Drugs Affecting the Gastrointestinal Tract

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Drugs Affecting the Gastrointestinal Tract
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Objectives

• To describe the functions of the various segments
  of the gastrointestinal tract
• To describe the processes of mechanical and
  chemical digestion
• To explain the process of gastric acid production
  and secretion
• To describe the mechanical processes of vomiting
  and defaecation
• To describe the main functions of the liver and
  gallbladder

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The Digestive System

• Structure
• Gross Anatomy
• Histology
• Function
• Mechanical
• Chemical
• Development
• Disorders

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Disorders

• Indigestion
• Gastritis
• Peptic ulcers
• Diarrhoea
• Constipation

• These problems are very common and are reported
  by a large proportion of the population.
• The cause of many GI diseases remains unclear and
  drug treatment is often focused on relieving
  symptoms rather than on control or cure.

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Major Activities of the GI System

• Secretion Of enzymes, acid, bicarbonate, and
  mucus
• Absorption Of water and almost all of the
  essential nutrients needed by the body
• Digestion Of food into usable and absorbable
  component
• Motility Movement of food and secretions through
  the system

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Overview of GI tract Functions

• Mouth---bite, chew, swallow
• Pharynx and esophagus----transport
• Stomach----mechanical disruption absorption of
  water alcohol
• Small intestine--chemical mechanical digestion
  absorption
• Large intestine----absorb electrolytes vitamins
  (B and K)
• Rectum and anus---defecation

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Layers of the Gastrointestinal Tract
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Control of the GI System

• GI system is controlled by the nerve plexus
• Maintains basic electrical rhythm
• Responds to local stimuli to increase or decrease
  activity
• Activity of GI tract can be influenced by the
  autonomic system
• Initiation of activity depends on local reflexes

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Muscularis

• Skeletal muscle voluntary control
• in mouth, pharynx , upper esophagus and anus
• control over swallowing and defecation
• Smooth muscle involuntary control
• inner circular fibers outer longitudinal fibers
• mixes, crushes propels food along by
  peristalsis
• Auerbachs plexus (myenteric)--
• both parasympathetic sympathetic innervation of
  circular and longitudinal smooth muscle layers

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Serosa

• An example of a serous membrane
• Covers all organs and walls of cavities not open
  to the outside of the body
• Secretes slippery fluid
• Consists of connective tissue covered with simple
  squamous epithelium

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Types of Secretions of the GI Tract

• Saliva
• Mucus
• Acid and digestive enzymes (gastin)
• Secretin
• Sodium bicarbonate
• Pancreatic enzymes, other lipases, and amylases
• Bile
• Endocrine hormones

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Peritoneum

• Peritoneum
• visceral layer covers organs
• parietal layer lines the walls of body cavity
• Peritoneal cavity
• potential space containing a bit of serous fluid

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Parts of the Peritoneum

• Mesentery
• Mesocolon
• Lesser omentum
• Greater omentum
• Peritonitis inflammation
• trauma
• rupture of GI tract
• appendicitis
• perforated ulcer

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Greater Omentum, Mesentery Mesocolon
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Lesser Omentum
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Peritonitis

• Acute inflammation of the peritoneum
• Cause
• contamination by infectious microbes during
  surgery or from rupture of abdominal organs

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Mouth

• Lips and cheeks-----contains buccinator muscle
  that keeps food between upper lower teeth
• Vestibule---area between cheeks and teeth
• Oral cavity proper---the roof hard, soft
  palate and uvula
• floor the tongue

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Digestion in the Mouth

• Mechanical digestion (mastication or chewing)
• breaks into pieces
• mixes with saliva so it forms a bolus
• Chemical digestion
• amylase
• begins starch digestion at pH of 6.5 or 7.0 found
  in mouth
• when bolus enzyme hit the pH 2.5 gastric juices
  hydrolysis ceases
• lingual lipase
• secreted by glands in tongue
• begins breakdown of triglycerides into fatty
  acids and glycerol

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Salivary Glands

• Parotid below your ear and over the masseter
• Submandibular is under lower edge of mandible
• Sublingual is deep to the tongue in floor of
  mouth
• All have ducts that empty into the oral cavity

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Composition and Functions of Saliva

