The Adverse Drug Reaction in the Gastrointestinal Tract: An Overview

Life International Journal of Pharmacology ISSN 1811-7775 Life science alert ansinet Asian Network for Scientific Information

International Journal of Pharmacology 1 (1): 1-8, 2005 ISSN 1811-7775 2005 Asian Network for Scientific Information The Adverse Drug Reaction in the Gastrointestinal Tract: An Overview 'Molouk Hadjibabaie, 'Noushin Rastkari, 'Ali Rezaie and Mohammad Abdollahi 'Department of Clinical Pharmacy, 'Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Abstract: Every drug can produce untoward consequences, even when used according to standard or recommended methods of administration. Adverse drug reactions can involve every organ and system of the body and are frequently mistaken for signs of underlying disease. Similarly, gastrointestinal tract can be affected by many drugs or chemicals. Regarding different parts of this system, these reactions can be categorized to colon, esophagus, esophagus-stomach, large intestine, liver, oral cavity, pancreas, peritoneum, rectum, small intestine, stomach, and stomach-duodenum. In this study, the drugs that may cause adverse effects in the gastrointestinal tract arc reviewed. The knowledge about drug-induced gastrointestinal adverse effects helps health professionals to conduct a better practice in diagnosis of gastrointestinal tract diseases, drug administration, improvement of patients' compliance during drug therapy and may influence a morc rational use of drugs. Key words: Gastrointestinal tract, adverse drug reactions INTRODUCTION Adverse drug reactions in general: Adverse drug reactions (ADRs) remain a major clinical problem. There are differences between populations in the occurrence of ADRs and other drug-related problems. This may be due to differences in drug production, in distribution or use, in genetics, diet and traditions of people, in the composition, excipients or pharmaceutical products and finally traditional local remedies. A meta-analysis suggested that in the USA in 1994, ADRs were responsible for more than 100000 deaths), making them the fifth commonest cause of deaths. In addition there is evidence that ADRs account for 5% of all hospital admissions and increase the duration of hospitalization by two days at compelling an additional $2500 cost per patients. Different types of ADRs particularly with regard to frequency, manifestations or mechanisms may need different methods of detection". From a clinical perspective, ADRs can be divided into two broad types, type A and type B Type A reactions are predictable from the known pharmacology of the drug and often represent an exaggeration of the known primary and/or secondary pharmacology of the drugs. By contrast, type BADRs are bizarre reactions that are unpredictable from the known pharmacology of the drug and show no apparent dose-response relationship. Typically, type A ADRs have been labeled as host independent. Clearly, this is an over simplification because there is now increasing evidence for a role for genetics in the determination of drug disposition and drug response and thus, susceptibility to ADRs. Type A effects can usually be produced and studied experimentally, and are often already identified before marketing. With type A effects of low specificity, quantitative and controlled assessment may be needed in order to confirm the relationship and measure the frequency. Type B effects are either immunological or non-immunological and occur in patients with often unidentified, predisposing conditions. Besides type A and B some adverse drug effects may be categorized as type C. Type C effects refer to situations where the use of a drug, often for unknown reasons, increases the frequency of a spontaneous disease. Type C effects may be both serious and common (and include malignant tumors) and may have pronounced effects on public health. Type C effects may be coincidental and often concern long term effects; there is often no suggestive time relationship and the connection may be very difficult to provel6.71 Corresponding Author: Professor Mohammad Abdollahi, Department of Toxicology and Pharmacology, Faculty of Pharmacy and Laboratory of Toxicology, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Tel/Fax: +98 21 6959104 E-mail: mohammad.abdollahi@utoronto.ca 1

