Antisecretory effect

PPIs block gastric acid secretion by inhibiting hydrogen potassium adenosine triphosphatase in gastric parietal cells, which results in profound and long-lasting antisecretory effects. 

Pharmacology Gl anticholinergics are used primarily to decrease motility (smooth muscle tone) in Gl, biliary, and urinary tracts and for antisecretory effects. Antispasmodics, related compounds, decrease Gl motility by acting on smooth muscle. 

Pharmacology BSS appears to have antisecretory and antimicrobial effects in vitro and may have some anti-inflammatory effects. The salicylate moiety provides the antisecretory effect, while the bismuth moiety may exert direct antimicrobial effects against bacterial and viral enteropathogens. 

Atropine causes dryness of mouth as side effect which is due to its antisecretory effect, and due to this action atropine is used in peptic ulcer. 

Omeprazole distributes widely and is rapidly eliminated from plasma by metabolism in liver. The antisecretory effect... 

I.c.v. and i.t. administration of the 5 opioid agonist deltorphin II in rodents inhibits diarrhea and colonic bead expulsion in a dose-dependent manner but does not delay small intestine transit time. 5 agonists have been found to mediate mainly antisecretory effects and influence gut motility only marginally. These effects can be antagonized by pretreatment with NTI (Shook et al. 1989). 

GASTROINTESTINAL EFFECTS OF ENKEPHALIN DEGRADING ENZYME INHIBITORS ROLE OF DELTA OPIOID RECEPTOR IN THE ANTISECRETORY EFFECT OF TIORFAN... 

Fig. 2.3 Structure-activity relationships of analogues of H 124/26. Biological testing was conducted in the gastric fistula dog. 0 = lacking antisecretory effect +++ = maximal...

The problem persisted, however, of how the antisecretory effect of substituted benzimidazoles could be optimized. As weak bases accumulate in the acidic compartment of the parietal cell close to the proton pump, substituents were now... 

Sundell G, Sjostrand SE, Olbe L. Gastric antisecretory effects of H83/69, a benzi-midazolyl-pyridyl-methyl-sulfoxide. Acta Pharmacol. Toxicol., 1977, Suppl. 4, 77. 

Beubler and Badhri (1990) used the PGE2-induced net fluid secretion in the jejunum and colon in the rat to evaluate the antisecretory effects of antidiarrhoeal drugs. Polyethylene catheters were placed into the jejunum and colon and Tyrode solution was instilled into the loops. Net fluid transfer rates were determined gravimetrically 30 min after instillation of Tyrode solution. 

Beubler E, Badhri P (1990) Comparison of the antisecretory effects of loperamide and loperamide oxide in the jejunum and the colon of rats in vivo. J Pharm Pharmacol 42 689-692... 

In addition to the antisecretory effect, it has been reported that omeprazole has cytoprotective properties in rats which are not mediated by... 

We studied the effect of omeprazole, lansoprazole, saviprazole, SK F 65601 and E-3810 on total serum T4 and T3, free serum T4 and T3 as well as on thyroid weights after oral treatment for 14 days at doses of 50,150 and 450 mg/kg [146]. The selected doses represent supra-maximal doses with respect to their antisecretory effects in rats (ED50 in pylorus-ligated rats 1-5 mg/kg intraduodenally). 

The assumption that SCH 28080 and SCH 32651 cause their antisecretory effect by direct interference of gastric HVK -ATPase was confirmed in 1985 [158]. SCH 28080 inhibits the enzyme activity in a concentration dependent manner with an IC50 in the micromolar range comparable to that of omeprazole. The effect of SCH 32651 was obviously less pronounced [158, 159]. 

Natural somatostatin is a cyclic decatetrapeptide (SS-14) originally discovered from rat hypothalamus during the purification of growth hormone-releasing factor and subsequently isolated from sheep and pig hypothalamus [32-34]. Synthetic SS-14 (Table 1) has been found to show antisecretory effects on various body tissues including pituitary, pancreatic a and p cells as well as decrease of serotonin and cholecystokinin secretion. 

Loperamide is a narcotic agonist acting on opioid JL receptors. Loperamide has mild antisecretory effects but its primary effects are to increase segmental intestinal contractions and slow the propulsion of intestinal contents (Ruppin 1987). Loperamide has been associated with reduction in diarrhea in many clinical studies in humans but has minimal impact on the patient s fluid and electrolyte balance because the secreted fluid remains in the bowel lumen. Loperamide can have dose-dependent CNS depressant effects. Loperamide also has been shown to promote intestinal bacterial overgrowth because of promoting the retention of fluid within bowel segments (Duval-Iflah et al 1999), which may favor the proliferation of enteropathogenic bacteria. 

True antisecretory agents, those that block a biochemical process that promotes intestinal fluid secretion, are not available for clinical use in horses. Loperamide can reduce the volume of diarrhea in foals with a primarily small intestinal secretory disorder. However, treated foals may become colicky as a result of fluid distention in the intestines because the mechanism of action is primarily retention of fluid within the intestine. Also, retention of intestinal content may promote the proliferation of enteropathogens. The enkephalinase inhibitor racecadotril appears to have true antisecretory effect in animal models and in humans with diarrhea (Izzo et al 1998). Its safety or effectiveness in foals and horses has not been reported. 

Haven M L, Dave K, Burrow J A et al 1999 Comparison of the antisecretory effects of omeprazole when administered intravenously, as acid-stable granules and as an oral paste in horses. Equine Veterinary Journal Supplement 29 54-58... 

Four hundred adults presenting with acute watery diarrhea were entered into a randomized, placebo controlled, double blind clinical trial of berberine, tetracycline, and tetracycline + berberine to study the antisecretory and vibriostatic effects of the alkaloid. Of 18S patients with cholera, those given tetracycline or tetracycline + berberine had considerably reduced volume and frequency of diarrheal stools, duration of diarrhea, and volumes of required intravenous and oral rehydration fluid. Berberine did not produce an antisecretory effect, but analysis by factorial design equations showed a reduction in diarrheal stools by one liter and a reduction in cyclic AMP concentrations in stools by 77% in the groups given berberine. Many fewer patients given tetracycline or tetracycline + berberine excreted vibrios in their stools after 24 hours in comparison with those given berberine alone. Neither tetracycline nor berberine had any benefit over placebo in 215 patients with noncholera diarrhea [219]. 

From the medicinal chemistry point of view, the imidazopyridine-based compound SCH 28080 was the prototype of the reversible proton-pump inhibitor (160). As early as 1983, it had been suggested that the antisecretory effect of this compound was directly mediated by the gastric proton pump, and this has been further demonstrated by its ability to antagonize the binding of the irreversible proton-pump inhibitor omeprazole (161). The marked liver toxicity of this compound necessitated follow-up compounds, of which SCH 32651 (162) is an example. Yamanouchi and Shin-... 

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