• Wet food for easier swallowing
• Dissolves food for tasting
• Bicarbonate ions buffer acidic foods
• bulemia---vomiting hurts the enamel on your teeth
• Chemical digestion of starch begins with enzyme
  (salivary amylase)
• Enzyme (lysozyme) ---helps destroy bacteria
• Protects mouth from infection with its rinsing
  action---1 to 1 and 1/2qts/day

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Salivation

• Increase salivation
• sight, smell, sounds, memory of food, tongue
  stimulation---rock in mouth
• cerebral cortex signals the salivatory nuclei in
  brainstem---(CN 7 9)
• parasympathetic nn. (CN 7 9)
• Stop salivation
• dry mouth when you are afraid
• sympathetic nerves

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Disorders affecting the Mouth

• Systemic diseases, nutritional and mechanical
  trauma can cause irritation or inflammation of
  mouth structures.
• Dental disorders (e.g. caries gingivitis)
• Bacterial, viral and fungal infections (e.g.
  candidiasis, herpes simplex) causing symptoms
  such as blistering or other lesions, swelling
  pain and inflammation.
• Mumps inflammation of the parotid glands.

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Pharynx

• Funnel-shaped tube extending from internal nares
  to the esophagus (posteriorly) and larynx
  (anteriorly)
• Skeletal muscle lined by mucous membrane
• Deglutition or swallowing is facilitated by
  saliva and mucus
• starts when bolus is pushed into the oropharynx
• sensory nerves send signals to deglutition center
  in brainstem
• soft palate is lifted to close nasopharynx
• larynx is lifted as epiglottis is bent to cover
  glottis

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Esophagus

• Collapsed muscular tube
• In front of vertebrae
• Posterior to trachea
• Posterior to the heart
• Pierces the diaphragm at hiatus
• hiatal hernia or diaphragmatic hernia

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Physiology of the Esophagus - Swallowing

• Voluntary phase---tongue pushes food to back of
  oral cavity
• Involuntary phase----pharyngeal stage
• breathing stops airways are closed
• soft palate uvula are lifted to close off
  nasopharynx
• vocal cords close
• epiglottis is bent over airway as larynx is lifted

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Gastroesophageal Reflex Disease

• If lower sphincter fails to open
• distension of esophagus feels like chest pain or
  heart attack
• If lower esophageal sphincter fails to close
• stomach acids enter esophagus cause heartburn
  (GERD)
• for a weak sphincter---don't eat a large meal
  and lay down in front of TV
• smoking and alcohol make the sphincter relax
  worsening the situation
• Control the symptoms by avoiding
• coffee, chocolate, tomatoes, fatty foods, onions
  mint
• take Tagamet HB or Pepcid AC 60 minutes before
  eating
• neutralize existing stomach acids with Tums

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Anatomy of Stomach

• Which side is it on?
• Size when empty?
• large sausage
• stretches due to rugae
• Parts of stomach
• cardia
• fundus---air in x-ray
• body
• pylorus---starts to narrow as approaches pyloric
  sphincter
• Empties as small squirts of chyme leave the
  stomach through the pyloric valve

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Pylorospasm and Pyloric Stenosis

• Abnormalities of the pyloric sphincter in infants
• Pylorospasm
• muscle fibers of sphincter fail to relax trapping
  food in the stomach
• vomiting occurs to relieve pressure
• Pyloric stenosis
• narrowing of sphincter indicated by projectile
  vomiting
• must be corrected surgically

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Absorption of Nutrients by the Stomach

• Water especially if it is cold
• Electrolytes
• Some drugs (especially aspirin) alcohol
• Fat content in the stomach slows the passage of
  alcohol to the intestine where absorption is more
  rapid
• Gastric mucosal cells contain alcohol
  dehydrogenase that converts some alcohol to
  acetaldehyde-----more of this enzyme found in
  males than females
• Females have less total body fluid that same size
  male so end up with higher blood alcohol levels
  with same intake of alcohol

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Vomiting (emesis)

• Forceful expulsion of contents of stomach
  duodenum through the mouth
• Cause
• irritation or distension of stomach
• unpleasant sights, general anesthesia, dizziness
  certain drugs
• Sensory input from medulla cause stomach
  contraction complete sphincter relaxation
• Contents of stomach squeezed between abdominal
  muscles and diaphragm and forced through open
  mouth
• Serious because loss of acidic gastric juice can
  lead to alkalosis