Intl. J. Pharmacol., 1 (1): 1-8, 2005 Etiology, pathogenesis and clinical features of gastrointestinal adverse drug reactions: Virtually any drug has the potential to cause an untoward reaction, but some have a greater ability to do so than others. The gastrointestinal tract is a common site of adverse drug reactions resulting from the fact that most drugs including prescription and over the counter drugs are administered by this route In USA, the gastrointestinal tract has been associated with 20 to 40% of the drug-induced adverse effects. Pathogenesis of drug reactions may be related to either immunologic or non-immunologic mechanisms. Most adverse reactions to drugs are mediated by the immune system and are drug allergies. Three mechanisms have been proposed for drug allergies. Firstly, IgE-mediated reactions occur when the drug reacts with IgE antibodies bound to mast cells. Secondly, drug allergies can involve a cytotoxic reaction in which an antibody binds to a drug that is already attached to a cell surface. The third mechanism in a drug allergy involves circulation of the antigen for extended periods allowing sensitization of the patient's immune system and production of a new antibody. Non-immunologic drug reactions are not antibody dependent and may directly affect mast cells causing the release of chemical mediators. Also some non-immunologic drug-induced reactions result from a drug overdose or toxicity. The adverse reactions that cause pathological changes (e.g. mucosal ulceration and stricture) should be differentiated from those that do not. Many gastrointestinal side effects like nausea, vomiting, diarrhea, constipation or abdominal cramps are transient and resolve shortly after the drug is discontinued. Patients should be alerted to the early signs of gastrointestinal disorders, in order to prevent long-term complications. Manifestations of drug reactions are dependent on the type of drug, drug dose, and individual patient differences. These reactions can be seen either rapidly or several days after drug use. They are usually transient and disappear after discontinuation of drug but there are some drugs that induce serious adverse effects Diagnosis of adverse drug reactions: The diagnosis of drug reactions requires a high index of suspicion and careful history taking. Recent use of a drug is important. Withdrawal of the suspected drug should result in improvement and reinstitution of the drug should exacerbate the patient's condition. The clinical expression of lesions in drug reactions is generally allergic in nature that can help with the diagnosis" Oral cavity: Drug induced oral cavity disorders include taste disturbance, xerostomia (dry mouth), oral lesions and gingival enlargement (Table 1). The mechanism Table 1: Drugs with potential to cause adverse reaction in oral cavity!""] Drug name Reported adverse effect Antiarrhythmics Anticholinergics Antihistamines Antihyperlipidemics Antiparkinson drugs Antispasmodic drugs Antiulcer agents Calcium channel blockers Carbamazepine Coronary vasodilators Cyclosporine Diuretics NSAIDs NSAIDS NSAIDs Penicillins Phenytoin Psychotropic drugs Sulfonamides Trimethoprim-sulfamethoxazole Xerostomia Xerostomia Xerostomia Xerostomia Xerostomia Xerostomia erostoma Xerostomia Gingival enlargement Oral lesion Xerostomia Gingival enlargement Xerostomia Oral lesion Xerostomia Oral lesion Gingival enlargement Xerostomia Oral lesion Oral lesion Reported adverse effect Table 2: Drugs with potential to cause adverse reaction in the esophagus||9-331 Drug name Alendronate Anticholinergics Anticholinergics Broad-spectrum antibiotics Busulphan Calcium channel blockers Chlormethiazole Clindamycin Clorazepate Doxycycline Emepromium bromide Ethanol Iron Nitrates NSAIDs Opiates Phenoxymethylpenicillin Potassium chloride Potassium chloride Progesterone Propranolol Quinidine Rabeprazole Salicylates Tetracycline Tetracycline Theophylline Thioguanine Tricyclic antidepressants Vitamin C Table 3: Drugs with potential esophagus-stomach Drug name Bromocriptine Cisplatin Digitalis glycosides Erythromycin Estrogens Iron Levodopa Mesalamine (delayed-release) Opioids Potassium Rabeprazole • Esophagitis Gastroesophageal reflux disease (GERD) Reflux of acid Fungal infection Esophageal varices GERD Dysphagia Esophageal ulceration Esophageal ulceration Esophageal ulceration Esophageal ulceration GERD Esophageal ulcer GERD Esophageal ulceration Reflux of acid Esophageal ulceration Esophageal ulcer Esophageal ulceration GERD Esophageal spasm Esophageal ulcer Dysphagia, esophagitis Esophageal ulcers Esophageal ulcer Esophageal ulceration GERD Esophageal varices GERD Esophageal ulcer to cause adverse reaction in the Serotonin selective reuptake inhibitors (SSRI) Sucralfate Reported adverse effect Nausea, vomiting Vomiting Nausea, vomiting Nausea Nausea, vomiting Nauces Nausea Nausea, vomiting Nausea, vomiting Nausea, vomiting Nausea Nausea, vomiting Nausea, vomiting Nausca 2

