IRRATIONAL USE OF IBUPROFEN LEADS TO HEMATEMESIS; A CASE REPORT
Amina Elahi, Ali F, Zahra S.S
Riphah Institute of Pharmaceutical Sciences, Riphah International University, G-7/4, 7th Avenue, Islamabad, Pakistan.
Keywords: Irrational use, Ibuprofen, Hematemesis
Abstract

This case study has been designed to report an incident of irrational use of Ibuprofen (NSAID) in a 10 year old child brought to a local hospital in Rawalpindi and describe the seriousness of adverse effects that are to be associated with irrational use of NSAIDS.Complete chronological history of child was taken including his past medication history by direct interview of the mother.The study has revealed that the efficacy and wide availability of OTC preparations of NSAIDS and irrational prescribing of physician has lead to their irrational use resulting in serious adverse effects to the consumers.So it is the responsibility of the health care professionals to optimize and help rationalize the use of these OTC drugs by the consumer.

Article Information

Identifiers and Pagination:
Year:2012
Volume:4
First Page:6
Last Page:11
Publisher Id:JAppPharm (2012 ). 4. 6-11
Article History:
Received:November 13, 2011
Accepted:January 28, 2012
Collection year:2011
First Published:February 25, 2012

INTRODUCTION

Rational use of medicines requires the patients to take medications that are appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time, and at the lowest cost to them and their community1. As stated by a famous humanitarian, A little simplification would be the first step toward rational living.

Thus simplifying ,Rational use of drugs require patients to take the Right medication, in the right dose, at right time through the appropriate route.2 Failure to follow this scheme has lead to medically inappropriate, un productive and unprofitable use of pharmaceuticals world wide especially in the developed countries. This misuse of drugs has resulted in wastage of resources as well as worldwide health hazards. While; the non steroidal anti-inflammatory drugs (NSAIDs), now constitute perhaps the most frequently prescribed class of medications.3

Although these are the most widely prescribed medications in the united states for fever, arthritis and a number of other inflammatory conditions to reduce pain and inflammation, according to a research conducted on Un necessary prescribing of NSAIDS in 1997 it was proved that they are associated with a high incidence of side effects.4

In the last decades, epidemiologic studies have revealed the risk of upper gastrointestinal tract bleeding/perforation (UGIB) associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs).5 A multicenter study revealed that Long-term NSAID use is associated with the development of mucosal ulceration with an incidence of 20%.6

Many patients with Upper Gastro Intestinal Bleeding who are taking NSAIDs present without dyspepsia but with hematemesis or melena as their first symptom, owing to the analgesic effect of the NSAID.7

The use of over-the-counter (OTC) formulations NSAIDS is very common. In this context, Data of 4164 consecutively diagnosed patients with rheumatoid arthritis was collected on the GI risks of OTC doses of aspirin, ibuprofen, naproxen, paracetamol, and no drug, from eight Arthritis, Rheumatism, and Aging Medical Information System centers in North America. Serious GI events such as bleeding, requiring hospitalization were reported in these patients.8

Serious side effects have been reported due to NSAIDS especially in children..A large randomized controlled trial conducted by Lesko  SM, Mitchell  AA (1995) showed that ibuprofen and acetaminophen were equivalent in their risk of adverse events .9

CASE REPORT

A 10 year old girl was brought to the emergency of a local hospital in Rawalpindi, Pakistan with chief complaints of epigastric pain (2 weeks), Bloody vomiting (a week) and fever (last 2 days). There was a sudden onset of pain after having meal .It was severe enough to hamper child’s activity. Her mother was called to school and child was brought to the Emergency.

The pain had been accompanied by Hematemesis i.e. vomiting of blood since a week.

It was sudden in onset and almost 2 tablespoons in volume. It was non projectile, bright red in color associated with abdominal pain. No blood clots were seen. The child had intermittent, low grade fever for the past 3 days. It was relieved by Ibuprofen. There were no associated symptoms with fever such as rigors or chills, burning sensation on stooping, acidity retrosternally etc.

Her physical examination showed temperature 101C, pulse 115/min, respiratory rate 22/min and B.P.She weighed 40Kg.Her examination had revealed pallor, weight loss and anorexia.

