GI Tract Dysfunction and Antiemetics

GI Tract Dysfunctions

• Antiemetics are used to prevent nausea and vomiting

Serotonin Receptor Antagonists

• Ondansetron (Zofran) is administered 4mg QID
• Ondansetron was the first drug approved for chemotherapy-induced nausea and vomiting (CINV)
• It is also used for nausea and vomiting related to radiotherapy and anesthesia
• Type 3 serotonin receptors on afferent vagal nerves are blocked by Ondansetron
• Ondansetron is more effective with dexamethasone
• Adverse effects include headache, diarrhea, dizziness, prolonged QT interval, and risk of torsades de pointes

Metoclopramide

• Metoclopramide (Reglan) is administered 10mg QID
• It blocks dopamine receptors in the CTZ (chemoreceptor trigger zone in the medulla)
• It is used for postoperative nausea/vomiting, anticancer drugs, opioids, toxins, and radiation therapy
• Adverse effects include headache, diarrhea, dizziness, tiredness, and muscle stiffness
• Metoclopramide may be less favorable than zofran

Diarrhea

• Diarrhea is characterized by stools of excessive volume, fluidity, and increased frequency of defecation
• Loose stool is only diarrhea if the frequency is higher than normal for the individual
• It is a symptom of GI disease
• Causes include infection, maldigestion, inflammation, and functional disorders of the bowel
• Complications may involve dehydration and electrolyte depletion, which are treated with fluids and electrolytes
• Management includes diagnosis and treatment of underlying disease, replacement of lost water and salts, relief of cramping, and reducing passage of unformed stools
• Two major groups of antidiarrheals are specific and nonspecific antidiarrheal drugs

Antidiarrheal Agents: Opioids

• Opioids cause constipation and help relieve diarrhea

• They are the most effective antidiarrheal agents

• Diphenoxylate, difenoxin, and loperamide are examples

• Opioids activate opioid receptors in the GI tract, which reduces intestinal motility and slows intestinal transit

• This allows more fluid to be absorbed

• Opioids decrease secretion of fluid into the small intestine and increase absorption of fluid and salt

• Diphenoxylate (Lomotil) and loperamide (Imodium) are most commonly used

• Imodium is available OTC, but Lomotil is prescription only

Abdominal Pain

• Visceral pain is transferred by C fibers (unmyelinated)
• It is caused by inflammation or distended abdominal organs, and can be diffuse, poorly localized, gnawing, burning, or cramping
• Somatic pain is transferred through A delta fibers
• It is caused by injury, and can be well localized, sharp, and intense

GI Bleeding

• GI Bleeding is when blood is present in vomit or stool

Upper GI Bleed

• Esophagus bleeds result in frank blood emesis
• Stomach bleeds result in frank blood or coffee ground emesis
• Duodenum bleeds result in coffee ground emesis

Lower GI Bleed

• Jejunum bleeds result in melena, which is dark and tarry stool
• Ileum bleeds result in melena
• Colon bleeds result in melena or frank blood in stool
• Rectum bleeds result in frank blood in stool
• Importance involves losing blood and/or volume

Inflammatory GI Disorders: Gastroesophageal Reflux Disease (GERD)

• Risk factors include decreased strength of the lower esophageal sphincter (LES), increased abdominal pressure, fatty foods, caffeine, alcohol, cigarette smoking, pregnancy, and spicy food
• Treatment implications involve avoiding aggravating factors, fundoplication for intractable cases, enhancing esophageal clearance, and suppressing gastric acidity
• Occasional treatment involves antacids and histamine (H2) antagonists
• Chronic treatment involves proton pump inhibitors

Pathogenesis of GERD

• It is caused by the backflow of gastric contents into the esophagus through the LES
• Inflammation is caused by reflux of highly acidic material (esophagitis) Clinical manifestations include heartburn, regurgitation, chest pain, and dysphagia
• Regurgitation involves backflow of food

Complications of GERD

• Barrett esophagus occurs when columnar tissue replaces normal squamous epithelium with an increased risk of esophageal cancer
• Other complications include ulceration, fibrotic scarring, esophageal strictures, pulmonary symptoms, cough, accelerated asthma, and laryngitis

