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Barrett's oesophagus, Omeprazole dosage and bile reflux: links
This is a listing of URLs relevant to Barrett's oesophagus, Omeprazole dosage and bile reflux. The search reveals some interesting pages! The page is a bit dis-ordered. Sorry. Maybe sometime I'll tidy it a bit more.
I did a search of Google search which prove that an inflamed oesophagus is more sensitive than a normal oesophagus, so Barrett's oesophagus sufferers are more prone to GERD pain than normal, at least in the early stages while their is still inflammation. There are other pages in the search that show the same results. I find no information on sensitivity after the inflammation has abated
A Google search for - omeprazole causes bile reflux -
http://www.google.co.uk/search?hl=en&source=hp&ie=ISO-8859-1&q=omeprazole+causes+bile+reflux&btnG=Google+Search
is of interest.
- Omeprazole induces altered bile acid metabolism by K Shindo, M Machida, M Fukumura, K Koide, R Yamazaki
WG
Without a subscription, only an abstract is available. The study was aimed at jejunal flora and found effects which it ascr ibed to the altered flora affecting the bile mechanism. It was not looking for bile production changes so its conclusions as to mechanism involved are suspect. The bile mechanism could just have easily be caused by the medication rather than the flora changes!
- Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus
Study was based on a 20mG twice daily study. However my findings are that a 20mG dose is in fact a massive overdose!
- Bile Reflux and a defective lower esophageal sphincter
Misses the point that for bile to be refluxed it must be present in the stomach in the absence of food - so something is in terfering with the bile release mechanism!
- GERD patients inadequately controlled with PPIs: New Dr ugs
An interview with professor Jean-Paul Galmiche, MD, PhD, Gastroenterology Unit, College of Medicine, University of Nantes, Nantes, France.
Again - misses the point that nobody seems to have realised - problems with any drug are likely to be minimal if the minimu m necessary dose is administered. Nobody has researched minimum dosage of PPIs, but see the paper on the effect of low-dose omeprazole!
- PPIs increase bile reflux
A quote from this paper:
"Finally, recent research has demonstrated that the use of proton-pump inhibitors (PPIs) in treating acid reflux actually incre ased the occurrences of bile reflux. The reason for this result isn't fully understood, but it does help explain why some people on PPIs don't appear to show a reduction of their acid reflux episodes."
well spotted - but they have not thought to try minimal dosing!
- Heartburn Treatment May Increase Bile Reflux an article from Science Daily.
- Omeprazole Side Effects on the Liver. Page says that PPIs disturb bile production!
- United States National Library of Medicine page entitles "Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats." Rats may not be humans, but many humans on PPI feel like lab rats!
- Effect of omeprazole 20 mg twice daily on duodenogastric and gastro- oesophageal bile reflux in Barrett‘s oesophagusby REK Marshall, A Anggiansah, DK Manifold. They found that Omeprazole reduces bile: again, only an abstract, but Omeprezole can alter bile flow by mechanisms unknown
- Determination and pharmacokinetic profile of omeprazole in rat blood, brain and bile by microdialysis and high-performance liquid chromatography by F. C. Chenga, Y. F. Hob, L. C. Hungc, C. F. Chenc and T. H. Tsai
They found that omeprazole can penetrate the blood—brain barrier. Could be cause of some of its side effects
So there seems to be few references to Omeprazole promoting bile reflux - but at more than one paper realises that it probably does. My own experience is that it certainly does!
Maybe a Google search for Barrett's bile will reveal more?
Barrett's oesophagus is said to be a cancer risk, sometimes leading to oesophageal cancer. However cats and dogs get Barrett's and it has been experimentally induced in rats - with great ease. So it is an evolved response to acid reflux and is probably possible in all mammals. This hardly satisfies me that Barrett's is any real cancer risk!
The actual figure of incidence of cancer developing in Barett's oesophagus is open to doubt: figures have been quoted as high as 5% of Barett's sufferers develop cancer per year, but other studies have shown the risk to be far smaller than that. 0.5% to 0.9% or even as low as 0.2% per year! In other words, the experts simply do not know!
Cancer risk is also linked varioously to certain foods: some foods reduce the risk of cancer, others seem to increase it. See my own thoughts on Cancer.
- Models of enzyme inhibition
This is part of a university course on Biochemistry by Dr. Jakubowski. It explains why such inhibitors are almost a switch: either the action is inhibited, it it is not. Increased dosage of PPIs won't result in lower acidity. A higher dose will last longer and will likely cause more side-effects.
- Larygopharyngeal Reflux
Something I used to suffer so I am well aware of how much nastier bile reflux is than mere acid: at one time (before I was diagnosed, shouting would cause me to cough violently!
One popular solution to the problems of reflux is a 'fundo' - properly a Nissen Fundoplication operation. When this is successful it appears to be excellent. However as in any operation there can be complications:
- Study on 10mG/day omeprazole PRICHARD, P. J., YEOMANS, N. D., SHULKES, A., JONES, D. B., BUCKLE, P. J., SMALLWOOD, R. A. and LOUIS, W. J. (1986)
The effect of omeprazole on 24 h intragastric pH and fasting plasma gastrin during low dosage (10 mg) in the morning or the evening. Journal of Gastroenterology and Hepatology, 1: 289—295.
Departments of Gastroenterology, Austin Hospital, Melbourne, Australia
One of the lowest dosage studies I have found - yet a 10mG single dose is still an overdose.
Google for PRICHARD, P. J., YEOMANS, N. D., SHULKES, A., JONES, D. B., BUCKLE,
reveals many more pages by these researchers.
- A paper on the effect of low-dose omeprazole on gastric acid secretion in duodenal ulcer patients does deal with a very low dosage of 5mG/day. However it does not deal with the effect of several 5mG doses per day!
- Omeprazole and Other Proton Pump Inhibitors: Pharmacology, Efficacy, and Safety, with Special Reference to Use in Children has much background information, including information on differing responses to the drug in different patients.
- Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy tries to suggest ways of overcoming the problems of PPIs not by little and often dosing but by a dual-action delayed release single dose. It is very clear that the doctors do not consider patients capable of taking medicines three or even four times daily so have not considered that. They may be correct. See my own pages for more on 'Microdosing':
A google search for oesophageal cough is revealing
Pepsin is little referred to but is a major digestive enzyme. It is said to require an acid environmemt to function, but only mildly acid.
PPIs have a short half life in the blood plasma as they are quickly eliminated by the liver. Their effectiveness is very much down to the area under the curve plotting blood plasma levels variation with time. However liver elimination is not the only time constant involved - see Half-life: what does it mean?
There are many papers that give more statistics on blood plasma half-life:
Incidentally a search for PPI plasma "half life" reveals many attempts to search for PPIS with longer plasma half lives, but nobody seems to realise that the way to deal with a short half-life is to increase the frequency of doses! That also means the doses can be reduced and the total intake also reduced.
- A Norwegian study explain the mechanism The authors of this are Helge L. Waldum, Gunnar Qvigstad, Reidar Fossmark, Per M. Kleveland & Arne K. Sandvik whose names may be rewarding in your searches
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Last modified: Wed, 21 Dec 2011 22:04:02 GMT