+ Intl. J. Pharmacol., 1 (1): 1-8, 2005 Table 4: Drugs with potential to cause adverse reaction in the peritoneum³ Drug name Methylperdnisolone Metoprolol Oxprenolol Practolol Timolol Reported adverse effect Susceptibility to infective peritonitis Peritonitis Peritonitis Peritonitis Peritonitis Table 5: Drugs with potential to cause adverse reaction in the liver Drug name Acetaminophen Allopurinol Amiodarone Androgenic steroids Azithromycin Baisalazide B-carotene Bromfenac Carbamazepinc Celecoxib Chlorpromazine Reported adverse effect Acute liver failure Mixed cholestatic injury Acute hepatitis Canalicular cholestasis, dilation of sinusoids Intrahepatic cholestasis Abnormality in hepatic function, SGOT and SGPT increase Cholestasis Acute liver failure Hepatotoxicity, jaundice) Acute cholestasis neonatal (cholestasis, Cholestasis, scattered focal areas of necrosis Prolonged cholestasis Progressive cholestasis Ciprofloxacin Clarithromycin Co-amoxyclav Cholestasis, injury Erythromycin Gatifloxacin Gliclazide Halothane Isoniazide Itraconazole Labetolo! Lamotrigine Mercaptopurine Cholestasis, hepatocellular or mixed Hepatic injury mixed cholestatic-cytotoxic Exacerbation of underlying liver disease Centraxonial necrosis, steatosis, massive necrosis Hepatotoxicity Hepatic injury Acute H-cell injury Hepatic injury Cholestasis with fatty hepatic necrosis Mesalamine (delayed-release) Hepatotoxicity (rare) Methimazolc Methotrexate Methronidazole Methyldopa Minocyclidine Mirtazapine Nefazodone Nicotinic acid Nitrofurantoin NSAIDs Octreotide Oxacillin Paroxetine Phenytoin Pioglitazone Propafenone Rifampin Salicylates Statins Sulphonamides Terbinafine Triazolam Troglitazone Trovafloxacin Valproic acid Cholestasis Hepatotoxicity Severe H-cell necrosis and cholestasis Cytotoxic injury, subacute necrosis, rare cholestasis, chronic active hepatitis Chronic hepatitis Hepatotoxicity Hepatotoxicity Hepatic necrosis, cholestasis Mixed cholestatic-cytotoxic injury, chronic active hepatitis Cholestasis. cytotoxic or mixed Hepatitis (rare), fatty liver (rare) Anicteric hepatitis Reversible hepatic injury Submassive necrosis, lobular hepatitis, cholestatic hepatitis, granulomatous hepatitis Jaundice Acute cholestasis Ilepatotoxicity Focal necrosis, steatosis Hepatic injury Mixed hepatocellular injury, subacute hepatic necrosis with cirrhosis, chronic active hepatitis, granulomatous hepatitis Cholestasis. necrosis Fulminant hepatic failure Hepatocelular, cholestasis Hepatotoxicity Microvesicular steatosis, focal or massive of action of drug-induced taste disorder is not known but in the elderly includes a distorted (dysgeusia) or a reduced (hypogeusia) sense of taste(12) After discontinuation of the drug, changes in the sense of taste are usually reversible, even though it may take several months to get resolved. Drug-induced xerostomia is reversible and usually do not cause permanent damage to the salivary glands but can affect patient's nutritional status. For example drug-induced oral lesions in erythema multiforme makes eating difficult for the patient. Gingival enlargement is an overgrowth of the periodontal tissue which in severe cases, the gingiva can cover almost the entire tooth. It happens when the drug is not discontinued Esophagus: Drug-induced esophageal changes (Table 2 and 3) is common and result from changes in motility, changes in mucosal integrity, infection secondary to drugs and obstruction due to formation of a mass of congealed material. The severity of drug-induced esophageal damage can range from mild, asymptomatic inflammation to severe ulceration and stricture formation. Drugs that impair the function of lower esophageal sphincter can produce symptoms of gastroesophageal reflux. The factors that can influence the severity of drug-induced changes to the esophagus include chemical and physical properties of the drug, delay in transit time of the drug and duration the drug is in contact with esophageal mucosa. Almost 100 different drugs can cause esophageal injury. The best management for drug-induced esophageal injury is the discontinuation of the causing drugs. Peritoneum: The peritoneum is the epithelial lining of the abdominal and pelvic cavities and supports and covers the organs within it. The part of the membrane lining the abdominal cavity