The onset of acute pancreatitis induced by statins has been observed from hours to years after treatment. Because of the variance in the latency period, the mechanism may be related to a direct toxic effect to the pancreas and the accumulation of a toxic metabolite. Other mechanisms of action of statin-induced acute pancreatitis are speculated to be associated with rhabdomyolysis, myalgia, and/or metabolism or drug interactions through cytochrome P-450 3A4 (CYP3A4).

Drugs are responsible for 0.1%-2% of acute pancreatitis incidents [1]. The majority of drug-induced pancreatitis cases are mild to moderate in severity; however, severe and even fatal cases can occur [2]. The newly emerged drugs like propofol infusion, antidiabetics (GLP1-Glucagon-like Peptide-1 Receptor) agonists and DDP4 (Dipeptidyl Peptase IV) inhibitors and SGLT2 (Sodium-glucose Cotransporter-2) inhibitors, particularly, canagliflozin), antibiotics (minocycline), antihypertensive agents (enalapril, lisinopril, captopril, ramipril, perindopril, and less frequently angiotensin receptor blockers) [3], proton pump inhibitors (omeprazole, pantoprazole, and lansoprazole), anticancer drugs (nivolumab, pembrolizumab, ipilimumab), the newer TKIs (Tyrosine kinase inhibitors- vemurafenib and ponatinib), proteasome inhibitors (bortezomib), and non-selective TACE (Transarterial chemoembolization), and direct-acting antiviral therapies (DAAs) of hepatitis C virus along with ribavirin and currently, more than 500 drugs have been reported in the World Health Organization database as offenders of acute pancreatitis [4]. The mechanism of doxycycline-induced pancreatitis is unknown, but is believed to be a direct toxic-effect or hypersensitivity reaction to the tetracycline class [5]. The onset of drug-induced pancreatitis after initiation of medications ranges from a few months to several years, with a median of 5 weeks; onset after rechallenge can occur within hours. The latency between initiation of the offending drug and developing acute pancreatitis can be short (less than 24 h), intermediate (1-30 days), and long (more than 30 days). According to Badalov classification system of drug induced pancreatitis, the latency is described as consistent with the drug-related pancreatitis when 75% of cases were related to any of the previously mentioned groups [6]. Potential mechanisms for drug-induced acute pancreatitis include pancreatic duct constriction, immune-mediated inflammatory response, direct cellular toxicity, arteriolar thrombosis, metabolic effects, hypersensitivity (Idiosyncratic) reactions, localized angioedema effect in the pancreas and influence of medication on the bile flow [7]

The onset of acute pancreatitis induced by statins has been observed from hours to years after treatment. Because of the variance in the latency period, the mechanism may be related to a direct toxic effect to the pancreas and the accumulation of a toxic metabolite. Other mechanisms of action of statin-induced acute pancreatitis are speculated to be associated with rhabdomyolysis, myalgia, and/or metabolism or drug interactions through cytochrome P-450 3A4 (CYP3A4). In several case reports, either myalgia or rhabdomyolysis occurred before development of acute pancreatitis and pravastatin does not metabolize CYP3A4, it may have fewer case reports of drug-induced acute pancreatitis than other statins [8]. A possible mechanism of action for angiotensin converting enzyme (ACE) inhibitor–induced acute pancreatitis is proposed to follow the mechanism of local angioedema of the pancreatic duct as they decrease the degradation of bradykinin which causes increased vascular permeability in the pancreas and can result in pancreatic edema. Since captopril is structurally dissimilar to enalapril and lisinopril, an allergic reaction seems less likely. In addition, angiotensin II receptors may be important in regulating secretion and microcirculation within the pancreas and may share a similar mechanism for pancreatitis.

The onset of acute pancreatitis is sudden. The patient presents with epigastric abdominal pain, vomiting and collapse. The pain is steady, boring and severe and often made worse by walking and lying supine and better by sitting and leaning forward [9]. Patients are restless and bringing their knees to their chest in an effort to alleviate the pain. The pain usually radiates to back, but may radiate to the right or left. Marked epigastric or diffuse tenderness on palpation with rebound tenderness and guarding is present in severe cases. The abdomen is often distended and tympanic, with bowel sounds decreased or absent in severe disease. The vital signs may be normal, but hypotension, tachypnea, tachycardia and low grade fever are often observed, especially with widespread pancreatic inflammation and necrosis. Jaundice is a common finding. In 3% of patients with severe acute pancreatitis, flank ecchymosis (Grey Turner sign) or periumbilical ecchymosis (Cullen sign) develops and is suggestive of retroperitoneal hemorrhage. Some patients display alterations in mental status, more common in drug-induced acute pancreatitis and reflects exposure to drugs or to ethanol but may also result from hypotension, hypoxemia, or the massive release of toxic agents from the inflamed pancreas. The condition has to be differentiated from other diseases producing acute abdomen such as acute appendicitis, perforated peptic ulcer, acute cholecystitis and infarction of intestine following sudden occlusion of the mesenteric vessel [10].