Rebound acid hypersecretion after withdrawal of gastric acid suppressing drugs: new evidence of similitude

Background: Homeopathy is based on the principle of similitude (similia similibus curentur) using medicines that cause effects similar to the symptoms of disease in order to stimulate the reaction of the organism. Such vital, homeostatic or paradoxical reaction of the organism is closely related to rebound effect of drugs.

Method: Review of the literature concerning the rebound effects of drugs used to suppress gastric acidity, particularly proton pump inhibitors (PPIs).

Results: The mechanism of action of these effects is discussed. Rebound in terms of clinical symptoms and physiological effects occur in about 40% of people taking PPIs, their timing depends on the half-life of the drug and the adaptation period of the physiological mechanisms involved. The wide use of PPIs may be linked to the rising incidence of carcinoid tumours.

Conclusions: These findings support Hahnemann’s concept of secondary action of drugs. We are developing a homeopathic materia medica and repertory of modern drugs on the basis of reported rebound effects.

Highlights: ► The vital reaction of the homeopathic model is based on studies of the rebound effect of modern drugs. ► Rebound of clinical symptoms and physiological effects occur in about 40% of people taking PPIs. ► Rebound of clinical symptoms and physiological effects occur in about 40% of people taking PPIs. ► The wide use of PPIs may be linked to the rising incidence of carcinoid tumors.

Keywords

Homeopathy - Similitude - Secondary effect - Rebound effect - Paradoxical reaction - Withdrawal syndrome - Proton pump inhibitor

• References

• 1 Hahnemann S. Essay on a new principle for ascertaining the curative power of drugs, with a few glances at those hitherto employed. In: Dudgeon R.E. (ed). The lesser writings of Samuel Hahnemann . 1995. New Delhi: B. Jain Publishers.;
• 2 Hahnemann S. Organ on of homeopathic medicine. Third American edition. English version of the fifth German edition New York: William Radde; 1849.
• 3 Hahnemann S. Organon of medicine. (Translated by William Boericke) 6th edn. New Delhi: B Jain Publishers; 1991.
• 4 Dudgeon R.E. Lectures on the theory and practice of homoeopathy. New Delhi: B Jain Publishers; 1982. (Reprint edition). Lectures VII e XII.
• 5 Hughes R. A manual of pharmacodynamics. 6th edn. New Delhi: B Jain Publishers; 1980. (Second reprint edition). Lecture II.
• 6 Teixeira M.Z. Semelhante cura semelhante: o princípio de cura homeopático fundamentado pela racionalidade médica e científica [Similar cures similar: the homeopathic cure principle based by the medical and scientific rationality]. São Paulo: Editorial Petrus; 1998.
• 7 Teixeira M.Z. Similitude in modern pharmacology. Homeopathy 1999; 88 (03) 112-120.
• 8 Teixeira M.Z. Evidence of the principle of similitude in modern fatal iatrogenic events. Homeopathy 2006; 95 (04) 229-236.
• 9 Teixeira M.Z. NSAIDs, myocardial infarction, rebound effect and similitude. Homeopathy 2007; 96 (01) 67-68.
• 10 Teixeira M.Z. Bronchodilators, fatal asthma, rebound effect and similitude. Homeopathy 2007; 96 (02) 135-137.
• 11 Teixeira M.Z. Antidepressants, suicidality and rebound effect: evidence of similitude?. Homeopathy 2009; 98 (01) 114-121.
• 12 Teixeira M.Z. Statins withdrawal, vascular complications, rebound effect and similitude. Homeopathy 2010; 99 (04) 255-262.
• 13 Schubert M.L. Gastric secretion. Curr Opin Gastroenterol 2004; 20 (06) 519-525.
• 14 Schubert M.L. Gastric secretion. Curr Opin Gastroenterol 2007; 23 (06) 595-601.
• 15 Schubert M.L. Gastric secretion. Curr Opin Gastroenterol 2010; 26 (06) 598-603.
• 16 Gillen D., McColl K.E. Problems related to acid rebound and tachyphylaxis. Best Pract Res Clin Gastroenterol 2001; 15 (03) 487-495.
