week 5

Question 1

mechanism of action of unfractionated heparin

Answer 1

Binds to antithrombin III (ATIII) → increases its activity
Inhibits: Thrombin (Factor IIa) Factor Xa

Question 2

mechanism of action of LMWH

Answer 2

Binds to antithrombin III (ATIII) → increases its activity
Selectively inhibits Factor Xa
Too small to inhibit thrombin effectively

Question 3

Adverse effects of Heparin

Answer 3

Bleeding (main risk)
Heparin-Induced Thrombocytopenia (HIT) – Type II (immune-mediated)
Osteoporosis (long-term use)
Hyperkalaemia (due to hypoaldosteronism)
Skin necrosis (rare)

Question 4

what is heparin induced thrombocytopenia

Answer 4

antibody mediated thrombocytopenia that is associated with paradoxical thrombosis.
Platelet count should be performed frequently.
Any new thrombus can be the result of heparin.

Question 5

Reversal agent of heparin

Answer 5

Protamine sulfate

Question 6

mechanism of action of protamine

Answer 6

binds to heparin to form a stable inactive complex
completely reveres UFH
partially reverses LMWH

Question 7

Warfarin interactions, examples causing increased INR?

Answer 7

Enzyme inhibitors; amiodarone, macroludes, metronidazole, antifungals
NSAIDs
3rd generation cephalosporins

Question 8

warfarin interactions, examples decreasing INR

Answer 8

Enzyme inducers; rifampicine, carbamazipine, phenytoin
Cholestyramine
Vitamin K rich foods
Diuretics

Question 9

mechanism of action of warfarin

Answer 9

Inhibits vitamin K epoxide reductase, reduces synthesis of vitamin K dependent clotting factors
Factors 2,7,9,10, protein C and S

Question 10

why is effect of warfarin delayed

Answer 10

Due to existing clotting factors that must degrade first.
especially Factor 2

Question 11

Reversal agents of warfarin

Answer 11

Vitamin K (phytonadione)
FFP
Prothrombinex/Vitamin K combo

Question 12

what is streptokinase

Answer 12

a fibrinolytic drug, derived from streptococci bacteria
works indirectly activating plasminogen to plasmin
degrades fibrin and clots

Question 13

mechanism of action of streptokinase

Answer 13

catalyses the formation of plasmin from plasminogen

Question 14

what can happen due to previous exposure of streptokinase

Answer 14

Previous exposure can result in antibodies forming
this can reduce efficacy or cause hypersensitivity

Question 15

mechanism of action of aspirin

Answer 15

Irreversible inhibition of COX1 and COX2 enzymes
decreases thromboxane and prostoglandin synthesis

Question 16

with aspirin what happens with regards to COX1 inhibition

Answer 16

decrease thromboxane A2 formation.
this decreases platelet aggregation for 7-10 days

Question 17

with aspirin what happens with regards to COX2 inhibition

Answer 17

decrease prostoglanding synthesis
this is the antiinflammatory, antipyretic and analgesic effect

Question 18

Distribution of aspirin

Answer 18

widely distributed, crosses placenta and BBB

Question 19

metabolism and half life of aspirin

Answer 19

hepatic metabolism
hydrolysis to salicylate (active metabolism)
renal excretion, pH dependant
half life aspirin 15-20 minutes
salicylate half life is dose dependent 2-19 hours

Question 20

mechanism of action of clopidogrel

Answer 20

irreversibly inhibits the P2Y12 subtype of ADP receptors on platelet cell membranes.
Prevents activation of GPIIb/IIIa receptor complex.

Question 21

how does clopidogrel compare with ticagrelor

Answer 21

Ticagrelor is reversible, an active drug and quicker onset

Question 22

examples of tissue plasminogen activators

Answer 22

Alteplase, Tenectoplase, retoplase

Question 23

mechanism of action of t-pA

Answer 23

Activates plasminogen to plasmin that is bound to fibrin.
Breaks down fibrin causing clot dissolution

Question 24

examples of G2b/3a inhibitors

Answer 24

abciximab, eptifabtide, tirofiban

Question 25

mechanism of action of G2b3a inhibitors

Answer 25

block the G2b/3a receptor on activated platelets (this receptor is the final pathway for platelet aggregation) Prevents fibrinogen mediated platelet aggregation

Question 26

5 mechanisms of oedema

Answer 26

1. increase capillary hydrostatic pressure (heart failure) 2. decrease plasma oncotic pressure (nephrotic pressure) 3. increase capillary permeability (sepsis, burns) 4. Lymphatic obstruction 5. Sodium and water retention (renal failure)

Question 27

what is the extrinsic coagulation pathway

Answer 27

Tissue factor activates factor 7 this complex activates factor 10 leads to the common coagulation cascade

Question 28

what test can test the extrinsic coagulation pathway

Answer 28

Prothrombin Time

Question 29

what is the intrinsic coagulation cascade

Answer 29

Factor 12 -> 11 -> 9 -> 8 ->10

Question 30

what test can test the intrinsic casade

Answer 30

aPTT

Question 31

what is the common pathway

Answer 31

X -> V -> II (thrombin) -> I (fibrin to fibrinogen)

Question 32

Anticlotting mechanisms

Answer 32

t-PA Urokinase like PA Plasminogen Thrombomodulin Anti thrombin III – inhibit thrombin and other intrinsic clotting factors Protein C and S – vit K dependent, block activated factor 5 and 8 Tissue factor pathway inhibitor – stops the extrinsic coagulation pathway by inactivating Facto 7a and 10a.

Question 33

Where are platelets are produced

Answer 33

In bone marrow by megakaryocytes

Question 34

what are the two types of granules in platelets

Answer 34

Alpha - for coagulation and repair Dense - for aggregation and vasoconstriction

Question 35

what is the platelet aggregation cascade

Answer 35

1. Adhesion 2. Activation 3. Aggregation 4. Clot stabilisation

Question 36

How does platelet adhesion happen?

Answer 36

platelets bind to vWF via GP1b receptor at damaged endothelium

Question 37

How do platelets aggregate

Answer 37

Platelets link via fibrinogen and GPIIb/IIIa receptors

Question 38

How are red cells produced

Answer 38

Erythropoiesis. Stimulated by erythropoietin made in the kidneys in response to hypoxia.

Question 39

What 3 things are required from red blood cell production

Answer 39

Iron - for haem. Vitamin B12 + folate - for DNA synthesis. Globon synthesis

Question 40

how does fibrinolysis happen

Answer 40

Plasminogen turns to plasmin via tPA. Plasmin breaks down fibrin

Question 41

other than fibrinolysis what are other anti clotting mechanisms

Answer 41

antihrombin III, protein C, protein S, thrombomodulin. These inactivate factor V and VII. Also inhibit tissue plasminogen inhibitor so there will be more plasmin