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ISSN: Print -2349-0977, Online - 2349-4387

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Year : 2015  |  Volume : 2  |  Issue : 3  |  Page : 133-135

Potential adverse effects of proton pump inhibitors mimicking other conditions

1 Department of Medicine, HIMS College, Jolly Grant, Dehradun, Uttarakhand, India
2 Department of Pediatrics, Jagrani Hospital, Lucknow, Uttar Pradesh, India

Date of Web Publication2-May-2016

Correspondence Address:
Saumya H Mittal
Department of Medicine, HIMS College, Jolly Grant, Dehradun, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2349-0977.181511

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Proton pump inhibitors, the most potent and safest acid inhibitory agents available, irreversibly bind and inhibit H+, K+-ATPase. They inhibit all phases of gastric acid secretion. Proton pump inhibitors are considered extremely safe and are regularly prescribed. They may, however, have side effects. They affect the clearance of other medicines. And the reactions to them may mimic other conditions and side effects of other medicines.

Keywords: Adverse reactions, allergies, proton pump inhibitors, reactions, side effects

How to cite this article:
Mittal SH, Govil T. Potential adverse effects of proton pump inhibitors mimicking other conditions. Astrocyte 2015;2:133-5

How to cite this URL:
Mittal SH, Govil T. Potential adverse effects of proton pump inhibitors mimicking other conditions. Astrocyte [serial online] 2015 [cited 2020 Sep 23];2:133-5. Available from: http://www.astrocyte.in/text.asp?2015/2/3/133/181511

  Introduction Top

Proton pump inhibitors, the most potent and safest acid inhibitory agents available, irreversibly bind and inhibit H +, K +-ATPase. They inhibit all phases of gastric acid secretion.[1]

Onset of action is rapid, with a maximum acid inhibitory effect between 2 and 6 h after administration and duration of inhibition lasting up to 72–96 h. With repeated daily dosing, progressive acid inhibitory effects are observed. These agents potently inhibit all phases of gastric acid secretion. With repeated daily dosing, progressive acid inhibitory effects are observed.[1]

The side-effect profile [Table 1] can mimic many other conditions and the side effects of the other concomitant medicines in use.
Table 1: Original Work, Side Effects of Proton Pump Inhibitors

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  Discussion Top

Proton pump inhibitors are considered extremely safe and are regularly prescribed. In almost all the patients, a proton pump inhibitor is usually prescribed.

Everything we consume may contain bacteria that colonize and infect the stomach and the intestines. Gastric acid precludes infection from such ingested bacteria. Proton pump inhibitors reduce the secretion of the acid, and the patients on these antacids may therefore have raised gastric bacterial concentration.  Clostridium difficile Scientific Name Search one of the commonest organisms found to have raised concentration. Possibility of community acquired and nosocomial pneumonias are also raised.[2]

Long-term proton pump inhibitor users show raised gastrin levels (up to 1.5–2 times the normal). If the use of proton pump inhibitors is stopped, the levels return to normal in 3–4 weeks. Hypergastrinemia is associated with hyperplasia of enterochromaffin-like cells. However, risk of colon cancer has not been found to be raised. No major teratogenic effects have been noted in 1st trimester. Caution is however advised.[3]

A decreased absorption of oral cyanocobalamin may be the cause of these low levels of Vitamin B 12 in people with prolonged use of proton pump inhibitors. Similarly, an impaired bioavailability of dietary Vitamin C has also been reported.[4] Malabsorption of food-bound minerals (iron, calcium, zinc) is noted but deficiencies have not been reported.[2] It has been considered that raised risk and incidence of hip fractures may be due to calcium malabsorption secondary to proton pump inhibitor-induced acid suppression.[5] On the other hand, it is known that iron absorption needs an acidic environment. In the absence of acid production secondary to proton pump inhibitors, the iron absorption may be reduced.[1] The increased bacterial growth cause increased deconjugation of bile acids in the jejunum, thereby leading to fat malabsorption.[6]

Gastrointestinal side effects include nausea, abdominal pain, constipation, flatulence, and diarrhea. Some of these side effects, chiefly diarrhea and abdominal pain, are reported in as high as 1–5% cases. A reversible association was observed with development of small benign gastric fundal polyps.[7] Hepatotoxicity is commonly seen in patients with hepatic cirrhosis. In other patients, raised liver enzymes have been noted.[8],[9],[10]

Inhibition of hepatic cytochrome P450 may lead to increase in the half-life and therefore the bioavailability of many drugs, e.g. benzodiazepines, warfarin, and phenytoin. This inhibition was higher for earlier drugs in this group (omeprazole, lansoprazole). The newer drugs (rabeprazole, pantoprazole, and esomeprazole) interact with cytochrome P450 system significantly less.[3]