is called the parietal peritoneum and the portion lining the internal organs is known as the visceral peritoneum. A serious medical condition called peritonitis occurs when the peritoneum becomes infected. Certain drugs, can cause adverse reaction in the peritoneum (Table 4). Liver: Many drugs cause liver injury (Table 5). Adverse effects of drugs on the liver can be presented by increasing of serum and aspartate alanine aminotransferases, serum alkaline phosphatase, gammaglutamyl transferase, or bilirubin to more than double their normal values. Most drug-induced liver disease occurs in adults rather than in children. Hepatotoxicity happens more in female gender. Previous history of adverse drug reaction on liver and multiple drug use are other factors that can increase the risk of drug induced liver injury. 3

Erosive enteritis Intl. J. Pharmacol., 1 (1): 1-8, 2005 Table 6: Drugs with potential to cause adverse reaction in the pancreas[559] Drug name Amoxapine (overdose) Asparginase Azathioprine Balsalazide Carbamazepine Clofibrate Didanosine Reported adverse effect Pancreatitis Acute pancreatitis Pancreatitis Pancreatitis Table 9: Drugs with potential to cause adverse reaction in the small intestine Drug name Reported adverse effect Cyclophosphamide+doxorubicin+vincristine S-Fluorouracil Actinomycin D Allopurinol Pancreatitis Gallstones, pancreatitis Pancreatitis Allopurinol Pancreatitis Diuretics (chlorthiazide, furosemide, chlorthalidone) Pancreatitis Dolasetron Ergotamine (overdose) Erythromycin Gold Lovastatin Mefenamic acid Mesalamine Methyldopa Metronidazole Nitrofurantoin Octreotide Olsalazine Oral contraceptives Pentantidinc Piroxicam Procyclidine Rabeprazole Sodium valproate Steroids (large doses) Sulindac Sulphamethizole, sulphasalazine Sulphonamide Pancreas Ischemic pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis (rare) Pancreatitis Pancreatitis Acute pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Pancreatitis Table 7: Drugs with potential to cause adverse reaction in the stomach-{k} Drug name Anticholinergics Chemotherapeutic drugs Chloroquine Dolasetron Gold Misoprostol Reported adverse effect Delayed gastric emptying Vomiting Gastric erosion Abdominal pain, dyspepsia Chronic gastritis Abdominal pain Overdose of sustained release theophylline tab. Formation of congealed Potassium chloride Rabeprazole Steroids (overdose) Sucralfate Theophylline (overdose) Table 8: Drugs with potential to stomach-duodenum24 Drug name Anticholinergics Balsalazide Cisaperide Opioids Rabeprazole Pancreas: Even though masses Formation of congealed masses Dyspepsia Gastric perforation Gastric discomfort Gastric perforation cause adverse reaction in the Reported adverse effect Delay in gastric emptying Gastroenteritis Increase gastric emptying Delay in gastric emptying Gastroenteritis drug-induced pancreatic dysfunction is much less than other gastrointestinal adverse effects, but it has been recognized as a complication of many drugs (Table 6). The mechanism of drug-induced pancreatic injury is not always known. Anticholinergics Anticoagulants Anticonvulsants Antiparkinson agents Arabinoside Atropine Bleomycin Calcium channel blockers Cathartics large amounts) Chlolestyramine Colchicine Cytosine Digitalis glycosides Flucytosine Gold Iron tablets Lithium Loperamide Mcsalamine (delayed-release) Metformin, phenformin Methotrexate Methotrexate Methyldopa Neomycin NSAIDs Omeprazole Opioids Oral contraceptives Phenindione Phenothiazines Potassium tablets Purgatives Sodium aminosalicylate Sulindac Tetracycline Tricyclic antidepressants Tricyclic antidepressants Vincristine Vincristine Warfarin Erosive enteritis Mucosal damage Jejunal mucosal changes, steatorrhea I small bowel motility, gastric motility Hemorrhage RBC, serum folate Dysmotility Erosive enteritis Paralytic ileus Erosive enteritis Dysmotility Mild steatorrhea Steatorrhea, malabsorption of fatsoluble vitamins Mucosal damage Erosive enteritis Haemorrhagic necrosis Erosive enteritis Panenteritis Gangrene of a Meckel's diverticulum Vasculitis Dysmotility, paralytic ileus Perforated peptic ulcer (rare) Impairment of vit. B₁ absorption, reduction in disaccharidase activity Mucosal damage Erosive enteritis Jejunal mucosal changes, steatorrhea Mucosal damage Ulceration, stricture, perforation Enteric infection Dysmotility Mesentric venous thrombosis Jejunal mucosal changes, steatorrhea Dysmotility Local lesions, stricture Steatorrhea Interference with ileal transport of vit. Biz Diarrhea, abdominal pain Impairment the absorption of Ca and Fe, steatorrhea Dysmotility Paralytic ileus Pseudo-obstruction, crosive enteritis Paralytic ileus Jejunal hamatomata Stomach: Nausea and vomiting are common side effects of many drugs that usually happen in the beginning of the therapy. They can be simple adverse effects that would disappear with continuation of use or can be a sign of drug toxicity. Some drugs by affecting the gastric neural and muscular activity can cause the stomach to empty its contents into the duodenum at a slow or fast rate and reduce or increase the rate of gastric emptying. Certain drugs, can cause adverse reaction in the stomach (Table 7). 4

