An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole.

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion in a dose-dependent manner via inhibition of H+/K+-adenosine triphosphatase in gastric parietal cells. It also exhibits antibacterial activity against Helicobacter pylori in vitro. During almost 10 years of clinical use, lansoprazole has proved effective and well tolerated in a wide range of acid-related disorders, including gastro-oesophageal reflux disease (GORD), duodenal ulcers, gastric ulcers, non-steroidal anti-inflammatory drug-related ulcers, as well as non-ulcer dyspepsia and acid hypersecretion. It is also used, in combination with antibiotics, for H. pylori eradication. In the above indications, lansoprazole has generally proved to be superior to the histamine H2-receptor antagonists, and is at least as effective as the other currently available proton pump inhibitors. This review aims to evaluate the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole in acid-related disorders, with particular emphasis on its use in GORD and H. pylori eradication regimens.

Colorectal carcinoma in patients with ulcerative colitis and recent colonoscopy.

Longstanding ulcerative colitis, particularly pancolitis, is associated with an increased risk of colorectal neoplasia. For this reason surveillance colonoscopy at regular intervals has been recommended to identify early cancers or high grade dysplasia. Three cases are described of patients with ulcerative colitis of greater than 10 years duration who presented with colorectal carcinoma within three years of colonoscopy.

Comparison of occult blood loss caused by pirazolac and diclofenac sodium: a double-blind crossover study.

A study was carried out in 10 healthy subjects to compare the faecal blood loss caused by pirazolac, a new non-steroidal anti-inflammatory drug, and diclofenac sodium, using chromium51-labelled red blood cells. After 1 week on placebo, subjects received at random either 200 mg pirazolac 3-times daily or 50 mg diclofenac sodium 3-times daily for 7 days. They were then crossed over to the alternative medication for a further 7 days, preceded and followed by 1 week on placebo. Stool samples were collected and bulked for each day and total blood loss over 14 days (7 days on treatment and 7 days immediately after) was calculated for each period. The results showed that both drugs caused a greater blood loss than that measured in the placebo run-in period, and diclofenac sodium caused significantly greater blood loss than did pirazolac. Three subjects reported gastro-intestinal side-effects during diclofenac sodium treatment but there were no reports of any side-effects whilst subjects were receiving pirazolac.

A controlled trial of alternate day prednisolone as a maintenance treatment for ulcerative colitis in remission.

A double-blind crossover trial compared prednisolone, 40 mg given orally on alternate days, with placebo as a maintenance treatment for ulcerative colitis in remission. In each patient, the study was over two periods of 3 months. Of 24 patients who completed both periods, 11 relapsed while taking placebo but not while taking prednisolone, and 1 relapsed on prednisolone but did not on placebo (p less than 0.01). 1 patient had to stop prednisolone because of hyperglycaemia; other side effects noted were mild. Prednisolone, cautiously used in this way, could be justified for the few patients who relapse frequently despite sulphasalazine.

Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease.

51 patients with Crohn's disease who were in good health while taking azathiprine, 2 mg/kg body-weight/day, for at least six months were allocated either to a group in which azathioprine was continued or to one in which a control tablet was substituted. The trial lasted one year unless relapse recurred earlier. The cumulative probability of relapse was nil at six months and 5% (+/-5 S.D.) at a year among those on azathioprine, compared with 25% (+/-9 S.D.) at six months and 41% (+/-11 S.D.) at a year among those in the control group (P less than 0.01). 1 patient in whom azathioprine was continued died of pancytopenia in the fourth month of the trial. Azathioprine is potentially toxic but appears to reduce the relapse-rate in Crohn's disease.

A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis.

Forty mg has been shown to be the optimal daily dosage of prednisone for outpatients requiring oral steroids for active proctocolitis. Although daily doses of oral steroids are commonly divided, a single dose each morning causes less adrenal suppression and is more convenient to take. A randomized controlled trial has been performed on patients with proctocolitis, in which 23 received 40 mg prednisolone each morning as one dose, and 22 received 10 mg four times a day, over two weeks. Physicians unaware of the dosage schedule scored the disease activity and assessed the steroid side-effects when the patient entered the trial, at day 7 and at day 14. Of those taking the divided dose the disease improved in 17 and failed to improve in five. No side-effects were observed in ten patients. Of those receiving a once daily regimen, 17 improved and six did not. Nine patients had no side-effects. Further assessment showed no difference between the two groups either in response rate or side-effects produced. When oral steroids are indicated for active proctocolitis, 40 mg prednisolone, as a single dose each morning can be recommended.

The contingent negative variation and psychological findings in chronic hepatic encephalopathy.

Early diagnosis of chronic hepatic encephalopathy (CHE) in the latent stage before the appearance of clinical signs, should reduce both morbidity and mortality as deterioration is often preventable by treatment. Since existing diagnostic procedures are inadequate, we have investigated a test in which morphine is used as a provocative agent and any resulting change in cerebral function assessed by measurement of the CNV in conjuction with a psychological trail test. Twenty six patients were studied, 6 of whom had clinically overt CHE. A significant correlation (P less than 0.05) between the change in CNV amplitude with morphine and the initial CNV amplitude, consistent with the theoretical model of Tecce (1972), was found. However, the CNV and trail test results taken as a whole did not allow even those patients with overt CHE to be distinguished and we conclude that it is unlikely that differing degrees of latent CHE could be detected.

Effects of lactulose and other laxatives on ileal and colonic pH as measured by a radiotelemetry device.

Using a pH-sensitive radiotelemetering device the effect of lactulose on luminal pH in the ileum, colon, and rectum has been compared with that of two other laxative agents. Lactulose produced marked acidification of proximal colonic contents but this effect was not consistently maintained into the distal colon. Sodium sulphate acidified distal rather than proximal colonic contents. However, for a similar degree of laxation it was not possible to produce a significantly more uniform reduction of pH along the length of the colon by combining these laxatives compared with lactulose alone. Magnesium sulphate had little effect upon luminal pH except in the rectum where a significant rise occurred. These results are discussed in relation to both normal colonic physiology and to their possible relevance to the treatment of chronic hepatic encephalopathy by colonic acidification.