Peptic Ulcer Disease (PUD)

• An ulcer is an epithelium rupture
• Diagnostic testing involves an endoscopy
• Causes include bleeding, endothelial damage, and peritonitis
• Risk factors include aspirin/NSAIDs, alcohol, bile acids, H. pylori, genetics, smoking and stress

PUD: Clinical Manifestations

• Epigastric burning pain is relieved by food or antacid ingestion

• Gastric ulcer pain occurs when the stomach is empty and soon after meals

• Duodenal ulcer pain occurs 2-3 hours after a meal

• Complications can be life threatening, such as GI bleeding with no warning, and GI perforation leading to peritonitis

• Treatment implications include healing injured mucosa and decreasing gastric acidity

• Antibiotics can treat H. pylori, along with H2 antagonists, proton pump inhibitors, and sucralfate

• Prevention involves smoking cessation, avoiding aspirin and NSAIDs, stress reduction, and avoiding irritating foods and beverages like caffeine and alcohol

Classes of Antiulcer Drugs

• Antibiotics, antisecretory agents, mucosal protectants, agents enhancing mucosal defenses, and antacids are all classes of antiulcer drugs

Nondrug Therapy: Diet

• A traditional "ulcer diet" does not accelerate healing
• There is no convincing evidence that caffeinated beverages promote ulcers or delay healing
• Eating five or six small meals a day reduces pH fluctuations
• Avoid smoking, aspirin, other NSAIDs, nicotine, and alcohol
• Stress reduction is recommended

H. pylori Treatment

• Prescribing a minimum of two antibiotics (up to three may be used) helps reduce the risk of resistance developing
• No antibiotic is effective alone
• Examples: amoxicillin, clarithromycin, tetracycline, metronidazole
• Minimize emergence of resistance by using at least two antibiotics, preferably three
• Use an antisecretory agent: PPI or histamine2 receptor antagonist (H₂RA)
• Eradication rates are good with a 10-day course and slightly better with a 14-day course

Histamine2-Receptor Antagonists

• These are first-choice drugs for treating gastric and duodenal ulcers
• They promote healing by suppressing secretion of gastric acid
• All four are equally effective, but serious side effects are uncommon
• Examples include Cimetidine (Tagamet), Ranitidine (Zantac), Famotidine (Pepcid), and Nizatidine (Axid)
• Cimetidine (Tagamet): adverse effects include antiandrogenic effects, CNS effects, pneumonia, and hypotension/dysrhythmias with IV bolus
• Cimetidine interacts with warfarin, phenytoin, theophylline, lidocaine, and antacids by reducing cimetidine absorbtion
• Administer cimetidine and antacids at least 1 hour apart

Proton Pump Inhibitors

• PPIs are the most effective drugs for suppressing production of gastric acid
• Therapeutic uses include short-term treatment of gastric/duodenal ulcers and GERD
• PPIs are well tolerated
• Selection is based on cost and prescriber's preference
• PPIs can increase the risk of serious adverse events, including fracture, pneumonia, acid rebound, and intestinal infection with Clostridium difficile
• Omeprazole (Prilosec) and Esomeprazole (Nexium) end in "prazole"

Omeprazole (Prilosec)

• Omeprazole: first available PPI, inhibits gastric secretion, and has a short half-life
• It is used for short-term therapy
• Ulcer prophylaxis is indicated only for patients in intensive care units who, have an additional risk factor, such as multiple trauma, spinal cord injury, or prolonged mechanical ventilation (longer than 48 hours)
• Adverse effects are usually inconsequential with short-term use, but may include headache, GI effects, pneumonia, fractures, hypomagnesemia, rebound acid hypersecretion, C. difficile infection, and gastric cancer

Sucralfate (Carafate)

• Sucralfate creates a protective barrier for up to 6 hours
• Therapeutic uses for acute ulcers and maintenance therapy
• Adverse effects of constipation in 2% of patients
• Drug interaction with minimal: antacids, which may interfere with effects of sucralfate

