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CLINICAL REVIEW: Andrew Kingsnorth and Derek O'Reilly Acute pancreatitis BMJ 2006; 332: 1072-1076 [Full text]

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Reduced Vision Following Acute Pancreatitis

Mohammad T Masoud   (6 May 2006)

the differential diagnosis of hyperamylassaemia ought to include diabetic ketoacidosis

Oscar Jolobe   (7 May 2006)

Acute pancreatitis,acute surgical emergency

Nazar R DESSOUKI   (7 May 2006)

Acute pancreatitis

Terry Wong   (8 May 2006)

surgery in necrotizing pancreatitis

prasenjit raychaudhuri   (10 May 2006)

The role of MRCP in acute pancreatitis

Clive Vandervelde, Ajay Varghese and David C Howlett   (12 May 2006)

Acute pancreatitis

Kathir G Yoganathan   (12 May 2006)

A chilling tale of acute pancreatitis

Jane E Alty, Helen Ford, Consultant.   (16 May 2006)

Severe Acute Pancreatitis - ? Cause

Rajesh K Choudhary   (29 May 2006)

pancreatitis associated with atypical antipsychotics

Saul Malozowski   (14 June 2006)

When a drug is the cause of acute pancreatitis

María Reverte, Segio Aparicio Erroz, Carlos A. Montilla Morales   (24 July 2006)

