histamine

Question 1

mechanisms of histamine release

Answer 1

• mast cells: skin, nose, mouth, lungs, intestinal mucosa
• Non-Mast Cell Release: CHS, fundus
• Allergen = B cell response of IgE; allergen + IgE on mast cells -> Ca release from CRAC channel = degranulation

Question 2

histamine receptor

Answer 2

• H1 coupled with Gq through IP3 pathway to cause Ca mobilization and NO = vasodilatory
• H2 couples with Gs = cAMP pathway

Question 3

histamine physiology

Answer 3

• Histamine has direct effect on SA nodes = increase HR
• Histamine has direct effect on myocytes = increase force of contraction
• Due to production of NO in H1 receptors in endothelium = vasodilation = reflex tachycardia via baroreceptors
• Can cause bronchoconstriction
• ECL cells in stomach can release histamine -> histamine works on H2 cells to increase cAMP and stimulate Na proton pump
• Skin: Red spot, flaring, and whealing (edema)

Question 4

h1 receptor antagonists

Answer 4

• Actually inverse agonists
• Diphenhydramine structure
• 2nd generation (Loratadine, Cetirizine, Fexofenadine, Dexloratadine): less CSN access, less sedation, less anticholinergic properties, and less action as anti-emetics
• Topical Antihistamines: used for seasonal allergic rhinitis and conjunctivitis
• Clinical Uses: chronic uticaria, motion sickness, anaphylaxis adjunct
• AEs: sedation, GI, anti-cholinergic, local anesthetic, anti-serotonin

Question 5

h2 receptor antagonists

Answer 5

• Cimetidine and Famotidine Structures

- Uses: Reduce gastric acid secretion, treat peptic ulcers and GERD