PANCREATITIS

THERAPY I
PHARMACY - 4th yr
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 Introduction to Pancreatic Gland
• Exocrine cells of the pancreas, acinar cells, produce
an alkaline fluid known as pancreatic juice that
contains various digestive enzymes.
• These enzymes are produced and stored as inactive
proenzymes within zymogen granules to prevent
autolysis and digestion of the pancreas.

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• The zymogen granules are also responsible for
enzyme transport to the pancreatic duct.
• Amylase and lipase are released from the zymogen
granules in the active form.

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• Pancreatitis is inflammation of the pancreas with variable involvement
of regional tissues or remote organ systems.
• Acute pancreatitis is characterized by severe pain in the upper abdomen
and elevations of pancreatic enzymes in the blood
• In the majority of patients, acute pancreatitis is a mild, self-limiting
disease that resolves spontaneously without complications.
• Chronic pancreatitis is characterized by long-standing inflammation that
eventually leads to a loss of pancreatic exocrine and endocrine functions
• It is a progressive disease that often goes unnoticed for many years

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 Epidemiology
• Peak incidence between ages 35 and 54 and about
85% of cases occurring in men
• Black patients being almost two to three times as
likely to be hospitalized for chronic pancreatitis
than for alcoholic cirrhosis

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 Etiologic Risk Factors Associated with Acute Pancreatitis
Structural
•Gallstone disease, sphincter of Oddi dysfunction, pancreatic tumors
Toxins
•Alcohol (ethanol) consumption, scorpion bite, organophosphate insecticides
Infectious
•Bacterial, viral (including HIV and H1N1 influenza), parasitic
Metabolic
•Hypertriglyceridemia, chronic hypercalcemia
Genetic
•Cystic fibrosis, α1-antitrypsin deficiency, hereditary (trypsinogen gene
mutations)
Trauma
•Blunt abdominal trauma
Vascular
•Vasculitis, atherosclerosis, cholesterol emboli, coronary artery bypass surgery
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 Medications Associated with Acute Pancreatitis

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 Pathophysiology
• The pathophysiology of acute pancreatitis is based on events that
initiate injury and secondary events that establish and perpetuate the
injury

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 Pathophysiology

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 Consequences of Acute Pancreatitis
• Pancreatic fluid collections
• Pancreatic abscesses can form during the course of acute
pancreatitis.
• Pancreatic necrosis can occur when pancreatic enzymes damage
the pancreatic tissue or when pancreatic abscesses become
secondarily infected.
• Infection usually due to bacteria that are normally found in the
GI, including
– Escherichia coli, Enterobacteriaceae, Staphylococcus aureus,
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viridians group streptococci,
GIT
and anaerobes. 11
 Clinical Presentation of Acute Pancreatitis
• Presentation ranges from moderate abdominal discomfort to
excruciating pain, shock, and respiratory distress(dyspnea,
tachypnea) decreased bowel sound,, pancreatic enlargement
• Abdominal pain is usually sudden, epigastric, often radiating to the
upper quadrants.
• Nausea and vomiting occur following the onset of pain

• Patients at greatest risk for mortality from acute pancreatitis are

those who have multi-organ failure (e.g., hypotension, respiratory
failure, or renal failure).

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 Cont’d…

• Lab findings

– Leukocytosis, thrombocytopenia

– Hyperglycemia

– Hypoalbuminemia

– Elevated ALT, AST, bilirubin, TG, serum Lipase and

amylase …..especially in gallstone pancreatitis

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 Diagnosis of Acute Pancreatitis
• Most guidelines agree that the diagnosis should be made
within 48 hours based on characteristic presence of
• Abdominal pain
• Elevated level of amylase, lipase, or both to at least 3x of the upper limit
of normal
• Abdominal CT may be used to confirm the diagnosis,
• US can be used to ascertain the presence of gallstones
• Lipase is more sensitive and specific than amylase and is
preferred for Dx because
– Serum amylase is elevated early in the disease process but may
return to normal within 12 hours. Whereas,
– Serum lipase will remain elevated for days after the acute event
and may lend itself more to the diagnosis depending on when
the patient presents for evaluation.
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 Treatment
Desired Outcomes
– Resolution of nausea, vomiting, abdominal pain, and
fever; ability to tolerate oral intake
– Normalization of serum amylase, lipase, and CBC,
glucose, and lipid abnormalities
– Resolution of abscess, and fluid collection.
– Minimizing systemic complications
– Preventing pancreatic necrosis and infection

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 Nonpharmacologic Therapy
• Primarily supportive unless specific etiology is identified.

• Supportive therapy involves

– Proper nutrition

– fluid repletion by discontinuation of oral intake

• Patients with acute pancreatitis are administered

intravenous fluids to maintain hydration and BP.

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 Pharmacotherapy of Acute Pancreatitis

Analgesics
• Meperidine is the most popular analgesic,
causes less sphincter spasm than other opioids.
• Morphine and fentanyl are reasonable
alternatives to meperidine and may be more
desirable due to other adverse effects associated
with meperidine.

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 Pharmacotherapy of Acute Pancreatitis

Antibiotics
• Appropriate for pancreatic necrosis, which can
be infected initially or be susceptible to a
secondary infection.
• If necrosis is confirmed, antibiotics are
insufficient as sole therapy
– surgical debridement is necessary for cure.