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Anatomy of the Pancreas

• 5" long by 1" thick
• Head close to curve in C-shaped duodenum
• Main duct joins common bile duct from liver
• Sphincter of Oddi on major duodenal papilla
• Opens 4" below pyloric sphincter

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Histology of the Pancreas

• Acini- dark clusters
• 99 of gland
• produce pancreatic juice
• Islets of Langerhans
• 1 of gland
• pale staining cells
• produce hormones

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Pancreatitis

• Pancreatitis---inflammation of the pancreas
  occurring with the mumps
• Acute pancreatitis---associated with heavy
  alcohol intake or biliary tract obstruction
• result is patient secretes trypsin in the
  pancreas starts to digest himself

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Anatomy of the Liver and Gallbladder

• Liver
• weighs 3 lbs.
• below diaphragm
• right lobe larger
• gallbladder on right lobe
• size causes right kidney to be lower than left
• Gallbladder
• fundus, body neck

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Pathway of Bile Secretion

• Bile capillaries
• Hepatic ducts connect to form common hepatic duct
• Cystic duct from gallbladder common hepatic
  duct join to form common bile duct
• Common bile duct pancreatic duct empty into
  duodenum

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Bile Production

• One quart of bile/day is secreted by the liver
• yellow-green in color pH 7.6 to 8.6
• Components
• water cholesterol
• bile salts Na K salts of bile acids
• bile pigments (bilirubin) from hemoglobin
  molecule
• globin a reuseable protein
• heme broken down into iron and bilirubin

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Liver Functions--Carbohydrate Metabolism

• Turn proteins into glucose
• Turn triglycerides into glucose
• Turn excess glucose into glycogen store in the
  liver
• Turn glycogen back into glucose as needed

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Liver Functions --Lipid Metabolism

• Synthesize cholesterol
• Synthesize lipoproteins----HDL and LDL(used to
  transport fatty acids in bloodstream)
• Stores some fat
• Breaks down some fatty acids

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Other Liver Functions

• Detoxifies the blood by removing or altering
  drugs hormones(thyroid estrogen)
• Removes the waste product--bilirubin
• Releases bile salts help digestion by
  emulsification
• Stores fat soluble vitamins-----A, B12, D, E, K
• Stores iron and copper
• Phagocytizes worn out blood cells bacteria
• Activates vitamin D (the skin can also do this
  with 1 hr of sunlight a week)

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Anatomy of the Small Intestine

• 20 feet long----1 inch in diameter
• Large surface area for majority of absorption
• 3 parts
• duodenum---10 inches
• jejunum---8 feet
• ileum---12 feet
• ends at ileocecal valve

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Functions of Microvilli

• Absorption and digestion
• Digestive enzymes found at cell surface on
  microvilli
• Digestion occurs at cell surfaces
• Significant cell division within intestinal
  glands produces new cells that move up
• Once out of the way---rupturing and releasing
  their digestive enzymes proteins

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Digestion of Carbohydrates

• Mouth---salivary amylase
• Esophagus stomach---nothing happens
• Duodenum----pancreatic amylase
• Brush border enzymes (maltase, sucrase lactose)
  act on disaccharides
• produces monosaccharides--fructose, glucose
  galactose
• lactose intolerance (no enzyme bacteria ferment
  sugar)--gas diarrhea

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Lactose Intolerance

• Mucosal cells of small intestine fail to produce
  lactase
• essential for digestion of lactose sugar in milk
• undigested lactose retains fluid in the feces
• bacterial fermentation produces gases
• Symptoms
• diarrhea, gas, bloating abdominal cramps
• Dietary supplements are helpful

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Digestion of Proteins

• Stomach
• HCl denatures or unfolds proteins
• pepsin turns proteins into peptides
• Pancreas
• digestive enzymes---split peptide bonds between
  different amino acids
• brush border enzymes-----aminopeptidase or
  dipeptidase------split off amino acid at amino
  end of molecule or split dipeptide

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Digestion of Lipids

• Mouth----lingual lipase
• Small intestine
• emulsification by bile
• pancreatic lipase---splits into fatty acids
  monoglyceride
• no enzymes in brush border

