Anti-Histamines

allergies

first exposure
B cells react to allergen, produce IgE antibodies
antibodies bind to receptors on mast cells/basophils
no current response
subsequent exposure
degranulation, release of inflammatory chemicals

Histamine receptors

Gq GPCR
4 classes; H1-H4

H1 receptors

activation--\>vascular permeability, vasodilation, cough, bronchoconstriction, eosinophilic chemotaxis
in smooth muscle, vascular endothelium, heart, CNS
throughout brain, especially in wake-promoting system

Diphenhydramine

first generation antihistamine and antitussive
H1 receptor inverse agonist (antagonist)
reduces allergy symptoms
requires high doses
crosses BBB, inversely agonizes H1 CNS receptor --\> drowsiness (on target side effect) --\> sleep aid
suppresses activity in nST (antitussive)
brand names: Benadryl (allergy), Nytol (sleep aid), Tylenol Complete (cough)

First generation antihistamines

bind with high affinity to muscarinic cholinergic receptors
anticholinergic (off target effects)
side effects: dry mouth, constipation, confusion (older people are more susceptible)

Diphenhydramine side effects

sedative tolerance (on target)
decreased sleep quality (on target)
long term --\> Alzheimer's and dementia (off target, anticholinergic)

second generation antihistimines

higher H1 selectivity
lower off target effects
poor BBB--\>no sedative effects
longer duration of action; require fewer doses

Certirizine

second gen H1 receptor antagonist
poor BBB permeability; minimal sedation
high duration of action with fewer doses
brand name: Zyrtec

loratadine

second gen H1 receptor inverse agonist (antagonist)
prodrug, bound to plasma proteins
first pass metabolism converts it to desloratidine, which is the active form
high duration of action with fewer doses
poor BBB permeability; weakly sedating
brand name: Claritin