Katzung 12th ed - Chapter 34 - Antiplatelets (1)

Question 1

Describe the basic pharmacodynamics of aspirin.

Answer 1

Aspirin IRREVERSIBLY inhibits cyclooxygenase, which means that production of thromboxane A2 is inhibited, and platelet aggregation is reduced.

Question 2

Describe the basic pharmacodynamics of clopidogrel.

Answer 2

Clopidogrel IRREVERSIBLY blocks the ADP receptor on platelets, which means that platelet aggregation is reduced.

Question 3

What dose of aspirin is required to push the metabolism into zero-order kinetics?

Answer 3

> 2g / day

Question 4

What is the significance of the P450 system with clopidogrel?

Answer 4

Clopidogrel is a prodrug that relies on activation by the P450 system (specifically the CYP2C19). Drugs that inhibit CYP2C19, such as omeprazole, will reduce the actions of clopidogrel.

Question 5

How long does the anti platelet effect of clopidogrel last for?

Answer 5

7-10 days

Question 6

Apart from clopidogrel, name two other drugs that reduce platelet aggregation by inhibiting the ADP receptor irreversibly.

Answer 6

Prasugrel and Ticlopidine

Question 7

Aspirin: Describe its absorption.

Answer 7

Aspirin is a weak acid, which means that in acidic environments such as the stomach, it does not dissociate and is therefore readily absorbable. It reaches peak plasma levels in 1-2hrs.

Question 8

Aspirin: Half-life?

Answer 8

The half-life of the parent drug (acetylsalicylic acid) is 15 mins, because it is rapidly hydrolysed by esterases in the tissues and blood. Then, the half-life of salicylates is 3hrs in low doses (e.g. 100-300mg), and 10hrs in higher anti-inflammatory doses.

Question 9

What is the more technical name for aspirin?

Answer 9

Acetylsalicylic acid.

Question 10

How can you increase the rate of excretion of aspirin?

Answer 10

Alkalinise the urine. This means that the salicylic acid will dissociate in the kidney tubules, and not be reabsorbed.

Question 11

Aspirin: Small or Large Vd?

Answer 11

Small (49% protein bound).