Pharmacological Prevention and Treatment of Acute Pancreatitis: Where Are We Now?

Abstract

Acute pancreatitis is a disease of increasing prevalence, unchanged mortality over many decades, and limited treatment strategies. Progress has been made in developing therapies that reduce the rate of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatitis and in preventing infected pancreatic necrosis with intravenous carbapenems. Attempts at reducing pancreatic enzyme output or inhibiting the activity of digestive enzyme proteases have not yielded encouraging results – nor have anti-inflammatory strategies for the treatment of acute pancreatitis been found to be effective so far. Future therapeutic options that are presently being developed or under investigation attempt to restore pancreatic secretory function, interfere with inflammatory pathways in a more effective manner, or inhibit digestive enzyme proteases more selectively.

Effects of everolimus on a rat model of cerulein-induced experimental acute pancreatitis

“…Although the other three scores did not show any significant difference, a decrease in inflammation and perivascular infiltrate score by 35% in experimental rat models with cerulein-induced acute pancreatitis administered with one dose of everolimus by oral gavage and a decrease by 75% in those administered with two doses of everolimus were the most significant and promising findings of this study (Table 4). Because the mortality rate significantly increases with multiple organ failure because of SIRS, the specific inhibition of inflammatory signalling pathways presents a great potential as pharmacological treatment (2,6,21). The significant decrease in inflammation and perivascular infiltrate score may imply that everolimus treatment directly or indirectly interferes with the inflammatory signalling pathway, thereby inhibiting SIRS.…”

Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

“…In SAP, MODS, a consequence of the systemic inflammatory response syndrome, is a contributor to high mortality in the early phase [1] . It is conceivable that the release of mediators from the excess of activated macrophages/monocytes and neutrophils may lead to remote organ injury [1] .…”

“…It is conceivable that the release of mediators from the excess of activated macrophages/monocytes and neutrophils may lead to remote organ injury [1] . Serum HMGB1 levels are significantly elevated in patients with SAP on admission [12] .…”

“…Excessive activation of the inflammatory mediator cascade during severe acute pancreatitis (SAP) is a major cause of multiple organ dysfunction syndrome (MODS), which leads to a high mortality rate [1] . Therapeutic strategies targeting these inflammatory mediators are thought to be an ideal way to reduce the severity of SAP.…”

Clodronate-containing liposomes attenuate lung injury in rats with severe acute pancreatitis

“…Histopathological scores were higher in the P and T groups than in the C group, and lower in the T group than in the P group at 2 and 6 h. * P<0.05 as compared with the C group, # P<0.05 as compared with the P group. Data are expressed as mean±SD (n=8) 4 Discussion SAP is associated complications including SIRS, MODS, ALI, and local complications within the pancreata (Ammori, 2003;Lankisch and Lerch, 2006). Among the extrapancreatic complications of SAP, ALI is most frequently associated with death.…”