Antacids

• Antacids adverse effects include constipation with aluminum hydroxide, diarrhea with magnesium hydroxide and sodium loading
• They interact with cimetidine, ranitidine, and sucralfate
• Magnesium Hydroxide (Milk of Magnesia) is a rapid-acting antacid with high acid-neutralizing capacity (ANC) and long-lasting effects
• It is an antacid of choice
• The most prominent adverse effect is diarrhea
• It is usually taken with aluminum hydroxide, to promote constipatio
• Avoid in patients with undiagnosed abdominal pain, frequently used as a laxative, and use with caution in patients with renal failure

Ulcerative Colitis (UC)

• UC usually affects the large intestine
• Inflammation and abscess formation of the intestinal glands leading to large ulcerations
• Clinical manifestations include bloody diarrhea and lower abdominal pain

Crohn's Disease

• Crohn's Disease usually affects the small intestine
• Blockage/inflammation of lymphatic vessels leads to chronic inflammation of all layers of intestinal wall, causing ulcerations, strictures, fibrosis, and fistulas
• Clinical manifestations include bouts of fever, diarrhea, constant RLQ pain, and possible RLQ tender mass
• Treatment implications include corticosteroids, antibiotics, immunomodulating agents, and antiTNF mono-clonal antibodies

Drugs for Inflammatory Bowel Disease (IBD)

• IBD is not curable but can be controlled with 5-Aminosalicylates, glucocorticoids, Immunosuppressants, and Immunomodulators

5-Aminosalicylates

• Sulfasalazine reduces inflammation
• It also suppresses prostaglandin synthesis and migration of inflammatory cells into the affected region
• It is most effective against acute episodes of mild to moderate ulcerative colitis
• Possible adverse effects are peptic ulcers

Glucocorticoids

• Budesonide is approved for mild to moderate Crohn's disease that involves the ileum and ascending colon
• Prolonged use can cause severe adverse effects, including adrenal suppression, osteoporosis, increased susceptibility to infection, and a Cushing's syndrome
• Glucocorticoid side effects can also include peptic ulcers and hypertension

Immunosuppressants

• Azathioprine and mercaptopurine induce and maintain remission in both ulcerative colitis and Crohn’s disease

• Onset of effects may be delayed for up to 6 months

• These are reserved for patients who have not responded to traditional therapy

• Adverse effects are pancreatitis and neutropenia

Immunomodulators

• Infliximab is a monoclonal antibody designed to neutralize tumor necrosis factor (TNF), a key immunoinflammatory modulator
• It affects cytokines
• There is no oral form, only subq or IV
• Can treat moderate to severe Crohn’s disease and ulcerative colitis
• Adverse effects include infusion reactions

Antibiotic-Associated Colitis

• Clostridium difficile infection of the large intestine:
• Antibiotic use decreases bacteria flora in GI + exposure to
• C. diff then leads to release of exotoxins which cause inflammation & necrosis of large intestine mucosa
• Endospore formation

Clinical Manifestations of Antibiotic-Associated Colitis

• • C. difficile infection of the large intestine
• Bloody/Mucous diarrhea
• Abdominal pain/cramping
• Fever
• Lack of appetite
• Leukocytosis
• Sepsis
• Colonic perforation

Treatment Implications of C. difficile

• Stop antibiotic use
• Give C. diff antibiotics, like oral/IV: metronidazole (Flagyl)
• Treat ischemia
• Perform Rare: fecal transplant
• Appendicitis is an obstruction by fecalith → inflammation of appendix
• Clinical manifestations include periumbilical pain, RLQ pain, N/V, fever, diarrhea
• Complications include ruptured appendix→abscess formation leading to peritonitis

Appendicitis: Treatment Implications

• Requires Immediate surgical removal, to prevent rupture
• Common in developing countries and the US
• Fluid/electrolyte replacement, managed with drainage devices and antibiotics are used

