Lecture 5 - Anticoagulant Drugs

Question 1

Anticoagulant indications?

Answer 1

arterial disease - coronary heart disease, cerebrovascular disease, peripheral vascular disease (combine w anti-platelets); thrombo-embolic disease - atrial fibrillation, venous thrombo-embolism, prosthetic cardiac valves

Question 2

Virchow’s Triad to indicate anti-coagulant use?

Answer 2

hypercoagulabiltiy, vascular damage, circulatory stasis

Question 3

Uses of heparin?

Answer 3

acute coronary syndromes, DVT, PE, AF, temporary warfarin replacement (pregnancy)

Question 4

Heparin physiology?

Answer 4

increases activity of anti-thrombin (III) (which inactivates IIa, XIa, Xa XIa, XIIa, requires APTT monitoring, no GI absorption (IV), rapid onset and offset`

Question 5

Problems with unfractionated heparin?

Answer 5

difficult, blood testing requirement, variable APTT control

Question 6

Adverse effects - heparin?

Answer 6

bruising/bleeding sites, heparin-induced thrombocytopenia (auto-immune, check platelets every 2 days as early complication), osteoporosis (long term)

Question 7

Reversal of UF therapy?

Answer 7

protamine, APTT test, protamine sulphate

Question 8

Low Molecular Weight Heparins (LMWH)?

Answer 8

binds to III, does not inactivate iia, affects Xa specifically, reliable dose-effect relationship

Question 9

LMWH advantages?

Answer 9

higher bioavailability (subcutaneous injection), doesn’t bind plasma proteins , macrophages or endothelial cells (no monitoring requirement), lower risk of HIT and bleeding

Question 10

LMEH cons?

Answer 10

cannot be monitored by APTT, nor reversed by protamine

Question 11

Warfarin mechanism of action?

Answer 11

vit K inhibitor in liver, reduces production of coagulation factors II, VII, IX, X, slow onsert of anticoagulation due to metabolism and excretion of factors

Question 12

Uses of warfarin?

Answer 12

DVT, PE, mural thrombus, mechanical heart valves, AF

Question 13

Duration of anti-coagulation action?

Answer 13

mechanical valves and AF - lifetime; VTE - balance between bleeding vs recurrence and cause (LMWH for cancer co-morbidity)

Question 14

Internatonal Normalised Ratio?

Answer 14

INR = patients PT (s)/mean normal PT (s); 2-3 or 3-4 in serious cases (mechanical valves, recurrent thromboses)

Question 15

Warfarin contraindication?

Answer 15

pregnancy, risk of haemmorhage (drugs, dementia, falls) poor concordance

Question 16

Individual variability of warfarin?

Answer 16

absorption, metabolism, vitK in diet, co-morbidity, drugs (cytc. P450 inducers and inhibitors)

Question 17

Drugs inducing warfarin (inhibiting P450)?

Answer 17

A drugs - antibiotics, alcohol, amniodrane, antacids, analgesics

Question 18

Drugs inhibiting warfain (inducing P450?)

Answer 18

alcohol (chronic constant use), barbiturates, contraceptives

Question 19

Initial regime?

Answer 19

dose loading then maintenance based on INR, LMWH cover whilst commencing warfarin (not required for AF)

Question 20

Patient advice?

Answer 20

bruising and bleeding, other medications, INR monitoring, surgery status

Question 21

Management of high iNR?

Answer 21

vitK admin (slow effect), IV prothrombinex

Question 22

Problems with warfarin?

Answer 22

narrow therapeutic window, lifetime risk of haemmorrhage, interactions, INR monitoring

Question 23

Other anticoagulants?

Answer 23

Hirudin (III independent IIa inhibitor), pentasaccharides (indirect Xa inhibitor), dabigatran

Question 24

Dabigatran?

Answer 24

competitive, reversible inhibitor, non-P450 dependent, mechanical valve contraindication, reversed by idarucizumab