Classically, adverse drug reactions had been considered as type A reactions which are related to the main pharmacological action of the drug and therefore are predictable. Such reactions are predictable, reversible, and usually can be managed by lowering the dose of the offending drug. However, other adverse effects of drugs can occur which are unrelated to the main pharmacological action of the drug – type B reactions. Such adverse effects are termed idiosyncratic and are often initiated by metabolites of the parent drug or by other indirect mechanisms. The detailed understanding of adverse drug events has become a major focus of the regulatory agencies throughout the world. The pharmacotherapy of gastrointestinal and liver disorders is becoming increasingly complex. In recent years, with the advent of novel therapeutic agents to treat a host of disorders, including viral hepatitis, gastrointestinal motility disorders, inflammatory bowel disease and others, the potential for serious clinically relevant drug reactions has increased. In the pharmacotherapy of gastrointestinal and liver diseases, a significant number of adverse events that occur can be explained by drug interactions. Some pharmacokinetic drug interactions are based on the competitive inhibition of the rate of drug metabolism of one of the drugs, leading to an increased concentration of the drug which was not intended. In other examples, the interaction can be mechanistic in which one or more drugs when co-administered potentiate each other’s actions without any change in drug levels, termed pharmacodynamic interactions.

1.
Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, Laffel G, Sweitzer BJ, Shea BF, Hallisey R, et al: ADE Prevention Study Group: Incidence of adverse drug events and potential adverse drug events. Implications for prevention. JAMA 1995;274:29–34.
2.
Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279:1200–1205.
3.
Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P: Maintenance infliximab for Crohn’s disease: the ACCENT I Randomised Trial. Lancet 2002;359:1541–1549.
4.
Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H Jr, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004;351:438–450.
5.
Volpe M, Chin D, Paneni F: The challenge of polypharmacy in cardiovascular medicine. Fundam Clin Pharmacol 2010;24:9–17.
6.
Jaruratanasirikul S, Sriwiriyajan S: Effect of omeprazole on the pharmacokinetics of itraconazole. Eur J Clin Pharmacol 1998;54:159–161.
7.
Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC: The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol 1992;42:121–125.
8.
Herlitz H, Edgar B, Hedner T, Lidman K, Karlberg I: Grapefruit juice: a possible source of variability in blood concentration of cyclosporin A. Nephrol Dial Transplant 1993;8:375.
9.
Prager D, Rosman M, Bertino JR: Letter: azathioprine and allopurinol. Ann Intern Med 1974;80:427.
10.
Jick H, Porter J: Drug-induced gastrointestinal bleeding. Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center. Lancet 1978;2:87–89.
11.
Zornberg GL, Bodkin JA, Cohen BM: Severe adverse interaction between pethidine and selegiline. Lancet 1991;337:246.
12.
Wang L, Pelleymounter L, Weinshilboum R, Johnson JA, Hebert JM, Altman RB, Klein TE: Very important pharmacogene summary: thiopurine S-methyltransferase. Pharmacogenet Genomics 2010;20:401–405.
13.
Egan LJ, Myhre GM, Mays DC, Dierkhising RA, Kammer PP, Murray JA: CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms Aliment Pharmacol Ther 2003;17:1521–1528.
14.
Oyetayo OO, Talbert RL: Proton pump inhibitors and clopidogrel: is it a significant drug interaction? Expert Opin Drug Saf 2010;9:593–602.
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