PubMed Health⌕ Search

Biomedical subjects

C W Howden

Publications and source records attributed to C W Howden.

At least 127 records · Page 7Linked to original sources
PubMed1986

Inhibition by omeprazole of adrenocortical response to ACTH: clinical studies and experiments on bovine adrenal cortex in vitro.

Omeprazole, a substituted benzimidazole, is a potent inhibitor of gastric acid secretion which is currently being evaluated in patients with peptic ulcer and Zollinger-Ellison syndrome. Drugs which possess an imidazole nucleus have previously been shown to inhibit cortisol release from the adrenal cortex, secondary to inhibition of mitochondrial cytochrome P-450 dependent hydroxylation reactions. In a double-blind placebo-controlled crossover study in healthy male volunteers, omeprazole (60 mg daily for 7 days) did not alter basal cortisol levels. The peak cortisol response to ACTH stimulation was significantly reduced. Cortisol levels 60 min after ACTH were 824 +/- 27 nmol/l on omeprazole (mean +/- SEM), and 929 +/- 35 on placebo (P less than 0.005). In vitro, omeprazole caused a concentration-dependent inhibition of ACTH-stimulated cortisol release from isolated bovine adrenal cells (ED50 = 20 micrograms/ml). This was associated with a decrease in deoxycortisol synthesis. Therefore, unlike some other imidazole-containing drugs, the inhibitory effects of omeprazole are not entirely due to steroid 11 beta-hydroxylase inhibition. Substantial inhibition occurred at omeprazole concentrations which are higher than plasma levels normally achieved in clinical use. However, impairment of adrenocortical function may occur in patients on long-term high dose omeprazole treatment for Zollinger-Ellison syndrome.

Adrenal Cortex↗
PubMed1986

Comparison of the effects of gastric antisecretory agents in healthy volunteers and patients with duodenal ulcer.

Thirty published studies of the clinical pharmacology of gastric antisecretory agents in normal volunteers and duodenal ulcer patients were reviewed. The aim was to investigate the relationship between antisecretory effect in the two populations. There was a significant correlation between effect in patients and normal subjects for suppression of 24 hour intragastric acidity (r = 0.732; p = 0.0068), nocturnal intragastric acidity (r = 0.861; p = 0.0033) and nocturnal acid output (r = 0.964; p = 0.0069). The regression lines for 24 hour and nocturnal acidity were very similar. The expected antisecretory effect of a particular dosage regimen in patients with duodenal ulcer can be predicted mathematically from data derived from studies in normal volunteers.

Anti-Ulcer Agents↗
PubMed1986

Spontaneous hypochlorhydria in man: possible causes and consequences.

There have been many reports of the development of achlorhydria in individuals and in groups of subjects with previously normal levels of gastric acid secretion. The evidence that this phenomenon is due to an infective agent has been considered. Retrospective identification of CLO in gastric mucosal biopsies from some of these patients is an interesting observation, but does not conclusively prove a causal relationship. The exact significance of CLO remains speculative at present; there is more evidence to suggest that it plays a role in gastritis than in peptic ulceration. Ongoing research in this area may have major consequences for the medical treatment of gastritis, 'non-ulcer dyspepsia' and perhaps also for peptic ulcer disease.

Achlorhydria↗
PubMed1986

The correlation between acid suppression and peptic ulcer healing.

Suppression of gastric acid forms the basis of treatment of duodenal and gastric ulcer, but the precise relationship between suppression of acidity and healing rates has not been defined. We examined the results of controlled trials and clinical pharmacological studies of 24-h intragastric acidity involving antisecretory agents. Data on 24-h and nocturnal hydrogen ion activity and nocturnal acid output were obtained, and the healing rates in duodenal ulcer were calculated. Duodenal ulcer healing rates after 4 weeks showed a significant correlation with suppression of 24-hour hydrogen ion activity (r = 0.63; P less than 0.05), and a highly significant correlation between healing and the suppression of nocturnal hydrogen ion activity (r = 0.93; P less than 0.0001). Nocturnal acid output was not significantly correlated. For gastric ulcer, no such association was seen for suppression of either 24-hour or nocturnal hydrogen ion activity. Duodenal ulcer is regarded as an acid-related disorder, but in gastric ulcer other factors may be more important in pathogenesis and treatment.

Anti-Ulcer Agents↗
PubMed1986

Effects of low dose omeprazole on gastric secretion and plasma gastrin in patients with healed duodenal ulcer.

The effects of seven days' treatment with omeprazole 5 and 10 mg daily on 24 hours gastric secretion and plasma gastrin concentrations were studied in a randomised double-blinded placebo-controlled study of six male patients with healed duodenal ulcer. Omeprazole 5 mg daily reduced mean daytime and nocturnal intragastric acidity by 31.4 and 40.1%, respectively. Omeprazole 10 mg per day produced very similar reductions of 33.6 and 42.0%, respectively. Total nocturnal acid output was reduced by 63.9% and 63.2%, respectively, by omeprazole 5 and 10 mg daily. There was a large degree of inter-subject variability in response to these low doses of omeprazole. Consequently, neither dose showed a statistically significant antisecretory effect when compared with placebo. Neither dose of omeprazole significantly affected fasting levels of gastrin, but omeprazole 10 mg daily produced a significant (P less than 0.05) increase in the integrated gastrin response to a meal. The lack of consistent antisecretory effect to low dose omeprazole is in accord with previous studies. This suggests that doses of 20 mg per day or greater are required to produce a consistent effect on acid secretion.

