Antidiarrheal compounds

The use of phenylpiperidinols rather than the meperidine-related piperidines as the basic component in antidiarrheal compounds results in retention of activity. The fact that the base is not directly related to a narcotic presumably leads to greater selectivity of action on the gut. Ring scission of butyrolactone 98 (obtainable by alkylation of a diphenylacetate ester with ethylene oxide) with hydrogen bromide gives the bromo acid 99. This is then converted to the dimethylamide by successive treatment with thionyl chloride and dimethylamine. 

Diagnosis and alleviation of the cause, if possible, is of primary importance. Often, however, this is not possible and therapy is used to alleviate the inconvenience and pain of diarrhea. These compounds usually only mask the underlying factors producing the problem. Diarrhea may cause significant dehydration and loss of electrolytes and is a particularly serious problem in infants. Antidiarrheals do not usually prevent the loss of fluids and electrolytes into the large bowel and, although these may prevent frequent defecation, often the serious imbalance of body electrolytes and fluids is not significantly affected. 

Nonspecific antidiarrheal agents may be useful in treating self-limiting diarrhea. Kaolin and pectin or chalk may adsorb noxious compounds but evidence that such adsorbents are effective is unconvincing. Disadvantages can be prolongation of the course of infection and interference with absorption of desired drugs. 

The dangers of dependency and addiction clearly preclude the use of such compounds as morphine, meperidine, and methadone as treatment for diarrhea. Antidiarrheal specificity therefore is of paramount importance in choosing among the synthetic opioids and their analogues (e.g., diphenoxylate and loperamide). 

Together, the chemistry of codeine and the drug s absorption into the bloodstream, distribution to various compartments and tissues in the body, metabolism (breakdown of the parent compound into smaller molecules, or metabolites), and excretion are intimately related to how codeine exerts its medicinal or therapeutic effects. Codeine s chemical properties and pharmacologic characteristics explain how, figuratively speaking, a spoonful of codeine can relieve pain, suppress cough, or act as an antidiarrheal. 

The opioids contain natural and synthetic compounds that are medicinally used as analgesic, antidiarrheal, and antitussive agents. Opioids are CNS depressants and decrease blood pres-... 

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

Despite the lack of studies correlating the antidiarrheic activity of crude drugs with the presence of flavonoids, these have been also studied as pure compounds in this regard. The most used assay of antidiarrhoeic activity is the castor oil test, in which diarrhea is induced by the oral administration of castor oil to mice. Different flavonoids have been shown to possess antidiarrheal activity in this test quercetin, kaempferol, morin, myricetin, rutin (i.p.) [117,118], quercitrin (p.o.) [114,119], and tematin (i.p.) [44], all showing a dose-dependent activity in the range between 25 and 100 mg/kg. However, flavonoids are not only able to exert a preventive antidiarrheal effect in this acute model of experimentally-induced diarrhea, but also in chronic models. Thus quercitrin showed beneficial effects in a model of lactose-induced chronic diarrhea in rats, since it reduced the diarrheal output and facilitated colonic mucosal repair in lactose fed [120]. 

Bismuth salicylate has a number of properties contributing to its antidiarrheal effects. This drug may stimulate water and electrolyte absorption from the lower GI tract, thus decreasing fecal fluid loss. In addition, the bismuth component of this compound may have antibacterial effects, and the salicylate component may inhibit the production of prostaglandins that irritate the intestinal lining. The combination of these properties makes this drug fairly effective in... 

Diphenoxylate and its metabolite, difenoxin, are not used for analgesia but for the treatment of diarrhea. They are scheduled for minimal control (difenoxin is schedule IV, diphenoxylate schedule V see inside front cover) because the likelihood of their abuse is remote. The poor solubility of the compounds limits their use for parenteral injection. As anti diarrheal drugs, they are used in combination with atropine. The atropine is added in a concentration too low to have a significant antidiarrheal effect but is presumed to further reduce the likelihood of abuse. 

Aluminum compounds are also used extensively in the manufacture of cosmetics (e.g., aluminum hexahydrate in deodorants) and in medical treatments (e.g., aluminum hydroxide in antacids to control gastric hyperacidity or aluminum oxide in dental ceramic implants) (Brusewitz 1984 NRC 1982). In addition, antacids and buffered aspirin contain 4-562 mg/kg (ppm) of aluminum (Schenck et al. 1989 Shore and Wyatt 1983). Lione (1985a) reported aluminum content/dose (single tablet or 5 mL liquid) for antacids, internal analgesics (buffered aspirins), antidiarrheals, and anti-ulcerative drugs (Table 5-7). 