Reduced Vision Following Acute Pancreatitis 6 May 2006
Mohammad T Masoud, Senior House Officer, Ophthalmology Stirling Royal Infirmary, Stirling. UK. FK8 2AU Send response to journal: Re: Reduced Vision Following Acute Pancreatitis	Dear Editor, I would like to bring to the attention of the readers a rare but interesting clinical condition that presents as sudden painless loss of vision following acute pancreatitis. Purtscher’s Retinopathy, a condition first described in 1910 in patients suffering severe head injury, is now also known to be associated with chest compression injuries, chronic renal failure, acute pancreatitis, pancreatic carcinoma, amniotic fluid embolization, lymphomas and connective tissue diseases (1). Inkeles and Walsh were the first to report an association between Purtscher's retinopathy and acute pancreatitis in three patients in 1975 (2). It is thought that pancreatic damage releases proteolytic enzymes which cause activation of the complement cascade and the formation of leukocyte, platelet and fibrin aggregates (3). This leads to retinal arteriolar occlusion which presents clinically as superficial patches of retinal whitening (resembling cotton-wool spots) and retinal haemorrhages around the optic disc. There are two reported cases of patients with history of alcohol abuse developing Purtscher’s retinopathy before acute pancreatitis (4,5). Patients with acute pancreatitis developing visual symptoms should therefore be considered for an ophthalmic referral. Purtscher’s retinopathy in patients with alcohol abuse may indicate a risk for development of a fulminant attack of acute pancreatitis. Reference: 1 Kanski JJ. Clinical Ophthalmology, A Systematic Approach. 5th ed. Butterworth-Heinmann, 2003:484. 2 Inkeles DM, Walsh JB. Retinal fat emboli as sequela to acute pancreatitis. Am J Ophthalmol. 1975;80(5):935-8. 3 Jacob HS, Goldstein IM, Shapiro I, Craddock PR, Hammerschmidt DE, Weissmann G. Sudden blindness in acute pancreatitis: possible role of complement-induced retinal leukoembolization. Arch Intern Med 1981;141:134 -136. 4 Sanders RJ, Brown CG, Brown A, Gerner EW. Purtscher’s retinopathy preceding acute pancreatitis. Ann Ophthalmol. 1992 Jan;24(1):19-21. 5 Sharma AG, Kazim NA, Eliott D, Houghton O, Abrams GW. Purtscher's retinopathy that occurred 6 months before acute pancreatitis. Am J Ophthalmol. 2006 Jan;141(1):205-7. Competing interests: None declared
the differential diagnosis of hyperamylassaemia ought to include diabetic ketoacidosis 7 May 2006
Oscar Jolobe, retired geriatrician 1 The Lodge, 842 Wilmslow Road, Didsbury, M20 2RN Send response to journal: Re: the differential diagnosis of hyperamylassaemia ought to include diabetic ketoacidosis	In the differential diagnosis of hyperamlassaemia(1), mention also needs to be made of diabetic ketoacidosis(DKA). The reason is that, even when hyperamylassaemia is within the diagnostic range for acute pancreatitis, it can still be solely attributable to dka(2). Severe abdominal pain can also be solely attributable to attributable to dka as shown in a prospective evaluation of 189 consecutive cases of dka including 86 with abdominal pain. In only 30 of those with abdominal pain was the etiology of the pain considered secondary to the precipitating cause of dka. In a substatiial proportion of the remainder(the text of the article not being user-friendly for working out the exact figures)the abdominal pain was solely attributable to dka as shown by its resolution when dka responded to treatment(3). Accordingly, when hyperamylassaemia co -exists with severe abdominal pain there is the potential to make a mistaken diagnosis of acute pancreatitis. Conversely, acute pancreatitis can itself be the sole underlying cause for dka as shown by a study comprising 100 consecutive episodes of dka in which eleven percent of patients had validation of acute pancreatitis by means of computerised axial tomography(4). In other words, in the presence of dka, the co- existence of hyperamylassaemia and abdominal pain might be a false positive indicator of acute pancreatitis but it is equally likely, in some intances, that it is a true positive for this diagnosis. The same logic , unfortunately not widely taught, operates when the application of Occam's razor has to be reconciled with the principles of Saint's Triad(5). In that kind of scenario whilst the logic of Occam's razor might be the true positive and Saint's triad the false positive, in some instances it is equally likely that the opposite might be the case. Oscar Jolobe MRCP(UK) References (1) Kingsworth A and O'Reilly D Acute pncreatitis British Medical Journal 2006:332:1072-6 (2) Vinicor F., Lehrer ML., Karn RC et al Hyperamylassaemia in diabetic ketoacidosis: sources and significance Ann Intern Med 1979:91:200-204 (3) Umpierrez G and Freire A Abdominal pain in patients with hyperglycemic crises J Crit Care 2002:17:63-7 (4) Nair S., Yadav D., Pitcomoni CS The association of diabetic ketoacidosis and acute pancreatitis: Observations in 100 consecutive episodes of DKA Am J Gastroentrol 2000:95:2795-2800 (5) Hilliard AA., Weinberger SE., Tierney LM et al Occam's Razor versus Saint's Triad N Engl J Med 2004:350:599-603 Competing interests: None declared
