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ANATOMY OF THE GI SYSTEM
COMMON DISEASE OF THE GI SYSTEM
ETIOLOGY
DRUGS TO TREAT PEPTIC ULCER
LAXATIVES
ANTI DIARRHEALS
ANTIMOTILITY
EMETIC/ANTIEMETIC

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Anatomy of the GI System

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Two Major Functions
1. Digestion-mechanical and/ or chemical process
:ingestion,mastication,deglutition,peristalsis,absorption and
defecation.
>Ingestion-taking of food into GI by mouth(M)
>Mastication-chewing(M),salivary action-©
>Deglutition-swallowing (M)
>Peristalsis-rhythmic contraction-moves food through the
GI

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>Absorption-passage of food molecules through the
mucus membrane of the GI into the circulatory or
the lymphatic system(M,C)
2. Elimination
>defecation-discharge of indigestible
wastes,called feces from the GI tract(M)

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Two Major Parts
I. Alimentary Canal/bucal or oral cavity (mouth,
pharynx, esophagus, stomach, small intestine, large
intestine)

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1.Mouth-grinds food and mix with
saliva(amylase),initial digestion of CHO,
2.Pharynx-receives bolus from oral cavity
3.Esophagus-transport bolus to stomach by
peristalsis

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4. Stomach
-temporary storage of food
-breaks down food into chyme
-moves gastric content into the small intestine
-gastrin, hydrochloric acid, pepsinogen, mucus

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5. Small intestine : duodenum, jejunum,
ileum
-complete food digestion
-absorbs food molecules
-secretes hormones that help control bile
(secretin) and pancreatic juice
(cholecystokinin) secretion

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6. Large intestine
-absorbs water, Na, CI
-secretes alkaline mucus
-eliminates digestive wastes

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Accessory Organs of Digestion
Liver
-carbohydrate metabolism, detoxifies endogenous &
exogenous toxins in plasma
-synthesizes plasma proteins, nonessential a.a., &
vit., stores Vit. K, D, B12 & iron
-removes ammonia from body fluids converting it t
urea for excretion in urine, helps regulate blood
glucose levels, secretes bile

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Bile
-greenish liquid composed of water, cholesterol, bile
salts, and phospholipids
-emulsification of fats, promotes intestinal
absorption of fatty acids, cholesterol, and other
lipids, aids in the excretion of bilirubin from the liver

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Gallbladder
-stores & concentrates bile produced by the liver
-releases bile to the duodenum
Pancreas
-performs both endocrine & exocrine function GI
Tract Innervations

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Parasympathetic stimulation
-increase gut & sphincter tone
-increase smooth muscle contraction & motor
secretory activities
Sympathetic stimulation
-reduces peristalsis & inhibits GI activity

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Common Diseases of the GI System
Peptic Ulcer Disease
– A group of disorders characterized by
circumscribed lesions of the mucosa of the upper
GI tract (stomach & jejunum)

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Manifestation
1. Duodenal ulcer
– 80% peptic ulcers are of this type
> pain restricted to midepigastrict area and may
radiate below the costal margins into the back or
right shoulder
> occurs between midnight and 2 am
> relieved by food
>patient gains weight

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2. Gastric ulcer – pain is referred to the left
subcostal region
> rarely produce noctumal pain
> aggravated by food
>patient loses weight

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3. GERD ( Gastroesophageal Reflux Disease)
> retrograde movement of gastric contents from the
stomach into the esophagus
> heartburn, chest pain, belching, regurgitation, etc.
4. Hypersecretory state ( Zolliger – Ellison syndrome )
> hyper secretion of HCI due to gastrin-secreting
tumor

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APUD ( Acid-Peptic Ulcer Disease )
-imbalance between aggressive and defensive factors
Aggressive
-HCI, Pepsin, H.pylori
Defensive
-Bicarbonate, Mucus, PG

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3 General Factors
1.infxn w/ H.pylori
2. Increase HCI secretion
3. Inadequate mucosal defense against gastric acid

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Treatment Plan
1. Eradicate H. pylori
Antimicrobial Agents
ROC: Triple therapy
1.Bismuth
2.Metronidazole
3. Tetracycline
*duration: 2 weeks
Antisecretory agent is usually added – PPI, antimuscarinic
2nd
line: Metronidazole + Amoxicillin/Clarithromycin