Bismuth compounds are used as an antidiarrheal. Topical applications are used in skin disorders. Overdose may cause acute bismuth intoxication but gastric lavage, purgation, use of chelating agents, 2,3-dimercapto-l-propane sulfonic acid, and hemodialysis are steps to be taken.170-172... 

Internal use in medicine can exploit the alkaline nature and adsorptive capacities of aluminium compounds (as in antacid mixtures, antidiarrheal drugs, and vaccines). Aluminium is found in medications for antacid therapy and phosphate depletion alternatives are under investigation (7). Patients on dialysis take large amounts of oral aluminium hydroxide as a means of reducing serum phosphate. Sucralfate is used to treat peptic ulceration and gastritis. 

Diphenoxylate is a synthetic compound designed to have the antidiarrheal effects of the opiates, but it also retains some less desirable opiate effects. It is generally combined with atropine, as co-phenotrope, which was originally added to the formulation in the hope of preventing misuse, although it can itself cause problems, especially if the combination is intentionally or accidentally used to excess. 

MAJOR PRODUCT APPLICATIONS pesticides, herbicides, fertilizers, absorbents, drilling mud, joint compounds, neutralizers, asphalt thickeners, adhesives, paints, coatings, sealants, environmental remediation materials, antidiarrheal medication, gels... 

In addition to modifications of the morphine molecule, many purely synthetic analgesics have been produced, the first of these, pethidine (meperidine), having been synthesized in 1939 in an attempt to make a substitute for atropine (276). As in the case of heroin, pethidine was at first thought to be nonaddictive. It has been followed by a hundred or so other compounds of several different types, but, as with the morphine derivatives, none, with the possible exception of pentazocine, has been found to have analgesic without addictive properties. However, it seems that the two effects may not be entirely inseparable, as diphenoxylate, which has come into use as an antidiarrheal drug, has been found to possess the power to cause addiction but no analgesic action at all (277). 

One important analogue of morphine is fentanyl, a clinically used narcotic that is about 100 times more potent than morphine. Several analogues have been synthesised such as sufentanil, alfentanil, lofentanil and, even more interestingly, structurally related compounds with different activities such as astemizole (antihistaminic), droperidol (tranquillizing), loperamide (antidiarrheal) and lorcainide (antiarrhythmic) [50]. 

Morphine was among the first compounds to undergo structure modification. Ethylmorphine (the 3-ethyl ether of morphine) was introduced as a medicine in 1898. Diacetylmorphine (heroin), which may be considered to be the first synthetic pro-drug, was synthesized in 1874 and marketed as a nonaddicting analgesic, antidiarrheal, and antitussive agent in 1898. 

Uses Bismuth compounds cosmetics opacifierin x-ray diagnosis enamel fluxes ceramic glazes artificial horn prods. pearly surfs, for plastics food additive pharmaceutical adsorbent (antidiarrheal prods.) pharmaceutical health care prods. topical protectant Regulatory FDA approved for orals... 

The leaves, flowers, and stems of Satureja hortensis (summer savory, Lamiaceae), a common plant widely spread in Turkey, are used as tea or as addition to foods on account of the aroma and the flavor. As a medical plant it is known for its antispasmodic, antidiarrheal, antioxidant, sedative, and antimicrobial properties. Also this EO was investigated for its antioxidative properties. The GC-MS analysis showed that besides 9% p-cymene, carvacrol and thymol are the main compounds of about 22 constituents of the oil. They occur at a ratio of approximately 1 1, which is representative for the genus Satureja, namely 29% of thymol and 27% of carvacrol. In a linoleic acid test system the EO showed an inhibition activity of 95%, this is an indicator for a strong antioxidative activity because the control BHT attained an inhibition of 96% (Giilliice et al., 2003). Thymol is one of the main components of the EO from Satureja montana L ssp. montana (savory) and also one of the glycosidically bound volatile aglycones that were found. The EO with 45% thymol shows a very strong antioxidative capacity that was a bit lower than the standards, BHT, and a-tocopherol. The... 

Haskins, N.J., Ford, G.C., Grigson, S.J.W., and Waddell, K.A., 1978. A carrier effect observed in assays for antidiarrheal drug compounds. Biomedical Mass Spectrometry. 5 423-4. 

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