Acute pancreatitis,acute surgical emergency 7 May 2006
Nazar R DESSOUKI, consultant surgeon NHS PA34 4HH Send response to journal: Re: Acute pancreatitis,acute surgical emergency	Acute pancratitis patients shuold be treated in intensive care units and once stabilised should be refered to specialised pancreatic units for the best outcome. Competing interests: None declared
Acute pancreatitis 8 May 2006
Terry Wong, Consultant Gastroenterologist St. Thomas' Hospital, SE1 7EH Send response to journal: Re: Acute pancreatitis	Editor- In Kingsnorth and O’Reilly’s clinical review of acute pancreatitis(1) the role of endoscopic ultrasound (EUS) and ERCP in the investigation of idiopathic acute pancreatitis and choledocholithiasis is an issue of intense debate. In the review ERCP and bile sampling is recommended for the detection of microlithiasis. Numerous studies have demonstrated the accuracy of EUS in the diagnosis of microlithiasis(2); this investigation is not associated with the risks posed by diagnostic ERCP, and is therefore the investigation of choice in the diagnosis of microlithiasis. The use of ERCP and manometry in patients with suspected pancreatic sphincter of Oddi (SOD) dysfunction is associated with the risk of inducing pancreatitis, but this can be reduced with the use of prophylactic pancreatic stenting(3), and is a useful investigation in patients with suspected Geenan Type I pancreatic SOD causing recurrent idiopathic pancreatitis. The optimal management of patients with mild gallstone pancreatitis and possible choledocholithiasis is controversial. The accuracy of EUS in the detection of choledocholithiasis approaches unity and is higher than cholangiography without common bile duct instrumentation(4). As the authors state “failure to definitively clear gallstones results in unacceptable readmission..”, and therefore we advocate a more sensitive algorithm in the detection of choledocholithiasis with EUS prior to cholecystectomy, and either pre-operative ERCP, or intraoperative exploration in patients found to have choledocholithiasis rather than intraoperative cholangiography without intraoperative choledochoscopy. 1. Kingsnorth A, O'Reilly D. Acute pancreatitis. BMJ 2006;332(7549):1072-1076. 2. Dahan P, Andant C, Levy P, Amouyal P, Amouyal G, Dumont M, et al. Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography. Gut 1996;38(2):277-81. 3. Fazel A, Quadri A, Catalano MF, Meyerson SM, Geenen JE. Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study.[see comment]. Gastrointestinal Endoscopy 2003;57(3):291- 4. 4. Prat F, Amouyal G, Amouyal P, Pelletier G, Fritsch J, Choury AD, et al. Prospective controlled study of endoscopic ultrasonography and endoscopic retrograde cholangiography in patients with suspected common-bileduct lithiasis.[see comment]. Lancet 1996;347(8994):75-9. Competing interests: None declared
surgery in necrotizing pancreatitis 10 May 2006
prasenjit raychaudhuri, clinical fellow,surgery kings mill hospital,mansfield,ng174jl Send response to journal: Re: surgery in necrotizing pancreatitis	Since the initial clinical description of acute pancreatitis by Fitz in 1889,the role of surgery in acute pancreatitis has been controversial.It was Fitzs' opinion that surgical intervention could only complicate matters.Senn,a chicago surgeon took exception to Fitzs' position and advocated removal of dead tissue(1).The role of surgery in acute pancreatitis continues to be debated. While advancement in investigation and surgery of pancreatitis continues,morbidity and mortality in severe disease is still high and excellent results produced by some centres are not uniformly reproducible.Many of the concepts involved like SIRS,MODS,Gut mucosal barrier and abdominal compartment syndrome,which play a pivotal role in the initiation and propogation of the disease,partic ularly in the context of severe attacks are fairly recent knowledge.Attempts to modulate SIRS ,support failing organs in critical care settings ,boost gut mucosal barrier by enteral nutrition and selective decontamination and to reduce intraabdominal pressure are still