Drug-Induced Acute Pancreatitis (Pharmacology Notes)
Reports of drug-induced acute pancreatitis (AP) have been published since the 1950s, and each year the list of drugs associated with AP increases. There are many etiological risk factors for AP, including a history of alcohol abuse, gallstones, endoscopic retrograde cholangiopancreatography and manometry, trauma or surgical procedures near the pancreas, certain medications, hyperlipidemia, infection, and chronic hypercalcemia (1, 2). Knowledge of the true incidence of drug-induced AP is dependent on clinicians excluding other possible causes and reporting the event. It can be difficult to rule out other causes of AP, especially in patients who have multiple comorbidities, use multiple medications, and have potentially unknown underlying risk factors. A retrospective study conducted in Germany concluded that the incidence of drug-induced AP is 1.4% (3). A national survey performed in Japan in 1999 reported that 1.2% of all cases of AP were drug induced (2). Drug-induced AP is rare but should not be over-looked in a patient who presents with idiopathic AP. The exocrine function of the pancreas includes the production of digestive enzymes for release into the gastrointestinal tract (1, 4). The acinar cells within the pancreas are responsible for producing the proenzymes, which then are packaged into storage vesicles called zymogens. The zymogens travel through the pancreatic duct and are secreted into the duodenum. Within the duodenum, enterokinase converts trypsinogen to trypsin, and then active trypsin facilitates the conversion of the other pancreatic proenzymes to the active form. AP can occur if there is damage to the acinar cells and/or injury to the pancreatic duct that leads to inappropriate accumulation and activation of proenzymes within the pancreas. The activated pancreatic enzymes digest the cell membranes of the pancreas and activate an inflammatory response, which increases the vascular permeability of the pancreas. Hemorrhage, edema, ischemia, and necrosis can result (1, 4). In severe AP, patients progress to systemic inflammatory response syndrome, sepsis, and multiple organ failure (5). About 3% to 13% of AP cases progress to chronic pancreatitis (2).