Feedback Control of Exocrine Secretion Nonenteric Coated Pancreatic Enzyme Perspective

The basis for the use of nonenteric-coated pancreatic enzyme preparations to decrease abdominal pain in patients with chronic pancreatitis is based on the concept of feedback control of pancreatic exocrine secretion (Isaksson and Ihse, 1983; Slaff et al, 1984). Nonenteric-coated pancreatic enzyme preparations appear to inhibit pancreatic secretion through a negative feedback mechanism involving intraduodenal serine proteases in the exocrine pancreas. These serine proteases modulate pancreatic secretion by regulating CCK release. Because patients with chronic pancreatitis often have decreased intraduodenal protease activity, they may not be capable of inactivating the CCK-releasing peptide that exists in the proximal small bowel and is largely responsible for stimulating CCK release. In these patients, it can be demonstrated that there are high levels of CCK in the blood. This is a proximal small intestine phenomenon and the pancreatic proteases must be delivered to the upper small intestine. This can be done consistently only by the administration of nonenteric-coated pancreatic enzyme preparations. Such nonenteric-coated enzyme preparations are susceptible to acid degradation as they pass through the stomach; therefore, it is recommended that a proton pump inhibitor (PPI) be given along with the pancreatic enzymes. We have found that the most consistent preparation that affords control feedback inhibition and relieves abdominal pain is the preparation of Viokase-16. This preparation should be given orally in a dose of four tablets, four times a day, along with the acid suppressive agent. These enzyme preparations are remarkably devoid of side effects. The remarkable side effect of colonic strictures noted in patients with CF receiving very large doses of enteric-coated pancreatic enzymes (see Chapter 140, "Cystic Fibrosis and other Hereditary Diseases of the Pancreas") does not occur in adult patients with chronic pancreatitis.

Six randomized trials have evaluated the effectiveness of pancreatic enzymes in the reduction of chronic pancreatitis pain (Warshaw et al, 1998). Of these, two trials using nonenteric-coated enzymes were effective in reducing pain, whereas the four trials using the enteric-coated preparations showed no statistical improvement in pain relief. In patients with big duct disease, there was, at best, a 25% response rate in decreasing abdominal pain, whereas the response rate was approximately 70% in those with small duct disease. A meta-analysis of these trials indicates that pancreatic enzyme therapy did not decrease abdominal pain in patients with chronic pancreatic (Brown et al, 1997). It should be pointed out that this meta-analysis has been sharply criticized for lumping together patients receiving nonenteric-coated and enteric-coated enzymes. Abundant information now exists both from randomized trials and extensive clinical experience that nonenteric-coated enzyme preparations are preferable for relief of the abdominal pain in such patients. Table 139-4 contrasts the nonenteric and the enteric-coated enzymes in this feedback control process.

Thus if one wants to optimize pancreatic enzyme therapy in treating the pain of chronic pancreatitis, the appropriate enzyme preparation must be employed in a suitable patient. A nonenteric enzyme preparation should be given

TABLE 139-4. Pancreatic Enzyme Preparations and

Feedback Control of Pancreatic Secretion

Criteria

Nonenteric-Coated

Enteric-Coated

Release proteases into duodenum

Yes

No

Lower CCK level

Yes

No

Decrease pancreatic secretion

Yes

No

Reduce pain

Yes

No

CCK = cholecystokinin.

CCK = cholecystokinin.

along with a PPI to a patient with small duct chronic pancreatitis who does not have steatorrhea. Great success will not be achieved when a patient with large duct disease and steatorrhea is treated with an enteric-coated preparation.

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