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 Cont’d…
• Broad-spectrum antibiotics with activity against enteric
gram-negative bacilli are appropriate.
• Imipenem/cilastatin reduces sepsis resulting from
necrotizing pancreatitis and provides antibacterial
coverage for the organisms causing pancreatic necrosis.
• fluoroquinolone (e.g., ciprofloxacin, levofloxacin) with
metronidazole should be considered for penicillin-
allergic patients
• Antifungal agents such as fluconazole may be
considered if peritonitis or gastrointestinal perforation
develops due to the presence of fungi such Candida
albicans in the GIT.

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 Intravenous Antimicrobial Regimens for
Pancreatic Necrosis

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 Outcome Evaluation
• Pain control, fluid and electrolyte status, and
nutrition should be assessed periodically.
• Patients with mild disease can be managed more
conservatively with observation & supportive.
• Patients with severe AP should be transferred
to an intensive care unit
• Critically ill patients may require surgery and
aggressive life support measures.

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 Chronic pancreatitis (CP)
 CP is a syndrome of destructive and inflammatory conditions resulting
from long-standing pancreatic injury.
 It is characterized by irreversible fibrosis and destruction of exocrine
and endocrine tissue.
 It has four different stages
 a preclinical inflammatory stage where patients remain
asymptomatic
 In the second stage patients present with acute attacks that often
resemble those of acute pancreatitis.
 The third stage consists of episodes of intermittent or constant
abdominal pain.
 Finally, in the burnout stage patients present with diminished or
absent pain, but develop malabsorption syndrome due to loss of
pancreatic exocrine function and may develop diabetes mellitus from
loss of endocrine function
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 Chronic Pancreatitis - Etiology
 Most common cause of chronic pancreatitis in
 idiopathic
 adults is ethanol abuse.
 children is cystic fibrosis.
 Various genetic alterations have also been associated with the
occurrence of chronic pancreatitis, including mutations of the
following genes: protease serine 1 (trypsin 1) (PRSS1), serine
peptidase inhibitor Kazal type 1 (SPINK1), and the cystic fibrosis
transmembrane conductance regulator (CFTR)
 Nutritional factors
 High-fat and protein diet, hyperlipidemia (especially
hypertriglyceridemia).

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 Pathophysiology of Chronic Pancreatitis
• The inflammation damages enzyme-producing cells
(exocrine) in the pancreas and can also destroy the endocrine
function of the pancreas by causing diffuse scarring and
fibrosis.
• Ethanol abuse may cause precipitation of pancreatic enzymes
in ducts of the pancreas leading to chronic inflammation and
damage.
• Ethanol may also be directly toxic to pancreatic cells.
 As patients lose exocrine function of the pancreas,
they have decreased ability to absorb lipids and
protein ingested with normal dietary intake.
 are also common.
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 Clinical presentations & Dx
• Abdominal pain(95%), malabsorption, weight
loss, and development of diabetic
• Fatty or protein-containing stools
• Jaundice occurs in about 10% of patients.
• Diagnosis
• clinical
• Surgical biopsy of pancreatic tissue through laparoscopy
or laparotomy is the gold standard for confirming the
diagnosis of CP.
• Ultrasonography and CT scan
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 Treatment of Chronic Pancreatitis
Desired Outcomes
The goals of pharmacotherapy for chronic
pancreatitis are:
 Prevention and resolution of chronic abdominal
pain
 Correction of dietary malabsorption with
exogenous pancreatic enzymes.

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 Nonpharmacologic Therapy
• Lifestyle modifications are an important part of
the therapy for chronic pancreatitis.
 Avoidance of ethanol and fatty meals can
decrease the pain of chronic pancreatitis.

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 Pharmacotherapy of Chronic Pancreatitis

 Analgesics
• Pain manangement is important component of therapy.
• Non-opioid analgesics are preferred, but the severe and
persistent nature of the pain often requires opioid therapy.
• Patients can require chronic doses of opioid analgesics,
with a resulting risk of addiction.

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 Pharmacotherapy of Chronic Pancreatitis
 Pancreatic Enzymes
• Goal of pancreatic enzyme supplementation is to
deliver exogenous enzyme to duodenum without
causing further GI side effects from the
medication.
• Supplementation with pancreatic enzymes may
reduce the pain and fatty diarrhea.
• Acid suppressant(H2RA, PPI)
– Improve enzyme supplementation therapy by
making effective in low dose
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 Pharmacotherapy of Chronic Pancreatitis
• Common pancreatic enzyme supplements contain lipase, amylase, and
protease in varying proportions.
• Enteric coated with bicarbonate

• Dose can be tailored to patient’s requirement for exogenous enzyme

supplementation and response to therapy.
• Enzyme supplements should be taken immediately prior to meals to aid
in the digestion and absorption of food.

• Exogenous insulin is the primary pharmacologic agent used in the

treatment of diabetes mellitus associated with chronic pancreatitis.

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 Outcome Evaluation
• The severity and frequency of abdominal pain should be
assessed periodically.
• Patients receiving opioids should be prescribed laxatives
• When dietary malabsorption exists, monitor patients for
weight gain or loss, activity level, and ability to perform
activities of daily living.
• Educate patients that compliance with and proper use of
dietary pancreatic enzyme supplementation is key to
improved outcomes.

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