She had flank pain in the renal area and her CVS examination revealed palpitation and fatigue.CNS is normal and intact.

There was no history of constipation, diarrhea, malena, allergy and respiratory infection. While medical history showed sub-vaginal delivery (SVD), mild anemia and pancytopenia.

Patient’s past medication history revealed frequent use of Ibuprofen (NSAID) for symptomatic relief of fever since thirteen months.

DISCUSSION

The patient presented with epigastric pain (2 weeks), bloody vomit (Hematemesis) (a week) and fever (last 2 days).The epigastric pain was sudden in onset after having meal and was severe enough to hamper her activities. The vomit was non projectile, contained blood and was almost 2 tablespoons in volume. Fever was mild intermittent and relieved by ibuprofen.

Past medication history of the patient showed frequent use of Ibuprofen for symptomatic relief of fever for the past 13 months (91 weeks).

Ibuprofen is an oral, Nonsteroidal Anti Inflammatory drug (NSAID) of the propionic acid chemical class. It competitively inhibits both cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, by blocking arachidonate binding resulting in analgesic, antipyretic and anti inflammatory properties.

Cyclooxygenase 1 (COX-1) is responsible for the physiologic production of prostanoids, that regulates the normal cellular processes such as gastric cytoprotection, vascular homeostasis, platelet aggregation and kidney function.COX-2 cause’s elevated production of prostanoids in case of a disease or at the site of inflammation.COX-2 is constitutively expressed in some tissues, such as brain, kidney and bone. Its expression at other sites is increased during inflammation.

Since ibuprofen is a nonselective COX inhibitor, it inhibits both of the COX enzymes resulting in wide range of side effects. Focusing on the above mentioned case, as already described, COX-1 is responsible for the physiologic production of prostanoids that regulate gastric cytoprotection i.e. Prostacyclin (PGI2) which inhibits gastric acid secretion, whereas PGE2 and PGF2a stimulate synthesis of protective mucus in both the stomach and small intestine .In the presence of Ibuprofen, these prostanoids are not produced resulting in increased gastric acid secretion and diminished mucus protection respectively. This results in epigastric distress, ulceration and hemorrhage which increases with dose and duration and can occur at any time.10

This fact is supported by Geis GS, Stead H, Wallermark C-B (1991)11 who reported the occurrence of mucosal lesions in patients, with rheumatoid arthritis, due to chronic use of NSAIDS. It was estimated that prevalence of NSAID induced gastric or duodenal ulcers, varies between 14.6% and 43.9%.

Gabriel and Bombardier (1990) estimated the absolute risk of gastric ulceration to be approximately 20%.12

The patient was prescribed ibuprofen 1 year back, when she had fever, by a local physician. She had immediate relief and from then onwards when ever she had fever in the past 13 months, she took ibuprofen for relief.

According to British National Formulary 13, the dose for children under 12 years is 20 mg/kg of body weight in divided doses per day. As she weighed 40Kg, her total daily dose becomes 800mg in divided doses. Depicting irrational use, she took more then the required dose, according to her mother two 400 mg tablets at a time for fever .Thus by  taking double dose each time  ,the serum level for the drug increased then the required leading to  exaggerated effect. Use of adult dosage form by the child also depicts irrational prescribing by the physician.

So as the child consumed ibuprofen for a long period, she developed ulceration leading to hemorrhage which presented as Hematemesis. The Blood CP of the child revealed mild anemia representing continuous blood loss and pancytopenia.

 Lindblad R,Rödjer S (1991) suggested that patients on prolonged therapy should undergo regular blood monitoring as ibuprofen causes iron deficiency anemia and pancytopenia.14

According to Autret-Leca E, Bensouda-Grimaldi L, Maurage C, Jonville-Bera  AP (2007) ,Regional Centre of Pharmacovigilance, France; NSAIDS, when used in children for pain or fever relief, are associated with serious Gastro Intestinal complications which increase with the length of exposure and dose.15

So lowest effective dose should be given for the shortest period of time to limit these adverse effects.

