Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most reports of interactions involving analgesics deal with their effects on the actions of other drugs rather than vice versa. Aspirin and ethanol have synergistic effects on the development of gastritis, gastrointestinal bleeding, and chronic gastric ulcer. This must be the most common and most important interaction affecting analgesic toxicity. Combined overdosage of aspirin with central nervous system depressants may be particularly hazardous because suppression of the salicylate-induced respiratory stimulation further shifts the disordered acid-base balance towards acidosis. The toxicity of acetaminophen (paracetamol) depends primarily on the balance between the rate of formation of the hepatotoxic metabolite and the rate of glutathione synthesis in the liver. In animals, prolonged pretreatment with ethanol increases the metabolic activation and acute toxicity of acetaminophen, and there is some evidence that chronic alcoholics are more susceptible to hepatotoxicity following acute overdosage. It has been assumed that this sensitivity in chronic alcoholics is due to microsomal enzyme induction with enhanced metabolic activation of acetaminophen. However, the metabolic activation of acetaminophen, as judged by the urinary excretion of its cysteine and mercapturic acid conjugates, is not increased in heavy drinkers or in patients induced by long-term treatment with anticonvulsants or rifampicin. Microsomal enzyme induction is complex. There are important species differences and different agents may selectively induce different variants of the multiple forms of cytochrome P-450. The acute administration of ethanol greatly reduces the metabolic activation of acetaminophen in heavy drinkers with more than a 50 percent decrease in cysteine and mercapturic acid conjugate production. Thus ingestion of ethanol should reduce the risk of liver damage following acetaminophen overdosage. Cimetidine, which inhibits the oxidative metabolism of some drugs, reduces the hepatotoxicity and increases the dose of acetaminophen in mice required to kill 50 percent of the animals. However, contrary to expectations, cimetidine does not inhibit the oxidative metabolism of acetaminophen in man. Salicylamide competes with acetaminophen for sulphate conjugation but is unlikely to potentiate toxicity following overdosage since sulphate conjugation is rapidly saturated anyway. Animal studies suggest that the hepatotoxicity of acetaminophen after overdosage may be increased by other agents which deplete glutathione, but there is no information on this point in man.
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PMID:Drug interactions affecting analgesic toxicity. 635 60

Aspirin and paracetamol (acetaminophen) are the most commonly used minor analgesics, but their effects on the gastrointestinal tract differ widely. Aspirin is significantly associated with major upper gastrointestinal hemorrhage, whereas acetaminophen is not. Short-term use of aspirin produces erythema, erosions, and occasionally ulcers; acetaminophen use does not. Chronic gastric ulcer is linked to aspirin intake in patients with rheumatic disease, and epidemiologically in all heavy aspirin users; paradoxically, in only one epidemiologic study was a significant association found between acetaminophen intake and chronic gastric ulcer. Fecal occult blood loss is increased in most regular aspirin users but not in those taking acetaminophen. Although studies in children have not apparently been made, in isolated small clinical series it has been shown that gastrointestinal bleeding and anemia do occur in the pediatric age group following the use of aspirin. Pathophysiologically, aspirin alters the gastric mucosal barrier to hydrogen ions and lowers gastric potential difference; acetaminophen has no effect on these parameters. Such changes correlate ultrastructurally with damage in surface epithelial cells and microerosions after the use of aspirin, but not after the use of acetaminophen. Aspirin causes a dramatic reduction in the ability of gastric mucosa to generate protective prostaglandins; however, acetaminophen also reduces prostaglandins. Other postulated mechanisms of aspirin damage include reduction in gastric mucosal secretion, bicarbonate output, and alteration of cell turnover. Because aspirin damage to gastric mucosa is often "silent," the clinician needs a high level of suspicion and awareness. In patients prone to gastric damage, or in those with a past history of aspirin-induced gastric damage, acetaminophen is the drug of choice when a minor, noninflammatory problem requires an analgesic.
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PMID:Gastrointestinal effects of antipyretic analgesics. 635 68

