Blockers of the Histamine-1 Receptor Flashcards
When is histamine released?
Released in a variety of allergic conditions e.g. seasonal rhinitis (hay fever), insect stings
Reactions to certain drugs e.g. penicillin, aspirin
Describe the process in which histamine is released
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)
Where does histamine mediate its activity?
At the H1 receptor
What properties do blockers of the H1 receptor require?
Potent
H1 selective
Hydrophilic - to prevent transport across the BBB = drowsy
List 3 examples of H1 blockers
Loratidine
Terfenadine
Fexofanadine
Describe Terfanadine
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
Why must terfenadine be metabolised to fexofenadine?
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
Describe Cetirizine
Does not exhibit anticholinergic properties
Only crosses BBB slightly
The *S)-enantiomer displays an improved pharmacological profile compared to the racemate