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Etiology
1. Infection with H. pylori ( >90% DU; 60-90% GU)
>able to survive in the acidic gastric environment by its
ability to produce UREASE, w/c hydrolyzes urea into
ammonia.
2. Genetic factors ( 20 – 50% )
>1st
degree relative of ulcer patient: 3x
>Blood type:O

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3. Use of NSAIDs
4. Cigarette smoking – delays ulcer healing
>accelerates emptying of stomach acid into the
duodenum
>prevents pancreatic & billiary bicarbonate
secretion

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5. Alcohol Intake – mucosal irritant
6. Coffee – contains peptides that stimulate release
of Gastrin

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Drugs Used To Treat Peptic Ulcer Disease
Antimicrobials
> Helps heal ulcers and decreae recurrence
> Two or more antibiotics in combination with other
drugs such as PPIs for 2 weeks and PPIs fo 6 more
weeks
> Amoxicillin, Clarithromycin, Metronidazole,
Tetracycline
>>>Dairy products decrease absorption of tetracycline

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Gastric Acid Secretion

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Proton-pump Inhibitor
 MOA: Binds to the H+/K+-ATPase enzyme system (proton
pump) suppressing secretion of gastric acid
> more potent and rapidly effective than H2-blockers
> enteric coated preparations
> highly protein-bound and metabolized extensively in the
liver
> administer in the morning before eating

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Lansoprazole
> prevention & healing of NSAID-induced GU
Rabeprazole
Pantoprazole
> IV preparation used for Zollinger-Ellison
syndrome

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>>Omeprazole & Lansoprazole
Approved for used in infants & children for the
short-term treatment of GERD & corrosive
esophagitis
 S/E: headache, n&v, abdominal pain, diarrhea
and flatulence

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Drug Interactions
> Increase half-life of diazepam, phenytoin &
warfarin
> Interferes with the absorption of drugs that depend
on gastric pH ( Ketoconazole, Digoxin, Ampicillin,
& iron salts )
> Lansoprazole will increase clearance of
theophylline
> Esomeprazole, Lansoprazole & Pantoprazole’s
biovailability are affected by food

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H2-Receptor Blockers
MOA: Inhibits the action of histamine at parietal
cell receptors sites, reducing the volume of
hydrogen ion concentration & gastric acid secretion
>used to treat GERD, duodenal ulcer, & erosive
esophagitis

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Cimetidine – Oral, IV, 1st
H2 blocker
approved, 50% reduction in gastric secretion
Ranitidine – Oral, IV, IM
> more potent, 70% reduction in gastric acid
secretion
Ranitidine Bismuth Citrate +
Clarithromycin: H. pylori eradication

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Famotidine – Oral, IV
> most potent, 94% reduction
Nizatidine – Oral
> newest H2- receptor blocker

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S/E: headache & dizziness
> Ranitidine – hepatotoxixity, bradychardia
> Cimetidine
- heoatotoxixity, bradychardia agranulocytosis, aplasti
anemia, weak androgenic effect (male gynecomastaia &
impotence)

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Drug Interactions
> Cimetidine – enzyme inhibitor
- reduce clearance of propranolol &
lidocaine
- inhibits excretion of procainamide
- absorption is impaired by antacid
(Ranitidine)

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Mucosal Protective
Sucralfate
– nonadsorbable dissacharide containing sucrose
MOA: adheres to the base of the ulcer crater
forming a protective barrier
A: 1g, 4x a day ( 1hr before meals & at bedtime )
S/E: constipation

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Bismuth compounds
MOA: Prevents adhesions of H. pylori to
mucosa & suppresses its growth & inhibits
release of proteolytic enzymes
>CBS – inhibits pepsin activity, stimulates
PG synthesis
> highly effective when combined with PPIs

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Bismuth subsalicylate
Colloifal Bismuth subcitrate
S/E: dark stools and tongue
salicylism at high dose

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Antacids
MOA: neutralize gastric acid, inhibit pepsin activity
& strengthen mucosal barrier
> equally effective as H2 blockers
> heal peptic ulcers and control ulcer pain
> liquid forms provider greater buffering action

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> Nonsytemic – Al or Mg
> Systemic antacids – Sodium bicarbonate
( alkalosis ), CALCIUM CARBONATE
> Antacid mixture – Aluminum OH &
Magnesium OH

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A: 1 hour and 3 hrs after meals and bedtime
S/E:
Aluminum – constipation
Magnesium – diarrhea
Calcium carbonate – constipation, acid rebound,
milk-alkali syndrom
Sodium bicarbonate – alkalosis, C/l in patients with
HTN, CHF, severe renal desease

