Toxicology and Drug Safety

Question 1

How is aspirin produced?

Answer 1

Aspirin is derived from willow bark salicin, which breaks down into salicylic acid (acetylsalicylic acid = aspirin).

Question 2

What is the condition caused by salicylate poisoning (aspirin) which children are prone to?

Answer 2

Reye’s syndrome (swelling of the liver and brain).

Question 3

What is the name of the drug also called Seldane, and what does it do?

Answer 3

Terfenadine, it is an antihistamine.

Question 4

What is the terfenadine metabolite and what enzyme is involved in this process?

Answer 4

Fexofenadine

CYP3A4

Question 5

What fruit interferes with CYP3A4

Answer 5

Grapefruit.

Question 6

What are the consequences of terfenadine and grapefruit juice?

Answer 6

Grapefruit juice inhibits the CYP3A4 enzyme from metabolising terfenadine (seldine) into fexofenadine. This means terfenadine will accumulate in concentration in the plasma which blocks the Ikr (delayed rectifier) potassium cardiac channel (coded for by the hERG gene).

This will affect ventricular repolarisation times and therefore Q-T intervals and cause conditions such as Torsades de Pointes (a type of VT).