Anticoagulant drugs

Question 1

Anticoagulant indication

Answer 1

Arterial disease (Platelets+anticoag): Coronary artery disease, cerebrovascular disease, PVD
Venous disease: AF, VTE, prosthetic valves

Question 2

Virchows triad revision

Answer 2

Stasis: AF, immobility, post op
Endothelial damage: Hypertension, atheroma, toxins
Hypercoaguabilitiy: factor V leiden, thrombin mutation, antiphospholipid, smoking, malignancy

Question 3

Unfractionated heparin uses

Answer 3

Acute coronary syndromes
thromboembolism (prophylaxis and treatment)
temp warfarin replacement (Pregnancy, can not use warfarin)

Question 4

Unfractionated heparin
Structure and consequences
mechanism
therapy?

Answer 4

• long chains, very negative so not absorbed orally, must be IV
• Varied length of chains means varied pharmacokinetic and dynamic effects
• augments activity of antithrombin 3 (inhibits thormbin, Xa, 9, 11 and 12, short half life
• Aptt monitoring (will prolong clotting) (aiming for 50-80)
• Therapy is difficult, complex and time consuming

Question 5

Unfractionated heparin adverse effects

how to correct?

Answer 5

Brusing/bleeding: intracranial, injection site, GI, epistaxis
Thrombocytopenia:
Osteoporosis

Protamine

Question 6

Advantages of LMWH (smaller heparin that binds A3, only blocking Xa)

enoxparin

Answer 6

Better absorbed
Does not bind plasma proteins
Longer half life
More predictable dose response
No monitoring
Can be given in s.c in outpatient setting
lower risk of averse effects

Question 7

LMWH vs UF heparin

Answer 7

Pros: improved PK(pharmacokinetics); monitoring not needed; less thrombocytopenia; less osteoporosis

Cons:Not monitored by APTT; not fully reversed by protamine; care in renal failure

Question 8

DVT treatment

Answer 8

Initially LMWH, then warfarin, then continue LMWH 5-7 days until INR therapeutic

Enoxaparin:

• prophylaxis: 2-40mg od sc (reduce if low eGFR)
• 1mg/kg bd sc

Question 9

Brief warfarin mechanism

Answer 9

Vitamin K antagonist, prevents synthesis of 2,7,9,10

slow onset of action, due to clotting factors in circulation still around

Question 10

Warfarin uses and duration of use

Answer 10

• treatment of DVT/PE or mural thrombus
• Prevention: heart valves, AF, factor 5 leiden

Duration: 3-6 months for DVT, 6 PE; lifelong if >1 episode, lifelong for AF/mechanical valves (thrombophilia). With cancer LMWH

Question 11

Warfarin metabolism

Answer 11

Orally once daily
crosses placenta (bad in pregnancy)
Metabolised by liver (P450)
t1/2 36 hours

Question 12

Warfarin adverse effects

Answer 12

• haemorrhage: intracranial or GI (older people, with previous bleeds)
• Teratogenic: first tri (bone and CNS problems, microcephaly), last 4 weeks cerebral haemorrhage

Question 13

Warfarin monitoring

Answer 13

INR: patients PT/mean normal PT
at start INR daily checks, weekly if after weeks, can be longer
INR targets:
VTE, AF- 2-3
Mechanical valve, recurrent, anti-phospholipid, thrombophilia: 3-4.5

Question 14

For what reasons do individuals vary on warfarin dosage

Answer 14

Absorption: diarrhoea/vomiting
Metabolism: liver disease
Nutrition: Vit K in diet
Co-existing illness
Drugs

Question 15

Drugs potentiating warfarin, (prolong anticoagulant effect)

Answer 15

P450 inhibitors

Amiodarone; antibiotics (erythromycin); anti-fungals; anti-convulsants; antacids; allopurinol; paracetamol

Question 16

Drugs inhibiting warfarin

Answer 16

P450 inducers
Azathioprine
barbiturates
carbamazepine
OCP
rifampicin

Question 17

Management of increased INR

Answer 17

IV vitamin K or oral
IV prothrombinex (2,7,9,10)

Question 18

Factor Xa inhibitor

Answer 18

Rivaroxaban (VTE and AF)

Question 19

Dabigatran features

Answer 19

thrombin inhibitor
Not P450
P-glycoprotein
T1/2-12-14 hours after multiple dosing
renal excretion, do not use in renal failure

Used in AF (150mg), VTE (prevention and treatment),
Do not use for heart valves metal

can reverse with idarucizumab