in their infancy. Surgical treatment of necrotizing pancreatitis has been particularly challenging and unsatisfactory.Surgery is indicated at a stage when the disease is substantially advanced and the patient already in a poor state.Adding further major surgical insult at such an advanced stage can add fuel to fire.Outcomes of open abdominal surgery have not been very good.Recent attempts at minimally invasive retroperitoneal debridement with local or locoregional lavage may prove promising(2). Surgical treatment has been advocated in the past by respected surgeons like Lord Moynihan.However the days of major surgical adventure in necrotising pancreatitis are numbered as trends become more conservative.Understandably micromanipulation at various levels of disease progression and minimally invasive surgery in selected cases are the directions for the future. References: 1.Bradley EL.Indications for surgery in necrotising pancreatitis-a millenial review.J Pancreas(Online)2000;1(1):1-3. 2.Besselink MG et al.Surgical intervention in patients with necrotising pancreatitis.Br J Surg 2006;93:593-99. Competing interests: None declared
The role of MRCP in acute pancreatitis 12 May 2006
Clive Vandervelde, Specialist Registrar Radiology Eastbourne District General Hospital, Kings Drive, Eastbourne, East Sussex. BN21 2UD, Ajay Varghese and David C Howlett Send response to journal: Re: The role of MRCP in acute pancreatitis	EDITOR- We read with interest the recent review article on acute pancreatitis by Kingsnorth and O’Reilly [1]. It would be useful to emphasise the role of Magnetic Resonance Cholangiopancreatography (MRCP) in the management of this condition, particularly in the investigation of suspected choledocholithiasis as an aetiological factor in the presence of sonographically non-dilated ducts. MRCP is a non-invasive and now widely available technique utilising T2-weighted MR sequences which can be acquired in a single breath-hold. Intravenous and oral contrast are not required and this investigation provides high quality delineation of the biliary tree and pancreatic duct. MRCP has replaced Endoscopic Retrograde Cholangiopancreatography (ERCP) as a diagnostic tool for the investigation of suspected choledocholithiasis in many centres, with ERCP reserved for therapeutic intervention. MRCP is particularly useful in patients with pancreatitis and gallbladder stones but non-dilated ducts, in whom exclusion of a bile duct calculus is important. MRCP can be supplemented with conventional MR sequences to assess the pancreas itself and detect fluid collections. There are some contraindications including pacemakers and recent surgery, and MRI may not be suitable for patients with claustrophobia, inability to breath-hold or those who are clinically unstable. 1 Kingsnorth A, O’Reilly D. Acute Pancreatitis. BMJ 2006 332:1072- 1076. (6 May.) Competing interests: None declared
Acute pancreatitis 12 May 2006
Kathir G Yoganathan, Consultant Physician Singleton Hospital,Sketty,Swansea,UK,SA2 8QA Send response to journal: Re: Acute pancreatitis	Acute pancreatitis in HIV infected population Kingsnorth et al gave an elegant clinical review of acute pancreatitis (AP) and its causes1. However important causes of acute pancreatitis in HIV positive patients has not been discussed. These causes include anti-retroviral therapy and opportunist infections. Didanosine,(ddI- neucleoside reverse transcriptase inhibitor) is known to cause AP in up to 7% of HIV positive patients2. It is dose dependent and concurrent use of tenofovir (nucleotide reverse transcriptase inhibitor) increases the level of ddI and associated risk of pancreatitis3. The use of stavudine and ribavirin with ddI also increases the incidence of pancreatitis due to mitochondrial toxicity. Also the risk of AP is increased four fold when hydroxurea is combined with ddI. The use of protease inhibitors (PIs) is associated with hypertriglyceridaemia which is a well-known cause of AP. However, despite this association, the use of PIs was not significantly linked with hyperlipidaemia induced pancreatitis in an HIV population4. Other causes of AP in HIV infected populations include infections with disseminated CMV, T gondii, M Tuberculosis, M avium intracellulare and Cyrptosporidium. Acute pancreatitis, possibly due to primary HIV infection during acute seroconversion, has also been reported5. With increased numbers of patients with HIV and wide spread use of antiretroviral therapy the incidence of AP is likely to rise. Clinicians should therefore include AP in a differential diagnosis of abdominal pain in HIV infected population. 1) Kingsnorth A, O’Reilly D, Acute Pancreatitis. BMJ 2006; 332:1072- 76. 