Motility GI Disorders

• Irritable Bowel Syndrome (IBS): increased slow wave activity in bowel
• Clinical manifestations: alternating diarrhea and constipation, mucus in stool, abdominal cramping pain, nausea, gas
• Treatment implications: antidiarrheal agents, antispasmodic meds, bulk-forming agents, tricyclic antidepressants, high fiber diet, and avoid aggravating foods/fluids
• Bowel Obstruction can be caused by Mechanical and Functional sources

Mechanical Bowel Obstruction

• Caused by Adhesions, Hernia, Tumors, Impacted feces, Volvulus, Intussusception

Functional obstruction:

• Decreased peristalsis
• Fluid, gas, water & electrolytes accumulation in the bowel

Clinical Manifestations of Bowel Obstruction

• Abd distention, Abd pain, N/V, BM changes, Hyper/hypoactive bowel sounds, Electrolyte depletion, and can cause Dehydration and hypovolemic shock
• Small Bowel obstructions cause Upper jejunum: vomiting, Distal small bowel: fluid
• Mechanical obstructions Initially cause hyperactive bowel sounds

Partial Bowel Obstruction

• Causes Diarrhea/ribbon-like stool and can cause Hyperactive bowel sounds

Large Bowel Obstruction

• Causes Massive gas distention
• Functional: absent bowel sounds

Complete Bowel Obstruction

• Causes Constipation and Hypoactive/absent bowel sounds

Treatment for Bowel Obstruction

• Remove mechanical blockage in Surgical intervention
• And Decompression with intestinal tube in Fluid/electrolyte replacement
• Complications include Ischemia, strangulation & necrosis leading to bowel gangrene, sepsis, peritonitis, and shock

Constipation

• One of the most common GI disorders
• People seek medical help for constipation in the United States 2.5 million times a year
• Hundreds of millions of dollars a year are spent on laxatives
• Constipation can be defined as: Hard stools, infrequent stools, excessive straining, prolonged effort, sense of incomplete evacuation, and unsuccessful defecation

Function of the Colon

• Absorbs water and electrolytes
• Absorption of nutrients is minimal
• Absorption of 1500 mL of fluid, the amount colon sees per day
• 90% of fluid is absorbed
• Delayed transport causes excessive fluid absorption and hard stool
• Frequency of bowel elimination varies from 2 to 3 times/day to 2 times/week

Classification of Laxatives

• Bulk-forming laxatives: Psyllium (Metamucil)
• Surfactant laxatives: Docusate sodium (Colace)
• Stimulant laxatives: Bisacodyl (Dulcolax)
• Osmotic laxatives: Milk of magnesia (MOM)

Stimulant Laxatives

• Have 2 effects on bowel, one being they stimulate intestinal motility

• As well as Increase amounts of water and electrolytes in intestinal lumen and Widely used and abused

• Legitimately used for opioid-induced constipation and for constipation from slow intestinal transit

Osmotic Laxatives

• Laxative salts, sodium phosphate, magnesium hydroxide: poorly absorbed salts that draw water into intestinal lumen; fecal mass softens and swells, wall stretches, and peristalsis is stimulated
• Low doses cause Results in 6 to 12 hours
• High doses cause Results in 2 to 6 hours
• Can cause Dehydration (Substantial water loss, Acute renal failure), and Sodium retention is an adverse effect in heart failure, hypertension, edema
• Selective Chloride channel activators through the By activating (opening) chloride channels in epithelial cells lining the intestine promote secretion of chloride-rich fluid into the intestine

Malabsorption GI Disorders

• This is the failure of small intestine to absorb or normally digest
• Causes can include Enzyme abnormalities, Infection, and Radiation enteritis
• As well as Mucosal dysfunction with surgical alterations decreasing transit time & absorptive surface area
• Can lead to Dumping syndrome or Short bowel syndrome and affect nutrient uptake

Clinical Manifestations

• Patients can experience Diarrhea and Abdominal pain
• Some may experience ineffective intake of vitamins and nutrients to feed the body
• Treatment Implications are to Antidiarrheal agents depending on the disorder and in the case of Celiac disease