+ Intl. J. Pharmacol., 1 (1): 1-8, 2005 Table 10: Drugs with potential to cause adverse reaction in the large intestine 74-83] Drug name Albendazole Aluminium hydroxide Anthraquinones (chronic use) Anticholinergics Antimicrobial agents Antiparkinson drugs Balsalazide Broad spectrum penicillins Calcium carbonate Cephalosporins Chenodeoxycholic acid Cisplatin Clarithromycin Clindamycin Corticosteroids (overdose) Danazole Debrisoquine Digitalis (overdose) Dolasetron Fluorouracil Gold Guanethidine Isotretinoin Lithium Magnesium Mesalamine (delayed-release) Methyldopa Misoprostol Nizatidine NSAIDs Olsalazine Ondansetron Opioids Oral contraceptives Penicillamine Rabeprazole Reported adverse effect Pseudomembranous colitis Constipation Constipation Constipation Diarrhea Constipation Aggravation of ulcerative colitis, diarrhea Clostridium difficile colitis Constipation Clostridium difficile colitis. Diarrhea Ischemia of colon Pseudomembranous colitis Clostridium difficile colitis, vasculitis Diarrhea Ischemia of colon Diarrhea Diarrhea Constipation Ischemia of colon Colitis Diarrhea Proctocolitis Constipation Osmotic diarrhea Diarrhea, colitis flare Diarrhea, colitis Diarrhea Diarrhea Colitis Diarrhea Constipation, diarrhea Constipation Ischemia of colon Colitis Diarrhea, constipation B-adrenoceptor blocking agents Diarrhea Stimulant laxatives Sucralfate Sulphiasalazine Vasopressin.. Cathartic colon Diarrhea Diarrhea Ischemia of colon Table 11: Drugs with potential to cause adverse reaction in the rectum²**86] Drug name Reported adverse effect Proclilis Alcohol Balsalazide Dexamethasone (IV) Ergot suppositories Indomethacin Octreotide Olsalazine Peppermint oil capsules Phenybutazone Rabeprazole Fecal incontinence, hemorrhoid Perineal irritation Anal ulcers Proctitis, rectal ulceration Hemorrhoids Rectal discomfort, rectal bleeding Anal burning Proctitis, rectal ulceration Rectal hemorrhage, proctitis Stomach and duodenum: The adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) have been documented since 1938 and today the toxicity profile of these drugs has been more clear. About 70 million prescriptions have been written each year and 30 billion over the counter (OTC) NSAIDs are sold each year in USA Elderly patients have increased risk of NSAID-induced gastrointestinal injury due to multiple medical conditions and polypharmacy (Table 8). Small intestine: Drug induced adverse effects in small intestine (Table 9) include ulceration, hemorrhage, malabsorption, and disordered motility. Drugs that can reduce small bowel motility, as well as gastric motility can cause paralytic ileus. Increased motility throughout the small intestine can lead to diarrhea, Slow release formulations can cause local lesions that may lead to stricture. Large intestine: Many different drugs can affect colon (Table 10), but the radiographic injury happens in the colon over a longer period of time and the clinical symptoms in compare to upper GI tract are more insidious. Drugs can influence the colon by induction of colitis (antimicrobial colitis, ischemic colitis), ulceration, bleeding and perforation. Drugs that disturb the normal physiologic process which play a role in regulating fluid absorption and secretion and damage the mucosa of the small and large intestine can cause diarrhea. It may be difficult to be precise about the exact site of action in an individual patient. Elderly are susceptible to drug-induced diarrhea because of their age and the number of medications that they use. Rectum: Some drugs can affect rectum (Table 11) by inducing irritation, ulceration, burning. Proctitis is an inflammatory change of the rectum causing pain, soreness, bleeding, and a discharge of mucus or pus. Proctitis occurs predominantly in adults and males arc affected more often than females. Many drugs can cause gastrointestinal injury and affect patient's nutritional