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D/l:
> Antacids bind to tetracycline & fluoroquinolones
inhibiting their absorption
> Antacids may destroy enteric-coating of drugs
leading to premature dissolution in the stomach
>>>administer drugs 30-60 minutes before
antacids

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Choice of Agents
Nonsystemic antacids – Mg or Al substances
preferred than Na bicarbonate to avoid risk of
alkalosis
Liquid Antacid forms – greater buffering capacity
than tablets
Antacid Mixtures – more sustained action, permits a
lower dosage of each compound and negate each
other untoward effects.

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Ca Carbonate – usually avoided because it causes
Acid Rebound, may delay pain relief and ulcer
healing and induce constipation
-Ca Carbonate + milk or other alkali subs results to
Milk-Alkali Syndrome

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*Al(OH)3
-adsorbs pepsin and removes it from solution at pH>3
-delays GET (constipation) by relaxing small muscles
of the stomach
-stimulate mucus secretion
-hypophosphatemia

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*Mg(OH)2
-keeps pH sufficiently high to keep pepsin absorbed to it
-lessens relaxant effect (diarrhea)
*CaCO3
-can caused rebound acidosis that is prolonged and prominent
*Absorption of cations from antacids may be an important
consideration in HPN/CHF Px.

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Dl:
Aviod concurrent use with other dx impair absorption of
Cimetidine and Ranitidine (give 1 hr apart), Digoxin, INH,
Anticholinergics, Iron products and Phenothiazine
*also interfere absorption of some drugs and enteric-coated
tablets
-can form insoluble complexes (e.g. AI and levodopa), bind
with Tetracycline and Fluoroquinolones

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Antimuscarinic
>MOA: delays or prolongs gastric emptying
> used with antacids
> has no use in ulcer healing
> Belladona leaf, atropine, propantheline
> S/E: CBUD
> C/I: glaucoma, gastric ulcer

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Muscarinic receptors:
Inc.GI motility
Inc.GI secretion
Muscarinic Receptor Blocker/anticholinergic
Dec.GI motility
Dec.GI secretion

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e.g. PIRENZEPINE
-specific M1 receptor antagonist
-currently investigated as an antisecretory agent
**suppresses gastric secretion at doses having
minimal effect on other organs

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Prostagladin
>Moa: Suppress gastric acid secretion and guards the mucosa
form NSAD-induces ulcers
>Misoprostol – a prostagladin analogue with antisecretory &
mucosal protective activity by increasing bicarbonate and
mucuc secretions
-indicated for NSAID-induces gastric ulcers
>S/E:diarrhea and abdominal pain
>C/I: pregnant, women with child-bearing potential

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CONSTIPATION
– difficult or infrequent passage of stool
S/S: abdominal bloating, headaches, sense of rectal fullness
Causes:
>Insufficient dietary fiber
>lack of exercise
>Medications (anticholinergic, antacids, narcotics)
>Organic problems- intestinal obstruction, IBS, tumor
etc.

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Treatment
>Nonpharmacologic
-increase fluid and fiber intake
-exercise regularly
-bowel training ti increase regularity

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Pharmacologic
Laxatives – stimulate defection, should not be taken if
nausea, vomiting, or abdominal pain is present

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1. Bulk-forming laxatives
MOA: natural or synthetic polysaccharide that
absorb water to soften stool and increase bulk,
which stimulates peristalsis
> slow onset of action (12-24 hrs, 72 hrs) thus
preventive
> take with 8 oz of water
> C/I obstruction bowel lesion, intestinal strictures,
Crohn’s disease

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> Natural bulk-forming laxatives
Psyllium (Metamucil, Fiberall, Konsyl-D, Perdium
Fiber Granules), Malt soup extract (Maltsupex)

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> Synthetic bulk-forming laxatives
Methylcellulose, Polycarbophil (Ca Polycarbophil impairs
Tetracycline absorption)

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2. Saline & Osmotic Laxatives
MOA: creates an osmotic gradient pulling water into the small
and large intestines, stimulates the activity of
cholecystokinin-pancreozymin which increases the
secretion of fluids into the GI tract
>Onset of oral: 3-6 hrs: rectal – 5-30 minutes

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> Saline laxatives – sodium and magnesium salts
> Should not be used in patients with HPN, CHF, & renal
impairment
> Magnesium citrate, Magnesium hydroxide, Magnesium
sulfate, Sodium `

