Presentation on theme: "Chapter 9 Antiallergic and antiulcer drugs. Histamine widely exists in a variety of plants, animals and micro-organisms. It comes from histidine which."— Presentation transcript:
Chapter 9 Antiallergic and antiulcer drugs
Histamine widely exists in a variety of plants, animals and micro-organisms. It comes from histidine which is decarboxylated by histidine decarboxylase. Its chemical name is 4 (5) - (2 - aminoethyl) imidazole, has a tautomer (a) and (b).
There are at least three histamine receptor subtypes: H1, H2 and H3 receptors. Acting on H1 receptor, causing intestinal, uterine, bronchial smooth muscle contractions, even in bronchial smooth muscle cramp and difficulty breathing, also caused capillary relaxation, resulting in increasing permeability of the blood vessel wall, resulting in swelling and itching, to take part in the occurrence of allergy.
Acting on H2 receptors, Histamine lead to the increasing secretion of gastric acid and pepsin. Excessive gastric acid is closely related with peptic ulcer. Although histamine H3 receptor has been discovered in the central nervous system and some peripheral tissues, but the mechanism is not clear.
White crystalline powder, odorless, bitter taste. Mp.131 ~ 135 ℃, with sublimation property. soluble in water, ethanol and chloroform, slightly soluble in diehtyl ether. 1% aqueous solution of pH 4.0 ~ 5.0. belong to Propylamine antihistamines. A quick and complete absorption after taking, excretion slow, long lasting time. N-demethylation, N- dedimethylation, N-oxidization and unknown polar metabolites excrete with the urine.
White or slightly yellow crystalline powder; almost odorless, bitter taste. Soluble in methanol,chloroform, slightly soluble in ethanol,slightly soluble in water, almost insoluble in ether. Aqueous solution is acidic.
Cyproheptadine is a strong H1 receptor antagonist with mild to moderate anti-5 – hydroxytryptamine serotonin and anticholine effects. Drugs for urticaria, eczema, skin itching and other allergic diseases. Can also inhibit hypothalamic satiety center, stimulating the appetite, so getting weight after a certain period of time.
White or almost white powder, mp.225 ℃. Soluble in water, almost insoluble in acetone and dioxane methane. Cetirizine is the piperazine antihistamine. Cetirizine selectively acts on H1 receptor, strong and durable. Clinical for antiallergics, Cetirizine is rapidly and well absorbed after taking. Vast majority eliminate through renal without metabolism.
Development and discovery of Mizolastine R & D by a French company named Syntelabo and came into the market in 1998 for the first time in European market, commodity called Mizolastine (Mizollen). Belong to the Second-generation histamine H1 receptor antagonist, is a highly specific and selective antagonists, fast onset, potent and durable, and inhibiting the release of other inflammatory mediators.
Good absorption in case of oral taking Bioavailability is 70% of intravenous injection Excrete mostly together with urine in prototype, 40-50% in 12 hours.
Clinical application Treatment for active duodenal ulcer, prevention of gastric ulcer recurrence, effective to reflux esophagitis, prevention and treatment of stress ulcer. High relapse after treatment, need maintenance therapy. Can be used to enhance immune function. Side effects Have estrogen-like effects,Can lead to impotence to men and breast to women, but the side effect will disappear after drug stopping.
Ranitidine The second listing H2 receptor antagonist
Treatment of duodenal ulcer, benign gastric ulcer, postoperative ulcer, reflux esophagitis and so on. Effective stronger than Cimetidine for 5-8 times. Highly effective to the stomach and duodenal ulcer, quick onset and durable. 较西咪替丁小 – 无抗雄性激素的副作用 与其它药物的相互作用也较 小
Treatment of duodenal ulcer, benign gastric ulcer, postoperative ulcer, reflux esophagitis and so on. Effective stronger than Cimetidine for 5-8 times. Highly effective to the stomach and duodenal ulcer, quick onset and durable. Side effect is smaller than cimetidine, without anti- androgen effect.
Other H 2 receptor antagonists
SAR of H 2 receptor antagonists
Proton pump inhibitor 胃酸分泌原理示意
Characteristics of proton pump inhibitor Wide-ranging acting, effective, specific and high selective, samller side-effects.