status. Elderly patients need extra attention because of their medical condition and concomitant drug therapy. Since most drug reactions occur within 1 to 2 weeks following initiation of therapy, reactions seen after 2 weeks are less likely to be due to medication use. Some reactions are dependent on dosage or cumulative toxicity. The majority of drug-induced gastrointestinal reactions are moderate in severity. However, severe reactions necessitate rapid withdrawal of the suspected drug. Readministration of the offending drug helps to establish whether the reaction is drug-induced. Reactions after rechallenge may be more severe and therefore, rechallenge should not be performed without medical supervision. The ability to evaluate these issues is necessary to accurately assess client status and prevent situations that compromise client safety. As a final notc, rapid progress in pharmacotherapeutics requires clinicians to constantly update their knowledge of drugs used by their patients. Attention must be paid to their toxic and unwanted effects that in many cases may be similar to characteristics of common diseases. 5

I. REFERENCES Intl. J. Pharmacol., 1 (1): 1-8, 2005 Lazarou, J., B.H. Pomeranz and P.N. Corey, 1998. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA., 279: 1200-5. 2. Einarson, T.R., 1993. Drug-related hospital admissions. Ann. Pharmacother., 27: 832-40. 3. 4. 5. 6. Bates, D.W., N. Spell, D.J. Cullen, E. Burdick, N. Laird, L.A. Petersen, S.D. Small, B.J. Sweitzer and L.L. Leape, 1997. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group. JAMA., 277: 307-11. Inman, W.H.W., 1981. Postmarketing surveillance of adverse drug reactions in general practice. Br. Med. J., 282: 1131-2. Pirmohamed, M. and B. Kevin Park, 2001. Genetic susceptibility to adverse drug reactions. Trends. Pharmacol. Sci., 22: 298-305. Park, B.K., M. Pirmohamed and N.R. Kitteringham, 1998. Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective. Chem. Res. Toxicol., 11: 969-88. 7. Meyboom, R.H., A.C. Egberts, I.R. Edwards, Y.A. Hekster, F.H. Koning and F.W. Gribnau, 1997. Principles of signal detection in pharmacovigilance. Drug. Saf., 16: 355-65. 8. 9. Ghahremani, G.G., 1999. Gastrointestinal complications of drug therapy. Abdom. Imaging, 24: 1-2. Gatenby, R.A., 1995. The radiology of drug-induced disorders in the gastrointestinal tract. Semin. Roentgenol., 30: 62-76. 10. Bramble, M.G. 1970. Record CO. Drug-induced gastrointestinal disease. Drugs, 15: 451-463. 11. Abdollahi, M. and M. Radfar, 2003. A review of drug-induced oral reaction. 1. Contemp. Pract., 4:010-031. 12. Schiffman, S.S., 1997. Taste and smell losses in normal aging and disease. JAMA., 278: 1357-1362. 13. Lae, A. and J. Morris, 1997. Drug-induced gastrointestinal disorders. The Pharmaceut. J., 258: 742-747. 14. Boyd, L.D., J.T. Dwyer and A. Papas, 1997. Nutritional implications of xerostomia and rampant caries caused by serotonin reuptake inhibitors: a case study. Nutr. Rev., 55: 362-368. 15. Korstanje, M.J., 1995. Drug-induced mouth disorders. Clin. Exp. Dermatol., 20: 10-18. 16. Laskaris, G. and R.A. Satriano, 1993. Drug-induced blistering oral lesions. Clin. Dermatol., 11: 545-550. 17. Brunet, L., J. Miranda and M. Farre et al., 1996. Gingival enlargement induced by drugs. Drug Safety, 15: 219-231. 18. Hart, R.S., B. Levin and C.F. Gholson, 1989. Esophageal obstruction caused by sucralfate impaction. Gastrointest. Endosc., 35: 474. 19. Graumlich, J.F., 2001. Preventing gastrointestinal complications of NSAIDs. Postgrad. Med., 109: 117-128. 20. De Groen, P.C., D.F. Lubbe and L.J. Hirsch et al., 1996. Esophagitis associated with the use of alendronate. New Engl. J. Med., 335: 1016-1021. 21. Bassoth, G., M. Gaburri and M.A. Pelli et al., 1987. Oesophageal pain exacerbated by propranolol. Br. Med. J., 294: 1655. 22. Dewis, P., F. local, D.C. Anderson et al., 1982. Reversible oesophageal dysphagia and long-term ingestion of chlormethiazole. Br. Med. J., 284: 705. 23. Al-Dujaili, M., E.G. Salole and A.T. Florence, 1983. Drug formulation and oesophageal injury. Adverse Drug Reaction. Acute. Poisoning. Rev., 2: 235. 24. Heller, S.R., I.W. Fellows, A.L. Ogilvie and M. Atkinson, 1982. Non-steroidal anti-inflammatory drugs and benign oesophageal stricture. Br. Med. J. (Clin. Res. Ed.), 285: 167-8. 25. Coates, A.G., T.T. Nostrant, J.A.P. Wilson et al., 1986. Esophagitis caused by non-steroidal anti-inflammatory medication: case reports and reviews of the literature on pill induced esophageal injury. South. Med. J., 79: 1094. 