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Biomedical subjects

C W Howden

Publications and source records attributed to C W Howden.

At least 109 records · Page 6Linked to original sources
PubMed1989

Twenty-four-hour intragastric acidity in duodenal ulcer patients during dosing with placebo, and 150 mg ranitidine twice or four times daily.

Twenty-four-hour intragastric acidity was measured in 10 patients with a past history of duodenal ulcer on the fourth day of dosing with placebo, and either 150 mg ranitidine given twice or four times daily. The order of the treatments was randomized and a double-blind design was employed. Ranitidine (150 mg) b.d. decreased median integrated 24-h intragastric acidity by 65.1%, nocturnal acidity by 89.1%, and daytime acidity by 54.6% (all P less than 0.01 compared to placebo). The corresponding decreases with 150 mg ranitidine q.d.s. were 62.3, 89.9 and 48.8%, respectively (all P less than 0.01) compared to placebo). There were no significant differences between the two dosage regimens of ranitidine (P greater than 0.05). This study shows that giving extra doses of 150 mg ranitidine during the day does not increase the degree of suppression of intragastric acidity.

Adult↗
PubMed1989

The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis.

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double-blind randomised crossover study in a group of patients with compensated biopsy-proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/- 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/- 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril.

Administration, Oral↗
PubMed1989

Probable Crohn's colitis mimicking ischaemic colitis in a young adult.

The features on barium enema of ischaemic colitis is characteristic and the radiological sign of "thumb printing" thought to be almost pathognomonic of the condition. We report a case of inflammatory bowel disease, probably Crohn's disease mimicking these radiological features. This has not to our knowledge been previously documented.

Adult↗
PubMed1988

Maintenance treatment with H2 receptor antagonists in patients with peptic ulcer disease: rarely justified in terms of cost or patient benefit.

Maintenance treatment reduces the frequency of ulcer relapse. Its routine use is unnecessary because the condition is benign and most patients do not relapse frequently. Routine maintenance treatment does not reduce the incidence of complications of ulcers overall, although it may do so in specific groups mentioned above. Routine maintenance treatment for all patients with ulcers would be expensive as well as largely unnecessary.

Aged↗
PubMed1988

The treatment of gastric ulcer with antisecretory drugs. Relationship of pharmacological effect to healing rates.

Published clinical trials (N = 56) of antisecretory drugs in the treatment of benign gastric ulcer were reviewed. Composite healing rates for various drug regimens were calculated using a method previously described for duodenal ulcer. Healing rates were compared with data on suppression of intragastric acidity to see if any relationship was evident. No significant correlations between the two existed, unless placebo data were included in the analysis. Correlations were stronger with suppression of total 24-hr rather than nocturnal acidity. Using Williams' method for assessing trends, it was found that an increase in antisecretory effect is not associated with a concomitant increase in healing rates. Duration of medical treatment is the single most important factor in healing of benign gastric ulcer; healing rates for all drug regimens and placebo show a consistent increase with prolongation of treatment.

Anti-Ulcer Agents↗
PubMed1988

Haemodynamic effects of intravenous human calcitonin-gene-related peptide in man.

1. The effects of intravenous bolus doses of human calcitonin-gene-related peptide (hCGRP) were studied in ten healthy male volunteers. 2.5, 10 and 25 micrograms of hCGRP and placebo were administered to each subject in a randomized double-blind study. 2. hCGRP had no effect on systolic or diastolic blood pressure in the supine or standing position. 3. hCGRP increased supine and standing heart rate. Both the extent and duration of the tachycardia were dose related. 4. Plasma noradrenaline levels were transiently increased after 10 and 25 micrograms of hCGRP. 5. All subjects displayed marked facial flushing after the two higher doses of hCGRP. 6. We conclude that systemic administration of hCGRP produces tachycardia and stimulation of the sympathetic nervous system in the absence of any change in blood pressure.

Adult↗
PubMed1988

Review: interactions between H2-antagonists and non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are being prescribed increasingly with an H2-antagonist. This article reviews those published studies which have examined the potential for pharmacokinetic and, where appropriate, pharmacodynamic interactions between these classes of drugs. Studies involving the administration of a single dose of a NSAID to young healthy volunteers are of limited relevance in establishing the likely effect of an H2-antagonist on the blood concentrations of an NSAID in patients. Appropriate studies are those which will examine the effects of H2-antagonists on the steady-state pharmacokinetics of NSAIDs in patients with inflammatory joint diseases. More of such studies are required, particularly involving elderly patients.