Pancreaticobiliary System

• Gallstone Formation Risk Factors
• Prolonged fasting or rapid weight loss
• A common complication of Pregnancy, and use use of Oral contraceptives
• Obesity
• Also high age, and are more problematic for Native Americans compared to American Caucasians

Gallstones

• Women see this complication twice as much as men

Gallstone Formation

• Supersaturation of bile with cholesterol leading to crystal formation and severe RUQ pain
• Pain can intensify and lead to referred pain in the back in addition to Jaundice
• Interventions include watching and waiting, performing a Cholecystectomy, Lithotripsy, or Chemically dissolve stones

Acute & Chronic Pancreatitis

Acute Pancreatitis causes Decreased pancreatic secretions

• Interventions in this case can include Withhold oral feedings, and Nasogastric suction
• Complication include adynamic ileus requiring additional IV fluid replacement and Analgesics as needed
• Finally Glycemic control and Antibiotics are necessary interventions
• Chronic Pancreatitis ETI is ETOH consumption, Hereditary, Hyperparathyroidism, Hypercalcemia, and Trauma
• Chronic Pancreatitis causes Chronic inflammatory lesions, calcification, and obstructs pancreatic flow creating ongoing symptoms

Clinical manifestation

• Persistence of symptoms secondary to pancreatic dysfunction over weeks and months
• Bouts of acute pancreatitis cause Progressive endocrine and exocrine pancreatic dysfunction
• Can cause Diabetes with progressive loss of pancreatic islets in addition to Fat malabsorption for vitamins A, D, E, and K.
• Poor intake leading to Weight loss as well as Steady boring epigastric pain radiating to back and potential N/V

Interventions for Chronic Pancreatitis

• Absolute abstention from alcohol
• Analgesics for pain management
• Surgical intervention (Biliary/pancreatic stents, Whipple procedure)
• Pancreatic enzyme replacement
• Low-fat diet and Glycemic control.

Liver Cellular Dysfunction

• Cause Dyslipidemias and hypertriglyceridemia as well as Abnormal storage/release of glucose ultimately
• Causing Impaired absorption of fat-soluble vitamins (ADEK) and Inadequate protein metabolism
• Ineffective clotting factors leading to Hypoalbuminemia and generalized edema/ascites
• Males experience gynecomastia, impotence, and testicular atrophy, where as Females experience irregular menses, palmar erythema, and spider telangiectasia
• Can also cause Jaundice as a result of Portal Hypertension with Ascites and Hepatic Encephalopathy

Jaundice

• Green/yellow hue to the skin due to bilirubin, presenting as a yellow hue in skin and eyes

Etiologies

• Can be Prehepatic causes or result from Hemolysis and Ineffective erythropoiesis
• In addition to Resorption of large hematomas stemming from Liver Cellular Dysfunction from ETOH damage
• Ingested conjugated bilirubin followed by Posthepatic causes and Mechanical obstruction to bile ducts contribute towards this diagnosis

Portal Hypertension

• Sluggish blood flow → increased pressure in portal circulation where Congested venous drainage of the GI tract causing Anorexia and Varices, in addition to Acites and Splenomegaly

Varices

• Blocked intestinal vessels force the blood into smaller blood vessels allowing for vessels to dilate and rupture
• Causing Hemate-mesis & Bright red rectal bleeding with Severe/diffuse rupture → Shock
• Treated with the implementation of Vasopressin or octreotide which is as effective as Nitroglycerin for lowering portal hypertension but can also create metabolic disturbances

The treatment of Portal Hypertension includes administration

• Metoclopramide with or without a combined of H2 blocker or B-blockers
• Antibiotic therapy
• As well as Emergency esophagogastroduodenoscopy

Ascites

• Pathologic accumulation of fluid in peritoneal cavity presents on Clinical Manifestations as follows
• Lab findings (abdominal paracentesis. Total protein, Albumin, Increased abdominal girth, and a + fluid wave test)
• Treatment: Sodium content should be within 2 grams/day whereas Diuretics should allow for a loss of 0.5 kg of body weight daily and the implementation of Paracentesis depending on results