2) Chima Okereke C, Davies L,Yoganathan K. Fatal Acute Pancreatitis in an HIV positive man: the result of an interaction between Tenofovir Disproxil fumerate (TDF) and Didanosine (DDI). Sixth International Congress on drug therapy in HIV infection. Glasgow 17-21 November 2002. 3) Moore RD, Keruly JC, Chaisson RE. Incidence of pancreatitis in HIV infected patients on nucleoside RTI’s 8th Congress of retroviruses and Opportunistic Infections. Chicago, IL. Feb 4-8. 2001. 4) Bush ZM, Kosmiski LA, Acute Pancreatitis in HIV infected patients: are etiologies changing since the introduction of protease inhibitor therapy. Pancreas 2003; 27 (1) 1-5. 5)Rizzard GP, Tambussi G, Lazzarin. Acute Pancreatitis during primary HIV- 1 infection. N Engl J Med. 1997; 336:18 36-37. I thank Dr A Blackwell for her helpful comments. Competing interests: None declared
A chilling tale of acute pancreatitis 16 May 2006
Jane E Alty, Specialist Registrar Department of Neurology, G Floor, Martin Wing, Leeds General Infirmary, Leeds, LS1 3EX, Helen Ford, Consultant. Send response to journal: Re: A chilling tale of acute pancreatitis	EDITOR- Hypothermia is an important cause of acute pancreatitis that was omitted from Kingsnorth and O’Reilly’s otherwise excellent clinical review.[1] 50-65% of hypothermic patients have a raised serum amylase level and acute pancreatitis has been found at post mortem in 20-30% of accidental hypothermia cases.[2][3] Thermoregulatory mechanisms may be impaired in the elderly and those with chronic neurological conditions such as multiple sclerosis making them particularly vulnerable to hypothermia during the winter months.[4] Unless hypothermia is actively sought with core temperature recordings, the window of opportunity to easily and swiftly reverse the provoking factor may be missed with the consequent demise of the patient. The management of patients with acute pancreatitis and mild hypothermia (core temperature 33-35oC) should include active external re-warming with a Bear Hugger or space blanket; in cases with severe hypothermia (core temperature < 28oC) active internal re-warming with warmed intravenous fluids, heated humidified oxygen and body cavity lavage may be necessary.[5] Competing interests: None declared 1. Kingsnorth A, O'Reilly D. Acute pancreatitis. BMJ 2006;332:1072- 1076. (6 May.) 2. Maclean D, Murison J, Griffiths PD. Acute pancreatitis and diabetic ketoacidosis in accidental hypothermia and hypothermic myxoedema. BMJ 1973;4:757-61. 3. Duguid H, Simpson RG, Stowers JM. Accidental hypothermia. Lancet 1961;11:1213-9. 4. White KD, Scoones DJ, Newman PK. Hypothermia in multiple sclerosis. JNNP 1996;61:369-375. 5. Epstein E, Anna K. Accidental hypothermia. BMJ 2006;332:706-709. Competing interests: None declared
Severe Acute Pancreatitis - ? Cause 29 May 2006
Rajesh K Choudhary, Staff Grade Surgeon, Department of Surgery,Darlington Memorial Hospital, Darlington DL3 6HX Send response to journal: Re: Severe Acute Pancreatitis - ? Cause	Severe Acute Pancreatitis -? Cause I read with interest the article, Acute pancreatitis by Professor Kingsnorth1. There is no mention of microcirculatory dysfunction, which is a key pathological process in the development of severe necrotizing pancreatitis and therapies targeted at mediators of the microvascular changes2. Approximately one-third of patients with acute pancreatitis develop pancreatic necrosis, which has mortality up to 30 percent3. This severe form of the disease is characterised by pancreatic necrosis, cytokine activation, systemic inflammatory response syndrome (SIRS), rapidly leading to multiple organ failure. Furthermore, bacteria which migrate from the gut may colonise necrotic pancreatic and peri-pancreatic tissue, converting sterile necrosis to infected necrosis. This has a serious adverse effect of outcome4. Microvascular compromise has been suggested as the critical event in the development of severe pancreatitis. Changes to the microvascular circulation are not confined to the pancreas but may affect the gastrointestinal tract, liver, lungs, kidney and skeletal muscle. Microcirculatory disorders are mechanism of multiple organ failure and marker of inflammation2, 4, 5. Therapies targeted at mediators of the microvascular changes in acute pancreatitis are currently being investigated. Resuscitation with colloid is better than crystalloid in improving microvascular variables with some crystalloid is necessary to help maintain urine flow2, 4. Clinical trials of Heparin in pancreatitis have so far been inconclusive. Somatostatin and Lexipafant, a PAF antagonist, failed to show improvement in organ injury score or mortality2, 4. Therapies directed at improving both local and systemic cellular perfusion may improve outcome and this offers exciting prospects for further clinical development2, 4. Competing interests: None declared. 