• 17 Gillen D., McColl K.E. Problems associated with the clinical use of proton pump inhibitors. Pharmacol Toxicol 2001; 89 (06) 281-286.
• 18 Waldum H.L., Qvigstad G., Fossmark R., Kleveland P.M., Sandvik A.K. Rebound acid hypersecretion from a physiological, pathophysiological and clinical viewpoint. Scand J Gastroenterol 2010; 45 (04) 389-394.
• 19 FDA. Ome-Mg briefing document 20-Oct-00. Rebound of gastric acid secretion. Available at 2000. http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3650b1a_11.pdf.
• 20 Texter Jr E.C. A critical look at the clinical use of antacids in acid-peptic disease and gastric acid rebound. Am J Gastroenterol 1989; 84 (02) 97-108.
• 21 Hade J.E., Spiro H.M. Calcium and acid rebound: a reappraisal. J Clin Gastroenterol 1992; 15 (01) 37-44.
• 22 Decktor D.L., Robinson M., Maton P.N., Lanza F.L., Gottlieb S. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995; 2 (08) 546-552.
• 23 Monés J., Carrio I., Sainz S. et al. Gastric emptying of two radiolabelled antacids with simultaneous monitoring of gastric pH. Eur J Nucl Med 1995; 22 (10) 1123-1128.
• 24 Hürlimann S., Michel K., Inauen W., Halter F. Effect of Rennie Liquid versus Maalox Liquid on intragastric ph in a double-blind, randomized, placebo-controlled, triple cross-over study in healthy volunteers. Am J Gastroenterol 1996; 91 (06) 1173-1180.
• 25 Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996; 21 (04) 351-357.
• 26 Aadland E., Berstad A. Parietal and chief cell sensitivity to pentagastrin stimulation before and after cimetidine treatment for duodenal ulcer. Scand J Gastroenterol 1979; 14 (01) 111-114.
• 27 Ghatei M.A., Jung R.T., Stevenson J.C. et al. Bombesin: action on gut hormones and calcium in man. J Clin Endocrinol Metab 1982; 54 (05) 980-985.
• 28 Jones D.B., Howden C.W., Burget D.W., Silletti C., Hunt R.H. Alteration of H₂ receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H₂ receptor antagonist. Gut 1988; 29 (07) 890-893.
• 29 el-Omar E., Banerjee S., Wirz A., Penman I., Ardill J.E., McColl K.E. Marked rebound acid hypersecretion after treatment with ranitidine. Am J Gastroenterol 1996; 91 (02) 355-359.
• 30 Bodemar G., Walan A. Maintenance treatment of recurrent peptic ulcer by cimetidine. Lancet 1978; 1 (8061): 403-407.
• 31 Forrest J.A., Fettes M.R., McLoughlin G.P., Heading R.C. Effect of long-term cimetidine on gastric acid secretion, serum gastrin, and gastric emptying. Gut 1979; 20 (05) 404-407.
• 32 Festen H.P., Lamers C.B., Tangerman A., van Tongeren J.H. Effect of treatment with cimetidine for one year on gastrin cell and parietal cell function and sensitivity to cimetidine in patients with duodenal or gastric ulcers. Postgrad Med J 1980; 56 (660) 698-701.
• 33 Mohammed R., Holden R.J., Hearns J.B., McKibben B.M., Buchanan K.D., Crean G.P. Effects of eight weeks’ continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin. Gut 1983; 24 (01) 61-66.
• 34 Frislid K., Aadland E., Berstad A. Augmented postprandial gastric acid secretion due to exposure to ranitidine in healthy subjects. Scand J Gastroenterol 1986; 21 (01) 119-122.
• 35 Fullarton G.M., McLauchlan G., Macdonald A., Crean G.P., McColl K.E. Rebound nocturnal hypersecretion after four weeks treatment with an H₂ receptor antagonist. Gut 1989; 30 (04) 449-454.
• 36 Fullarton G.M., Macdonald A.M., McColl K.E. Rebound hypersecretion after H₂-antagonist withdrawal – a comparative study with nizatidine, ranitidine and famotidine. Aliment Pharmacol Ther 1991; 5 (04) 391-398.
