Antihistamines (Fondell) Flashcards
FC´∑ receptor
Receptor on mast cell that binds IgE in initial exposure. In secondary exposure (type I hypersensitivity reaction), FC∑ receptors cross link, causing histamine release
H1 Histamine receptor
- Found in smooth muscle
- Receptor signaling via Gå subunit q
- Increases IP3/DAG (causing degranulation)
- Causes vasodilation (via NO), edema, bronchoconstriction, gut contraction, itch, pain
H2 Histamine Receptor
- Found in Gastric mucosa, cardiac muscle, VSM, mast cells, basophils
- Uses Gå-subunit S
- Increases cAMP
- Causes increased gastric secretion, vasodilation (via cAMP), increased HR
H3 Histamine Receptor
- Found in presynaptic histaminergic receptors of brain, other neurons
- Uses Gå-subunit i
- Decreases cAMP (opposes H2 effects)
- Decreases histamine release
H4 Histamine Receptor
- Found in hematopoietic cells (basophils, eosinophils etc)
- Uses Gå-subunit i (same as H3)
- Decreases cAMP (same as H3)
- Causes immune cell differentiation, chemotaxis, cytokine secretion
Cromolyn and Nedocromil
Prophylactic use block histamine effect
- Block Ca entry, preventing histamine release
- Can be used for asthma
Epinephrine
Main treatment of anaphylaxis
-å/ß adrenergic receptor agonist, causes vasoconstriction and bronchodilation to oppose histamine
Histamine receptor model (Inverse agonists)
“Inverse Agonists”- Receptor exists in active and inactive conformation equilibrium. Histamine release promotes active. Antihistamines bind inactive, shifting equilibrium to inactive
1st Generation H1 Anti-Histamine
- Hydrophobic, enter CNS, highly sedative
- Anti-emetic
- Used vs insomnia, motion sickness, pruritis
- short acting
- Includes 6 classes: ethanolamines, ethylenediamines, alkylamines, phenothiazines, piperazines, piperidines
2nd-Generation H1 Antihistamines
- Hydrophilic, CNS insoluble, non-sedative
- no sedative/anti-emetic effects
- longer acting
Diphenhydramine
Benadryl
- 1st Gen. H1 antihistamine
- Used for hives, itch, allergy
- Side effects antiemetic, anti motion sickness, sleep inducing
Tripelennamine
PBZ
-1st gen. H1 antihistamine
Chlorpheniramine
Chlor-Trimeton
-1st gen. H1 antihistamine
Promethazine
Phenergan
-1st gen. H1 antihistamine
Hydroxyazine
Atarax, Vistaril
-1st gen. H1 antihistamine
Cyclizine
Marezine, Meclizine, Antivert
-1st gen. H1 antihistamine
Cyproheptadine
Periactin
-1st gen. H1 antihistamine
Cetirizine
Zyrtec
-2nd gen. H1 antihistamine
Histamine-producing cells (4)
- Enterochromaffin-like (ECL) cells of stomach
- Mast cells
- Basophils
- Neurons (brain)
Loratidine
Claritin
- 2nd gen. H1 antihistamine
- *metabolized by CYP3A4, so avoid conflicting food/drugs (grapefruit juice)
Fexofenadine
Allegra
-2nd gen. H1 antihistamine
Levocetirizine
Xyzal
- 3rd gen. H1 antihistamine
- more potent version of cetirizine (R-enantiomer)
Desloratidine
Clarinex
- 3rd gen. H1 antihistamine
- more potent version of loratidine (no longer needs CYP to get activated)
H2 Antihistamines
Block stomach acid production by inhibiting H2 receptors in stomach, preventing histamine secretion and Na/H pump activation
- Hydrophilic- dont enter CNS
- Specific- no H1/H3 overlap
- Treat GERD, ulcers, Zollinger-Ellison
- CYP metabolism, watch out for drug interactions
Cimetidine
Tagamet
- H2 antihistamine (inhibits gastric acid secretion)
- *inhibits a bunch of CYP pathways, so watch out
Ranitidine
Zantac
- H2 antihistamine
- Less CYP problems than cimetidine
Famotidine
Pepcid
- H2 antihistamine
- No CYP interference unlike cimetidine, ranitidine
- Most potent
Nizatidine
Tazac, Axid
- H2 antihistamine
- No CYP interference (like famotidine, unlike ranitidine and cimetidine)
Omeprazole
Irreversibly binds Na/H ATPase, preventing gastric pH acidity.
-More effective than H2 antihistamines, but longer regimen and more expensive so they’re still useful