1. Kingsnorth A, O’Reilly D. Acute pancreatitis. BMJ 2006; 332:1072- 1076 (6 May). 2. Cuthbertson C M, Christophi C. Disturbances of the microcirculation in acute pancreatitis. BJS 2006; 93:518-530. 3. Mitchell R M, Byrne M F, Ballie J. Pancreatitis. Lancet 2003;361:1447- 1455 4. Taylor I, Johnson C D. Recent advances in Surgery 1999; 22:147-155 5. Plusczyk T, Witzel B, Menger M D, Schilling M. ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. Am J Physiol Gastrointest Liver Physiol 2003; 285: G145- G153 Competing interests: None declared
pancreatitis associated with atypical antipsychotics 14 June 2006
Saul Malozowski, Senior Advisor for Endocrine Physiology DEM/NIDDK/NIH Bethesda , MD 20892-5460 USA Send response to journal: Re: pancreatitis associated with atypical antipsychotics	Dear Editor: In their excellent review on Acute Panecreatitis1, Kingsnorth and O’Reilly properly listed a number of drugs known to be associated with this condition. This information was presented in a table that was extracted from a manuscript2 dated in 2001. A more recent and comprehensive article reviewing drug induced pancreatitis3 was published in 2005 could be a better source for those seeking information on potentially drug induced pancreatitis. In addition, I would like to highlight the association of acute pancreatitis with the use of atypical antipsychotics (clozepine, olanzepine and resperidone)4 ; this paper reports on 192 cases of pancreatitis received by the FDA (10 of those in individuals 18 years old and younger) in subjects exposed to these medications. Although the risk for pancreatitis may not be similar with all agents, the underlying psychiatric conditions may present additional diagnostic dilemmas to the practitioner. Psychiatric patients may be at increased risk for pancreatitis because drug and alcohol abuse are more common in this population and because many also receive also valproic acid2,3 that has been reported as associated with pancreatitis. Saul Malozowski, MD, PhD, MBA Senior Advisor for Endocrine Physiology Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Democracy Two 6707 Democracy Blvd RM 607 Bethesda MD 20892-5460 e-mail: sm87j@nih.gov References 1) Kingsnorth A, O'Reilly D. Acute pancreatitis BMJ 2006;332:1072- 1076. 2) Somogyi L, Martin SP, Venkatesan T, Ulrich CD 2nd. Recurrent acute pancreatitis: an algorithmic approach to identification and elimination of inciting factors. Gastroenterology 2001;120: 708-17. 3) Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol. 2005: 39:709-16. 4) Koller EA, Cross JT, Doraiswamy PM, Malozowski SN, Pancreatitis associated with atypical antipsychotics: from the Food and Drug Administration's MedWatch surveillance system and published reports. Pharmacotherapy. 23:1123, 2003. Disclaimer This letter represents the authors’ views and does not constitute an official position of the Department of Health and Human Services. Competing interests: None declared
When a drug is the cause of acute pancreatitis 24 July 2006
María Reverte, Professor of Pharmacology Dpto.Fisiología y Farmacología. Facult. Medicina. Univ. Salamanca. 37007 Spain. socorro@usal.es, Segio Aparicio Erroz, Carlos A. Montilla Morales Send response to journal: Re: When a drug is the cause of acute pancreatitis	Dear Editor, Kingsnorth and O´Reilly (1) have observed in a recent review that several drugs would induce acute pancreatitis (DIP), as an adverse drug reaction (ADR). There are often ignored by physicians, because of the difficulty in implicating a drug as its cause (2). Perhaps, the differences in the latent periods between the time of exposure to a drug and the development of the acute pancreatitis (AP) could be the most important reason. In 1995 Lankisch et al. (3) observed that the incidence of DIP is 1.4%. Nevertheless, this data would be increased as published Trivedi & Pitchumoni (2) in 2005. Those authors have written that the incidence of suspected DIP is 2% for general population; a value that would be elevated to 40%, for the case of patients with Human immunodeficiency virus infection (HIV). Additionally, if we think in children, we could also observe a higher incidence of DIP, more than general population, because it is 12% (4). Perhaps, the rise in the incidence may be due to a greater prevalence of risk factors in children. Actually, the list of DIP is also increased. In a recent publication it is observed that propofol (5) and antilymphocyte