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Biomedical subjects

C W Howden

Publications and source records attributed to C W Howden.

At least 91 records · Page 5Linked to original sources
PubMed1993

The consequences of H2 receptor antagonist--piroxicam coadministration in patients with joint disorders.

A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.

Adult↗
PubMed1993

Nonsteroidal antiinflammatory drugs and lower gastrointestinal bleeding.

To define the association of the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA), and lower gastrointestinal bleeding (GIB) a retrospective, case-controlled study was undertaken of 188 patients admitted to three community hospitals in three cities with a diagnosis of lower GIB. Information was obtained about NSAID usage among these patients, and the data were compared with an age- and sex-matched control group of 185 patients admitted with a nongastrointestinal diagnosis, derived from a daily admission list. At the time of admission, in the New Jersey group, NSAID consumption was present in 26 of 90 (29%) patients with lower GIB compared with 16 of 90 (18%) of controls (P < 0.05, odds ratio 1.88, 95% CI 1.2-3.1) whereas, in the South Carolina group 34 of 98 (35%) were taking NSAID compared with 18 of 95 (19%) of controls (P < 0.01, odds ratio 2.27, 95% CI 1.2-4.4). These data indicate that there is a significantly increased rate of NSAID ingestion in patients admitted with lower GIB, implying that NSAID may unmask bleeding from a variety of lower gastrointestinal lesions.

Aged↗
PubMed1992

Omeprazole (20 mg) daily given in the morning or evening: a comparison of effects on gastric acidity, and plasma gastrin and omeprazole concentration.

Although omeprazole has a long duration of action and has usually been given in the morning, there are theoretical advantages in administering antisecretory drugs in the evening as has been shown for the H2-receptor antagonists. The aim of this study was to compare the effects of placebo and 20 mg omeprazole given either in the morning or evening, on gastric acidity, plasma gastrin levels and plasma omeprazole in 6 duodenal ulcer patients. The 24-hour mean pH (+/- S.E.M.) was: placebo 1.7 +/- 0.1; morning doing, 3.9 +/- 1.8 (P less than 0.01); evening dosing, 2.9 +/- 1.1 (N.S.). There was a large inter-individual variability of intragastric acidity in response to omeprazole, which was reflected both in the plasma gastrin and in the area under the plasma omeprazole concentration-time curve. Morning administration of omeprazole is optimal, but variability in the patient response to 20 mg omeprazole is still seen.

Double-Blind Method↗
PubMed1992

Appropriate acid suppression for the management of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GORD) results from an abnormally prolonged dwell time of acidic gastric contents in the oesophagus. Although GORD is primarily a motor disorder, the injurious effects of gastric acid are central to the pathogenic process of oesophagitis, and the severity of disease correlates with the degree and duration of oesophageal acid exposure. In the majority of patients with mild disease, oesophageal acid exposure occurs predominantly during post-prandial periods. Conventional doses of H2-receptor antagonists cannot overcome the integrated stimulus to acid secretion resulting from a meal, and are thus relatively ineffective in preventing daytime, post-prandial oesophageal acid exposure. In patients with more severe grades of oesophagitis, there are abnormally high levels of nocturnal acid exposure, with the intra-oesophageal pH being less than 4.0 for 36% of the time, compared with 5% of the time in patients with mild GORD. Control of nocturnal acid secretion thus becomes increasingly important. This may be made worse by relative gastric acid hypersecretion in some patients with severe GORD. The long duration of action and effective inhibition of meal-stimulated acid secretion probably explains the superiority of omeprazole in treating GORD. Preliminary meta-analysis shows that the healing rate of erosive oesophagitis at 8 weeks by antisecretory agents is directly related to the duration of suppression of gastric acid secretion achieved over a 24-hour period (r = 0.87; p less than 0.05).

Anti-Ulcer Agents↗
PubMed1992

Potent versus mild acid suppression in peptic ulcer disease.

In the consideration of potent versus mild suppression of gastric acid secretion in the treatment of peptic ulcer disease, it must be remembered that pharmacological effect in terms of degree of suppression of acidity is closely linked to therapeutic efficacy in terms of numbers of ulcers healed. More potent degrees of suppression of acidity result in faster ulcer healing. Moderate suppression of acidity, such as is achieved by the H2RA, can heal just as many ulcers if treatment is continued longer. Mild acid suppression will take still longer to produce the same healing rates. Therapeutic benefit of any treatment must be assessed also in terms of the side-effect profile of the drug or drugs used. There is an enormous cumulative experience with the H2RA as a group and they are known to have an excellent safety profile.

Adenosine Triphosphatases↗
PubMed1991

Omeprazole. Overview and opinion.

Omeprazole, a substituted benzimidazole, is a specific inhibitor of the enzyme H+/K(+)-ATPase, which is found on the secretory surface of the parietal cell. This enzyme, the "proton pump," catalyzes the final step in acid secretion. Omeprazole is a powerful inhibitor of gastric acid secretion. At the time of writing, omeprazole has been licensed in the United States for the treatment of severe grades of gastroesophageal reflux disease (GERD) as well as GERD unresponsive to treatment with currently available agents, and for the treatment of Zollinger-Ellison syndrome and other gastric hypersecretory states. Most recently, it has been recommended by the FDA advisory committee for approval as first-line therapy in duodenal ulcer disease.