26. Crowson, T.D., L.H. Head and W.A. Ferrante, 1976. Esophageal ulcers associated with tetracycline therapy. JAMA., 1235: 2747. 27. Sutton, D.R. and J.K. Gosnold, 1977. Oesophageal ulceration due to clindamycin. Br. Med. J., 1: 1598. 28. Suissa, A., M. Parason, J. Lachter et al., 1987. Penicillin VK-induced esophageal ulceration. Am. J. Gastroenterol., 82: 482. 29. Bateman, D.N., E.E. Aziz, 1998. GI Disorders. In: Davies's Text Book of Adverse Drug Reaction. 5th Edn., Chapman and Hall Medical, London, pp: 259-274, 30. Oto, A., A. Oktay and T. Sozen, 1983. Methylprednisolone pulse therapy and peritonitis. Ann. Intern. Med. 99: 282. 31. Ostapowicz, G., R.J. Fontana, F.U. Schiodt et al., 2002. Results of a prospective study of acute liver failure at 17 tertiary care centers in the us. Ann. Intern. Med., 137: 947-954. 32. Prati, D., E. Taloll, A. Zanella et al., 2002. Updated definitions of healthy ranges of serum alanine aminotransferase levels. Ann. Intern. Med., 137: 1-9. 6

Intl. J. Pharmacol., 1 (1): 1-8, 2005 33. Dargan, P.I. and A.L. Jones, 2002. Should a lower treatment line be used when treating paracetamol poisoning in patients with chronic alcoholism? A case agonist. Drug. Saf., 25: 625-632. 34. Andrade, R.J., M.I. Lucena, M.C. Fernendez et al., 2002. Cholestatic hepatitis related to use of irbesatran: A case report and literature review of angiotensin II antagonist-associated hepatotoxicity. Eur. J. Gastroenterol. Hepatol., 14: 887-890. 35. Bataille, L., J. Rahier and A. Geubel, 2002. Delayed and prolonged cholestatic hepatitis with ductopenia after long-term ciprofloxacin therapy for crohn's disease. J. Hepatol., 37: 696-699. 36. Hui, C.K., M.F. Yuen, W.M. Wong et al., 2002. Mirtazapine-induced hepatotoxicity. J. Clin. Gastroenterol., 35: 270-271. 37. Chitturi Le, V., J. Kench et al., 2002. Gliclazideinduced acute hepatitis with sensitivity features. Dig. Dis. Sci., 47: 1107-1110. 38. Van Outryve, S., D. Schrijvers, V.D. Brande et al., 2002. Methotrexate-associated liver toxicity in a patient with breast cancer. Neth. J. Med., 60: 216-222. 39. Overstreet, K., C. Costanza, C. Behling et al., 2002. Fatal progressive hepatic necrosis associated with lamotrigine treatment. Dig. Dis. Sci., 47: 1921-1925. 40. Kalapos, M.P., 2002. Carbamazepine-provoked hepatotoxicity and possible actiopathologic role of glutathione in the events. Adverse. Drug. React. Toxicol. Rev., 21: 123-141. 41. Finch, C.K., C.R. Chrisman, A.M. Baciewcz et al., 2002. Rifampin and rifabutin interactions. Arch. Intern. Med., 162: 985-992. 42. Al-Homaidhi, H., N.M. Abdol-Haq, M. El-Baba et al., 2002. Several hepatitis associated with oxacillin therapy. South. Med. J., 95: 650-652. 43. Suriawinta, A. and A.D. Min, 2002. A 33-year old woman with jaundice after azithromycin use. Semin. Liver. Dis., 22: 207-210. 44. Sommers, L.M. and R.B. Schoene, 2002. Allopurinol hypersensitivity syndrome associated with pancreatic exocrine abnormalities and new-onset diabetes mellitus. Arch. Intern. Med., 162: 1190-1192. 45. Gupta, A.K., E. Chwetzoff, J. Del Rosso et al., 2002. Hepatic safety of itraconazole. J. Cutan. Med. Surg., 6: 210-213. 46. Fox, J.C., R.S. Szyjkowkski and S.O. Sanderson, 2002, Progressive cholestatic liver disease associated with clarithromycin treatment. J. Clin. Pharmacol., 42: 676-689. 47. Pfeffer, M.A., A. Keech, F.M. Sacks et al., 2002. Safety and tolerability of prevastatin in long-term clinical trials. Circulation, 105: 2341-2346. 48. Bjorkman, D., 1998. Nonsteroidal anti-inflammatory drug-associated toxicity of the liver, lower gastrointestinal tract, and esophagus. Am. J. Med. 105: 175-215. 49. Clarkson, A. and L. Choonara, 2002. Surveillance for fatal suspected adverse drug reactions in the UK. Arch. Dis. Child., 87: 462-466. 50. Deviere, J., D. Reuse and R. Askenasi, 1987. Ischaemic pancreatitis and hepatitis secondary to ergotamine poisoning. Clin. Gastorenterol., 9: 350. 51. Siefkin, A.D., 1980. Sulindac and pancreatitis. Ann. Intern. Med., 93: 932. 52. Van Walraven, A.A., M. Edels and S. Fong, 1982. Pancreatitis caused by mefenamic acid. Can. Med. Assoc. J., 126: 894. 53. Greenstein, R., C. Nogeire, T. Ohnuma et al., 1979. Management of pseudocyst, Cancer, 43: 718. 54. Max Son, C.J.I., S.M. Greenfield and J.L. Turner, 1992. Acute pancreatitis as a common complication of 2,3-dideoxyinosine therapy in the acquired immunodeficiency syndrome. Am. J. Gastroenterol., 87: 708. 55. Eisemann, A.D., N.J. Becker and J.R. Miner, 1989. Pancreatitis and gold treatment of rheumatoid arthritis. Ann. Intern. Med., 111: 860-1. 