Medication Summary
No curative treatment for chronic pancreatitis exists. Medical therapy is determined primarily by symptoms. If no anatomic explanation for abdominal pain can be found, medical therapy can be attempted. This therapy includes pain control with analgesic agents and a trial of noncoated pancreatic enzymes.
The use of exogenous pancreatic enzymes to reduce pain is linked to the hypothesis that pancreatic stimulation by food causes pain. Cholecystokinin (CCK) is one of the possible mediators of this response.
Analgesics, Other
Class Summary
Initial therapy consists of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). For severe, refractory pain, narcotic analgesics often are required, starting with the least potent agents and progressing to more potent formulations as necessary.
Acetaminophen (Acephen, Cefotan, Mapap, Tylenol, FeverAll, Aspirin Free Anacin)
Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs, those with upper GI disease, and those who are taking oral anticoagulants.
Opioid Analgesics
Class Summary
These medications provide control of moderate to severe pain.
Hydrocodone and acetaminophen (Vicodin, Lorcet, Lortab, Norco, Zolvit)
This drug combination is indicated for moderate to severe pain.
Acetaminophen with codeine (Tylenol-3)
This drug combination is indicated for treatment of mild to moderate pain.
Tramadol (Ultram, Ryzolt)
Tramadol inhibits the ascending pain pathways, altering the perception of and response to pain. It also inhibits the reuptake of norepinephrine and serotonin.
Nonsteroidal Anti-Inflammatory Drugs
Class Summary
NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.
Naproxen (Naprosyn, Aleve, Naprelan, Anaprox)
Naproxen is indicated for relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease in prostaglandin synthesis.
Diclofenac (Voltaren, Cataflam, Cambia, Zipsor)
These NSAIDs inhibit prostaglandin synthesis by decreasing cyclooxygenase activity and by decreasing the formation of prostaglandin precursors.
Ketorolac
Ketorolac is an intravenously administered NSAID and a very powerful analgesic. It inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors. In turn, this results in reduced inflammation.
Ibuprofen (Advil, Motrin, Caldolor)
Ibuprofen is usually the drug of choice for the treatment of mild to moderate pain, if no contraindications exist. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclo-oxygenase, resulting in inhibition of prostaglandin synthesis.
Celecoxib (Celebrex)
Celecoxib inhibits primarily cyclooxygenase-2 (COX-2). COX-2 is considered an inducible isoenzyme; it is induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, celecoxib does not inhibit the COX-1 isoenzyme; thus, GI toxicity may be decreased. The increased cost of celecoxib must be weighed against the benefit of avoidance of GI bleeds. Seek the lowest dose of celecoxib for each patient.
Hormones
Class Summary
Hormones can be used for the reduction of pancreatic exocrine secretion.
Octreotide (Sandostatin)
Octreotide has an 8 ̶ amino acid sequence containing the active portion of somatostatin. In a study, subcutaneous injection of octreotide 3 times daily at 200mcg provided pain relief in 66% of patients. Note that 35% of the control group also experienced pain relief.
Antidepressants, TCAs
Class Summary
In addition to alleviating coexistent depression, tricyclic antidepressants may ameliorate pain and potentiate the effects of opiates.
Amitriptyline hydrochloride
This agent is an analgesic for certain chronic and neuropathic pain.
Clomipramine (Anafranil)
Clomipramine is a dibenzazepine compound belonging to the family of TCAs. The drug inhibits the membrane pump mechanism responsible for the uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.
Clomipramine affects serotonin uptake while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine. It is believed that these actions are responsible for its antidepressant activity.
Doxepin (Silenor)
Doxepin increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by presynaptic neuronal membrane. It inhibits histamine and acetylcholine activity and has proven useful in the treatment of various forms of depression associated with chronic pain.
Nortriptyline (Pamelor)
Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.
Desipramine (Norpramin)
This is the original TCA used for depression. These agents have been suggested to act by inhibiting the reuptake of noradrenaline at synapses in the central descending pain-modulating pathways located in the brainstem and spinal cord.
Pancreatic Enzyme Supplements
Class Summary
These are used as dietary supplementation to aid digestion in patients with pancreatic enzyme deficiency. Several preparations are available. The aim is to provide at least 30,000 units of lipase. Because the cost of different preparations is variable, consider the unit price of the enzyme supplement based on the lipase content.
Uncoated pancrelipase is used to treat painful chronic pancreatitis based on the following rationale. Serum CCK levels are higher in patients with severe chronic pancreatitis, ductal or parenchymal hypertension is believed to cause pain, increased CCK levels stimulate pancreatic secretion (which increases ductal hypertension and exacerbates pain), and exogenous pancreatic enzyme supplements trigger a negative feedback inhibition.
