Pancreatitis, chronic treatment

New data on the sulfonylurea receptor as part of the ATP-dependent potassium channel (SUR-1 in the beta pancreatic cells, involved in insulin secretion, and SUR-2 in the myocardium, involved in cardiac adaptation during ischemia) has still not yielded a definitive answer. The available experimental and clinical data have been systematically reviewed (29). The conclusion was that experimentally the effects of sulfonylureas on heart muscle are both deleterious and protective for glibenclamide while tolbutamide, glimepiride, and gliclazide have no effects. There seem to be no adverse cardiac consequences of chronic treatment with sulfonylureas. 

Only one study to date has been conducted on the treatment of acute pancreatitis with antioxidants. Clemens et al. (1991) were unable to show any difference in the incidence or severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in a prospective, randomized, double-blind, placebo-controlled trial of allopurinol. However, Salim (1991) performed a similar trial of the effect of allopurinol and DMSO in patients with pain from recurrent pancreatitis, and found significant benefit. On the basis that depletion of antioxidants is important in the pathogenesis of chronic pancreatitis, the administration of a cocktail of antioxidants was assessed for its effect on pain in this disease. Treatment with a combination of organic selenium, d-carotene, vitamins C and E, and methionine was of benefit in the initial pilot study, and in a placebo-controlled trial (San-dilands etal., 1990 Uden et al., 1990). 

Studies of both acute and chronic pancreatitis in humans and in animals support the hypothesis that free radicals are involved in the pathogenesis of pancreatitis. There is some conflicting data from the animal work, which may in part be due to differences in the models used. It does also indicate that free radicals are not the only factors involved and su ests that activation of pancreatic enzymes are also imprortant, particularly in the development of haemorrhagic pancreatitis (Sanfey, 1991). The findings of decreased antioxidant defences and the success of treatment reported in chronic pancreatitis with a cocktail of antioxidants and with allopurinol surest further studies are required to establish the role of antioxidants in pancreatic disease and its prevention. 

Salim, A.S. (1991). Role of oxygen-derived free radical scavengers in the treatment of recurrent pain produced by chronic pancreatitis. A new approach. Arch. Surg. 126, 1109-1114. 

Sandilands, D., Jeffrey, I.J.M., Haboubi, N.Y., MacLennan, I.A.M. and Braganza, J.M. (1990). Abnormal drug metabolism in chronic pancreatitis. Treatment with antioxidants. Gastroenterology 98, 766-772. 

Treatment of chronic pancreatitis is aimed at removing the cause (ethanol abuse or biliary stones), providing analgesia, supplementing with pancreatic enzyme preparations, and implementing dietary restrictions. 

FIGURE 28-2. Algorithm of guidelines for the treatment of pancreatic steatorrhea in chronic pancreatitis. (C, capsule ECMS, enteric-coated microsphere ECMT, enteric-coated microtablet ECS, enteric-coated sphere H2RA, histamine-2 receptor antagonist P, powder PPI, proton pump inhibitor UCT, uncoated tablet.)... 

Pancreatic enzyme replacement or supplement when enzymes are absent or deficient, such as with chronic pancreatitis, cystic fibrosis, or ductal obstruction from cancer of the pancreas or common bile duct to reduce malabsorption treatment of steatorrhea associated with bowel resection or postgastrectomy syndrome PO 1-3 capsules ortablets before or with meals or snacks. May increase to 8 tablets/dose. 

Exocrine pancreatic insufficiency is most commonly caused by cystic fibrosis, chronic pancreatitis, or pancreatic resection. When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss. Pancreatic enzyme supplements, which contain a mixture of amylase, lipase, and proteases, are the mainstay of treatment for pancreatic enzyme insufficiency. Two major types of preparations in use are pancreatin and pancrelipase. Pancreatin is an alcohol-derived extract of hog pancreas with relatively low concentrations of lipase and proteolytic enzymes, whereas pancrelipase is an enriched preparation. On a per-weight basis, pancrelipase has approximately 12 times the lipolytic activity and more than 4 times the proteolytic activity of pancreatin. Consequently, pancreatin is no longer in common clinical use. Only pancrelipase is discussed here. 