The effects of prostacyclin (PGI2) and its stable thia-thimo-analogue (Hoe 892) on gastric and intestinal secretions and gastric mucosal lesions have been determined in conscious rats. Both PGI2 and Hoe 892 given subcutaneously (s.c.) reduced dose-dependent gastric acid secretion, the ID50 (dose producing 50% inhibition) being about 48.6 and 11.8 micrograms/kg, respectively. In contrast, intragastric (i.g.) PGI2 and Hoe 892 did not cause any change in gastric acid secretion at doses ranging from 1 to 100 micrograms/kg. Both PGI2 and Hoe 892 reduced significantly intestinal fluid secretion (antienteropooling activity). PGI2 and Hoe 892 given i.g. or s.c. reduced dose-dependent gastric ulcer formation induced by acidified aspirin (ASA), Hoe 892 being somewhat less potent than PGI2. Both PGI2 and Hoe 892 were equally effective against gastric mucosal necrosis induced by absolute ethanol and this effect was observed both after i.g. and s.c. administration of these agents. We conclude that stable thia-imino-PGI2 analogue, Hoe 892, has similar gastric and intestinal antisecretory and protective activity as PGI2 and may be useful in the prevention of gastric damage by various noxious agents.
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PMID:Comparison of gastric and intestinal antisecretory and protective effects of prostacyclin and its stable thia-imino-analogue (Hoe 892) in conscious rats. 639 96

Gastric ulcer induced by the injection of acetic acid (0.025 ml of 20%) into the gastric wall of rats was healed considerably 5 days after the injection of acetic acid. Non-steroidal anti-inflammatory drugs (NSAID) such as aspirin, indomethacin, and phenylbutazone were given consecutively for 5 days, and they exacerbated the ulcer and enlarged the ulcer area. Aspirin caused exacerbation when it was given for the initial 5 days of the ulcer healing process. Phenylbutazone caused exacerbation by the administration for 5 days at the middle stage of the ulcer healing process. In contrast, indomethacin caused exacerbation not only when it was given for the initial 5 days but also when it was given for the middle 5 days. The effect of the antiulcer agent N-acetyl-L-glutamine aluminum complex (KW-110) on the exacerbation was studied. KW-110 at an oral dose of 500 mg/kg inhibited remarkably the exacerbation induced by all of the NSAID used. The development of gastric lesions induced by these NSAID was also prevented by KW-110. Further study was carried out with regard to the influences of KW-110 on the pharmacological properties of NSAID. The results showed no influences of KW-110 on the antiedematous and antipyretic actions of the NSAID.
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PMID:Effect of N-acetyl-L-glutamine aluminum complex (KW-110), an antiulcer agent, on the non-steroidal anti-inflammatory drug-induced exacerbation of gastric ulcer in rats. 709 47

Drug damage to the stomach provides a model for study of the development of peptic ulcer, gastritis, and duodenitis in man. Aspirin damage is the best understood. Pathophysiologically, aspirin alters the gastric mucosal barrier to hydrogen ions and lowers gastric potential difference. Ultrastructurally, aspirin damage to surface epithelial cells leads to microerosions. Macroscopically, acute hemorrhage and erosions are seen in both the stomach and duodenum by endoscopy after ingestion of a large dose of aspirin. Patients with chronic rheumatic diseases taking aspirin have a 50% incidence of gastric erosions and 20% incidence of gastric ulcer, suggesting an association between erosions and chronic ulcer formation. Acute gastric damage is lessened by neutralizing acid with bicarbonate, reducing acid secretion with cimetidine, or administering aspirin in enteric-coated form. Rheumatic patients on enteric-coated aspirin have a significantly lower incidence of gastric ulcer (5%) than those taking regular aspirin. Damage may also be prevented by increasing mucosal resistance; acute damage can be prevented by exogenous prostaglandins, regardless of their effect on acid secretion (cytoprotection). Other commonly used drugs, such as alcohol, acetaminophen, and indomethacin, reported to have paradoxical effects with respect to erosions and peptic ulcer, provide additional information on the development of gastric erosions and ulcers.
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PMID:Drugs, gastritis, and peptic ulcer. 732 Apr 67

The patterns of analgesic ingestion in gastric and duodenal ulcer patients were compared with those of matched community controls in order to ascertain differences that may exist between ulcer and nonulcer subjects of comparable age and sex. The differences sought concerned amounts and types of analgesics ingested. The types of analgesics studied were aspirin and acetaminophen, ingested either alone or together. Analgesics such as dextropropoxyphene and codeine were disregarded. It was found that there was a strong positive association between heavy analgesic intake and chronic gastric ulcer with a relative risk of 29.5. The association was most marked in female patients (relative risk = 51.8). The involvement of aspirin-containing and acetaminophen-containing drugs was of similar significance with relative risk of 17.3 and 24.4, respectively. Aspirin alone was the least frequently ingested. The association was only partly related to painful nonulcer health problems and to ulcer pain. No association was found between chronic duodenal ulcer and analgesic intake. The strong association found between gastric ulcer and heavy analgesic intake does not, per se, necessarily indicate a causal relationship.
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PMID:Analgesic ingestion and chronic peptic ulcer. 745 Apr 36

