VTE

Question 3

Contraindications of NOACs

Answer 3

Valvular heart disease, mechanical heart valve
Renal failure (CrCl <30)
Liver failure
Active bleeding/history of bleeding disorder
Pregnancy/ breastfeeding

Question 4

Reversal of NOAC

Answer 4

Not straightforward like warfarin
IDRACIZUMAB reverses dabigatran
Xa inhibitors- prothrombin complex may normalise thrombin time, dialysis may help remove active drug from blood
Activated charcoal in last 2 hours

Question 5

NOACs vs Warfarin

Answer 5

No monitoring and standardised dosing- onset of action within 3hrs unlike warfarin (heparin first few days)
Less likely to interact with other drugs/pre-existing conditions than warfarin

Reversal impossible/difficult
Narrower range of indications (valvular instances)
Potential higher GI bleed risk

Question 6

Warfarin- mechanism of action

Answer 6

Vitamin K agonsist that can be taken orally (unlike heparins)
Acts on extrinsic pathway (heparin intrinsic)
Inhibits enzymatic reduction of vitamin K to hydroquinone (active form)- competitive binding to enzymes
Takes several days to develop (half lives of existing factors) > reduce fII, VII, IX and X

Question 7

INR

Answer 7

Extrinsic proudces some fibrin quickly, intrisic large amounts slowly
PT measurement of how quickly small clot forms
INR = internal normalised ratio- comparison of patient’s clotting abilitycompared to average (PT TEST/ PT NORMAL)^ ISI

Question 8

Side effects of warfarin

Answer 8

Haemhorrage- bowel and brain, admin Vit K/ fresh plasma (clotting factors)
Teratogenicity
Necrosis of soft tissue- buttock and breast: thrombosis in venules
result of inhibitioin of protein C synthesis (START ON HEPARIN)

Question 9

Increasing the effect with warfarin

Answer 9

Disease: Liver disease (reduces F 2,7,9,10), High metabolic rate e.g thyrotoxicosis/fever (CF degraded increasingly as these increase)

Drugs- o-devices inhibit CP450 > INC warfarin effects
O (omeprazole)
D (disulfiram)
E (erythromicin)
V (valproate)
I (isoniazid)
C (cimetidine/ciprofloxacin)
E (ethanol- acutely)
S (sulphonamides)
NSAIDS (aspirin)- antiplatelets, or can displace warfarin from albumin binding site
Inhibit hepatic metabolism e.g antifungals, amiodarone, cimetidine etc
Cephalosporins- inhibit vit K synthesis

Question 10

Decreasing the effect of warfarin

Answer 10

Pregnancy
Hypothyroidisim- reduced metabolic rate and therefor red. breakdown coag. factors

Drugs- Vitamin K
Drugs that induce CP450 enzymes-
P- PHENYTOIN
C- CARBAMAZEPINE
B- BARBITURATES
R- RIFAMPICIN
A- ALCOHOL (CHRONIC)
S- SULPHONYLUREAS

Question 11

Special instances

Answer 11

Surgery- stopped before surgery- heparin can be used in short term in high risk
Cancer patients- LMWH better at reducing embolism risk
IV drug users- LMWH preferred due to difficulties monitoring INR (lifestyle)