antiplatelet

Question 1

What are the 3 ways of using drugs to achieve anti-clotting

Answer 1

anti platelet drug

anti coagulant drug

thrombolytics

Question 2

How does prostacyclin result in antiplatelet effect

Answer 2

prostacyclin binds to platelet membrane receptors causing synthesis of cAMP, cAMP inhibits release of granules containing aggregating agents

Question 3

what does the aggregating agents include

Answer 3

serotonin and ADP

Question 4

How does thromboxane A2 cause platelets to aggregate

Answer 4

thromboxane A2 and exposed collagen cause the release of AA from the platelet membrane. TXA2 is synthesized from AA and released from platelet. TXA 2 binds to receptors on other platelets thereby initiating release of additional aggregating agents

Question 5

What is the pathway of AA synthesizing more TXA2 inhibited by

Answer 5

aspirin

Question 6

What are some examples of anti-platelet drugs

Answer 6

1. platelet GP2B/3A receptor blocker
2. NSAIDS
3. ADP receptor blockers
4. PDE inhibitor

Question 7

What is NSAIDS like aspirin used for clinically

Answer 7

a. prophylactic treatment of transient cerebral ischemia

2. reduce incidence of recurrent myocardial infarction
3. decrease mortality of postmyocardial infarction patient

Question 8

What are the adverse effect of NSAIDS

Answer 8

bleeding (PGI2)

gastric upset and ulcers

Question 9

what is the GP2B/3A receptor

Answer 9

It is a platelet membrane surface protein, activation of receptor complex is the final common pathway for platelet aggregation

Question 10

How does GP2B/3A receptor result in platelet aggregating effect

Answer 10

Receptor complex anchor on fibrinogen allowing crosslinking to become fibrin

Question 11

What are some example of GP2B/3A receptor blocker drugs

Answer 11

Epitifibatide
-mediates binding of fibrinogen to receptor

Abciximab
- is a monoclonal antibody, taken IV, reversibily inhibit binding of fibrinogen and other ligands to the 2B/3A receptor

Tirofiban
- taken orally, small molecule blocker of 2B/3A receptor

Question 12

What are some example of ADP receptor blockers

Answer 12

Clopidogrel, Ticlopidine

Question 13

How does PDE inhibitor help with anti-platelet

Answer 13

Prevents cAMP from degradation. cAMP inhibits degranulation

Question 13

How does PDE inhibitor help with anti-platelet

Answer 13

Prevents cAMP from degradation. cAMP inhibits degranulation, lesser aggregating agents produced, resulting in antiplatelet effect

Question 14

What is an example of a PDE inhibitor

Answer 14

Dipyridamole

Question 15

What are some examples of anticoagulant drugs

Answer 15

warfarin, heparin

Question 16

What is heparin

Answer 16

a family of sulfated glycosaminoglycans

Question 17

how does heparin work

Answer 17

○ Active heparin molecules bind tightly to AT3 and cause a conformational change which exposes its active site for more rapid interaction with the proteases
○ To inhibit thrombin, necessary for heparin to bind to enzyme and AT3. Where as for factor 10 it is only necessary to bind to AT3
○ LMWH increase action of AT3 on factor 10a, but not action on thrombin. Because LMWH cannot allow binding of AT3 and thrombin together

Question 18

what are the clinical uses of heparin

Answer 18

○ Treat deep vein thrombosis, pulmonary embolism, acute myocardial infarction
○ Used in combination with thrombolytics for revascularisation and in combination with GPIIb/IIIa inhibitors during angioplasty and placement of coronary stents
Can be used in pregnancy if really bobian

Question 19

what would happen if heparin is given intramuscularly

Answer 19

hematoma

Question 20

What are the adverse effect of heparin

Answer 20

haemorrhage, thrombosis and thrombocytopenia

Question 21

how is vitamin K important in the coagulation pathway

Answer 21

reduced vitamin K is an essential cofactor in gamma carboxylation of glutamate residues found in factor 2,7,9,10

Question 22

What is vitamin K used for clinically

Answer 22

used to treat and prevent bleeding resulting from the use of anticoagulant drugs like warfarin

for babies to prevent haemorrhagic disease

for vit K deficiencies in adults

Question 23

What does warfarin do

Answer 23

inhibit vitamin K reductase, inhibits quinone( oxidised form of Vit K) from reducing to hydroquinone ( the reduced form of Vit K). without hydroquinone, y- carboxylation of glutamate residues cannot occur, thrombin and other coagulation pathway is limited

Question 24

What are the adverse effect of warfarin

Answer 24

bleeding,,, warfarin crosses placenta readily, can cause hemorrhagic disorder in the fetus,,, fetal proteins with gamma carboxyglutamate residues found in bone and blood may be affected by warfarin

drug interaction that affect availability of cy450 can affect how much warfarin get metabolised and eliminated

Question 25

What are the pharmacokinetics of warfarin

Answer 25

warfarin given orally absorbed quickly and totally

small distribution volume as it is strongly bounded to albumin

elimination depends on metabolism by hepatic cytochrome p450

Question 26

what can increase cyp450

Answer 26

barbiturates, carbamezepine, phenytoin increase cyp450, can result in underdosing of warfarin

Question 27

what can decrease cyp450

Answer 27

amiodarone, cimetidine, disulfiram, imipramine

Question 28

What are the 4 main type of thrombolytic agents

Answer 28

t-pa, urokinase, streptokinase, antistreplase

Question 29

what does thrombolytic agents do

Answer 29

activate plasminogen to form plasmin. Plasmin tries to break down fibrin into fibrin degradation products

Question 30

what are the clinical uses of anti-thrombotic agents

Answer 30

emergency treatment of coronary artery thrombosis, peripheral arterial thrombosis and emboli, ischaemic stroke