Adult↗
PubMed1985

Antisecretory effect and oral pharmacokinetics of omeprazole in patients with chronic renal failure.

The inhibitory effect of omeprazole on gastric acid secretion was tested in a group of patients on haemodialysis for chronic renal failure. Single 30 mg doses almost totally inhibited basal acid output on both dialysis and non-dialysis days. Plateau acid output was reduced by a mean of 77% and 90% on non-dialysis and dialysis days respectively. The absorption and pharmacokinetic profile of omeprazole were not affected by dialysis. Omeprazole was not recoverable from dialysis fluid. It is concluded that omeprazole is a potent inhibitor of gastric acid secretion in patients with chronic renal failure, and its effect is not influenced by haemodialysis.

Adult↗
PubMed1985

Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man.

The effects of single and repeated doses of omeprazole 10 mg on gastric secretion were studied in a group of six healthy subjects. Single doses had no significant effect on basal or stimulated acid output. After 7 days of treatment, there was a 93.1% reduction in basal acid output (P less than 0.02) and a 66.5% reduction in stimulated output (P less than 0.01). Pepsin output was not affected. Systemic availability of omeprazole, as reflected in the AUC, increased significantly (P less than 0.05) with repeated dosing. Low doses of omeprazole can produce substantial reductions in acid output after repeated dosing.

Administration, Oral↗
PubMed1985

Single nocturnal doses of pirenzepine effectively inhibit overnight gastric secretion.

The gastric antisecretory effects of two dose levels of pirenzepine given at night were investigated in a group of healthy male volunteers. Compared with placebo, three days of treatment with pirenzepine 100 mg nocte or 150 mg nocte inhibited mean nocturnal intragastric acidity by 54% and 53%, respectively (p less than 0.01). The volume of gastric juice secreted was reduced by 47% and 52% (p less than 0.005), by 100 mg and 150 mg nocte, respectively. Each dose suppressed mean gastric acid output by 67% (p less than 0.001). Pepsin output was not significantly altered. There were no differences in effect between the two dose levels studied, but side-effects such as dry mouth were only seen with the higher dose. Pirenzepine 100 mg is the optimum dose which can conveniently be given at night. This will limit side-effects, and may be a useful treatment for patients with duodenal ulcer.

Adult↗
PubMed1984

Omeprazole, a gastric 'proton pump inhibitor': lack of effect on renal handling of electrolytes and urinary acidification.

Omeprazole has previously been shown to be a potent inhibitor of gastric acid secretion in man. In a new study, oral omeprazole 60 mg/day was given to 8 healthy male subjects for 8 days. The daily urinary electrolyte output and urine pH in response to ammonium chloride were not significantly altered. This provides further support for the specificity of its action on gastric acid secretion.

Adenosine Triphosphatases↗
PubMed1984

Oral pharmacokinetics of omeprazole.

The pharmacokinetics of omeprazole were studied in a group of healthy male subjects after single and repeated oral doses of 30 and 60 mg. Absorption of omeprazole from its enteric-coated formulation was unpredictable. There was a highly significant increase in the area under the plasma concentration time curve (AUC) after repeated dosing. Omeprazole increases its own relative availability following repeated dosing. This may be due to inhibition of gastric acid secretion by omeprazole which is an acid-labile compound.

Administration, Oral↗
PubMed1984

Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man.

The effects of omeprazole, a substituted benzimidazole, on gastric acid and pepsin secretion have been studied in twelve healthy subjects. From six to eight hours after a single oral dose of 30 mg, there was a 66% reduction in basal acid output, and a 71.2% reduction in pentagastrin stimulated acid output. A single dose of 60 mg produced a 91.7% reduction in basal acid output and a 95.3% reduction in pentagastrin stimulated acid output. After seven days treatment with 30 or 60 mg daily, there was almost 100% inhibition of both basal and pentagastrin stimulated acid output. Omeprazole did not significantly affect pepsin secretion which is in keeping with its proposed mode of action, as an inhibitor of the H+/K+-ATPase enzyme on the secretory membrane of the parietal cell. There were no side effects after omeprazole either with single or repeated dosing.

Adult↗
PubMed1984

Clinical pharmacological studies with the vasodilator endralazine in normotensive subjects and essential hypertensives.

Endralazine is a peripherally-acting vasodilator with chemical and pharmacological similarities to hydralazine. In both normotensive volunteers and essential hypertensives, single oral doses of 10 mg endralazine (in combination with a beta-adrenoceptor antagonist) led to substantial falls in blood pressure, with no significant additional orthostatic effect. Maintenance treatment of hypertensive patients with the addition of 5 or 10 mg B.D. endralazine significantly improved blood pressure control: the mean supine blood pressure improved from 197/107 mmHg, on baseline treatment with a thiazide and beta blocker, to 160/86 after one week and 161/91 mmHg after one year with endralazine as third drug therapy. Apart from facial flushing and mild headache following the early doses, no significant side-effects were observed or reported. In the long term, there was no weight gain to suggest fluid retention and in all patients treated with endralazine for at least one year the anti-nuclear factor remained negative. Following acute administration the terminal elimination half-life of endralazine was approximately 2.5 h and the oral bioavailability was 75%. During chronic dosing with endralazine the terminal elimination half-life significantly increased to a mean of 7.5 h, but there was no accumulation of drug. There were no significant differences related to acetylator phenotype either for the dosage, the pharmacokinetics or the hypotensive effect.

Adult↗