Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

Users Online : 90415

AbstractReferencesDOI and Others
Article in PDF How to Cite Citation Manager Readers' Comments (0) Audio Visual Article Statistics Link to PUBMED Print this Article Send to a Friend
Advertisers Access Statistics Resources

Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2012 | Month : August | Volume : 6 | Issue : 6 | Page : 1101 - 1104 Full Version

Managment of Paracetamol Poisoning: The Old and the New


Published: August 1, 2012 | DOI: https://doi.org/10.7860/JCDR/2012/.2342
Natasha Jayaprakash Nambiar

1. Assistant Professor, Department of Pharmacology Father Muller Medical College Mangalore-575002, India.

Correspondence Address :
Dr. Natasha Jayaprakash Nambiar Assistant Professor Department of Pharmacology Father Muller Medical College Mangalore-575002, India. Phone: 8095952367 E-mail: dr.natasha7@gmail.com

Abstract

Paracetamol is involved in a large proportion of accidental exposures and deliberate self-poisoning cases, although subsequent hepatic failure and death are the uncommon outcomes. The optimal management of most of the patients with a paracetamol overdose still remains unclear. The following article attempts to compile a management advice with the current clinical toxicology practice, revised guidelines and recent advances

Keywords

Acetaminophen, N acetyl cysteine

Introduction
Paracetamol (acetaminophen) is the most widely used over-the-counter analgesic agent in the world and it is the leading pharmaceutical agent in overdose which leads to hospital admissions (1).

Paracetamol is involved in a large proportion of accidental paediatric exposures and deliberate self-poisoning cases, although hepatic failure and death are the uncommon outcomes (2),(3).

In UK, the proportion of the overdoses with paracetamol increased from 14.3% in 1976 to 42% in 1990, and in 1993, 47.8% of all the overdoses which were reported, involved paracetamol or paracetamol-containing drugs (4). It has also become increasingly common in countries which include Denmark and Australia (5),(6).

In India, the data on paracetamol self poisoning is uncommon and it is insufficient as compared to that of the west. A 10 year retrospective hospital based study reported 0.32% cases of acute paracetamol overdoses due to accidental exposures (7).

The existing treatment recommendations use oral and intravenous N acetyl cysteine to prevent a hepatic injury and to replenish the glutathione stores.

This review summarizes the toxicokinetics and it outlines the management of paracetamol poisoning, along with the recent advances in its treatment and prevention.

Background

Paracetamol Kinetics

Paracetamol is rapidly absorbed from the small intestine. Its peak serum concentrations occur within 1–2 hours for the standard tablet or the capsule forms. 20% of the ingested dose undergoes first-pass metabolism in the gut wall (sulphation), while the rest undergoes hepatic biotransformation.

The mechanism of paracetamol induced hepatotoxicity can be explained in the following steps:

1. 5% of the ingested paracetmol is converted by mixed function oxidases in the hepatocytes into a reactive metabolite, N acetyl p benzoquinonimine.

2. In therapeutic doses, this reactive metabolite is conjugated with glutathione and its byproducts, mercapturic acid and cysteine are excreted in urine.

3. In cases of a paracetamol overdose, the excess amount of the reactive metabolite accumulates, while the glutathione stores diminish.

4. A hepatic toxicity ensues if the glutathione stores drop to approximately 30% of their normal amounts. 5. The accumulated reactive metabolite forms covalent bonds with the SH groups in the hepatocytes, resulting in hepatic necrosis (8).

Risk Assessment

The key factors to consider for paracetamol poisoning are: 1. The dose and concentration (early) . 2. The clinical and laboratory features which suggest liver damage (late). 3. A history which suggests an increased susceptibility to the toxicity in alcoholics and malnourishment.

The serum paracetamol levels should be checked to assess the need for N-acetylcysteine administration in all the patients with deliberate paracetamol self-poisoning, regardless of the stated dose. A clinical or biochemical evidence of a liver injury may not be apparent for up to 24 hours after the acute paracetamol overdose. The best surrogate marker which indicates the potential for this injury is a timed serum paracetamol level which is plotted on a nomogram.

