Histamine Flashcards
Examples of first generation anti-histamines
Diphenhydramine
Chlorphenamine
Promethazine
Examples of second generation anti-histamines
Loratidine
Cetirizine
Examples of third generation anti-histamines
Levocetirizine
Fexofenadine
Side effects of first + second generation anti-histamines
Drowsiness
Effects can last for 24h + more for first gen.
Less of an issue in second gen.
Biological origin of histamine
Decarboxylation of L-histidine
Which nitrogen in histamine is protonated at pH 7
Aliphatic nitrogen (not in the ring)
Function of H1 receptor
Hayfever treatment (loratidine)
Function of H2 receptor
Stomach ulcer treatment (cimetidine)
Function of H3 receptor
Brain function
Function of H4 receptor
Regulation of immune system
SN1 nucleophilic substitutions
SN2 nucleophilic substitution
Structure activity relationship of first generation anti-histamines
What generation anti-histamine is promethazine?
First generation
Causes drowsiness - prescribed for insomnia
To treat for hayfever, often with decongestant
H1 - antagonist, some affinity for alpha1- adrenoceptor
What nucleophilic substitution is used?
Synthesis of Promethazine
What type of molecular properties cause drugs to pass through blood-brain barrier?
Neutral, oily molecules with high log P
What generation anti-histamine is Cetirizine?
2nd generation
Selective H1 - receptor inverse agonist
Formulated as racemate
Does cetrizine cause drowsiness?
No - hardly crosses BBB
Which form of cetirizine is more active?
L-cetirizine
Synthesis of Cetirizine
Name a 3rd generation anti-histamine
Levocetirizine
(an enantio-pure version of cetirizine as its more specific)
What are 3rd generation anti-histamines thought to have?
Fewer side effects
What are 3rd generation anti-histamines derived from
2nd generation anti-histamine (enantio-pure/metabolised versions)
3rd gens. are more specific so cause less side effects
