Pharmacologic therapy for acute pancreatitis

Table 1 Summary of pharmacologic agents studied in experimental acute pancreatitis

Pharmacologic agent	Animal model		Outcome assessment	Citations
	Species name	Mechanism of pancreatitis induction
Anti-secretory agents
Glucagon	Dog	Duodenal obstruction, pancreatic duct infusion of lactated ringer solution or pancreatic duct infusion of bile-trypsin solution	Not beneficial when compared to simple volume resuscitation	[15]
	Pig	Hemorrhagic pancreatitis induced by bile injection into pancreatic duct	Reduced mortality	[16]
Somatostatin	Rat	Taurocholate	No decrease in mortality	[21, 22]
Protease inhibitors
Aprotinin	Dog	Hemorrhagic pancreatitis surgically induced	Prophylactic and therapeutic potential	[17-19]
Chlorophyll-a	Guinea pig	Taurocholate-induced necrotizing pancreatitis	Benefit in survival	[25-27]
Anti-inflammatory/immunomodulators
PGE therapy	Rat, mice	Taurocholate, CDE diet, or caerulein	Protective effect	[29-31]
Indomethacin	Rat	Olive oil or taurocholate	Beneficial particularly early in induction	[32-34]
Lipoxygenase inhibitor	Rat	Taurocholic acid	Protective effect	[35]
Steroid	Rat	Caerulein and taurocholate	Decreased inflammation and protective	[37-43]
IL-10	Rat, mice	Caerulein	Reduction in severity of disease	[44, 48-50]
Lexipafant	Rat, mice	Intraductal administration of 5% sodium taurodeoxycholate or caerulein	Reduction in severity, SIRS, and bacterial translocation	[46, 47]
Hemin/panhematin/ biliverdin/CO/IL-22	Rat, mice	caerulein, taurocholate, or CDE diet	Protective and therapeutic effects	[61-67]
Anti-TNF alpha	Mice	caerulein, taurocholate, or CDE diet	Decreased inflammatory response and cell death	[72-75]
Anti-oxidants
Tempol	Mice	carrageenan injected into pleural cavity	Decrease in inflammation and shock	[54]
Selenium	Rat	L-arginine hydrochloride	Reduction in pancreatic injury	[53, 145]

CO: Carbon monoxide; PGE: Prostaglandin E1; SIRS: Systemic inflammatory response syndrome; TNFα: Tumor necrosis factor α; CDE: Choline deficient ethionine-supplemented.

Table 2 Summary of pharmacologic agents studied in clinical acute pancreatitis

Pharmacologic agent	Study design	Sample size	Outcome assessment					Citations
			Decreased SIRS	Decreased organ failure	Decreased length of stay	Decreased mortality	Other
Anti-secretory agents
Glucagon	RCT	22-69	Not reported	Not reported	No	No		[76-82]
Atropine	RCT	51	Not reported	Not reported	No	No		[83]
Calcitonin	RCT	94	Not reported	Not reported	Not reported	No	↓ pain, earlier normalization of labs	[84-86]
Somatostatin	RCT/meta-analysis	50-703	Not reported	Indeterminate (no effect on multi-organ failure but ↓ local complications)	Indeterminate	Indeterminate	↓ pancreatic abscess and necrosis, ↓ local inflammation	[90-95]
Octreotide	RCT/meta-analysis	19-948	Yes	Yes	Indeterminate	Indeterminate		[97-99]
Protease inhibitors
Aprotinin	RCT	48-105	Not reported	No	Yes	No	↓ pancreatic necrosis, ↓ complement activation	[101-105]
Gabexate mesilate	RCT/meta-analysis	42-898	Not reported	No	No	No	CRAI ↓ hospitalization stay and SIRS	[108-113]
Nafomostat	RCT	51-78	Not reported (↓ pancreatic necrotic tissue infection)	Not reported	Not reported	Yes	Only CRAI + abx has benefit	[114-116]
Immunomodulators
Lexipafant	RCT	50-290	Yes	Yes	Not reported	Yes	↓ local complications (pancreatic abscess, pseudocyst)	[117-119]
Dotrecogin alfa	RCT	32	Yes	No	Not reported	No		[122, 123]
Acetylcysteine, selenium, vitamin C combinations	RCT	39-53	Indeterminate (↓ CRP but not sig)	No (trend toward ↑ MOF)	No	No		[132-134]
Glutamine	RCT/meta-analysis	505	Yes	Yes	No	Yes		[135, 136]

RCT: Randomised controlled trials; SIRS: Systemic inflammatory response syndrome; CRAI: Continuous regional arterial infusion; ERCP: Endoscopic retrograde cholangiopancreatography; MOF: Multiple organ failure; RCT: Randomized controlled trial.