Warfarin

Question 1

therapeutic window and variability

Answer 1

Warfarin has a narrow therapeutic window and wide inter-individual variability

Question 2

uses

Answer 2

anticoagulant/blood thinner

• atrial fibrillation, DTV, pulmonary embolism, myocardial infarction, congestive heart failure

Question 3

side effects

Answer 3

Under-anticoagulation can result in thrombosis

• Over-anticoagulation can result in dangerous bleeding episodes

Question 4

dosing is determined by

Answer 4

empirically, often based on age and underlying condition with adjustments made until the target therapeutic INR for clotting is achieved

Question 5

what % of people are expected to benefit from increased, intermediate or lower does of warfarin

Answer 5

65% - increased dose
32% - intermediate dose
3% - lower does

Question 6

what does warfarin antagonise/

Answer 6

the vitamin K dependent clotting pathway

Question 7

what converts vitamin K epoxide to reduced active vitamin K

Answer 7

VKORC1

Question 8

what factors are decent of reduced vitamin K

Answer 8

VII, IX and X

Question 9

increased enzyme activity

Answer 9

more active clotting factors (more warfarin required)

Question 10

Decreased enzyme activity

Answer 10

ess active clotting factors (less warfarin required).

Question 11

what could affect enzyme activity

Answer 11

VKORC1 variants

Question 12

what is CYP2D9 involved in

Answer 12

clearing warfarin form the system

Question 13

which CYP2D9 variants are less functional

Answer 13

CYP2C92 and CYP2C93 variants less functional

Question 14

what would less functional variants of CYP2D9 require you to do to dose and why

Answer 14

lower does

Leaving more Warfarin in the body for longer
• Lower dose of Warfarin to keep within the INR