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Histamine release
allergen presented to B-lymphoctes
B transrom to IgE-secreting plasma cell
secreted IgE bound to mast cells
mast cells release histamine and cytokines
Allegric rhinitis
nasal congestion, runny nose, post nasal drip
Acute Urticaria (Hives)
itching, pain, blister like rash
Wheal and Flare response
skin testing, allergic response
can be seen in allergic rhinitis
bronchoconstriction, vasodilation (shock), extravsation
Bronchiole smooth muscle
bronchocontriction, asthma-like symptoms, H1
Vascular Smooth muscle
vasodilation, erytehema (redness) and flare, hypotension, shock (anaphylaxis) H1 and some H2
Vascular endothelium (apillaries, venules)
extravasation or contraction of cells, local edema, wheel, H1
Peripheral nerves
sensitization and activation of afferent fibers; itching, pain; H1
Non vascular histamine activation
GTP-binding protein activates PLC > increase IP3 >IP3 bings to SR and releases Ca2+ > Ca2+ activates calmodulin and activates protein kinase C that phosphorylates myosin heads for contraction
Vascular histamine activation
GTP-binding protein  activates PLC > increase IP3 >IP3 binds to SR release Ca2+ > Ca2+ activates calmodulin that activates nitric oxide synthase > NO > NO activates guanalyl cyclase > increase cGMP > smooth muscle relaxation
Wheal formation
loss of tight junictions between cells
Anaphylaxis shock
vasodiation, brochocontriction, epiglottal swelling
Sedation due to
antagonism of CNS H1 receptors
agents that have high levels of sedation are
lipophilic and can have significant amount of unionized drug at physiological pH
1st gen antihistamines can cause
anticholinergic effects
Loratadine _________ the ___________ channel
blocks, HERG potassium
Non-sedating H1 antihistamines
loratidine, desloatidine, cetirizine, fexofenadine, acrivastine
drugs that inhibit _____________ could present a problem
3A4, 2D6
cetirizine absorption by
active transport
Fexofenadine absorption by
organic ion transporter (inhibited by grapefruit juice and OJ
Acrivastine absorption by
non-sedating agents are good substrates for
Poor brain penetration
desloratadine, fexofenadine
Topical Antihistamines
Azelastine, Ketotifen, Epinastine, Oloptadine
mostly ocular that cases redness, irritation
1st gen agents avoid:
anticholinergics, other proarrythmic drugs
loratadine avoid:
3A4 inhibitors, amiodarone
fenofexadine avoid:
grapefruit, orange juice
anihistamines avoid
other sedating agents
potent serotonin 5-HT2a antagonist, used for prophylaxis of migraines
Diphenhydramines should be avoided
patients below age 2
use non-sedating agents for treatment of allergic rhinitis in pediatric population
serotonin reuptake inhibitor and post-synaptic 5-HT1a agonist with known antidepressant and anti-anxiolytic effects
use with great caution with SSRI
x of y cards