pharmacology of anticoagulants, antiplatelet drugs and fibrinolytics

Question 1

anticoagulants

Answer 1

prevent unwanted thrombosis. takes several days to act.

Question 2

oral anticoagulants- warfarin

Answer 2

Vitamin K antagonist.
Vit K is essential for prod. of prothrombin and factors VII, IX and X (post-ribosomal carboxylation of glutamic acid residues of these proteins.
warfarin blocks vitamin K reductase, needed for Vit K to act as a cofactor (VKORC)

Question 3

International Normalised Ratio INR

Answer 3

monitored by INR (prothrombin time) with a specific target value and the dose is adjusted.
many drug interactions-
may be potentiated by a range of drugs
may be reduced by enzyme inhibitors.
increased actions lead to bleeding

Question 4

injectable anticoagulants

Answer 4

unfractionated heparin/ LMWHs. activate antithrombin III (natural protein).
antithrombin- inactivates some clotting factors and thrombin by complexing with serine protease of the factors. more controlled.

Question 5

heparin

Answer 5

immediate action
used to prevent thrombosis(venous, unstable angina) and used to prevent blood clotting on collection.
used whilst warfarin takes effect. unfractionated heparins monitored vie APTT

Question 6

novel oral anticoagulants (NOACs)

Answer 6

dabigatran: an oral thrombin inhibitor.
prevents thromboembolism.
rivaroxaban and apixaban: oral inhibitor of activated factor X

Question 7

Prostacyclin

Answer 7

PGI2- prevents platelet aggregation- acts on platelets to increase cAMP

Question 8

Thromboxane

Answer 8

TXA2- promotes aggregation, decreases cAMP

Question 9

nitric oxide

Answer 9

L-arginine + oxygen —> NO + citrulline. by nitric oxide synthase. NO prevents both platelet adhesion and aggregation by increasing platelet cGMP

Question 10

antiplatelet drugs

Answer 10

low dose aspirin (75mg). used to prevent MI is patients who have previously had an MI.
recommended for secondary but not primary prevention.
reduces incidence of stroke.
inhibits cyclo-oxygenase (irreversible)

Question 11

why is PGI2 production favoured over TXA2

Answer 11

platelets have no nuclei- can’t produce any more COX- no more TXA2- until new platelets synthesised (7 days). endothelial cells have nuclei- can produce more COX (2 hours)

Question 12

GP IIb/IIIa

Answer 12

ADP from aggregating platelets, leads to expression of glycoprotein IIb/IIIa (GP IIa/IIIb)- binds fibrinogen which leads to cross-linking of platelets

Question 13

pharmacology of clopidogrel

Answer 13

inhibits ADP-induced expression of GP. for patients who cannot take aspirin/ similarly effective/safe

Question 14

pharmacology of abciximab

Answer 14

monoclonal antibody against GP IIB/IIIa- giben to patients undergoing angioplasty- only use once

Question 15

fibrinolysis

Answer 15

e.g. streptokinase
Endogenous system to dissolve clots.
activated in parallel with clotting system.
plasminogen —–>plasmin

plasmin-digests the fibrin of the clot (and also some of the clotting factors)
fibrinolytic agents (clot busters): activate plasminogen to plasmin conversion

Question 16

thrombolytics

Answer 16

give immediately after an MI- dissolve thrombus that has caused blockage of coronary arteries and the MI- emergency angioplasty now primary treatment.
also used for pulmonary embolism.
Effective, best given with aspirin, but can cause bleeding.
used in thromboembolic stroke- Alteplase licensed for ischaemic stroke; dissolves clot and restores blood flow.