摘要:

SUMMARYThe haemodynamic effects and clinical uses of drugs used in the management of patients with oesophageal variceal bleeding are reviewed. Vasoconstrictor agents (vasopressin, teripressin) alone or in combination with nitrates continue to be used for acute bleeding episodes, while somatostatin is an alternative. Alpha‐ and beta‐adrenergic blocking drugs and vasodilators which lead to a sustained decrease in portal pressure can be used for the prevention of bleeding episodes, but despite numerous studies the pharmacological treatment of variceal bleeding remains controvers

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00712.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYThe management of peptic ulcer disease with up to 6 years of continuous cimetidine treatment has been studied at four centres in the UK and Ireland. Cimetidine, 1 g daily for up to 12 weeks, was used to heal duodenal or gastric ulceration, alternating with 400 mg each night to maintain remission.After an initial healing phase, 402 patients started maintenance therapy. Classical life‐table analyses showed that after 5 years one‐quarter of the patients had suffered a symptomatic relapse, about half during the first year of maintenance treatment. Prevalence analyses (reflecting the cyclical nature of H2‐antagonist use in peptic ulcer disease) over 6 years show that, on average, over 97% remain free of symptomatic ulceration at any one time. Patients ‘lost’ to the study due to withdrawal or default may, however, bias the results. A model designed to account for these estimates that during the long‐term management of peptic ulcer with cimetidine, on average around 95% of patients remain free of symptomatic ulceration at any one time.Safety studies, including haematological and biochemical testing over the whole period, revealed no previously unknown adverse reaction. Seven patients were withdrawn for events considered to be related to the drug. Eleven patients died; none of the deaths appears to be connected with the treatment.It is concluded that long‐term use of cimetidine is effective in the management of peptic ulcer disease, and continuous treatment for up to 6 years has not revealed any previously u

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYAt present the effects of maintenance treatment for peptic ulcer disease are usually calculated by using ‘life‐table’ analyses. Whilst these accurately demonstrate the speed with which an initial relapse occurs they make no allowance for the fact that, in clinical practice, a relapse often responds to a further course of full‐dose treatment and the patient then returns to maintenance therapy. A further compounding factor is that, in any long‐term study, patients will be lost to follow‐up for a variety of reasons not all related to failure of the treatment.In this paper we describe the use of ‘prevalence rates’ to better reflect the outcome of peptic ulcer management. Three ‘computer models’, which have been developed to address the problems of patients leaving the study for any reason during such a long time‐period, are also described, as are the underlying assumptions made.Using the results from a long‐term study of continuous treatment with cimetidine,1the ‘prevalence rates’ of ulcer disease over 6 years were calculated. Observed relapse rates appeared to fall with time (from 2.7% for duodenal ulcer (DU) and 2.5% for gastric ulcer (GU) to 1% and 2% respectively). However, on applying the models to the data, prevalence rates tended to rise slowly with time for the first 3 years in each of the models tested. At 6 years, two of the models suggested that the prevalence rate for DU would be about 8%; this is not very different to the reported recurrence rate after surgical treatment by truncal vagotomy and pyloroplasty.It is concluded that ‘prevalence rates’ should be used to assess long‐term medical treatments for ulcer disease. Similar methods could also be used to examine the medical treatment of any other disease where multiple relapses, capable of responding to re‐treatment, occur. The use of models proved beneficial in compensating

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYIn dogs beta‐adrenoreceptor agonists inhibit gastric acid secretion stimulated by exogenous gastrin to a much greater extent than acid secretion stimulated by exogenous histamine. One possible explanation for this observation is that endogenous histamine is important in gastrin‐mediated acid secretion and that isoprenaline and related beta‐adrenoreceptor agonists block gastric mucosal histamine release. This possibility was tested in the present study in gastric lumen‐perfused anaesthetized rats. Intravenous infusion of isoprenaline (12 μg kg−1h−1) inhibited maximal, pentagastrin‐stimulated acid output by 50–70% (P<0.01), but had no significant inhibitory effect on the maximal acid secretory response to histamine. In contrast to its inhibitory effect on gastrin‐stimulated acid output, isoproterenol had no effect on gastric histamine output during pentagastrin infusion. We conclude that isoprenaline selectively inhibits gastrin‐stimulated acid secretion in the rat, as in the dog, and by a mechanism other than inhibiting gastr

