Anticoagulants

Question 1

how do mutations in VKOR1 affect warfarin Rx

Answer 1

they result in resistance, you have to increase dose

Question 2

how is warfarin metabolized

Answer 2

by CYP2C9, mutation in this mean you need less warfarin for therapy. CYP activity decreases with age

Question 3

describe effect time of warfarin

Answer 3

Need to wait until IX and X reach their half lives. Requires at least 5 days of dosing

Question 4

INR

Answer 4

ratio of patient PT to control PT raised to ISI power. Goal INR for anti coags is 2-3

Question 5

Rx of elevated INR warfarin

Answer 5

Hold warfarin, give vitK, fresh frozen plasma

Question 6

mech of warfarin gangrene

Answer 6

deficiency of vitK leads to low levels of proteins C,S so you get thrombosis

Question 7

heparin

Answer 7

polymer with pentasaccharide. binds to antithrombin and this complex binds FXa and IIa on a 1:1 ratio. Immediate acting

Question 8

what do you use to monitor heparin

Answer 8

aPTT

Question 9

Adverse heparin effects

Answer 9

HIT (high risk of thrombosis), osteoporosis

Question 10

LMWH

Answer 10

anti Xa but loses antithrombin activity

Question 11

how are heparins cleared

Answer 11

renal except for Enoxaparin (liver and renal)

Question 12

compare cost of unfractioned and LMW heparin

Answer 12

LMWH is much more expensive but doesnt require monitoring so it can be given outpatient

Question 13

how to treat overdose of heparin

Answer 13

protamine reverses effect of unfractioned

Question 14

fondaparinux

Answer 14

pentasaccharide. inhibits Xa through activation of antithrombin III (ATIII)

Question 15

direct thrombin inhibitors

Answer 15

desirudin, bivalirudin, argatroban, dabigatran

Question 16

advantage of direct thrombin inhibitors

Answer 16

dont require antithrombin, not inactivated by PF4. They inactivate clot-bound thrombin in addition to soluble thrombin

Question 17

direct Xa inhibitors

Answer 17

fondiparinux, rivaroxaban, apixiban