The nomogram which is used appears to be a local decision, but these local nomograms are often derived from monograms which have been devised overseas. The Prescott nomogram was based on a cohort of patients in Edinburgh and it extends from 1320μmol/L (200mg/L) at 4 hours to 200μmol/L (30mg/L) at 15 hours. The Rumack–Matthew nomogram is based on the same data, but it has been extrapolated to 24 hours. It also uses a “treatment line” that is plotted 25% lower (1000μmol/L [150mg/L] at 4 hours) to comply with a United States Food and Drug Administration requirement, to provide a “safety buffer” for research and clinical purposes. Many guidelines have recommended an arbitrary, further lowering of the nomogram line (ie, to 660μmol/L [100mg/L] at 4 hours) for patients with such risk factors as chronic ethanol misuse, use of enzyme-inducing drugs, prolonged fasting, and dehydration (9),(10).

Lab Assessment

In patients who present within 8 hours after ingestion, the evaluation of the serum paracetamol and the alanine aminotransferase (ALT) levels should be performed as soon as possible. Other recommended investigations if the patient is brought in after 8 hours are, Prothrombin time/INR, blood urea and creatinine levels, blood glucose levels and estimation of the arterial blood gas concentration.

Management of the Paracetamol Overdose
A recovery is usually seen with supportive management with N-acetylcysteine which is administered in routine doses, although prolonged infusions may be required.

The role of haemodialysis has been described in many settings, but the indications for its use have not been clearly outlined.

1. Gastrointestinal decontamination
The administration of activated charcoal within 4 hours of the paracetamol ingestion reduces its further absorption and the further need for N acetyl cysteine administration. The usual dose of activated charcoal in adults is 25-50 gm in 100-200 ml of water (0.5 -1 gm/kg body weight) (11).

2. Antidotes
Since it is the relative scarcity of the SH groups that leads to the hepatotoxicity which is caused by paracetamol, the definitive therapy has been directed towards the measures which are taken to restore it. The first of such agents were cysteine and methionine, which provided encouraging results by replenishing the lost glutathione stores. The use of these agents resulted in dramatic increases in the survival of the patients, but the side effects (flushing, vomiting, etc) which were associated with these therapies led the researchers to seek alternative treatments .These gave way to trials with N-acetyl cysteine, which is now the preferred antidote of choice (12).

N-Acetylcysteine
Acetylcysteine (also known as N-acetylcysteine) prevents the hepatic injury, primarily by restoring hepatic glutathione. It is thought to provide cysteine for the glutathione synthesis and possibly to form an adduct directly with the toxic metabolite of acetaminophen and N-acetyl-p-benzoquinoneimine and to thus prevent its covalent bonding to the hepatic proteins (13). In addition, in patients with acetaminophen-induced liver failure, acetylcysteine improves the haemodynamic and oxygen use, it increases the clearance of indocyanine green (a measure of the hepatic clearance), and it decreases the cerebral oedema. The exact mechanism of these effects is not clear, but it may involve scavenging of the free radicals or changes in the hepatic blood flow (14), (15). When the risk assessment indicates that N-acetylcysteine is required, it is administered as a three-stage infusion, with each stage containing different doses, totaling 300mg/kg over 20–21 hours (Table/Fig 1). If hepatic injury is suspected after the three infusion stages, N– acetylcysteine is continued at the rate of the last infusion stage (100mg/kg each 16 hours or 150mg/kg/24 hours), until there is a clinical and biochemical evidence of improvement. N-acetylcysteine is packaged as an intravenous infusion in 10mL ampoules, each of which contains a 2000mg (20%) dose. The prescription of N-acetylcysteine requires a two-stage calculation to compute the appropriate weight-based dose and then the volume is required (16).

Calculation or transcription errors may lead to potentially fatal dosing errors. It is recommended that dosing tables which provide the required volume of 20% N-acetylcysteine by weight categories be used to chart the volume which is required in each infusion. This precludes the need for calculations and it decreases the potential for error. Such tables are found in the N-acetylcysteine product information and they have also been reproduced in the new guidelines. The calculation of the N-acetylcysteine doses is based on the estimated lean bodyweight to the nearest 10kg. A formula is provided to calculate the N-acetylcysteine volume in each infusion for patients who weigh more than 90kg. For children, the dose of N-acetylcysteine is calculated in the same way, but with the volume being reduced appropriately. Intravenous administration of the oral N-acetylcysteine preparation appears to have limited adverse effects and this offers another mechanism of delivery of the potentially lifesaving N-acetylcysteine when an oral administration is not possible.