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Absorption of Water

• 9 liters of fluid dumped into GI tract each day
• Small intestine reabsorbs 8 liters
• Large intestine reabsorbs 90 of that last liter
• Absorption is by osmosis through cell walls into
  vascular capillaries inside villi

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Anatomy of Large Intestine

• 5 feet long by 2½ inches in diameter
• Ascending descending colon are retroperitoneal
• Cecum appendix
• Rectum last 8 inches of GI tract anterior to
  the sacrum coccyx
• Anal canal last 1 inch of GI tract
• internal sphincter----smooth muscle involuntary
  
• external sphincter----skeletal muscle voluntary
  control

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Appendicitis

• Inflammation of the appendix due to blockage of
  the lumen by chyme, foreign body, carcinoma,
  stenosis, or kinking
• Symptoms
• high fever, elevated WBC count, neutrophil count
  above 75
• referred pain, anorexia, nausea and vomiting
• pain localizes in right lower quadrant
• Infection may progress to gangrene and
  perforation within 24 to 36 hours

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Mechanical Digestion in Large Intestine

• Smooth muscle mechanical digestion
• Peristaltic waves (3 to 12 contractions/minute)
• haustral churning----relaxed pouches are filled
  from below by muscular contractions (elevator)
• gastroilial reflex when stomach is full,
  gastrin hormone relaxes ileocecal sphincter so
  small intestine will empty and make room
• gastrocolic reflex when stomach fills, a strong
  peristaltic wave moves contents of transverse
  colon into rectum

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Chemical Digestion in Large Intestine

• No enzymes are secreted only mucous
• Bacteria ferment
• undigested carbohydrates into carbon dioxide
  methane gas
• undigested proteins into simpler substances
  (indoles)----odor
• turn bilirubin into simpler substances that
  produce color
• Bacteria produce vitamin K and B in colon

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Absorption Feces Formation in the Large
Intestine

• Some electrolytes---Na and Cl-
• After 3 to 10 hours, 90 of H2O has been removed
  from chyme
• Feces are semisolid by time reaches transverse
  colon
• Feces dead epithelial cells, undigested food
  such as cellulose, bacteria (live dead)

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Defecation Problems

• Diarrhea chyme passes too quickly through
  intestine
• H20 not reabsorbed
• Constipation--decreased intestinal motility
• too much water is reabsorbed
• remedy fiber, exercise and water

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Dietary Fibre

• Insoluble fibre
• woody parts of plants (wheat bran, vegie skins)
• speeds up transit time reduces colon cancer
• Soluble fibre
• gel-like consistency beans, oats, citrus white
  parts, apples
• lowers blood cholesterol by preventing
  reabsorption of bile salts so liver has to use
  cholesterol to make more

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Aging and the Digestive System

• Changes that occur
• decreased secretory mechanisms
• decreased motility
• loss of strength tone of muscular tissue
• changes in neurosensory feedback
• diminished response to pain internal stimuli
• Symptoms
• sores, loss of taste, peridontal disease,
  difficulty swallowing, hernia, gastritis, ulcers,
  malabsorption, jaundice, cirrhosis, pancreatitis,
  hemorrhoids and constipation
• Cancer of the colon or rectum is common

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Diseases of the GI Tract

• Dental caries and periodontal disease
• Peptic Ulcers
• Diverticulitis
• Colorectal cancer
• Hepatitis
• Anorexia nervosa

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Underlying Causes of GI Disorders

• Dietary excess
• Stress
• Hiatal hernia
• Esophageal reflux
• Adverse drug effects
• Peptic ulcer disease

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Effect of Drugs on GI Secretions

• Decrease GI secretory activity
• Block the action of GI secretions
• Form protective coverings on the GI lining to
  prevent erosion from GI secretions
• Replace missing GI enzymes that the GI tract or
  ancillary glands and organs can no longer produce

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Peptic Ulcers

• Definition
• Erosions in the lining of the stomach and
  adjacent areas of the GI tract
• Symptoms
• Gnawing, burning pain, often occurring after
  meals
• Cause
• Bacterial infection by Helicobacter pylori
  bacteria

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Drugs Used in the Treatment of Ulcers

• Histamine-2 (H2) antagonists
• Block the release of hydrochloric acid in
  response to gastrin
• Antacids
• Interact with acids at the chemical level to
  neutralize them
• Proton pump inhibitors
• Suppress the secretion of hydrochloric acid into
  the lumen of the stomach

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Drugs Used in the Treatment of Ulcers (cont.)

