Therapeutics GI Ronald Flashcard

Exocrine Functions of the Pancreas

Acinar cells secrete 1-2 L/day of isotonic fluid (water, electrolytes, pancreatic enzymes)

 

Primary Components


1.  Bicarbonate

  • neutralizes gastric acid in small intestine
  • provides appropriate pH for maintaining activity of pancreatic enzymes

2.  Digestive Enzymes

  • secreted as zymogens which are activated in the duodenum
  • regulation of secretion is complex and depends on hormonal and neuronal mechanisms
  • 2 hormones: secretin and CCK are important in post-prandial secretion
  • Proteolytic: trypsinogen, chymotripsinogen, procarboxypeptidase, protealase
  • Amylolytic: amylase
  • Lipolytic: lipase, phospholipase A, carboxylesterase lipase
  • Nucleolytic: ribonuclease
  • Other: trypsin inhibitor, colipase


Interstitial Pancreatitis

A form of Acute Pancreatitis

  • Milder and less painful than necrotizing
  • Limited to pancreas and surrounding area

Necrotizing Pancreatitis

A form of Acute Pancreatitis

  • More painful and severe than interstitial
  • Necrosis in and around the pancreas
  • Higher risk of infection, sepsis, organ failure, and death

Pathophysiology of Acute Pancreatitis

Events that initiate injury

  • activation of zymogens within acinar cells
  • pancreatic ischemia
  • pancreatic duct obstruction

Secondary events that determine duration and severity

  • release of active pancreatic enzymes — local or distant tissue damage
  • cytokine generation –> inflammation –> TNF-α, IL-1
  • release of vasoactive substances –> capillary permeability

Net effects

  • vascular damage – ischemia and edema
  • tissue damage and cell death

Pancreatic infections may result from translocation of colonic bacteria due to increase intestinal permeability

Signs/Symptoms of Acute Pancreatitis

1. Abdominal Pain

  • epigastric – radiates to either upper quadrants or the back
  • sudden onset and steady with no decrease in pain with repositioning
  • intensity – “knife-like”

2. Nausea/Vomiting

3. Epigastric tenderness

4. Abdominal distension

5. Fever

 

Symptoms suggestive of severe pancreatitis

  • shock
  • respiratory distress
  • absent bowel sounds
  • ARF
  • moderate-severe hypocalcemia

Lab Findings of Acute Pancreatitis

  1. Increased WBC (10-25 K)
  2. Serum Amylase (> 3x ULN)
  • rises within 4-8 hrs, pks @ 24 hrs, returns to nl within 8-14 days
  • persistent elevations suggest pancreatic necrosis and complications

3. Serum Lipase (> 3x ULN)

  • longer t1/2 than amylase — can be elevated after amylase has returned to normal
  • more specific than amylase for pancreatic disease

4.  ↑ bilirubin (mild), ↑ ALP, ↑ AST/ALT, ↓ albumin

Non-Pharmacologic Treatment of Acute Pancreatitis

Fluid Resuscitation

  • agressive fluid resuscitation is KEY
  • Initial fluid resuscitation –> isotonic crystalloids
  • IV colloids may be needed to aid in restoration of intravascular volume
  • Correct electrolyte deficiencies (Ca, K, Mg)

Nutrition

  • Oral nutrition held at onset of attack
  • Mild attack — resume oral feeding within several days
  • Severe dz — nutritional deficits develop rapidly
  • If expect NPO > 1 week or pt. malnourished — begin parenteral or enteral feedings immediately

Parenteral vs Enteral

  • Both are effective
  • Parenteral — increase risk of infection, hyperglycemia, and risk of increasing triglycerides
  • Enteral — safer, less expensive, and may prevent infection by decreasing risk of bacterial translocation across the GI wall
  • Enteral — the tip of the OG/NG tube should be in the jejunum (J-tube) — distal to the bile duct

Meperidine

Treatment for Acute Pancreatitis

  • Old drug of choice
  • Little effect on sphincter of Oddi
  • Not as effective as other narcotics — requires high doses
  • Drug metabolite accumulates in renal failure, increasing risk of adverse CNS events (seizures, psychosis)

Morphine

Treatment for Acute Pancreatitis

  • Good pain relief
  • May lead to spasm of sphincter of Oddi
  • Increases serum amylase
  • Possible etiology of pancreatitis

Hydromorphone

Treatment for Acute Pancreatitis

  • Similar effects of morphine
  • May be better tolerated by patients (< ADRs)