Only a small proportion of the patients who present late develop severe hepatotoxicity and fulminant hepatic failure. The clinicians should consult a specialist from the liver unit for advice on the management of patients with liver failure or with signs that indicate a poor prognosis (17).

Adverse Effects
The most commonly reported adverse effects of intravenous acetylcysteine are anaphylactoid reactions, including rash, pruritus, angio-oedema, bronchospasm, tachycardia, and hypotension. The most severe adverse effects occur with the erroneous dosing of intravenous acetylcysteine in children. These effects includes cerebral oedema and hyponatraemia (due to its administration in 5% dextrose). There are rare reports of deaths which were caused due to anaphylactoid reactions (18),(19),(20).

Recent Advances
The pathophysiology of hepatic necrosis following an overdose of acetaminophen has been studied extensively. The following are the hypothesized molecular mechanisms that have been put forth, as has been depicted in (Table/Fig 2). 1. Oxidative stress

2. Kupfer cell activation
3. Nitration of the acetaminophen adducts with peroxynitrate formation 4. NOS

5. IL-1β and other cytokines such as IL-10, macrophage inhibitory protein-2 (MIP-2), and monocyte chemoattractant protein-1 (MCP-1), appear to be involved in hepatocyte repair and in the regulation of proinflammatory cytokines (21).

Many animal models have used agents that will reverse the oxidative stress mediated hepatic damage which is caused by acetaminophen. Allopurinol, which attenuated acetaminophen protein-adduct formation, mitochondrial dysfunction and oxidant stress, eliminated the hepatocellular nitrotyrosine staining and injury (22).

The protective effect of deferoxamine against the APAP-induced liver injury may be attributable to the chelation of iron, which can catalyze the generation of active oxygen species in hepatocytes H. Najafzadeh et al., observed that vanadium had a better effect than deferoxamine in the prevention of the hepatotoxicity which was induced by APAP, although the mechanism of its effect was unclear (23). Conclusion

The antidote, N- acetylcysteine should be given to all the patients with a serum paracetamol concentration of >200 mg/l. The treatment with N-acetylcysteine guarantees a survival if it is administered within 8 hours of the paracetamol ingestion, and the outcome is the same, regardless of when the treatment is given within this 8-hour window. If the antidote is not given, over 60% of the patients with serum paracetamol concentrations above the treatment line may develop serious liver damage, and of these, about 5% will die. Beyond 8–10 hours after the ingestion, the efficacy decreases with an increasing delay in the treatment. The optimal route and the duration of the administration for N-acetylcysteine in the management of the acetaminophen (paracetamol) poisoning are controversial. Recent studies have stated that a shorter hospital stay, patient and doctor convenience, and the concerns over the reduction in the bioavailability of oral N-acetylcysteine by charcoal and vomiting make intravenous N-acetylcysteine preferable for most of the patients with acetaminophen poisoning.