• Antipeptic agents
• Coat any injured area in the stomach to prevent
  further injury from acid
• Prostaglandins
• Inhibit the secretion of gastrin and increase the
  secretion of the mucous lining of the stomach,
  providing a buffer

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Sites of Actions of Drugs Affecting
Gastrointestinal Secretions
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Patients Who May Require Digestive Enzyme
Supplements

• Saliva supplements
• Stroke
• Salivary gland disorder
• Extreme surgery of the head and neck
• Pancreatic enzyme supplements
• Common duct problems
• Pancreatic disease
• Cystic fibrosis

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H2 Antagonists

• Cimetidine (Tagamet, Tagamet HB) The first drug
  in this class to be developed
• Ranitidine (Zantac) Longer acting and more
  potent than cimetidine
• Famotidine (Pepcid, Pepcid AC) Similar to
  ranitidine, but much more potent
• Nizatidine (Axid) Newest drug in this class
  similar to ranitidine indicated for patients
  with liver dysfunction

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Indications for H2 Antagonists

• Short-term treatment of active duodenal ulcer or
  benign gastric ulcer
• Treatment of pathological hypersecretory
  conditions such as ZollingerEllison syndrome (a
  condition characterised by severe peptic
  ulceration, gastric hypersecretion, elevated
  serum gastrin, and gastrinoma (a tumour) of the
  pancreas or duodeum)
• Prophylaxis of stress-induced ulcers and acute
  upper GI bleeding in critical patients
• Treatment of erosive gastroesophageal reflux
• Relief of symptoms of heartburn, acid
  indigestion, and sour stomach (OTC preparations)

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Types of Antacids

• Sodium bicarbonate (Bell/Ans)
• Calcium carbonate (Calciday-667, Tums, and
  others)
• Magnesium salts (Milk of Magnesia and others)
• Aluminum salts (Amphojel and others)
• Magaldrate (Lowsium, Riopan)

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Focus on the Prototype Antacid Sodium Bicarbonate

• Indications Hyperacidity GI bleeding and stress
  ulcers severe diarrhea metabolic acidosis
  certain drug intoxications minimize uric acid
  crystallization
• Actions Neutralizes or reduces gastric acidity
  resulting in an increase in gastric pH inhibits
  the proteolytic (pertaining to any substance that
  promotes the breakdown of protein) activity of
  pepsin
• Oral route Onset rapid peak 30 min duration
  13 h
• T½ Unknown excreted unchanged in urine

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Proton Pump Inhibitors

• Action
• Suppress gastric acid secretion by specifically
  inhibiting H,K-ATPase enzyme system on the
  secretory surface of the gastric parietal cells
• Types
• Omeprazole (Prilosec), esomeprazole (Nexium),
  lansoprazole (Prevacid), pantoprazole (Protonix),
  rabeprazole (Aciphex)

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Antipeptic Agent

• Sucralfate (Carafate)
• Forms a protective coating over the eroded
  stomach lining
• Protects it from acid and digestive enzymes
• Aids healing

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Prostaglandin

• Misoprostol (Cytotec)
• Blocks gastric acid secretion
• Increases the production of bicarbonate and
  mucous lining in the stomach

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Maintaining Homeostasis of the GI Tract

• A series of local reflexes within the GI tract
  helps maintain homeostasis within the system
• Overstimulation can result in
• Constipation (underactivity)
• Diarrhea (overactivity)

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References

• Marieb, E. 2006, Essentials of Human Anatomy
  Physiology, 8th edition, Pearson, Benjamin,
  Cummings. USA
• Herlihy, B. 2007 , The Human Body in Health and
  Illness, 3rd edition, Saunders Elsevier. St
  Louis, USA
• Thibodeau, G. Patton, K. 2002, The Human Body in
  Health Disease, 3rd edition, Mosby. St Louis,
  USA
• Cohen, B. Taylor, J. 2005, Memmler's Structure
  and Function of the Human Body, 8th edition,
  Lippincott,Williams Wilkins. USA
• Anatomy Physiology made Incredibly Easy, 2000.
  Springhouse. Pennsylvania, USA
• Anatomica, 2000, Random House Australia Pty Ltd

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