Anti-platelets and Anti-thrombotics (details)

Question 1

What is the MOA of aspirin?

Answer 1

It inhibits cyclooxygenase, which is important in the arachidonic acid pathway. This then blocks the production of thromboxane A2, which is a danger signal that promotes platelet aggregation

Question 2

What are the clinical uses of aspirin?

Answer 2

1) Prophylactic treatment of transient cerebral ischemia
2) Reduces the incidence of recurrent myocardial infarction
3) Decreases mortality in post-MI patients

Question 3

What are the PK properties of aspirin?

Answer 3

It irreversibly inhibits cyclooxygenase, which thus lasts for the lifetime of the platelet (ie: 7-10 days). After this period of time, the platelet will be broken down and the effects will wear off.

Question 4

What are the adverse effects of aspirin?

Answer 4

1) Bleeding (PGI2)
2) Gastric upset and ulcers (PGE2)

Because of the inhibition of the arachidonic acid pathway, the production of all prostaglandins are affected. This includes PGI2, PGE2 and PGF2A.

Question 5

What is the MOA of platelet GPIIB/IIIA receptor blockers?

Answer 5

They bind to the GPIIB/IIIA receptor and thus prevent the cross-linking of fibrinogen, thus preventing the formation of a fibrin mesh

Question 6

What is the clinical use of platelet GPIIB/IIIA receptor blockers?

Answer 6

1) Prevent restenosis after coronary angioplasty
2) Acute coronary syndromes

Question 7

What is the MOA of ADP receptor blockers?

Answer 7

Block the ADP receptor to preventing ADP from binding –> lack of recognition of ADP as a danger signal –> platelet aggregation prevented

Question 8

What is the MOA of PDE inhibitors

Answer 8

Inhibition of PDE –> prevention of breakdown of cAMP –> allows cAMP to prevent degranulation –> no danger signals produced –> platelet aggregation prevented

Question 9

What is the MOA of heparins?

Answer 9

Heparins potentiate the action of antithrombin III (an endogenous anticlotting protein that irreversibly inactivates clotting factor proteases, especially thrombin, IXa and Xa)

The active heparin molecules bind tightly to ATIII and cause a conformational change, which exposes the active site of ATIII for more rapid interaction with the proteases

Question 10

Compare the PK properties of low molecular weight heparin to regular (unfractionated) heparin

Answer 10

LMWHs have better bioavailability and longer half-life compared to regular (unfractionated) heparin.

Question 11

What type of heparin is needed to inhibit thrombin?

Answer 11

Regular (unfractionated) heparin only.

To inhibit thrombin, it is necessary for heparin to bind to the enzyme as well as to ATIII

Question 12

What type of heparin is needed to inhibit factor X?

Answer 12

LMHW or regular (unfractionated) heparin

To inhibit factor X, it is only necessary for heparin to bind to ATIII

Question 13

What are the clinical uses of heparin?

Answer 13

Same as warfarin but can be used in pregnancy

1) treatment of DVT, pulmonary embolism and AMI
2) Can be used in combination with thrombolytics for revascularisation
3) Can be used in combination with GPIIA/IIIB inhibitors during angioplasty and placement of coronary stents
4) Can be used when an anticoagulant must be used in pregnancy

Question 14

Can heparin be used for thrombi which have already been formed?

Answer 14

NO!!

heparin can only prevent the worsening of the condition. thrombolytics should be used to break down thrombi which have already formed

Question 15

Which drug can be used for anticoagulation in pregnancy?

Answer 15

Heparin ONLY!! The rest are contraindicated in pregnancy

Question 16

What is the mode of administration of heparin?

Answer 16

IV or SC

Question 17

(popular exam question) Why can’t heparin be given via IM injection?

Answer 17

Because it’s liable to hematoma formation!!!

Question 18

What are the adverse effects of heparin?

Answer 18

1) Haemorrhage
2) Thrombosis and thrombocytopenia

Question 19

How to treat excessive heparin?

Answer 19

Stop heparin therapy and give protamine sulfate (sequesters heparin)

Question 20

How to treat warfarin overdose?

Answer 20

Give patients vitamin K in its reduced form

But to immediately correct the coagulation abnormality due to the overdose, you need to give fresh frozen plasma which contains all the clotting factors the patient would be deficient in

Question 21

What are the clinical uses of warfarin?

Answer 21

Same as heparin but cannot be used in pregnancy

1) treatment of DVT, pulmonary embolism and AMI
2) Can be used in combination with thrombolytics for revascularisation
3) Can be used in combination with GPIIA/IIIB inhibitors during angioplasty and placement of coronary stents

Question 22

What are the PK properties of warfarin?

Answer 22

1) Given orally and absorbed quickly and totally (good oral bioavailability)
2) Small distribution volume, being strongly bound to plasma albumin (>99%)
3) Hepatic elimination (metabolised by CYP450)

Question 23

What are the adverse effects of warfarin?

Answer 23

1) Bleeding
(if given during pregnancy; which should NEVER happen!!!)
2) Haemorrhagic disorder in fetus
3) fetal proteins with gamma-carboxyglutamate residues found in bone and blood may be affected

Question 24

When is warfarin contraindicated?

Answer 24

PREGNANCY!! NEVER GIVE WARFARIN DURING PREGNANCY!!

Question 25

What is the MOA of thrombolytic agents?

Answer 25

Promote the conversion of plasminogen to plasmin –> plasmin break down fibrin mesh –> dissolution of thrombus

Question 26

What are the clinical uses of thrombolytic agents?

Answer 26

has to be used within less than 4.5 hours of thrombus formation

1) emergency treatment of coronary artery thrombosis
2) peripheral arterial thrombosis and emboli
3) ischemic stroke

Question 27

What are the possible modes of administration of thrombolytic agents?

Answer 27

Intracoronary injection, IV injection

Question 28

What are the adverse effects of thrombolytic agents?

Answer 28

Bleeding

Question 29

In what situations are thrombolytic agents contraindiated?

Answer 29

1) Pregnancy
2) Presence of healing wound (because thrombolytic agents would interfere with wound healing)