Pancrelipase (Creon, Pancreaze, Ultresa, Viokace, Zenpep)
Pancrelipase assists in the digestion of protein, starch, and fat. Nonenteric-coated products are used for pain caused by pancreatitis (ie, Viokace) in combination with a proton pump inhibitor. The enteric-coated products may be used for the restoration of digestion and absorption.
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This endoscopic retrograde cholangiopancreatography (ERCP) shows advanced chronic pancreatitis. The pancreatogram has blunting of the lateral branches, dilation of the main pancreatic duct, and filling defects consistent with pancreatolithiasis. The cholangiogram also shows a stenosis of the distal bile duct and a dilated biliary tree.
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Chronic pancreatitis. Abdominal CT scan showing a pancreatic pseudocyst causing distortion of the ductal system.
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This patient has recurrent abdominal pain. She used alcohol heavily in the past and was involved in a motor vehicle accident. The pancreatogram shows subtle blunting of the side branches consistent with chronic pancreatitis. A stricture also is present in the body of the pancreas where it drapes over the spine, probably resulting from the trauma she sustained in the motor vehicle accident. Air in the stomach makes it difficult to observe that contrast is filling a pseudocyst on the other side of the stricture. These findings are not amenable to endoscopic intervention, and the patient was sent for a distal pancreatectomy.
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Chronic pancreatitis. This magnetic resonance cholangiopancreatography (MRCP) shows a healthy biliary system. The pancreatic ductal system is not well visualized. A subsequent endoscopic retrograde cholangiopancreatography (ERCP [not pictured]) showed pancreas divisum, with no evidence of a communication with the pseudocyst. The endoscopic features were ideal for an endoscopic transgastric pseudocystogastrostomy.
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Chronic pancreatitis. CT scans of the abdomen following an endoscopic transgastric pseudocystogastrostomy. Note that 2 stents are placed through the stomach and into the pseudocyst. Before undertaking this type of endoscopic intervention, the endoscopist must be confident that a cystadenoma has not been mistaken for a pseudocyst.
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Chronic pancreatitis. This patient had a persistent postoperative leak from the site of a distal pancreatectomy. In the mid-1990s, the author sought to facilitate enteric drainage using transpapillary stents placed into the pancreatic duct. While this changed the fluid dynamics in favor of healing the disrupted duct, some patients developed complications from this technique.
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Chronic pancreatitis. The persistent postoperative leak from the site of a distal pancreatectomy has healed at 1-month follow-up (see the image above). However, after 4 weeks of transpapillary stenting, the pancreatogram now shows a stent-induced stenosis near the surgical genu (arrow). Based on this experience, the author stopped using pancreatic stents in this setting.
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Chronic pancreatitis. This patient developed abdominal pain several weeks after being accidentally hit with a baseball bat. A CT scan showed a large splenic hematoma, and the patient underwent a splenectomy. His postoperative course was notable for recurrent pain, abdominal distension, and elevation of serum amylase levels over the course of 2-3 months. This repeat CT scan shows postsurgical changes in the left upper quadrant and a large fluid collection.
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Chronic pancreatitis. The pancreatogram shows a small leak from the tail of the gland.
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Chronic pancreatitis. A nasopancreatic tube courses through the esophagus, stomach, and duodenum and into the pancreatic duct. Externally, the end of the tube is attached to a suction bulb to decompress the ductal system and monitor its function on a daily basis. In contrast to patients treated with transpapillary stents, none of these patients ever has failed to return for a follow-up appointment. In addition, while stent obstruction and subsequent infection can occur with transpapillary stents, the author has not observed this complication while using nasopancreatic tubes.
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Chronic pancreatitis. Nine days after placement of a nasopancreatic tube, a pancreatogram obtained via the tube showed that the disruption had healed (see the above image). The tube then was removed.
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Chronic pancreatitis. This follow-up CT scan (see the above 2 images) shows a percutaneous tube in the left upper quadrant that was used to drain a fluid collection. It was removed after 4 weeks. The patient returned to work, regained his weight, and had no recurrence of abdominal pain or signs of a recurrent pancreatic leak.
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Chronic pancreatitis. Pancreatogram in a patient with a pancreatic pseudocyst. Note how the pancreatic ducts are extrinsically distorted by a mass lesion.
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This pancreatogram shows a pseudocyst communicating with the main pancreatic duct in a patient with chronic pancreatitis and recurrent abdominal pain. He was treated endoscopically with a transpapillary stent placed into the pancreatic duct.
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Four weeks after placement of a transpapillary stent, a patient with a pseudocyst communicating with the main pancreatic duct (chronic pancreatitis with recurrent abdominal pain) had not had a recurrence of pain. The CT scan showed resolution of the cyst, and the follow-up pancreatogram showed marked improvement. Transpapillary stenting of the pancreatic duct should be reserved for patients with established chronic pancreatitis.