Fentanyl

Treatment for Acute Pancreatitis

  • Possibly best choice in acute pain management
  • Potent analgesic
  • Little effect on sphincter of Oddi
  • Well tolerated
  • Lower accumulation risk than hydromorphone and morphine
  • Very expensive

Patient-Controlled Analgesia

Treatment for Acute Pancreatitis

  • Benefit in patients who need high dose and frequent administration of narcotic dosing

When can pancreatic enzymes be used in patients with acute pancreatitis?
It can be used to help alleviate pain in patients with inadequate response to narcotic analgesics
Octreotide

Treatment for Acute Pancreatitis

  • Potent inhibitor of pancreatic enzyme secretion, but it also increases sphincter of Oddi pressure and decrease splanchnic blood flow
  • Limited to patients with severe disease due to lack of data to support use

Antibiotics for Acute Pancreatitis

  • Therapy should be guided by cultures
  • High risk patients may benefit (necrotizing pancreatitis with signs of infection, pancreatic abscess or infected pseudocyst)
  • Regimen should cover enteric G- and anaerobes
  • Commonly used agents — Imipenem/cilastatin, Fluoroquinolone + metronidazole (PCN allergy)
  • Initiate therapy within 48 hrs and continue for 2-3 weeks
  • G+ and fungal infections increasing in patients receiving antibiotic prophylaxis — empiric fungal prophylaxis commonly added

 

Pathophysiology of Chronic Pancreatitis

  • Slow progression from inflammation to cellular necrosis to fibrosis
  • Changes in pancreatic fluid –> environment for formation of intraductal protein plugs –> block small ductules –> progressive structural damage of ducts and acinar cells
  • Calcium complexes with protein plugs –> injury and destruction of tissue
  • Abdominal pain associated with increased intraductal pressure
  • Malabsorption occurs when enzyme secretion decreased by ~ 90% (lipase secretion decreases before proteolytic enzymes, bicarbonate secretion may or may not fail)

Signs/Symptoms of Chronic Pancreatitis

Abdominal pain

  • constant or episodic
  • pain radiates to back
  • deep-seated, positional, and frequently nocturnal
  • Unresponsive to medication
  • May be aggravated by eating
  • Nausea and vomiting accompany the pain

Malabsorption

  • Steatorrhea
  • Azotorrhea
  • Vitamin B12 deficiency

Weight loss

Diabetes (late manifestation)

Jaundice


Lab Values for Chronic Pancreatitis

  • Serum amylase and lipase usually normal
  • WBC count, fluids, and electrolytes are usually normal

Non-Pharm Treatment for Chronic Pancreatitis

  • Alcohol abstinence
  • Smoking cessation
  • Small, frequent meals (6 meals per day)
  • Fat restricted diet (50-75 g/day)
  • Increased dietary fiber
  • Surgical procedures

Acetaminophen

Chronic Pain Management for Chronic Pancreatitis

  • Caution in patients w/ history or current use of alcohol
  • Limit to 2 g/day in alcohol-induced pancreatitis

NSAIDs

Chronic Pain Management for Chronic Pancreatitis

  • Increased risk of GI bleed
  • COX-2 for patients at high-risk of GI bleed
  • Caution in renal failure

Tramadol

Chronic Pain Management for Chronic Pancreatitis

  • 50-100 mg po q 4-6 hrs
  • Narcotic-like effect
  • Contraindicated in alcohol intoxication
  • Caution in elderly and renal failure (CNS effect)

Narcotics

Chronic Pain Management for Chronic Pancreatitis

  • Abuse-potential — concern in alcoholic patients
  • Be aware of total APAP dose in combo products
  • Numerous combinations, doses, and potencies

Corticosteroid Injection

Chronic Pain Management for Chronic Pancreatitis

  • Celiac nerve block
  • Injected into celiac nerve
  • Effects last ~ 1 month

Pancreatic Enzymes

  • Indicated when steatorrhea and wt. loss are present
  • Enteric-coating and increasing gastric pH increases bioavailability of enzymes

Non-Enteric Coated

  • Addition of antisecretory agent may increase efficacy
  • ADRs — nausea, cramping, hyperuricemia
  • CI — hypersensitivity to pork protein

Enteric Coated

  • Requires fewer capsules/tablets per meal
  • Does not require additional antisecretory therapy
  • ADRs — nausea, cramping, hyperuricemia
  • CI — hypersensitivity to pork protein

H2RA or PPI

  • Improves efficacy of pancreatic enzyme supplementation by increasing gastric pH and helping to prevent enzymatic degradation in the stomach
  • Little or no effect in reducing steatorrhea

Get instant access to
all materials

Become a Member