In patients with chronic hepatic B or C the respective prevalences of pancreatic autoantibodies increased from 2% and 3% at baseline to 5% and 7% after interferon (544). In all, 31 published cases of type 1 diabetes mellitus attributed to interferon alfa treatment were detailed, mostly in patients with hepatitis C. Irreversible diabetes required permanent insulin treatment in all but eight cases. At least one marker of pancreatic autoimmunity was positive in nine of 18 patients before treatment, and in 23 of 30 patients at the onset of diabetes. In accordance with these results and the likelihood of a genetic predisposition, the authors recommended screening for islet cell and glutamic acid decarboxylase autoantibodies before and during interferon alfa treatment. However, owing to the low number of reported cases and the paucity of studies that have examined the relation between pancreatic autoimmunity and the occurrence of diabetes, further research on the predictive potential of such a systematic investigation is warranted. 

Due. Treatment of pain in chronic pancreatitis with pancreatic enzymes. Am-... 

The course of pancreatic fibrosis in rats induced by dibutyltin dichloride was studied 2-36 weeks after single i.v. treatment of rats with dose of 6 or 8 mgkg-1. The pancreatic fibrosis induced by Bu2SnCl2 differs from other experimental models of acute pancreatitis. Extensive infiltration is present in fibrotic areas without pancreatic atrophy or lipomatosis. The presence of chronic inflammatory lesions characterized by the destruction of exocrine parenchyma and fibrosis, and in the later stages the endocrine parenchyma, indicates a chronic pancreatitis45. 

Pancreatic function tests are therefore indicated if and when one or more of the following aspects need be clarified Is a symptom or sign caused by pancreatic exocrine insufficiency Has pancreatic exocrine insufficiency developed in the course of chronic pancreatitis Does a patient require enzyme supplementation treatment ... 

Direct tests of secretory function such as fecal chymotrypsin and elastase 1 are the tests of first choice if the main diagnostic goal consists of noninvasive confirmation of chronic pancreatitis. Indirect tests may be preferred, however, if the main goal is to verify maldigestion (which needs not be due to loss of pancreatic secretory capacity) or to optimize enzyme treatment. For patients for whom noninvasive direct or indirect tests are negative or equivocal and diagnosis or exclusion of pancreatic exocrine insufficiency appears relevant, the invasive secretin-cerulein (SC) test should be considered. 

Enzyme replacement therapy (ERT) is a therapeutic approach in which the specific enzyme that is absent or inactive in affected individuals is replaced with a functional enzyme molecule. Pancreatic enzyme preparations of porcine or bovine origin have been available in the United States for treatment of exocrine pancreatic insufficiency (EPI) in children and adults with cystic fibrosis and chronic pancreatitis since before the enactment of the Federal Food, Drug and Cosmetic Act of 1938 (ref FDA guidance on EIP April 2004). A... 

Lamivudine (3TC) is a reverse transcriptase inhibitor with a relatively long intracellular half-life (14 h plasma t 6 h). In combination with zidovudine, lamivudine appears to reduce viral load effectively and to be well tolerated, although bone marrow suppression may be produced. Rarely, pancreatitis may occur. Lamivudine has also been used for treatment of chronic hepatitis B infection, but resistant strains of virus have been reported. 

A palindromic arthropathy with effusion and pancreatitis occurred in association with stibogluconate treatment for kala-azar in a 30-year-old man on hemodialysis for chronic renal insufficiency (SEDA-16, 311). 

Niemann T, Madsen LG, Larsen S, Thorsgaard N. Opioid treatment of painful chronic pancreatitis. Int J Pancreatol 2000 27(3) 235-40. 

Female rats are also more susceptible than males to such organophosphorus insecticides as azinphosme-thyl and parathion. Castration or estrogen treatment of the male reverses this difference. The male rat is far more susceptible to carcinoma than the female as shown in the following examples Males are more susceptible to the induction of pancreatic tumors by azaserine, colonic carcinoma by dime-thylhydrazine, intestinal tumors by dimethylnitrosa-mine, renal tumors by decalin, and liver cirrhosis by AAF. In the case of hydroquinone, which is present in photographic material, acute exposure produced renal toxicity in the female but in a chronic 2 year study, the male and not the female was found to have tubular degeneration and adenoma. 

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