globulin (6) are able to produce an AP. Perhaps, other risk factors of AP (hypertriglyceridemia, alcohol and dysfunction of the sphincter of Oddi; 1) or cholecystectomy (7) are not in mind of physicians before used new drugs with an exocrine pancreotoxic potential. Why is DIP produced? At the moment, it is the main question, because the mechanisms of action of drugs toxicity, which are not the same for all the drugs, are not well known. For the case of NSAIDs like sulindac, ibuprofeno, aspirin, felbamate, rofecoxib or indomethacin; their mechanism of action could be related with their capacity to reduce the amount of systemic glutathione and, in consequence, evoke an oxidative stress reaction (8). Mitochondrial toxicity is the cause that dinadosine-induced acute pancreatitis (9). Erythromycin may increase the sphincter of Oddi as a possible mechanism (10). An immune-mediated mechanism has been proposed for sulphonamides (11) and aminosalicylate (12) induced AP. Evenmore, valproic acid, the most important drug that evoke AP in children (4), could reduce plasma carnitive levels and, in consequence, alter mitochondrial function (13). In the particular case of morphine, Gustein & Akil (14) have observed textually in a textbook for medical students: `After the subcutaneous injection of 10 mg morphine sulphate, the sphincter of Oddi constricts, and the pressure in the common bile duct may rise more than tenfold with 15 min, this effect may persists for two hours or more´. Probably, the spam of this sphincter, which is also observed in experimental human studies (15), would be related with the increase of plasma amylase and lipase determined after the administration of morphine. It is curiously to observe, that codeine, an opioid drug, which is o-demethyland to morphine (10%) in the human body (14), is also able to induce an acute pancreatitis at low dose (7). Both morphine and codeine have been classified recently as class I drugs-associated with pancreatitis (2). However, DIP damage is much rarer than hepatotoxicity (16). The serious course of this AP produced by drugs (18), death and hospitalisation are part of the history of DIPs, obligates to say that further investigation about drugs with exocrine pancreotoxic potential is necessary. References 1. Kingston A, O´Reilly D. Acute pancreatitis. BMJ 2006;332: 1072-6. 2. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol 2005;39:709-16. 3. Lankisch PG, Dröge M, Gottesleben F. Drug induced acute pancreatitis: incidence and severity. Gut 1995;37:565-7. 4. Werlin SL, Kugathasan S, Cowan Frautschy B. Pancreatitis in Children. J Pediatric Gastroenterol Nutrit 2003;37:591-5. 5. Bustamante SE, Appachi E. Acute pancreatitis after anaesthesia with propofol in a child with glycogen storage disease type IA. Paediatr Anaesth 2006; 16:680-3. 6. Lee WC, Wu MJ, Cheng CH, Chen CH, Wen MC, Chen HC, Shu KH. Acute pancreatitis following antilymphocyte globulin therapy in a renal transplant recipient. Clin Nephrol 2006;65:144-6. 7. Hastier P, Longo F, Buckley M, Chichmanian RM, Delmont JP. Pancreatitis induced by codeine: a case reporth with positive rechallenge. Gut 1997;41:705-6. 8. Spicak S. Etiological factors of acute pancreatitis. Vnitr Lek 2002;48:829-41. 9. Memis D, Akalin E, Yucel T. Indomethacin-induced pancreatitis. A case report. JOP. J Pancreas (online) 2005;6:344-7. 10. Flexner C. Antiretroviral agents and treatment of HIV infection. In: Bruton LL, Lazo JS & Parker KL, eds. Godman and Gilman´s. The Pharmacological Basic of Therapeutics. New York: McGraw-Hill Co, 2006; 1273-314. 11. Fang CC, Wang HP, Lin JT. Erythromycin-induced acute pancreatitis. J Toxicol Clin Toxicol 1996;34:93-95. 12. Brazer SR, Mcdoff JR. Sulfonamide-induced pancreatitis. Pancreas 1988;3:583-6. 13. Adachi E, Okazaki K, Matsushima Y, Seno H, Uchida K, Nakasi H, et al. Acute pancreatitis secondary to 5-aminosalicylic acid therapy in a patient with ulcerative colitis. J Pancreatol 1999;5:217-21. 14. More FA, Macey H, Schreiber B. Carnitine levels in valproic acid- treated psychiatric patients: a cross-sectional study. J Clin Psychiatry 2005;66:555-8. 15. Gustein HB, Akil H. Opioid analgesics. In: Bruton LL, Lazo JS & Parker KL, eds. Godman and Gilman´s. The Pharmacological Basic of Therapeutics. New York: McGraw-Hill Co, 2006; 547-90. 16. Wu S-D, Zhang ZH, Jin JZ, Kong J, Wang W, Zhang Q, Li DY, Wang MF. Effects of narcotic analgesic drugs on human Oddi´s sphincter motility. World J Gastroenterol 2004;10:2901-4. 17. Andersen V, Sonne J, Andersen M. Spontaneous reports on drug- induced pancreatitis in Denmark from 1968 to 1999. Eur J Clin Pharmacol 2001;57:517-21. Competing interests: None declared