Cardiac issues have been raised intermittently about possibly increased risk of conditions like myocardial infarction, cardiac failure, and sudden cardiac death. The Food and Drug Administration, however, has concluded that association of these cardiac problems with the long-term use of proton pump inhibitors is unlikely.[11],[12]

Subacute myopathy has been reported, probably by the whole group. The induction of autoimmune antibodies may be the possible mechanism. Myalgia, polymyositis, and rhabdomyolysis have been reported too. Fever and headache can occur along with myalgia. Two possible mechanisms are suspected for fever: (a) Hypersensitivity reaction and (b) effect on hypothalamic regulatory centers of body temperature.[13],[14],[15],[16],[17]

Many neuropsychiatric symptoms have been reported to occur in patients that resolved on stopping the drugs. These include ataxia, anxiety with panic attacks, episodic night terrors, confusion, and attention deficit.[18]

Hematological manifestations are rarely reported including one or all cell lineages-leucopoenia, agranulocytosis, thrombocytopenia, and pancytopenia.[19],[20],[21]

Dermatological manifestations are reported. These include toxic bullous skin lesions, exfoliative dermatitis, erythema multiforme, toxic erythema, dermatomyositis, lichenoid reaction, and vitiligo.[22],[23],[24],[25],[26],[27]

Renal manifestations have been reported in the form of interstitial nephritis. The patients presented with variable symptoms of weight loss, malaise, fever, nausea, polyuria, and polydypsia. Patients had raised urea and/or creatinine levels.[28],[29],[30]

Some other miscellaneous reports have been found reporting anaphylactic reactions, gynecomastia (reduced after stopping medicines). In a report, intractable, dry, non-productive cough was reported.[19],[29],[30],[31],[32],[33]

  Conclusion Top

Proton pump inhibitors are commonly used effective medicines for acid peptic disease and gastroesophageal reflux disease. But these medicines are probably overprescribed and should be prescribed only when required. These medicines can have side effects as well.