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYThe anti‐secretory effects and pharmacokinetics of omeprazole were investigated in ten patients with chronic liver disease. Plasma omeprazole concentrations were measured after a 10‐mg intravenous dose of omeprazole and on the first and seventh days of a 7‐day course of 10 mg oral omeprazole daily. Pentagastrin tests were performed on the day before oral omeprazole was commenced and 24 h after the last oral dose.The pre‐treatment basal and peak gastric acid outputs were low (mean rates of 1.44 mmol/h and 9.26 mmol/h, respectively) and following 7 days of oral 10 mg omeprazole daily, were lowered by 95% and 90% respectively. Following 10 mg intravenous omeprazole, plasma clearance was reduced, and plasma half‐life and area under the concentration curve were increased, in comparison with previous studies in healthy subjects. The plasma concentration curves for oral and intravenous doses were very similar. After both the first and seventh oral doses, maximum plasma concentration and area under the curve were higher than in healthy subjects. No accumulation of omeprazole was demonstrated.The pharmacokinetics of omeprazole in chronic liver disease could be influenced by low gastric acidity, poor liver function and/or portasystemic shunting. A dose of 10 mg omeprazole daily has been shown to be an effective anti‐secretory agent in chronic li

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYStudies were performed in rats and mice to investigate the mechanisms of the comparatively low irritancy in the gastrointestinal (GI) tract of oxaprozin, relative to that of other non‐steroidal anti‐inflammatory drugs. A single dose of oxaprozin (100 mg/kg), given orally to rats, reduced the concentration of prostaglandin E2, but did not produce any gastric lesions or mucosal irritation, either visibly or when the mucosa was examined by scanning or transmission electronmicroscopy. The low gastric irritancy was reflected by lower concentrations of the drug in the gastric mucosa, compared with those in the upper intestinal tract, following oral administration of 100 mg/kg of [14C]oxaprozin. This distribution of the drug in the gastrointestinal tract reflected the absence of gastric irritancy when the drug was given repeatedly for 5 days by the oral route to rats. It was only after intraperitoneal administration of high doses of the drug that intestinal ulcers and peritonitis became evident, and then no gastric irritancy was observed. As with other non‐steroidal anti‐inflammatory drugs, there was some, but appreciably less, enhancement of gastric irritancy observed when the drug was given to mice treated with the cholinomimetic, bethanechol chloride (to enhance secretion of acid and pepsin). It is suggested that the inhibition of mucosal prostaglandin production by oxaprozin may be considered a ‘priming’ reaction, and that subsequent enhancement of irritancy occurs by stimulation of acid and pepsin. Structure—activity relationships of oxaprozin analogues were studied. The addition of electron‐withdrawing substituents, which markedly enhance the gastric ulcerogenic effects of other non‐steroidal anti‐inflammatory drugs, only slightly enhanced the irritancy of oxaprozin, thus providing further evidence for the inherent low ulcerogenici

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYCurrent interest in the pharmacological manipulation of portal pressure centres on the long‐acting somatostatin analogue SMS 201‐995. Nine haemodynamically stable cirrhotic patients who had previously bled from oesophageal varices had wedged and free hepatic venous pressures and cardiac index measured, using a Swan—Ganz catheter, before and at 60, 120 and 180 min after beginning a 60‐min infusion of 25 μg/h of SMS 201‐995. Seven clinically similar patients had the same measurements performed without SMS 201‐995. In all patients cardiac index was found to decrease and systemic vascular resistance increase at 60 min, although heart rates and arterial blood pressures were unchanged. The group given SMS 201‐995 was significantly different from the control group in sustaining a fall in wedged hepatic venous pressure and trans‐hepatic venous gradient at 60 min. SMS 201‐995 causes a fall in portal pressure without a significant systemic h

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY

摘要:

SUMMARYA model of an ‘artificial stomach’ has been constructed in order to take into account some of the parameters lacking in conventionalin vitroantacid evaluation, namely the interaction between secretory flux and variation in emptying fluxes, the presence of proteins, and the use of human gastric juice instead of an aqueous solution of hydrochloric acid.The ‘artificial stomach’ has two elements, the ‘stomach’ and the pH recording system. The ‘stomach’ includes a ‘gastric’ reservoir receiving secretory flux and is emptied by variable fluxes.Aluminium phosphate gel has been studied in 100 ml of 0.1nHCl, without and with 1 or 5% meat extracts and also in 100 ml of human gastric juice. The antacid effect of 1 or 5% meat extracts has also been assessed.The antacid effect of aluminium phosphate was characterized by the pH rise of the ‘gastric’ contents, the buffering capacity, and the dilution of gastric contents. These factors were modulated by emptying fluxes. The same characteristics were found when antacid was studied in gastric juice. Proteins exerted a neutralizing effect and modified aluminium phosphate's antacid capacity. A mechanism for buffering capacity by cation

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1988.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1988

数据来源: WILEY