Pharmacology of Haemostasis and Anticoagulation

Question 1

what are the four types of drugs for haemostasis and anticoagulation?

Answer 1

anticoagulants
postracyclin/ nitric oxide
anti-platelet drugs
fibrinoylsis

Question 2

what to anticoagulants do?

Answer 2

prevent unwanted thrombosis

Question 3

oral anticoagulants

Answer 3

warfarin: vit. K antagonist (can be reverse by vit K injections)

block vit. K reductase (acts as cofactor for vit K) in liver

Question 4

function of vitamin K

Answer 4

production of prothrombin and factors VII, IX and X

post- ribosomal carboxylation of glutamic acid residues of the factors

Question 5

when is warfarin used

Answer 5

after surgery
patients with replaced heart valves- foreign surface can form clots 
AF
PE- prevent further clots 
DVT

Question 6

how is warfarin monitored?

Answer 6

INR

2.5 narrow TW as risk of haemorrhage bleed in brain

Question 7

drug interactions of warfarin

Answer 7

can be potentiated by drugs

reduced by enzyme inducers

Question 8

increased actions of warfarin can lead to bleeding:

Answer 8

gastric
cerebral
haemoptysis(coughing up blood)
blood in faeces, urine
easy bruising

Question 9

injectable anticoagulants

action

Answer 9

unfractioned heparin (liver derived) 
LMWH 

activate antithrombin III- serine protease inhibitor (no thrombin made)
- inactivate factor X
immediate action
prevent thrombosis and prevent clotting on collection

Question 10

when are injectable anticoagulants given

Answer 10

when warfarin takes effect, not long term as can cause thrombocytopenia

pregnancy- first 3 months then swap to heparin

monitored via APTT

Question 11

Direct oral anticoagulants DOACs

Answer 11

Dabigatran: oral thrombin inhibitor

Rivaroxaban: oral inhibitor of factor X

prevents thromboembolism- less bleeding than warfarin, fewer drug interactions, doesnt need monitoring,

not as easily reversed

Question 12

Prostacyclin/ nitric oxide are

Answer 12

endothelial derived vasodilators

Question 13

PGI2 prostacyclin mechanism

Answer 13

Arachidonic acid in membrane -> free AA (PLA2)-> endoperoxides (COX)-> PGI2, prostaglandin, thromboxane

Question 14

Prostaglandins increase/ associated with

Answer 14

pain, asthma, uterine function

Question 15

PGI2 function

Answer 15

prevents platelet aggregation, acts on platelets to incresase cAMP

Question 16

Thromboxane function

Answer 16

promotes platelet aggregation by decreasing cAMP

Question 17

Nitric Oxide mechanism

Answer 17

L-arginine + O2-> NO+ citrulline

Question 18

Nitrix oxide function

Answer 18

prevents platelet adhesion and aggregation by increasing platelet cGMP

Question 19

Anti-platelet drugs

Answer 19

low dose aspirin
prevents secondary MI (patients had previous MI)
used to prevent CVD
reduces stroke incidence
inhibits cyclo-oxygenase irreversibly by acetylating N terminal serine on COX

Question 20

how do anti-platelet drugs favour PGI2 production over TXA2

Answer 20

PGI2 produced in endothelium and TXA2 in platelets

platelets have no nuclei- cant produce anymore COX until new platelets are synthesised (7 days)- no TXA2

endothelial cells have nuclei- can produce more COX mRNA (2 hours) so PGI2 produced to inhibit platelets

Question 21

Dipyridamole is

Answer 21

anti-platelet drug
phosphodiesterase inhibitor: prevents breakdown of cAMP and cGMP

ATP-> cAMP-> inhibits aggregation

cAMP-> AMP (phosphodiesterase)

Question 22

when is dipyridamole used

Answer 22

in conjunction with aspirin
prevent thrombosis
also inhibits adenosine uptake

Question 23

Glycoprotein IIb/ IIa

Answer 23

ADP from aggregating platelets leads to expression of GP IIb/ IIa
binds fibrinogen- crosslinking of platelets

Question 24

Clopidogrel

Answer 24

irreversibly inhibits ADP-induced activation of GP. new for patients who cannot take aspiring

in ischaemic stroke it is given with aspirin

Question 25

Abciximab

Answer 25

monoclonal antibody against GP IIb/IIa- for patients undergoing angioplasty (prevent from being thrombotic)
used once

Question 26

Fibrinolysis

Answer 26

activate plasminogen to plasmin conversion

give immediately after MI to dissolve thrombus caused coronary artery block

best given with aspirin but can cause bleeding

used in thromboembolic stroke

Question 27

Thrombolytics

Answer 27

after MI

with aspiring but can cause bleeding

TE stroke- alteplase

Question 28

primary treatment for MI

Answer 28

emergency angioplasty

• catheter, balloon to open blockage and fit stent
• antiplatelets given to prevent further clot formation from damage due to procedure