Effects on the Gastrointestinal Tract

No information was located regarding the gastrointestinal toxicity of chlordecone in humans. Only very limited evidence of gastrointestinal effects has been observed in oral studies in experimental animals (Fujimori et al. 1983 Larson et al. 1979b). Thus, it is unlikely that chlordecone exposure would result in adverse effects on the gastrointestinal tracts of persons exposed to low levels at hazardous waste sites. 

Atropine and scopolamine have antispasmodic effects on the gastrointestinal tract. It partly inhibits vagal influence in the gut, reducing motility. However, the enteric nervous system also employs serotonin and dopamine, so parasympathetic innervation plays a modulatory role. 

Ingestion of fibers in the diets or water, to test effects on the gastrointestinal tract. 

Theophylline and other methylxanthines also display a pharmacological effect on a number of other organ systems. Of course the most pronounced effect is relaxation of smooth musculature in the respiratory tract. However, theophylline is a CNS stimulant, and it lowers arterial blood pressure, increases diuresis, displays cardiotonic activity, and has a specific effect on the gastrointestinal tract. The effects listed are the most frequently encountered side effects upon taking theophylline as a broncholytic. 

Gastrointestinal Effects. Humans who ingest oral doses in excess of 30 or 40 mL (680-910 mg/kg) frequently experience nausea, vomiting, and abdominal pain (Hardin 1954 New et al. 1962 Smetana 1939 Umiker and Pearce 1953 von Oettingen 1964). Nausea has been reported after an oral dose of as little as 100 mg/kg (Ruprah et al. 1985). However, these effects are probably secondary to effects on the central nervous system, rather than to a direct effect on the gastrointestinal tract. Oral doses of 3-5 mL (70-110 mg/kg) were widely used in the past for the treatment of hookworms with only mild gastrointestinal distress (Hall 1921 Leach 1922). 

B. Greenwood, Muscarinic analgesics with potent and selective effects on the gastrointestinal tract Potential application for the treatment of irritable bowel syndrome, J. Med. Chem. 40 (1997) 538-546. 

No unusual effect on the gastrointestinal tract has been reported with enflurane anaesthesia, however, certain evidence of hepatic impairment has been obtained during and after surgical anaesthesia. Hepatic necrosis probably occurs with enflurane in rare instances. 

Cardiac glycosides affect all excitable tissues, including smooth muscle and the central nervous system. The gastrointestinal tract is the most common site of digitalis toxicity outside the heart. The effects include anorexia, nausea, vomiting, and diarrhea. This toxicity is caused in part by direct effects on the gastrointestinal tract and in part by central nervous system actions. 

A relative indication for corticotropin is the occasional gastrointestinal intolerance that occurs with oral glucocorticoids. In these cases, however, only the local effects of the glucocorticoids can be avoided, and not their systemic effects on the gastrointestinal tract (25). 

This toxicity may be partially caused by direct effects on the gastrointestinal tract but is also the result of central nervous system actions, including chemoreceptor trigger zone stimulation. 

Local formulations of budesonide are used in the management of inflammatory bowel disease. In mild to moderate Crohn s disease it is given by mouth as modified release capsules intended for a topical effect on the gastrointestinal tract. This approach offers new hope for Crohn s disease sufferers. 

Pharmacological evaluation of the ethers and their water-soluble salts revealed a marked sedative action in dogs without any demonstrable antihypertensive effect. The tranquilizing activity differs from that of reserpine in that its onset occurs within minutes rather than hours and the duration of action is considerably shorter than that of reserpine. Cumulation is not evident on repeated administration there is no effect on the gastrointestinal tract and no diarrhea occurs (182). Clinically, the normal, as well as the 18-epi, ethers were found to be effective when given to patients with mild or moderate anxiety. However, the tranquilizing activity of the normal ethers is considerably higher, and for all practical purposes the 18-epi ethers are not suitable for human therapy. 

The side-effects are associated with vagal effects on the gastrointestinal tract (anorexia, abdominal discomfort/pain, vomiting and diarrhoea), while cardiotoxic effects include premature ventricular depolarizations, nodal rhythms and AV dissociation, Toxicity is enhanced by hypokalaemia, and this may predispose to more complex arrhythmias. 

Indometacin is the best-known and most thoroughly tested indoleacetic acid derivative. It is one of the most effective NSAIDs, and most of its toxic and therapeutic effects appear to be due to marked inhibition of prostaglandin sjmthesis. Because of its potency, its clinical efficacy is comparable, if not superior, to any other NSAID, but for precisely the same reason its adverse effects on the gastrointestinal tract and the nervous system inevitably limit its use. However, patients who tolerate it reasonably well are naturally not anxious to exchange it for any newer drugs with fewer problems but less potency. A meta-analysis of patients preference in 37 crossover comparisons of indometacin with newer NSAIDs did not provide evidence of a trend to replace indometacin with newer NSAIDs (1). 

Inorganic Mercury. Ingestion of metallic mercury results in negligible absorption and little effect on the gastrointestinal tract. The two case histories identified are unusual in that the dose levels could be reasonably well quantified. The first case history reported ingestion of 15 mL (204 g) of metallic mercury by a 17-year-old male storekeeper who swallowed mercury from the pendulum of a clock (apparently out of curiosity rather than as a suicide attempt). On admission, and 24 hours later, he was symptom free, and physical examination was normal. The patient complained of no gastrointestinal symptoms, and was treated with a mild laxative and bedrest (Wright et al. 1980). 

Salicylic acid (1) is not employed internally as an analgesic due to its local irritating effect on the gastrointestinal tract. It is employed externally on the skin, where it exerts a slight antiseptic action and a marked keratolytic action. The latter property makes salicylic acid a beneficial agent in the local treatment of warts, corns, fungous infections, and certain forms of eczematoid dermatitis. Tissues cells swell, softer, and ultimately desquamate. Salicylic acid is applied as a 2 to 20% concentration in collodion, lotions, or ointments, and as a 10 to 40% concentration in plasters. Salicylic acid plaster is used for the destructive effect of salicylic acid on hardened, keratinized tissue. The so-called corn plaster are typical. 

Effects on the Gastrointestinal Tract. Somatostatin inhibits both the gastric secretion induced by gastrin and the release of gastrin,20 which suggests a potential utility for the treatment of ulcers. 

No histological evidence for formaldehyde effects on the gastrointestinal tract was found in intermediate-duration inhalation studies using a 6 hour/day, 5 days/week exposure protocol with mice exposed to up to 40 ppm for 13 weeks (Maronpot et al. 1986), Rliesus monkeys exposed to 6 ppm for 6 weeks (Monticello et al. 1989), rats exposed to up to 20 ppm for 13 weeks (Woutersen et al. 1987), or rats exposed to up to 10 ppm for 13 or 52 weeks (Appelman et al. 1988). Similarly, no evidence for formaldehyde effects on gastrointestinal tissues were found in chronic inhalation studies with rats exposed to up to 15 ppm,... 

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