56. Celifarco, A., C. Warschauer and R. Burakoff, 1989. Metronidazole-induced pancreatitis. Am. J. Gastroenterol., 84: 958. 57. Hawksworth, C.R.E., 1989. Acute pancreatitis associated with infusion of erythromycin lactobionate. Br. Med. J., 298: 190. 58. Hay, O.L., 1989. Piroxicam and pancreatitis. Ann. Intern. Med., 104: 895. 59. Puckett, J.B., W.M. Butler and J.A. McFarland, 1982. Pancreatitis and cancer chemotherapy. Ann. Intern. Med., 97: 453. 60. Ratnaike, R.N. and T.E. Jones, 1998. Mechanisms of drug-induced diarrhea in the elderly. Drug Aging, 13: 245-253. 61. Antonescu, C.G., 1989. Potassium chloride and gastric outlet obstruction. Ann. Intern. Med., 111: 855-6. 62. Smith, W.D.F., 1987. Endoscopic removal of a pharmacobezoav of slow-release theophylline. Br. Med. J., 294: 125. 63. Geltner, D., M. Sternfield, S.A. Becker et al., 1986. Gold-induced ileitis. J. Clin. Gastroenterol., 8: 184. 64. Guss, C., A.T. Schneider and L.T. Chiaramonte, 1986. Perforated gastric ulcer in an asmathic treated with theophylline and steroids. Ann. Allergy, 56: 237. 65. McNeil, D.C., 1966. A dynamic ileus and nortriptyline. Br. Med. J., 5499; 1360. 7

Intl. J. Pharmacol., 1 (1): 1-8, 2005 66. Freeman, H.J., 1986. Sulindac associated small bowel lesion, J. Clin. Gastroenterol., 8: 569. 67. Boley, S.J., A.C. Allen, L. Schuttz et al., 1965. Potassium-induced lesions of the small bowel. JAMA, 193: 997. 68. Azizkhan, R., W. Piepgrass and M.C. Wilhelm, 1982. Anticoagulant-induced haematomas of the small intestine. South. Med. J., 75: 242. 69. Gazes, P.C., C.R. Holmes, V. Moseley et al., 1961. Acute haemorrhage and necrosis of the intestines Associated with digitalization. Circulation, 23: 358. 70. White, C.A. and J. Traube, 1982. Ulcerating enteritis associated with flucytosine therapy. Gastroenterology, 83: 1127. 71. Neal, K.R., H.M. Scott, R.C.B. Slack et al., 1996. Omeprazole as a risk factor for campylobacter gastroenteritis. Br. Med. J., 312: 414. 72. Schneerson, J.M. and B.G. Gazzard, 1977. Reversible malabsorption syndrome caused by methyldopa. Br. Med. J., 2: 1456-7. 73. Juel-Jensen, B.E., 1959. Sensitivity to phenindione: report of a case of severe diarrhoea. Br. Med. J., 5145: 173-4. 74. Reiner, E. and M. Patterson, 1966. The effect of neomycin on disaccharidase activity of the small bowel. Clin. Rcs., 14: 49. 75. Sheff, B., 1999. Minimizing the threat of C. difficile. Nursing, 29: 33-38. 76. Shah, V., O.C. Marin and F.L. Altice, 1996. Albendazole-induced pseudomembranous colitis. Am. J. Gastroenterol., 91: 1453. 77. Lambert, M., R. De Peyer and A.F. Muller, 1982. Reversible ischemic colitis after intravenous vasopressin therapy. JAMA., 247: 666. 78. Sweeney, E.C. and J.P. Sheehan, 1979. Clindamycinassociated colonic vasculitis. Br. Med. J., 2: 1188-9. 79. Schneiderman, D.J. and J.P. Cello, 1986. Intestinal ischaemia and infarction associated with oral contraceptives. West. J. Med., 145: 350. 80. Miyata, T., Y. Tamechika and M. Torisu, 1988. Ischaemic colitis in a 33-year-old woman on danazol treatment for endometriosis. Am. J. Gastroenterol., 83: 1420. 81. Kirkham, B., L. Wedderburn and D.G. Macfarlane, 1989. Gold-induced colitis. Br. J. Rheumatol., 28: 272. 82. Bonkowsky, H.L. and J. Brisbrane, 1976. Colitis and hepatitis caused by methyldopa. JAMA., 236: 1602. 83. Martin, P., P.N. Manley and W.T. Depew, 1987. Isotretinoin-associated proctosigmoiditis. Gastroenterology, 93: 606. 84. Robinson, H.M., T. Wheatly and I.H. Leach, 1995. Nonsteroidal anti-inflammatory drug-induced colonic stricture. An unusual cause of bowel obstruction and perforation. Dig. Dis. Sci., 40: 315. 1974. Proetiti 85. Cheli, R. and G. Ciancamerla, emorragiche da medicamenti locali. Minerva Gastroenterol., 20: 56. 86. Bhalotra, R., 1988. Alcohol-induced proctitis in a human. J. Clin. Gastroenterol., 10: 592. 8

Other Health Sciences Concepts:

[back to top]

Discover the significance of concepts within the article: ‘The Adverse Drug Reaction in the Gastrointestinal Tract: An Overview’. Further sources in the context of Health Sciences might help you critically compare this page with similair documents:

Coliti, Xerostomia, Gastrointestinal Tract, Peritonitis, Adverse drug reaction, Acute Pancreatitis, Hepatotoxicity, Liver Injury, Gastroesophageal reflux disease (GERD), Gastric emptying, Proctitis, Gingival enlargement, Peritoneum, Type B ADR, Pancreatic Dysfunction, Pharmacotherapeutic, Allopurinol hypersensitivity syndrome, Fatal suspected adverse drug reactions.