References

1.
Buckley N, Eddleston M. Paracetamol (acetaminophen) poisoning. Clin Evid 2005; (14): 1738-44.
2.
Dart RC, Erdman AR, Olson KR, et al. Acetaminophen poisoning: an evidence-based consensus guideline for an out-of-hospital management. Clin Toxicol (Phila) 2006; 44: 1-18.
3.
Linden CH, Rumack BH. Acetaminophen overdose. Emerg Med Clin North Am 1984; 2: 103-19.
4.
Hawton K, Ware C, Mistry H, Hewitt J, Kingsbury S, Roberts D, et al. Paracetamol self-poisoning: characteristics, prevention and harm reduction. Br J Psych 1996; 168:43-48.
5.
Ott P, Dalhoff K, Hansen PB, Loft S, Poulsen HE. Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark. J Int Med 1990; 227:423-28.
6.
Gow PJ, Smallwood RA, Angus PW. Paracetamol overdose at a liver transplantation centre: An 8-year experience. J Gastroenterol Hepatol 1999; 14:817–21.
7.
Lall S. B , Paul R.. Paracetamol poisoning in children. Indian Journal of Pediatrics 65( 3): 393-400.
8.
Anatharaman V. Paracetamol poisoning. Singapore Medical Journal 1993; 33:292-94.
9.
Dargan PI, Jones AL. Should a lower treatment line be used during the treatment of paracetamol poisoning in patients with chronic alcoholism?: a case against. Drug Saf 2002; 25: 625-32.
10.
Rossi S, editor. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook, 2006.
11.
Buckley NA, Whyte IM, O’Connell DL, Dawson AH. Activated charcoal reduces the need for N-acetylcysteine treatment after an acetaminophen (paracetamol) overdose. J Toxicol Clin Toxicol 1999; 37: 753-57.
12.
Buckpitt AR, Rollins DE, Mitchell JR. Varying effects of sulfahydryl nucleophiles on acetaminophen oxidation and sulfahydryl adduct formation. Biochem Pharmacol 1979;28:2941-46.
13.
Lauterburg BH, Corcoran GB., Mitchell JR. Mechanism of action of N-Acetylcysteine in the protection against the hepatotoxicity of acetaminophen in rats in vivo. J Clin Invest. 1983 April; 71(4): 980-91.
14.
Harrison PM, Wendon JA, Gimson AES, Alexander GJM, Williams R. Improvement of the hemodynamics and the oxygen transport by acetylcysteine in fulminant hepatic failure. N Engl J Med 1991;324:1852-57.
15.
Devlin J, Ellis AE, McPeake J, Heaton N, Wendon JA, Williams R. N-acetyl-cysteine improves the indocyanine green extraction and the oxygen transport during a hepatic dysfunction. Crit Care Med 1997;25:236-42.
16.
Prescott LF, Illingworth RN, Critchley JA, et al. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 1979; 2: 1097-100.
17.
Little M, Murray L, McCoubrie D, Daly FFS. A potentially fatal prescribing error in the treatment of paracetamol poisoning. Med J Aust 2005; 183: 535-36.
18.
Hershkovitz E, Shorer Z, Levitas A, Tal A. Status epilepticus following intravenous N-acetylcysteine therapy. Isr J Med Sci 1996;32:1102-04.
19.
Sung L, Simons JA, Dayneka NL. Diluted intravenous N-acetylcysteine as a cause of hyponatremia. Pediatrics 1997;100:389–91.
20.
Appelboam AV, Dargan PI, Knighton J. Fatal anaphylactoid reaction to N-acetylcysteine: caution in patients with asthma. Emerg Med J 2002;19:594–95. [PubMed: 12421803].
21.
James LP., Mayeux PR, Hinson JA. Acetaminophen induced hepatotoxicity. Drug Metabolism and Disposition. December 2003; 31 (12):1499-506.
22.
Knight T R., Kurtz A, Bajt ML, Hinson JA. Vascular and hepatocellular peroxynitrite formation during acetaminophen toxicity:the role of mitochondrial oxidant stress. Toxicol. Sci. 2001; 62 (2): 212-20.
23.
Najafzadeh H, Rezaie A, Masoodi AM, Mehrzadi S. Comparison of the effect of vanadium and deferoxamine on the acetaminophen toxicity in rats. Indian J Pharmacol. 2011 Jul-Aug; 43(4): 429–32.

DOI and Others

Date of Submission: Nov 5, 2011
Date of Peer Review: Dec 31, 2011
Date of Acceptance: Jun 29, 2012
Date of Publishing: Aug 10, 2012

Financial OR OTHER COMPETING INTERESTS:
None.

JCDR is now Monthly and more widely Indexed .
  • Emerging Sources Citation Index (Web of Science, thomsonreuters)
  • Index Copernicus ICV 2017: 134.54
  • Academic Search Complete Database
  • Directory of Open Access Journals (DOAJ)
  • Embase
  • EBSCOhost
  • Google Scholar
  • HINARI Access to Research in Health Programme
  • Indian Science Abstracts (ISA)
  • Journal seek Database
  • Google
  • Popline (reproductive health literature)
  • www.omnimedicalsearch.com