The side-effect profile can mimic many other conditions and the side effects of the other concomitant medicines in use. This may be more important in the Intensive Care Unit setup of seriously ill patients as well where the effects of the proton pump inhibitors may cause the critical care physician to consider other illnesses and complications. The use of these medicines should therefore be planned for population that needs the medicine.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Valle JD. Peptic ulcer diseases. In: Fauci AS, Kasper DL, Hauser SL, Jameson JL, Anthony S, Braunwald E, et al. Harrison's Principles of Internal Medicine. 18th ed. New York: The McGraw-Hill Companies, Inc.; 2012. p. 2448.  Back to cited text no. 1
McQuaid KR. Drugs used in the treatment of gastrointestinal diseases. Basic and Clinical Pharmacology. 10th ed., Ch. 63. New York: McGraw Hill; 2006.p. 1017.  Back to cited text no. 2
Hoogerwerf WA, Pasricha PJ. Agents used for control of gastric acidity and treatment of peptic ulcers and gastroesophageal reflux disease. Goodman and Gilman. The Pharmacological Basis of Therapeutics. 10th ed., Ch. 37. New York: McGraw Hill; 2001. p. 1009.  Back to cited text no. 3
Henry EB, Carswell A, Wirz A, Fyffe V, McColl KE. Proton pump inhibitors reduce the bioavailability of dietary Vitamin C. Aliment Pharmacol Ther 2005;22:539-45.  Back to cited text no. 4
Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296:2947-53.  Back to cited text no. 5
Shindo K, Machida M, Fukumura M, Koide K, Yamazaki R. Omeprazole induces altered bile acid metabolism. Gut 1998;42:266-71.  Back to cited text no. 6
Martin RM, Dunn NR, Freemantle S, Shakir S. The rates of common adverse events reported during treatment with proton pump inhibitors used in general practice in England: Cohort studies. Br J Clin Pharmacol 2000;50:366-72.  Back to cited text no. 7
Jochem V, Kirkpatrick R, Greenson J, Brogan M, Sturgis T, Cook-Glenn C. Fulminant hepatic failure related to omeprazole. Am J Gastroenterol 1992;87:523-5.  Back to cited text no. 8
Koury SI, Stone CK, La Charité DD. Omeprazole and the development of acute hepatitis. Eur J Emerg Med 1998;5:467-9.  Back to cited text no. 9
Andersson T, Olsson R, Regårdh CG, Skånberg I. Pharmacokinetics of [14C] omeprazole in patients with liver cirrhosis. Clin Pharmacokinet 1993;24:71-8.  Back to cited text no. 10
FDA. Early communication about an ongoing safety review: Omeprazole (Prisolec) esomeprazole (Nexium)-cited 9th August, 2007. Available from:   Back to cited text no. 11
FDA. FDA's safety review of prisolec and nexium find no evidence of increased rates of cardiac events- Cited 10th December, 2007. Available from: http://www.fda.gov/NewsEvents/Newsroom/Press Announcements/2007/ucm109037.htm  Back to cited text no. 12
Clark DW, Strandell J. Myopathy including polymyositis: A likely class adverse effect of proton pump inhibitors? Eur J Clin Pharmacol 2006;62:473-9.  Back to cited text no. 13
Sweetman SC, editor. Martindale. The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009.p. 1753-5.  Back to cited text no. 14
Grattagliano I, Portincasa P, Mastronardi M, Palmieri VO, Palasciano G. Esomeprazole-induced central fever with severe myalgia. Ann Pharmacother 2005;39:757-60.  Back to cited text no. 15
Su SS, Yu KH, Woung PS. Comment: Esomeprazole-induced central fever with severe myalgia. Ann Pharmacother 2005;39:1764.  Back to cited text no. 16
Grattagliano I, Portincasa P. Comment: Esomeprazole induced central fever with severe myalgia. Ann Pharmacother 2005;39:1765.  Back to cited text no. 17
Polimeni G, Cutroneo P, Gallo A, Gallo S, Spina E, Caputi AP. Rabeprazole and psychiatric symptoms. Ann Pharmacother 2007;41:1315-7.  Back to cited text no. 18
Holt TL, Coombes ID, Pillans PI, Scott IA. Neutropenia associated with omeprazole. Med J Aust 1999;170:141-2.  Back to cited text no. 19
Zlabek JA, Anderson CG. Lansoprazole-induced thrombocytopenia. Ann Pharmacother 2002;36:809-11.  Back to cited text no. 20
Watson TD, Stark JE, Vesta KS. Pantoprazole-induced thrombocytopenia. Ann Pharmacother 2006;40:758-61.  Back to cited text no. 21
Stenier C, Fiasse R, Bourlond J, Horsmans Y, Bourlond A. Bullous skin reaction induced by omeprazole. Br J Dermatol 1995;133:343-4.  Back to cited text no. 22
Epelde Gonzalo FD, Boada Montagut L, Tomás Vecina S. Exfoliative dermatitis related to omeprazole. Ann Pharmacother 1995;29:82-3.  Back to cited text no. 23
Cockayne SE, Glet RJ, Gawkrodger DJ, McDonagh AJ. Severe erythrodermic reactions to the proton pump inhibitors omeprazole and lansoprazole. Br J Dermatol 1999;141:173-5.  Back to cited text no. 24
Pan Y, Chong AH, Williams RA, Green J, Sinclair R. Omeprazole-induced dermatomyositis. Br J Dermatol 2006;154:557-8.  Back to cited text no. 25
Bong JL, Lucke TW, Douglas WS. Lichenoid drug eruption with proton pump inhibitors. BMJ 2000;320:283.  Back to cited text no. 26
Schallreuter KU, Rokos H. From the bench to the bedside: Proton pump inhibitors can worsen vitiligo. Br J Dermatol 2007;156:1371-3.  Back to cited text no. 27
Australian Adverse Drug Reactions Advisory Committee. Interstitial nephritis with the proton pump inhibitors. Aust Adverse Drug React Bull 2003;22:3.  Back to cited text no. 28
Geevasinga N, Kairaitis L, Rangan GK, Coleman PL. Acute interstitial nephritis secondary to esomeprazole. Med J Aust 2005;182:235-6.  Back to cited text no. 29
Ra A, Tobe SW. Acute interstitial nephritis due to pantoprazole. Ann Pharmacother 2004;38:41-5.  Back to cited text no. 30
Natsch S, Vinks MH, Voogt AK, Mees EB, Meyboom RH. Anaphylactic reactions to proton-pump inhibitors. Ann Pharmacother 2000;34:474-6.  Back to cited text no. 31
Carvajal A, Macias D, Gutiérrez A, Ortega S, Sáinz M, Martín Arias LH, et al. Gynaecomastia associated with proton pump inhibitors: A case series from the Spanish pharmacovigilance system. Drug Saf 2007;30:527-31.  Back to cited text no. 32
Howaizi M, Delafosse C. Omeprazole-induced intractable cough. Ann Pharmacother 2003;37:1607-9.  Back to cited text no. 33


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