Duodenal Ulcer↗
PubMed1991

Increased intestinal permeability in ankylosing spondylitis--primary lesion or drug effect?

We have found increased small intestinal permeability to 51Cr-ethylenediaminetetra acetate in patients with ankylosing spondylitis compared with controls. There is no significant difference between patients with ankylosing spondylitis and patients with rheumatoid arthritis taking non-steroidal anti-inflammatory drugs (NSAID). The increased intestinal permeability in ankylosing spondylitis is independent of disease activity. These findings suggest that the increased permeability is caused by NSAID treatment and is probably not a primary lesion of small bowel mucosa.

Adult↗
PubMed1991

Clinical pharmacology of omeprazole.

Omeprazole is a specific inhibitor of H+,K(+)-ATPase or 'proton pump' in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. Single doses produce dose-dependent inhibition with increasing effect over the first few days, reaching a maximum after about 5 days. Doses of omeprazole 20mg daily or greater are able to virtually abolish intragastric acidity in most individuals, although lower doses have a much more variable effect. Omeprazole causes a dose-dependent increase in gastrin levels. Omeprazole must be protected from intragastric acid when given orally, and is therefore administered as encapsulated enteric-coated granules. Absorption can be erratic but is generally rapid, and initially the drug is widely distributed. It is highly protein-bound and extensively metabolised. Its elimination half-life is about 1h but its pharmacological effect lasts much longer, since it is preferentially concentrated in parietal cells where it forms a covalent linkage with H+,K(+)-ATPase, which it irreversibly inhibits. Omeprazole binds to hepatic cytochrome P450 and inhibits oxidative metabolism of some drugs, the most important being phenytoin. Omeprazole has produced short term healing rates superior to the histamine H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. It has also been shown to be highly effective in healing ulcers which have failed to respond to H2-receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.

Drug Interactions↗
PubMed1991

Comparison of different measurements of intestinal permeability in inflammatory bowel disease.

We have compared different measurements of small intestinal permeability in 28 patients with Crohn's disease affecting the small intestine, 14 with ulcerative colitis and 17 controls. Patients and controls were given a drink containing 100 microCi (3.7 MBq) of 51Cr-ethylene diamine tetraacetic acid (51Cr-EDTA), 5 g lactulose, 5 g cellobiose, 1 g rhamnose, and 2 g mannitol. Urine was collected to 6 h after dosing, and then from 6 until 24 h. Recoveries of 51Cr-EDTA, lactulose, rhamnose, and mannitol were expressed as percentages of the amount administered. The only measurement that distinguished patients with Crohn's disease from both controls and patients with ulcerative colitis was the recovery of 51Cr-EDTA in the first 6 h after dosing. The mean recovery in patients with Crohn's disease was 1.07%; in controls, it was 0.35% (p = 0.013); in ulcerative colitis it was 0.39% (p = 0.032 compared to Crohn's; p = 0.492 compared to controls). No other measurement of permeability differentiated the three groups. Recoveries of 51Cr-EDTa and lactulose were highly correlated in each of the three groups. Recovery of rhamnose was significantly correlated with that of mannitol. In the patients with Crohn's disease, recovery of 51Cr-EDTA to 6 h was significantly correlated with some nonspecific laboratory indicators of inflammatory activity, namely, erythrocyte sedimentation rate, platelet count, white blood cell count, serum albumin, and C-reactive protein, but not with hemoglobin.

Adolescent↗
PubMed1990

The relationship between suppression of acidity and gastric ulcer healing rates.

We have investigated the relationship between the suppression of acidity by antisecretory drugs for the treatment of benign gastric ulcer and their corresponding ulcer-healing rates. For a variety of antisecretory drug regimens, there was a significant correlation between suppression of 24-h intragastric acidity and ulcer healing rates after 2, 4 and 8 weeks of treatment. There was a lesser degree of correlation between healing and suppression of nocturnal acidity and the association between suppression of acidity and gastric-ulcer healing rates was less marked than that previously described for duodenal ulcer.

Antacids↗
PubMed1990

Twenty-four-hour intragastric acidity and nocturnal gastric secretion in gastric ulcer patients--the effects of cimetidine.

In a double-blind randomized study, the profile of 24-h intragastric acidity and nocturnal gastric secretion was measured in a group of patients with healed gastric ulcer on placebo and 400 mg cimetidine b.d. and 800 mg nocte. Neither cimetidine regimen significantly decreased daytime intragastric acidity, but the 800 mg nocte dose caused a significant decrease in both nocturnal acidity (18.1 to 5.5 mmol/L; P less than 0.05) and acid output (11.0 to 1.7 mmol 7 h; P less than 0.05). The decrease in nocturnal gastric secretion by 400 mg cimetidine b.d. was not significant. As in duodenal ulcer, 800 mg cimetidine nocte will effectively suppress night-time acid secretion in patients with gastric ulcer while leaving acid secretion during the day unaffected.

Adult↗