Antiplatelet drugs

Question 1

How many platelets does the bone marrow produce per day?

Answer 1

100 billion platelets per day

Question 2

What is the lifespan of platelets?

Answer 2

About 8-10 days

Question 3

What is the mechanism of action of aspirin?

Answer 3

Acetylates COX serine 529 causing irreversible inhibition of COX (COX1, COX 2 at higher concentrations) leading to a decrease in prostaglandine production (most importantly Thromboxane)

Question 4

Which COX enzyme does aspirin target?

Answer 4

It has a slightly higher affinity for COX 1 with respect to COX 2

Question 5

What are the different categories of antiplatelet drugs available?

Answer 5

• COX-1 inhibitors
• P2Y12 antagonists (irreversible)
• P2Y12 inhibitors (reversible)
• Phosphodiesterase inhibitors
• GP2b/3a blockers
• Thromboxane receptor (TP) receptor antagonists
• Thrombin receptor (PAR-1) antagonists

Question 6

At which dose of aspirin do we get the desired antithrombotic effect?

Answer 6

The antithrombotic effect is saturable for doses 75-100 mg/day

Question 7

Why does aspirin have a at low doses have an antithrombotic biochemical selectivity?

Answer 7

• Because of its pharmacokinetic and pharmacodynamic properties
• When you give aspirin it will inhibit COX 1 in platelets in the portal circulation because there the 75-100mg of it will be produced in high concentrations (due to low volume of portal blood)
• Therefore all the platelets that aspirin encounters during the travel from the intestinal wall to the liver are irreversibly inhibited
• Pharmacodynamically, since the inactivation of COX1 is irreversible and platelets can’t synthesize more of the enzyme (since no nucleus), the platelets are

Question 8

When is the maximal anti-platelet effect reached? Why?

Answer 8

• After 5-7 days
• This is because the first day you only have a percentage of platelets that irreversibly inhibited and the following days higher percentages

Question 9

What are examples of phosphodiesterase inhibitors?

Answer 9

Dipyridamole and cilostazol

Question 10

What are examples of glycoprotein 2b/3a blockers?

Answer 10

Abciximab, eptifibatide, tirofiban

Question 11

What are examples of thrombin receptor antagonists?

Answer 11

Vorapaxar (not used in Europe anymore)

Question 12

What are examples of P2Y12 antagonists?

Answer 12

Ticlopidine, Clopidogrel and Prasugrel

Question 13

How can P2Y12 antagonists be classified into?

Answer 13

Irreversible and reversible inhibitors

Question 14

What are examples of irreversible P2Y12 antagonists?

Answer 14

Irreversible agents are thienopyridines and they are:

• Ticlopidine
• Clopidogrel
• Prasugrel

Question 15

What are examples of reversible P2Y12 antagonists?

Answer 15

Ticagrelor and Cangrelor