CONCLUSION

Irrational use of OTC drugs is a major problem of present day medical practice. All NSAIDs can cause gastrointestinal discomfort and rarely serious but potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation, which may increase with dose or duration of use but can, occur at any time without warning. So it is the responsibility of the health care professionals to optimize and help rationalize the use of these OTC drugs by the consumer.

 

REFERNCES

1 medicines/areas/rational use. Department of Essential Medicines and Pharmaceutical Policies (EMP), World Health Organization Head quarters , 20 Avenue Appia 1211, Geneva 27,Switzerland.

2  Henri Richard Manasse ,Kasey K. Thompson, American Society of Health-System Pharmacists. Medication safety: A guide for health care facilities. American Society of Health-System Pharmacists,7272 Wisconsin Avenue,Bethesda,MD,20814,attn

3 Baum C, Kennedy DL, Forbes MB,1985. Utilization of nonsteroidal anti-inflammatory drugs. Arthritis Rheum., (Vol ,28 , pg 686-92). PMID:4004978

4 Tamblyn R, Berkson L, Dauphinee WD, Gayton D, Grad R, Huang A, Isaac L, McLeod P, Snell L.McGill University, Montreal, Quebec, Canada ( Sep 15,1997). Unnecessary prescribing of NSAIDs and the management of NSAID-related gastropathy in medical practice. Ann Intern Med.vol 127, pg 429-38. PMID:9312999

5 Hernandez-Diaz S, Rodriguez LA. 2000. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: An overview of epidemiologic studies published in the 1990s. Arch Intern Med ,vol160, pg 2093-2099. PMID:10904451

6  Pilotto A, Maggi S, Noale M, Franceschi M, Parisi G, Crepaldi G. Development and validation of a new questionnaire for the evaluation of upper gastrointestinal symptoms in the elderly population: a multicenter study. J Gerontol A Biol Sci Med Sci. Feb 2010, vol 65(2), pg 174-8. PMID:19528359

7 Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. May 2011, vol124(5) , pg 426-33. PMID:21531232 

8 Singh G .The Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, California, USA. Gastrointestinal complications of prescription and over-the-counter non steroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System.

Am J Ther. 2000 , vol Mar;7(2), pg 115-21. PMID:11319579

9 Lesko  SM, Mitchell  AA.  An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial. The Journal Of Amercan Medical Association 1995, vol 273(12), pg 929–933. PMID:7884951

10 Richard A. Harvey, Michelle A Clark, Richard Finkel, Jose A. Rey, Karen Whalen.Lippincott's Illustrated Reviews: Pharmacology, .Lippincott Williams & Wilkins; Fifth, North American Edition edition (June 17, 2011)

11 Geis GS, Stead H, Wallermark C-B, et al. Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAIDs in patients with rheumatoid arthritis or osteoarthritis and interim report on prevention by misoprostol of diclofenac associated lesions. J Rheumatol 1991, vol 18(Suppl 28), pg 11-14. PMID:1903808

12 Gabriel SE, Bombardier C. NSAID induced ulcers. An emerging pandemic? J Rheumatol 1990, vol 17, pg 1-4. PMID:2179547

13British Medical Association, Pharmaceutical Society of Great Britain, Joint Formulary Committee (Great Britain).British national formulary, Issue 58. British Medical Association, 2003, 16 Jun 2011,pg 565.

14Lindblad R,Rödjer S.A case of severe pancytopenia caused by ibuprofen.Department of Medicine, Ostra Hospital, Gothenburg University, Sweden. J Intern Med. 1991 , vol Mar229(3), pg 281-3. PMID:2007846

15 Autret-Leca E, Bensouda-Grimaldi L, Maurage C, Jonville-Bera AP. CHRU of Tours, Regional Centre of Pharmacovigilance, Department of Pharmacology, Hôpital Bretonneau, 2 boulevard Tonnellé, 37044 Tours Cedex 9, France. Upper gastrointestinal complications associated with NSAIDs in children. Therapie. 2007 , vol Mar-Apr;62(2), pg 173-6. Epub 2007 Jun 21.PMID:17582320


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Editor in Chief
Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
Marburg, Germany

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Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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