Aspirin, a common analgesic-antipyretic and anti-inflammatory drug, often induces gastric ulcer, but its pathogenesis remains unsettled. The purpose of this study was to identify the CNS neurons that express FOS protein after i.p. injection of aspirin (100-300 mg/kg). This was done in the unanesthetized Wistar rats with careful physiological controls. Dose-dependently, many FOS-immunoreactive (FOS-ir) neurons were found in the medial part of the nucleus tractus solitarii (NTSm) and the dorsal motor nucleus of the vagus nerve (DMX) of the lower medulla, but none in the paraventricular nucleus of the hypothalamus (PVH). Distribution of FOS-ir neurons in the DMX corresponds with that of the visceromotor neurons involved in gastric secretion. This study suggests that the aspirin-induced gastric ulcer may not originate in the PVH but in the NTSm-DMX system.
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PMID:Neuronal expression of FOS protein in the nucleus tractus solitarii and the dorsal motor nucleus of the vagus nerve after i.p. injection of ulcerogenic aspirin. 775 94

We have examined the protective effect of liquorice or its derivatives against gastric ulcer induced by aspirin. A granular mixture of aspirin alone and coated with liquorice or its derivatives including the deglycyrrhized form, a high glycyrrhized form, carbenoxolone, and enoxolone were studied. Aspirin coated with liquorice reduced the number and size of ulcers, reducing the ulcer index from 1.5 +/- 0.12 to 0.5 +/- 0.12 and the incidence from 96% to 46%. Coating with derivatives was less effective (ulcer index, 0.70-0.94; incidence 62-76%).
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PMID:The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats. 802 6

Many animal and human studies have shown aspirin to cause gastric mucosal erosions and enhanced spontaneous microbleeding. Chronic use is associated with uncomplicated gastric ulcer (but not clearly with uncomplicated duodenal ulcer) and with presentation with haematemesis and melaena. Sub-group analysis suggests that the risks of bleeding duodenal ulcer as well as bleeding gastric ulcer (and possibly non-ulcer bleeding) are increased. These data imply that an anti-haemostatic as well as an ulcerogenic effect contributes to such presentation and acute data support this proposition. A broken mucosa and inhibition of thromboxane synthesis both appear to be necessary for bleeding to occur. Aspirin enhances the bleeding associated with mucosal biopsy analogous to its prolongation of the skin bleeding time. Anti-haemostatic properties could account for the apparent increase in presentation with haematemesis and melaena in patients taking low doses of aspirin for cardiovascular prophylaxis. However, acute studies also show aspirin 300 mg to cause a level of mucosal injury which is substantial, though significantly less than with aspirin 600 mg q.d.s. The risk attached to aspirin consumption needs to be kept in perspective. It can be calculated that aspirin use is associated with approximately 700 bleeds per annum in the UK. The relative risk for upper gastrointestinal bleeding is roughly similar to that for non-aspirin non-steroidal anti-inflammatory drugs but those affected are generally younger, in an age group where death from upper gastrointestinal bleeding is very uncommon. In keeping with this and in contrast to non-aspirin non-steroidal anti-inflammatory drugs, no study has shown increased mortality from aspirin-related upper gastrointestinal complications.
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PMID:Review article: aspirin and gastrointestinal bleeding. 803 46

The use of acetylsalicylic acid and other non-steroidal, anti-inflammatory drugs was studied prospectively in 207 patients admitted for suspected upper gastrointestinal bleeding. In addition to detailed drug history, plasma samples for drug analyses were obtained from the majority of the patients. 64 of the patients admitted recent intake of ulcerogenic drugs, and the plasma samples revealed another 11 users. Acetylsalicylic acid was the most prevalent substance, but all available non-steroidal, anti-inflammatory drugs were represented in the material. Gastroduodenal ulcers were found in 94 (44%) of the patients; two thirds of the users and one third of the non-users. Gastric ulcer was slightly more prevalent than duodenal ulcer in both groups. Six patients with drug-associated bleeding had previously had a verified drug-associated ulcer. Only 12 users and 16 non-users denied dyspeptic complaints before admission. The users were older, they generally had a lower Hgb on admission than non-users had, and a slightly higher transfusion requirement, but these factors did not result in significant differences as to clinical outcome. The drug analyses of plasma samples showed a discrepancy to the anamnestic data in 25% of the patients and may be a useful addition to drug history in these studies.
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PMID:[Use of acetylsalicylic acid and other antiphlogistics in hematemesis/melena]. 819 27


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