Anticoagulant Drugs and Antiplatelets

Question 1

what is haemostasis?

Answer 1

arrest of blood loss from damaged blood vessels

Question 2

how does haemostasis occur?

Answer 2

• vascular constriction
• formation of platelet plug
• formation of blood clot as a result of coagulation
• growth of fibrous tissue into clot to close hole permanently

Question 3

what are some causes of acquired clotting defects?

Answer 3

• liver disease
• vitamin k deficiency
• ingestion of oral anti-coagulants

Question 4

how are acquired clotting defects treated?

Answer 4

• natural vitamin k (phytomenadione)

- menadiol sodium phosphate (synthetic)

Question 5

what are clinical uses of vitamin k?

Answer 5

• treatment and/or prevention of bleeding from excessive oral anticoagulant use
• in babies to prevent haemorrhagic disease of newborn
• vitamin k deficiency in adults

Question 6

what are features of warfarin?

Answer 6

• main oral anticoagulant in uk
• prevents reduction of vitamin k
• many hours to act (time taken for degradation of factors already formed)
• main side effect haemorrhage

Question 7

when does vitamin k acts as a co-factor?

Answer 7

in the post-translational processing of factors II, VII, IX and X

Question 8

what factors increase the effect of oral anticoagulants?

Answer 8

• decreasing availability of vitamin k
• broad spectrum antibiotics
• liver disease
• some drugs

Question 9

what properties of drugs increase effect of oral anticoagulants?

Answer 9

• impair platelet function
• displace warfarin from binding sites in plasma albumin
• agents which inhibit microsomal enzymes in liver

Question 10

what factors decrease the effect of oral anticoagulants?

Answer 10

• drugs which increase drug metabolism

- oral contraceptive

Question 11

what are some injectable anticoagulants?

Answer 11

• heparin (e.g dalteparin)

- heparin sulphate (not used therapeutically)

Question 12

what are features of heparin?

Answer 12

• e.g. dalteparin
• family of sulphated gylcosaminoglycans
• naturally occurring
• found in mast cells, plasma, endothelial cells
• starts acting almost immediately

Question 13

what are features of heparan sulphate

Answer 13

• not used therapeutically
• a related glycosaminoglycan
• occurs extracellularly in many tissues
• important endogenous anticoagulant

Question 14

what is the role of heparin?

Answer 14

acts mainly on fibrin formation:

• acts on antithrombin III (naturally occuring inhibitorof thrombin) and other serine proteases in coagulation cascade (XIIa, XIa, IXa and Xa)
• antithrombin forms 1:1 complex by with thrombin by binding to active site
• heparin accelerates rate of this inhibition

Question 15

what are direct inhibitors of factor Xa?

Answer 15

rivaroxaban or apixaban

Question 16

what are features of direct factor Xa inhibitors?

Answer 16

• both orally active
• do not require PT/INR monitoring
• takes a few hours to act
• effects last 8-12 hours
• no antidote

Question 17

what do antiplatelet drugs do?

Answer 17

decrease platelet aggregation and inhibit thrombus formation - not anticoagulants

Question 18

what are some examples of antiplatelets?

Answer 18

• aspirin

- clopidogrel

Question 19

what is the action of aspirin?

Answer 19

inhibit cyclooxegenase

Question 20

what is the action of clopidogrel?

Answer 20

• inhibits P2Y12 purinergic receptors

- inhibits ADP-induced platelet aggregation

Question 21

what is fibrinolysis?

Answer 21

• clot dissolving system
• set in motion when intrinsic coagulation system is activated
• involves generation of plasminogen activators

Question 22

what is plasminogen?

Answer 22

inactive pro-enzyme

- deposited in fibrin strands within thrombus

Question 23

what is plasmin?

Answer 23

• trypsin-like enzyme acting on ARG-LYS bonds

- formed and acts locally on fibrin meshwork of the clot

Question 24

what does plasmin do?

Answer 24

• digests not only fibrin but other blood proteins such as factors II, V and VII
• plasmin which escapes into circulation is inactivated by various plasmin inhibitors

Question 25

name a fibrinolytic agent?

Answer 25

streptokinase

Question 26

what are features of streptokinase?

Answer 26

• non-enzymatic protein
• acts indirectly
• forms a stable complex with plasminogen

Question 27

what is an example of a TPA (tissue plasminogen activator)?

Answer 27

alteplase

Question 28

what are features of alteplase?

Answer 28

• synthesised in vivo by endothelial cells
• can be made by recombinant technology
• enzymatic activity enhanced more in presence of fibrin-bound plasminogen than plasma plasminogen (clot selective)

Question 29

which anticoagulant is used for venous thromboembolism?

Answer 29

heparin: short-term action

oral anticoagulants: prolonged therapy

Question 30

what are therapeutic anticoagulants used for?

Answer 30

• DVT
• PE
• thromboembolism from atrial fibrillation
• prosthetic heart valves
• clotting during kidney dialysis

Question 31

what are therapeutic uses for fibrinolytic agents plus aspirin (antiplatelet)?

Answer 31

• used in therapy of acute myocardial infarction

- former needs to be given within 4-6 hours of onset

Question 32

what are therapeutic uses for aspirin?

Answer 32

can reduce risk of occlusive cardiovascular disease in patients already diagnosed as being at risk