• 37 Nwokolo C.U., Smith J.T., Sawyerr A.M., Pounder R.E. Rebound intragastric hyperacidity after abrupt withdrawal of histamine H₂ receptor blockade. Gut 1991; 32 (12) 1455-1460.
• 38 Kummer A.F., Johnston D.A., Marks I.N., Young G.O., Tigler-Wybrandi N.A., Bridger S.A. Changes in nocturnal and peak acid outputs after duodenal ulcer healing with sucralfate or ranitidine. Gut 1992; 33 (02) 175-178.
• 39 Smith A.D., Gillen D., Cochran K.M., El-Omar E., McColl K.E. Dyspepsia on withdrawal of ranitidine in previously asymptomatic volunteers. Am J Gastroenterol 1999; 94 (05) 1209-1213.
• 40 Prichard P.J., Jones D.B., Yeomans N.D., Mihaly G.W., Smallwood R.A., Louis W.J. The effectiveness of ranitidine in reducing gastric acid-secretion decreases with continued therapy. Br J Clin Pharmacol 1986; 22 (06) 663-668.
• 41 Wilder-Smith C.H., Ernst T., Gennoni M., Zeyen B., Halter F., Merki H.S. Tolerance to oral H₂-receptor antagonists. Dig Dis Sci. 1990; 35 (08) 976-983.
• 42 Wilder-Smith C., Halter F., Ernst T. et al. Loss of acid suppression during dosing with H₂-receptor antagonists. Aliment Pharmacol Ther 1990; 4 (Suppl. 01) 15-27.
• 43 Nwokolo C.U., Smith J.T., Gavey C., Sawyerr A., Pounder R.E. Tolerance during 29 days of conventional dosing with cimetidine, nizatidine, famotidine or ranitidine. Aliment Pharmacol Ther 1990; 4 (Suppl. 01) 29-45.
• 44 Smith J.T., Gavey C., Nwokolo C.U., Pounder R.E. Tolerance during 8 days of high-dose H₂-blockade: placebo-controlled studies of 24-hour acidity and gastrin. Aliment Pharmacol Ther 1990; 4 (Suppl. 01) 47-63.
• 45 Rogers M.J., Holmfield J.H., Primrose J.N., Johnston D. The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or sufotidine 600 mg twice daily upon 24-hour intragastric acidity and 24-hour plasma gastrin. Aliment Pharmacol Ther 1990; 4 (Suppl. 01) 65-74.
• 46 Nwokolo C.U., Prewett E.J., Sawyerr A.M., Hudson M., Lim S., Pounder R.E. Tolerance during 5 months of dosing with ranitidine, 150 mg nightly: a placebo-controlled, double-blind study. Gastroenterology 1991; 101 (04) 948-953.
• 47 Merki H.S., Wilder-Smith C.H. Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing?. Gastroenterology 1994; 106 (01) 60-64.
• 48 Misiewicz J.J. Clinical relevance of tolerance to peptic ulcer healing and relapse. Aliment Pharmacol Ther 1990; 4 (Suppl. 01) 85-96.
• 49 McQuaid K.R. Much ado about gastrin. J Clin Gastroenterol 1991; 13 (03) 249-254.
• 50 Green Jr. F.W., Kaplan M.M., Curtis L.E., Levine P.H. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978; 74 (01) 38-43.
• 51 Low J., Dodds A.J., Biggs J.C. Fibrinolytic activity of gastroduodenal secretions – a possible role in upper gastrointestinal haemorrhage. Thromb Res. 1980; 17 (06) 819-830.
• 52 Bell N.J., Burget D., Howden C.W., Wilkinson J., Hunt R.H. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion 1992; 51 (Suppl. 01) 59-67.
• 53 Huang J.Q., Hunt R.H. Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician. Best Pract Res Clin Gastroenterol 2001; 15 (03) 355-370.
• 54 Lind T., Cederberg C., Forssell H., Olausson M., Olbe L. Relationship between reduction of gastric acid secretion and plasma gastrin concentration during omeprazole treatment. Scand J Gastroenterol 1988; 23 (10) 1259-1266.
• 55 Olbe L., Cederberg C., Lind T., Olausson M. Effect of omeprazole on gastric acid secretion and plasma gastrin in man. Scand J Gastroenterol Suppl 1989; 166: 27-32.
