Histamine actions

Haas, H. L. (1974). Histamine action on single hypothalamic neurones. Brain Res. 76, 363-6. 

Hj-receptor antagonists reversibly and competitively inhibit histamine action on H2 receptors. They are pure antagonists since they do not affect Hj receptors, j3-adrenorecep-tors, or muscarinic receptors. 

Mecftanism of Action AGI Hj-blocker and gastric acid secretion inhibitor that inhibits histamine action at histamine 2 receptors of parietal cells Therapeutic Effect Inhibits gastric acid secretion when fasting, at night, or when stimulated by food, caffeine, or insulin. 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

Meiaholism (Fig. 21.4)." The must common pathway for terminating histamine action involves enzymatic inactivation. 

Antihistamines compete for the same receptor sites as histamines. An antihistamine latches to the site, blocking the histamine from latching to the site and therefore preventing the histamine action. This results in a reduction of redness, itching, and swelling. 

A series of anti-ulcer drugs such as cimetidine and ranitidine were the most successful drugs of all time when they first appeared. They work by inhibiting histamine action in the stomach. We shall look at a more modern version, a drug from what was then SmithKline Beecham, another H2 receptor histamine antagonist24 202. It is particularly appropriate for this chapter as it contains three heterocyclic rings with two heteroatoms each an imidazole, a pyrimidone, and a thiazole and it allows us to revise material from other chapters as well as this. 

The FDA proposed in 1995 that its compliance policy guide be revised on decomposition and histamine to (1) lower the histamine action level for decomposition to 50 ppm from 100 ppm (2) extend application of the new action level to raw and frozen tuna and mahi-mahi (3) eliminate the provision that findings of less than 200 ppm need to be confirmed by organoleptic testing (4) allow other species to be considered as decomposed when histamine levels reach, 50 to 500 ppm and (5) consider fish, other than tuna, implicated in histamine poisoning outbreaks as health hazards when histamine levels reach 500 ppm. It is anticipated that final action on this proposal will be announced after 1996 (Craven et ai, 1995 National Fisheries Institute, Inc., 1995). 

Epinephrine and isoproterenol (via cAMP mechanisms) and theophylline (via cAMP or block of adenosine receptors) inhibit the release of mediators from mast cells and basophils and cause bronchodilation. Diphenhydramine competitively blocks histamine actions at H, receptors, actions that would otherwise cause bronchoconstriction and increased capillary permeability. Dexamethasone has multiple cellular effects, including inhibition of IgE-producing clone proliferation, block of T helper cell function, and anti-inflammatory actions. Most of the actions of glucocorticoids result from decreases in the synthesis of cytokines (eg, interleukins, platelet activating factor) or eicosanoids (leukotrienes, prostaglandins). 

Phenothiazines (anti-histamine action) promethazine HCl (Phenergan) PO/IM 12.5-25 mg q4-6h PRN Maximum dose 150mg/d Before meals and bedtime Pregnancy category C Protein bound Unknown Half-life Unknown... 

Vinter, J.G. and Trollope, K.I. (1995) Multiconformational composite molecular-potential fields in the analysis of drug-action. 1. Methodology and first evaluation using 5-HT and histamine action as examples. Journal of Computer-Aided Molecular Design, 9, 297-307. 

D106/ / /, Poisoning by Drugs, Local Anaesthetics, Antagonists of ACh, Diuretics, Histamine and Anti Histamines, Action of Drugs on CNS [Central Nervous System], and Therapy of Allergic Disease, 1950—1956 and n.d. (1950—56)... 

Code CF, Varco RL. Chronic histamine action. Proc Soc Exp Biol Med 44 475-477, 1940. 

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