histamines/antihistamines Flashcards
What is the 1/2 life of histamine in plasma?
~5-10 minutes, meaning plasma needs to be drawn very soon after/during an allergic reaction in order to accurately quantify serum histamine levels
Major cellular sources of histamine
basophils, mast cells, histaminergic neurons, and gastric ECL cells
What is the IgE receptor called on basophils/mast cells?
Fc-epsilon R I
What are some of the physiological effects of histamine?
Smooth muscle contraction (bronchoconstriction), vasodilation via increased NO production by endothelial cells, increased vascular permeability (endothelial contraction increases the size of gap junctions), activation of sensory neurons –> itchiness/pain, autocrine effect promoting further degranulation, and modulation of CNS via histaminergic neurons
What type of receptors are histamine receptors?
GPCRs coupled to Galphaq –> PLC signalling
These H1 receptor inverse agonists function by stabilising the inactive form of the histamine receptor
antihistamines
This 1st generation anti-histamine is commonly used for the treatment of vestibular disorders, nausea/vomiting, and for perioperative sedation. Contraindicated for glaucoma patients due to M3 antagonistic activity
diphenhydramine, has lots of off target effects because it’s highly lipophilic and low MW, therefore can pass the BB very easily. Also has low H1 selectivity relative to 2nd gen antihistamine such as ceterizine and fexofenadine, has activity at cholinergic muscarinic receptors
This 2nd generation antihistamine has 30% CNS H1 receptor occupancy
cetirizine
This 2nd generation antihistamine has zero CNS H1 receptor occupancy, meaning it is prescribed to pilots/heavy machinery operators
fexofenadine
1st gen antihistamines
promethazine, chlorpheniramine, diphenhydramine
2nd gen antihistamines
loratidine, cetirizine, fexofenadine
