S Zhang Histamine and Antihistamine Flashcards
What is the structure of histamine?
Which protonated form of histamine is active?
Monocation
Which amino acid is the precursor to histamine? By which enzyme? Which moiety is changed?
Histidine is converted to histamine by histidine decarboxylase (replaces carboxylic group with amine)
Where are H1 and H2 receptors located? Their major effects once activated?
H1 is present on smooth muscle and endothelial cells
- involved in allergy
H2 is present on gastric parietal cells
- involved in gastric acid secretion
What are the three categories of antihistamine medications?
Histamine synthesis inhibitors
Histamine release inhibitors
Histamine receptor antagonists
Name some inhibitors of histamine synthesis. How do they inhibit it?
Inhibit histamine decarboxylase activity
What is an example of an inhibitor of histamine release? What is the MOA?
MOA: stabilize mast cells and prevents histamine release
- phosphorlyation of protein that stabilize granules
What is the general structure of H1 receptor antagonists?
In the aryl domain of H1 receptor antagonists, what are some key points regarding activity?
Both aryl amines contribute to the best activity
- planar or non aromatic moeities lead to inactive structures
Does stereochemistry matter in H1 antagonists? If so, which configuration?
Yes, S is more potent
The shorter the spacer and branchging, the better the activity of H1 antagonists
T or F
True
Regarding the alkyl amine region of the H1 antagonist, which structure has optimal activity?
Tertiary amines
Why are there no quaternary amine compounds developed as H1 antagonists?
Due to its resemblance to acetylcholine (anticholinergic effects)
What is the structure of diphenhydramine? What class is it part of?
Ethanolamines
Which configuration of the pyridine is mostly present in doxylamine?
Ortho position methyl to nitrogen
Name some ethylenediamines
Which isomer is more potent?
The left isomer (E configuration)
Why was there a concern in using terfenadine? Which drug was made that lacked this risk? Draw the structure
Risk of ventricular arrhythmias
Fexofenadine (Allegra)
