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|Year : 1982 | Volume
| Issue : 2 | Page : 73-7
Short term therapy with cimetidine of endoscopically proved chronic duodenal ulcer.
Nanivadekar SA, Govindani NF, Tandon NH, Dixit SD, Thomas GG
|How to cite this article:|
Nanivadekar S A, Govindani N F, Tandon N H, Dixit S D, Thomas G G. Short term therapy with cimetidine of endoscopically proved chronic duodenal ulcer. J Postgrad Med 1982;28:73
|How to cite this URL:|
Nanivadekar S A, Govindani N F, Tandon N H, Dixit S D, Thomas G G. Short term therapy with cimetidine of endoscopically proved chronic duodenal ulcer. J Postgrad Med [serial online] 1982 [cited 2020 Nov 26];28:73. Available from: https://www.jpgmonline.com/text.asp?1982/28/2/73/5588
Duodenal ulcer is a common disease with reported prevalence of 6-15%, and mortality rates of 0.5 to 10%. It is primarily due to acid-pepsin attack. Until recently, antacids and anticholinergics were the mainstay in the treatment of peptic ulcer. Black et al, in 1972, synthesized, for the first time, Burimamide, a prototype of a new class of drugs which specifically blocked the action of histamine on gastric acid secretion. However, this drug went into disrepute as it was required to be given parenterally. Metiamide, a congener of Burimamide, produced a profound fall in acid secretion after a single oral dose of 400 mg which lasted for several hours; however, it was found to produce neutropenia in some patients.
Next synthesized was the drug cimetidine by Brimblecombe et al. This drug is a potent H2-receptor antagonist which can virtually block the gastric acid output in response to histamine or pentagastrin. Nocturnal acid secretion, believed to be vagally mediated, is also suppressed completely in human subjects having inactive duodenal ulcer disease by 400-800 mg of cimetidine.,  After chronic cimetidine administration, gastric acid secretion, either basal, meal stimulated or drug stimulated, is not enhanced. Cimetidine continues to inhibit gastric acid secretion even after prolonged therapy. Cimetidine is sparingly soluble in lipids and hence cannot cross the blood-brain barrier.
The recommended dose of cimetidine in duodenal ulcer is 1 g/day orally in divided doses for initial therapy and 1.6 g/day for recurrence. The usual dose schedule initially is 0.2' g with every meal and 0.4 g at bed time.
This was a double-blind randomised controlled study of the efficacy of cimetidine in duodenal ulcer patients proven by oesophago-gastro-duodenoscopy. The control group comprised subjects with similar upper gastro-intestinal symptoms, who did show an ulcer on endoscopy. Their symptoms were recorded on a standard proforma. Cimetidine was administered in a dose of 200 mg (1 tablet) with breakfast, lunch and dinner and 400 mg (2 tablets) at bed time. The control subjects were given a placebo tablet with breakfast, lunch and dinner and 2 placebo tablets at bed time. Patients in both groups were allowed to take as many antacid tablets as they wished to take. All the subjects were interviewed and examined once a week during therapy. The endoscopy was repeated after two and four weeks of treatment. The treatment code was opened at the end of four weeks after the third endoscopy. The results were evaluated statistically. The Fisher's exact probability test was used to evaluate the significance of difference in the proportion of drop-outs and the proportion of patients with healing of duodenal ulcer in the two groups. The significance of change in the average daily consumption of antacid tablets within each group was tested by Wilcoxon's Signed Rank Sum Test for paired data; to test the difference between the groups, Wilcoxon's Rank Sum Test for two independent samples was used.
There were 19 men and one woman in the cimetidine group and 19 men in the placebo group. The ages of the patients ranged between 21 and 65 (mean = 37.5) years and between 23 and 62 (mean = 38.2) years in the two groups respectively. The duration of symptoms ranged between 1.5 and 25 years (mean = 7.1) and between 1.5 and 20 (mean = 6.9) years in the two groups respectively. Nine patients in the cimetidine group had anterior ulcer whereas 11 patients had posterior ulcers. In the placebo group 12 patients had anterior ulcer, 6 had posterior ulcer and one had both anterior and posterior ulcers. Thus, the two groups were comparable.
At the end of 4 weeks, there was one drop-out in the cimetidine group (5%) and 6 drop-outs in the placebo group (30%) (p < 0.05). These were excluded from the analysis. The causes of dropouts could not be ascertained in all the patients, but 3 patients from the placebo group complained that they had no relief of symptoms at all.
In the cimetidine group, at the end of 2 weeks, 10 ulcers healed completely, 7 healed partially and 3 cases could not be assessed as they did not report for endoscopy. At the end of 4. weeks, one of the 3 above dropped out. Six more patients (total 16) showed complete healing. Three remained partially healed.
In the placebo group, only one showed healing at the end of 2 weeks; two healed partially and 13 remained unchanged; three did not report for endoscopy and hence could not be assessed. At the end of 4 weeks, all 3 above as well as another three whose ulcers were unchanged at 2 weeks, dropped out. Only 3 showed complete healing, one had partial healing and 9 remained unchanged [Table 1]. The difference in the complete healing of duodenal ulcer in the two groups both at 2 and 4 weeks, was statistically significant (p < 0.01).
Daily consumption of antacid tablets fell from an average of 7.05 to 0.42 at the end of 4 weeks in the cimetidine group. However, the decrease was from an average of 6.31 to 4.46 only in the placebo group. The difference in the fall of antacid consumption was statistically significant (p < 0.002).
WBC count, platelet count, BUN, creatinine and SGOT did not show any significant changes during therapy in patients of either group. No side effects were reported by either group. [Table 1] summarises the results of this study.
In our study, ulcer healing on cimetidine was superior to placebo both at 2 and 4 weeks. Results of our study match with those of Cargil et al whose study comprised 96 patients. In their study, 92% of ulcers healed after one month's treatment. However, they continued the study further and 5% of ulcers healed during the next 2 months. This is in contrast to the results of Gilsang et al, who have shown impressive performance by the placebo group wherein, out of 27 patients on 1 g cimetidine per day, 16 showed healing (60%), as opposed to 14 (45%) out of 31 patients on placebo. However, in their study, placebo group consumed seven times the amount of antacid as that consumed by patients on cimetidine.
Three patients showed duodenal erosions on cimetidine therapy at 4 weeks in our series. Bardhan et all have shown, in a very large trial in the U.K., that erosions are a normal event in the natural history of the ulcer syndrome. In their 250 cases they showed that after cimetidine, ulcers would disappear, but erosions would persist or appear for the first time. If the treatment was continued for a further 4 to 12 weeks, the erosions would heal.
Various adverse effects have been reported in the literature.,,,,,,,,,,,,, None of these was seen in our study.
This study thus confirms that cimetidine is effective in bringing about healing of duodenal ulcer and is reasonably safe during short term administration.
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