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> Osmotis laxatives
> Glycerin – rectal burning
> Lactulose – decrease blood ammonia levels in hepatic
encephalopathy, S/E flatulence & cramping
> Sorbitol – nonabsorbable sugar
> Polyethylene glycol

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3. Stimulant laxatives
MOA: stimulate intestinal motility and increase secretion
of fluid into the bowel
> Onset of action of oral: 6-10 hrs; rectal 30-60 minutes
> Chronic use can lead to cathartic colon (should not be
used for more than 1 week)
S/E: abdominal cramping

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> Anthraquinone glycoside – melanoma coli
Sennosides – most potent
Cascara sagrada
Casanthranol – mild stimulant laxative
> Bisacodyl (Dulcolax) – diphenylmethane derivative,
enteric-coated
> Castor oil – onset: 2-6 hrs; works in the small
intestine which C/I in pregnant women

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4. Emollient laxatives
MOA: act as surfactants by allowing absorption of water into
stool
> Slow onset of action: 24-72 hrs
> Should not be used with mineral oil because it facilitates
systemic absorption of mineral oil leading to hepatotoxicity
> Docusate sodium
Docusate calcium
Docusate potassium

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5. Lubricant laxative (Mineral oil)
MOA: works at the colon to increase water retention in the
stool
> onset of action: 6-8 hrs
> May cause anal seepage, lipid pneumonotis, decrease vit.
A,D,E,K absorption

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* ANTIDIARRHEA
DIARRHEA
> Abnormal increase in the frequency and looseness of stools
> Happens when some factors impair the ability of the
intestines to absorb water from the stool

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Causes:
1. Infection – virus, bacteria,protozoa
2. Diet – induced ( high fiber, fatty or spicy food, large
amounts caffeine, milk intolerance)
3. Drug – induced

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Treatment
> Antidiarrheal may prevent an attack or relieve
existing symptoms
Non-pharmacological approach
Food – BRAT diet (Banana, Rice, Applesauce, Toast)
not advised anymore

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Fluids – ORS (NaCI, KCI, Na bicar, Glucose, Water)
-Fluids to be avoided: Hypertonic fruit juice, apple
juice, powdered drink mixes, gelatin water,
carbonated and caffeine-containing beverages
-Gatorade diluted in Water (1:1)provided necessary
combination of glucose, Na and K

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1. Antimotility/Antiperistaltic
MOA: stimulate mu opioid receptor slowing motility of the
small and large intestines
Loreramide, Diphenoxylate/atropine
S/E: abdominal pain, distension, dizziness, drowsiness, dry
mouth

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2. Adsorbent
MOA: adsorb toxins, bacteria, gases & fluids
Kaolin, Bismuth subsalicylate
3. Anti-infectives

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Irritable Bowel Syndrome
> pain, cramping, gassiness, constipation and/or
diarrhea
> symptoms appear after eating or during stress and
result from abnormal motility

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Treatment
Alosetron – a serotonin antagonist which blocks serotonin in
the GI tract thereby reducing the abdominal cramping,
urgency, and diarrhea associated with IBS
Antispasmodic – hyoscyamine, dicyclomine
Bulk – forming agents –psyllium
Antiflatulent – simethicone
Loperamide

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Crohn’s Disease – chronic, segmental inflammation
of the GI tract (ileum)
Sulfasalazine – 5-aminosalicylate (anti-inflammatory)

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Pseudomembranous colitis – inflammation of the
colon resulting from the use of antibiotics
> Clostridium difficile
> Mild to bloody diarrhea, abdominal pain, fever
> Metronidazole or Vancomycin

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*Emetic/Antiemetics
Emetic
> Used to induce vomiting in cases of poisoning
> Ipecac syrup is used to induce vomiting in the early
management of oral poisoning or drug overdose
MOA: Stimulates the chemoreceptor trigger zone in the
medulla
Antimetic – Agents that decrease the nausea, reducing the
urge to vomit

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> Ondansetron – antiemetic of choice in the US
-serotonin receptor antagonist
> Metoclopramide – effective against Cisplatin-
induced vomiting
> Butyrophenones- drromperodol, haleperidol,
droperidol

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> Phenothiazines- prochlorperazine
> Benzodiazepines – alprazolam, lorazepam
> Marijuana
> Corticosteroids- dexamethasone,
methylpednisolone

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