• 56 Driman D.K., Wright C., Tougas G., Riddell R.H. Omeprazole produces parietal cell hypertrophy and hyperplasia in humans. Dig Dis Sci. 1996; 41 (10) 2039-2047.
• 57 Prewett E.J., Hudson M., Nwokolo C.U., Sawyerr A.M., Pounder R.E. Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole. Gastroenterology 1991; 100 (04) 873-877.
• 58 Tielemans Y., Willems G., Sundler F., Håkanson R. Self-replication of enterochromaffin-like cells in the mouse stomach. Digestion 1990; 45 (03) 138-146.
• 59 Solcia E., Rindi G., Silini E., Villani L. Enterochromaffin-like (ECL) cells and their growths: relationships to gastrin, reduced acid secretion and gastritis. Baillieres Clin Gastroenterol. 1993; 7 (01) 149-165.
• 60 Håkanson R., Chen D., Tielemans Y. et al. ECL cells: biology and pathobiology. Digestion 1994; 55 (Suppl. 03) 38-45.
• 61 Waldum H.L., Arnestad J.S., Brenna E., Eide I., Syversen U., Sandvik A.K. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut 1996; 39 (05) 649-653.
• 62 Gillen D., Wirz A.A., Ardill J.E., McColl K.E. Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology 1999; 116 (02) 239-247.
• 63 Gillen D., Wirz A.A., McColl K.E. Helicobacter pylori eradication releases prolonged increased acid secretion following omeprazole treatment. Gastroenterology 2004; 126 (04) 980-988.
• 64 Fossmark R., Johnsen G., Johanessen E., Waldum H.L. Rebound acid hypersecretion after long-term inhibition of gastric acid secretion. Aliment Pharmacol Ther 2005; 21 (02) 149-154.
• 65 el-Nujumi A., Williams C., Ardill J.E., Oien K., McColl K.E. Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term omeprazole treatment. Gut 1998; 42 (02) 159-165.
• 66 Brenna E., Waldum H.L. Trophic effect of gastrin on the enterochromaffin like cells of the rat stomach: establishment of a dose response relationship. Gut 1992; 33 (10) 1303-1306.
• 67 Wallace J.L., Cucala M., Mugridge K., Parente L. Secretagogue-specific effects of interleukin-1 on gastric acid secretion. Am J Physiol 1991; 261 (4 Pt 1): G559-G564.
• 68 Taché Y., Saperas E. Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1. Ann N Y Acad Sci. 1992; 664: 353-368.
• 69 Kuipers E.J., Uyterlinde A.M., Peña A.S. et al. Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: implications for long-term safety. Am J Gastroenterol 1995; 90 (09) 1401-1406.
• 70 El-Omar E.M., Oien K., El-Nujumi A. et al. Helicobacter pylori infection and chronic gastric acid hyposecretion. Gastroenterology 1997; 113 (01) 15-24.
• 71 Eissele R., Brunner G., Simon B., Solcia E., Arnold R. Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia. Gastroenterology 1997; 112 (03) 707-717.
• 72 McColl K.E., el-Omar E., Gillen D. Helicobacter pylori gastritis and gastric physiology. Gastroenterol Clin North Am. 2000; 29 (03) 687-703.
• 73 Marshall B.J. Campylobacter pylori: its link to gastritis and peptic ulcer disease. Rev Infect Dis 1990; 12 (Suppl. 01) S87-S93.
• 74 Tytgat G.N., Rauws E.A. Campylobacter pylori and its role in peptic ulcer disease. Gastroenterol Clin North Am 1990; 19 (01) 183-196.
• 75 Klinkenberg-Knol E.C., Nelis F., Dent J. et al. Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa. Gastroenterology 2000; 118 (04) 661-669.
• 76 McCarthy D.M. Adverse effects of proton pump inhibitor drugs: clues and conclusions. Curr Opin Gastroenterol 2010; 26 (06) 624-631.
• 77 Yang Y.X., Hennessy S., Propert K., Hwang W.T., Sedarat A., Lewis J.D. Chronic proton pump inhibitor therapy and the risk of colorectal cancer. Gastroenterology 2007; 133 (03) 748-754.
