Blockers of the Histamine-1 Receptor

Question 1

When is histamine released?

Answer 1

Released in a variety of allergic conditions e.g. seasonal rhinitis (hay fever), insect stings
Reactions to certain drugs e.g. penicillin, aspirin

Question 2

Describe the process in which histamine is released

Answer 2

IgE binds to the surface of mast cells after first exposure to antigen
After renewed exposure, degranulation (vesicles opened) of the mast cells causes the release of pro-inflammatory mediators (e.g. histamine)

Question 3

Where does histamine mediate its activity?

Answer 3

At the H1 receptor

Question 4

What properties do blockers of the H1 receptor require?

Answer 4

Potent
H1 selective
Hydrophilic - to prevent transport across the BBB = drowsy

Question 5

List 3 examples of H1 blockers

Answer 5

Loratidine
Terfenadine
Fexofanadine

Question 6

Describe Terfanadine

Answer 6

2nd generation H1 blocker = free from anticholinergic (ACh) and CNS-related side effects
Undergoes almost complete first pass metabolism to the pharmacologically active fexofenadine by action of cytochrome P450

Question 7

Why must terfenadine be metabolised to fexofenadine?

Answer 7

Hepatic impairment can lead to a high terfenadine concentration in plasma = serious cardiac events
Fexofenadine does not build up so is devoid of cardiac events

Question 8

Describe Cetirizine

Answer 8

Does not exhibit anticholinergic properties
Only crosses BBB slightly
The *S)-enantiomer displays an improved pharmacological profile compared to the racemate