Animals↗
PubMed1988

Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist.

The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1.2 to 2.8 mmol/h and after maximal impromidine stimulation from 36.9 (4.7) to 44.2 (6.2) mmol/h (p less than 0.02). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8.5 (1.2) mmol/h before, to 3.8 (1.5) mmol/h (p less than 0.05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors ('up-regulation').

Adult↗
PubMed1987

The effects of omeprazole on endocrine function in man.

We have assessed the effect of omeprazole on various endocrine functions in man. Eight healthy subjects took 60 mg omeprazole or placebo daily for 1 week in a double-blind, randomized, cross-over study. On Day 7 basal concentrations of follicle-stimulating hormone (FSH), luteinising hormone (LH), prolactin, testosterone, thyroid-stimulating hormone (TSH), and serum thyroxine (T4) and tri-iodothyronine (T3) were measured, followed by the gonadotrophin response to luteinising hormone releasing hormone (LHRH) and the prolactin and TSH responses to thyrotrophin releasing hormone (TRH). There were no differences in basal or stimulated values between omeprazole and placebo. In a second study, a further 8 subjects were similarly treated, and on Day 7 serial measurements of cortisol and 11-deoxycortisol were made before and for 2.5 h after intravenous adrenocorticotrophin (ACTH). There were no differences in basal values or pattern of response to ACTH for either hormone. Omeprazole in clinical practice is unlikely to cause any significant interference in endocrine function.

Adult↗
PubMed1987

Marked suppression of stimulated gastric acid and pepsin secretion by enisoprost, a new PGE1 analogue.

The gastric antisecretory effects of three different doses of enisoprost, a new synthetic PGE1 analogue, were compared with placebo and misoprostol in 20 healthy male volunteers. Enisoprost 100, 200 and 400 micrograms all significantly (P less than 0.0001; ANOVA) suppressed histamine-stimulated acid and pepsin output when compared with placebo or misoprostol 200 micrograms. Misoprostol produced a significant decrease of stimulated acid output when compared with placebo (P = 0.0012). The concentration of pepsin in gastric juice was significantly (P less than 0.0001) decreased by enisoprost at the commencement of histamine stimulation. This effect was short-lived, and was maximal with enisoprost 400 micrograms. There was a significant dose-response relationship for enisoprost for inhibition of stimulated acid output (P = 0.0065). Enisoprost was well tolerated, and no consistent drug-related adverse effects were detected. The profile of antisecretory effect of enisoprost, producing marked suppression of both acid and pepsin secretion independently, is unusual. This combination of activity along with any mucosal protective properties might be particularly effective in the treatment of peptic ulcer disease.

Adult↗
PubMed1987

Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs.

FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended. The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs. We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens. For the H2 receptor antagonists alone, the most significant correlation with healing rates was with suppression of intragastric acidity at night (r = 0.926; p = 0.0001). When other classes of drug: high dose antacid, omeprazole and a synthetic prostaglandin (enprostil) were included in the analysis, the closest correlation was with suppression of total 24 hour intragastric acidity (r = 0.911; p less than F0.0001). Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night. Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates. No further benefit was obtained with daytime suppression for H2 receptor antagonists; suppression of acidity at night accounted for 86.1% of the observed variation in healing rates among different regimens of H2 receptor antagonists. When all classes of drugs were analysed, inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone. Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials. The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity. For the H2 receptor antagonists, suppression of nocturnal acidity is the most relevant in this context. Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks. Increasing degrees of suppression merely accelerate healing.

Anti-Ulcer Agents↗
PubMed1986

Effects of ranitidine and cimetidine on plasma lipoproteins in healthy subjects.

Serum lipoproteins were monitored in 24 healthy subjects receiving either ranitidine or cimetidine for four weeks. Ranitidine produced a significant (P less than .05) reduction in high-density lipoprotein (HDL)-cholesterol in both men and women. Cimetidine caused a nonsignificant increase in HDL-cholesterol and a reduction in LDL-cholesterol that was significant (P less than .05) only in women. As these drugs had opposite effects on HDL-cholesterol levels, the mechanism of action is unlikely to be medicated by H2-receptor blockade.

Adult↗