• 78 Robertson D.J., Larsson H., Friis S., Pedersen L., Baron J.A., Sørensen H.T. Proton pump inhibitor use and risk of colorectal cancer: a population-based, case-control study. Gastroenterology 2007; 133 (03) 755-760.
• 79 Hatlebakk J.G., Hyggen A., Madsen P.H. et al. Heartburn treatment in primary care: randomised, double blind study for 8 weeks. BMJ 1999; 319 (7209): 550-553.
• 80 Loffeld R.J., van der Putten A.B. Rising incidence of reflux oesophagitis in patients undergoing upper gastrointestinal endoscopy. Digestion 2003; 68 (02/03) 141-144.
• 81 Wang J.S., Varro A., Lightdale C.J. et al. Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett’s esophagus. Am J Gastroenterol 2010; 105 (05) 1039-1045.
• 82 Wang T.C., Dangler C.A., Chen D. et al. Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology 2000; 118 (01) 36-47.
• 83 Fossmark R., Zhao C.M., Martinsen T.C., Kawase S., Chen D., Waldum H.L. Dedifferentiation of enterochromaffin-like cells in gastric cancer of hypergastrinemic cotton rats. APMIS 2005; 113 (06) 436-449.
• 84 Burkitt M.D., Varro A., Pritchard D.M. Importance of gastrin in the pathogenesis and treatment of gastric tumors. World J Gastroenterol 2009; 15 (01) 1-16.
• 85 Poulsen A.H., Christensen S., McLaughlin J.K. et al. Proton pump inhibitors and risk of gastric cancer: a population-based cohort study. Br J Cancer 2009; 100 (09) 1503-1507.
• 86 Ekman L., Hansson E., Havu N., Carlsson E., Lundberg C. Toxicological studies on omeprazole. Scand J Gastroenterol Suppl 1985; 108: 53-69.
• 87 Ryberg B., Axelson J., Håkanson R., Sundler F., Mattsson H. Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology 1990; 98 (01) 33-38.
• 88 Modlin I.M., Lye K.D., Kidd M.A. 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?. Am J Gastroenterol 2004; 99 (01) 23-32.
• 89 Hodgson N., Koniaris L.G., Livingstone A.S., Franceschi D. Gastric carcinoids: a temporal increase with proton pump introduction. Surg Endosc 2005; 19 (12) 1610-1612.
• 90 Waldum H.L., Gustafsson B., Fossmark R., Qvigstad G. Antiulcer drugs and gastric cancer. Dig Dis Sci. 2005; 50 (Suppl. 01) S39-S44.
• 91 Hunfeld N.G., Geus W.P., Kuipers E.J. Systematic review: rebound acid hypersecretion after therapy with proton pump inhibitors. Aliment Pharmacol Ther 2007; 25 (01) 39-46.
• 92 Fossmark R., Waldum H. Rebound acid hypersecretion. Aliment Pharmacol Ther 2007; 25 (08) 999-1000.
• 93 Reimer C., Søndergaard B., Hilsted L., Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009; 137 (01) 80-87.
• 94 Niklasson A., Lindström L., Simrén M., Lindberg G., Björnsson E. Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Am J Gastroenterol 2010; 105 (07) 1531-1537.
• 95 Björnsson E., Abrahamsson H., Simrén M. et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther 2006; 24 (06) 945-954.
• 96 Reimer C., Bytzer P. Discontinuation of long-term proton pump inhibitor therapy in primary care patients: a randomized placebo-controlled trial in patients with symptom relapse. Eur J Gastroenterol Hepatol 2010; 22 (10) 1182-1188.
• 97 Bashford J.N., Norwood J., Chapman S.R. Why are patients prescribed proton pump inhibitors? Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database. BMJ 1998; 317 (7156): 452-456.
• 98 Nardino R.J., Vender R.J., Herbert P.N. Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol 2000; 95 (11) 3118-3122.
• 99 Pillans P.I., Kubler P.A., Radford J.M., Overland V. Concordance between use of proton pump inhibitors and prescribing guidelines. Med J Aust 2000; 172 (01) 16-18.
• 100 Raghunath A.S., O’Morain C., McLoughlin R.C. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther 2005; 22 (Suppl. 01) 55-63.
• 101 Forgacs I., Loganayagam A. Overprescribing proton pump inhibitors. BMJ 2008; 336 (7634): 2-3.
• 102 Danish Medicines Agency. Medicinal product statistics in Denmark 2007. Copenhagen: Danish Medicines Agency; 2008.
• 103 Hollingworth S., Duncan E.L., Martin J.H. Marked increase in proton pump inhibitors use in Australia. Pharmacoepidemiol Drug Saf 2010; 19 (10) 1019-1024.
• 104 Lassen A., Hallas J., Schaffalitzky De Muckadell O.B. Use of anti-secretory medication: a population-based cohort study. Aliment Pharmacol Ther 2004; 20 (05) 577-583.
• 105 Reimer C., Bytzer P. Clinical trial: long-term use of proton pump inhibitors in primary care patients – a cross sectional analysis of 901 patients. Aliment Pharmacol Ther 2009; 30 (07) 725-732.
• 106 National Institute for Clinical Excellence (NICE). 2000/022 NICE issues guidance on proton pump inhibitors for dyspepsia. London, UK . 2000.
• 107 Talley N.J., Vakil N. Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol 2005; 100 (10) 2324-2337.
• 108 Barton P.M., Moayyedi P., Talley N.J., Vakil N.B., Delaney B.C. A second-order simulation model of the cost-effectiveness of managing dyspepsia in the United States. Med Decis Making 2008; 28 (01) 44-55.
• 109 Naunton M., Peterson G.M., Bleasel M.D. Overuse of proton pump inhibitors. J Clin Pharm Ther 2000; 25 (05) 333-340.
• 110 Limmer S., Ittel T.H., Wietholtz H. [Secondary and primary prophylaxis of gastropathy associated with nonsteroidal antiinflammatory drugs or low-dose-aspirin: a review based on four clinical scenarios]. Z Gastroenterol 2003; 41 (08) 719-728.
• 111 Marie I., Moutot A., Tharrasse A. et al. [Validity of proton pump inhibitors’ prescriptions in a department of internal medicine]. Rev Med Interne 2007; 28 (02) 86-93.
• 112 Ntaios G., Chatzinikolaou A., Kaiafa G., Savopoulos C., Hatzitolios A., Karamitsos D. Evaluation of use of proton pump inhibitors in Greece. Eur J Intern Med 2009; 20 (02) 171-173.
• 113 Adamopoulos A.B., Sakizlis G.N., Nasothimiou E.G. et al. Do proton pump inhibitors attenuate the effect of aspirin on platelet aggregation? A randomized crossover study. J Cardiovasc Pharmacol 2009; 54 (02) 163-168.
• 114 Van Soest E.M., Siersema P.D., Dieleman J.P., Sturkenboom M.C., Kuipers E.J. Persistence and adherence to proton pump inhibitors in daily clinical practice. Aliment Pharmacol Ther 2006; 24 (02) 377-385.
• 115 McColl K.E., Gillen D. Evidence that proton-pump inhibitor therapy induces the symptoms it is used to treat. Gastroenterology 2009; 137 (01) 20-22.
• 116 American Hospital Formulary Service Drug Information. Bethesda: American Society of Hospital Pharmacists; 1990. pp. 1667–1668.
• 117 Teixeira M.Z. Homeopathic use of modern medicines: utilisation of the curative rebound effect. Med Hypotheses 2003; 60 (02) 276-283.
• 118 Teixeira M.Z. ‘Paradoxical strategy for treating chronic diseases’: a therapeutic model used in homeopathy for more than two centuries. Homeopathy 2005; 94 (04) 265-266.
• 119 Teixeira M.Z. New homeopathic medicines: use of modern drugs according to the principle of similitude. Homeopathy 2011 DOI: doi:10.1016/j.homp.2011.01.002
• 120 Teixeira M.Z. São Paulo: Marcus Zulian Teixeira; New homeopathic medicines: use of modern drugs according to the principle of similitude. Vol. 1–3. 2010. Available at www.newhomeopathicmedicines.com.